Background The epidemiologic pictures of Kawasaki disease （KD） in Shanghai from 1998 through 2002 were reported while the current status of KD in the following five years remains unknown. Methods A questionnaire for...Background The epidemiologic pictures of Kawasaki disease （KD） in Shanghai from 1998 through 2002 were reported while the current status of KD in the following five years remains unknown. Methods A questionnaire form and diagnostic guidelines for KD were sent to 50 hospitals providing pediatric medical care in Shanghai, China. All patients with KD diagnosed during January 2003 through December 2007 were recruited. Results In total, 1187 cases of KD were enrolled. The incidence of KD was 36.78 to 53.28 （mean 46.32±6.51） per 100 000 children under the age of 5 years between 2003 and 2007, which was higher than the year from 1998 to 2002 of （27.32±7.11） per 100 000, （t=4.406, P=0.002）. Ages at onset ranged from 12 days to 13.6 years （median 1.8 years）. It occurred more frequently in summer and spring. Coronary arterial lesions （CAL）, defined as ectasia or aneurysm, accounted for 19.8% （232 cases）. Flattened or inverted T wave was the most frequent finding （194 cases, 20.5%） by electrocardiogram. Intravenous gamma-globulin was administrated to 1028 cases （86.6%）. The occurrence of CAL seemed less frequent in the patients received gamma-globulin from day 5 to day 9 after the onset with the regimen of 1000 mg/kg once or 1000 mg/kg twice. Conclusions The incidence of KD was increasing in Shanghai. Treatment with intravenous gamma-globulin from day 5 to day 9 after the onset with the regimen of 1000 mg/kg once or 1000 mg/kg twice resulted in less coronary seauelae.展开更多
Kawasaki disease(KD) is a common medium vessel systemic vasculitis that usually occurs in small children. It has a predilection for the coronary arteries, but other medium sized arteries can also be involved. The etio...Kawasaki disease(KD) is a common medium vessel systemic vasculitis that usually occurs in small children. It has a predilection for the coronary arteries, but other medium sized arteries can also be involved. The etiology of this disorder remains a mystery. Though typical presentation of KD is quite characteristic, it may also present as incomplete or atypical disease in which case the diagnosis can be very challenging. As both incomplete and atypical forms of KD can be associated with serious coronary artery complications, the pediatrician can ill afford to miss these diagnoses. The American Heart Association has enunciated consensus guidelines to facilitate the clinical diagnosis and treatment of this condition. However, there are still several issues that remain controversial. Intravenous immunoglobulin remains the cornerstone of management but several other treatment modalities, especially glucocorticoids, are increasingly finding favour. We review here some of the contemporary issues, and the controversies thereon, pertaining to management of KD.展开更多
Background Currently,there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease.Methods A total of 300 patients with Kawasa...Background Currently,there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease.Methods A total of 300 patients with Kawasaki disease were studied retrospectively.Laboratory data were compared between the intravenous immunoglobulin resistant (29 patients) and responsive groups,and between the groups with coronary artery lesions (48 patients) and without coronary artery lesions.Results The intravenous immunoglobulin resistant group had significantly higher D-dimer,globulin,interleukin-6 and serum ferritin levels in comparison to the intravenous immunoglobulin responder group.D-dimer level had a sensitivity of 87.0% and a specificity of 56.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 1.09 mg/L.Globulin had a sensitivity of 62.1% and a specificity of 82.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 34.7 g/L.Serum ferritin level had a sensitivity of 42.9% and a specificity of 88.8% for predicting intravenous immunoglobulin resistance at a cutoff point of 269.7 ng/mL.The patients with coronary artery lesions had higher D-dimer and tumor necrosis factor-α level.D-dimer level had a sensitivity of 50% and a specificity of 78.6% for predicting coronary artery lesions at a cutoff point of 1.84 mg/L.Based on analysis by multivariate logistic regression,serum ferritin and globulin were independent risks for intravenous immunoglobulin resistance,D-dimer was independent risk for coronary artery lesions.Conclusions Elevated serum ferritin,globulin and D-dimer levels are significantly associated with intravenous immunoglobulin resistance in Kawasaki disease.Moreover,serum D-dimer is significantly increased in Kawasaki disease with coronary artery lesions.展开更多
The biomarkers associated with coronary artery lesions （CAL） secondary to Kawasaki disease （KD） in Chinese children were investigated by using Meta-analysis. We searched documents published from January 1997 to De...The biomarkers associated with coronary artery lesions （CAL） secondary to Kawasaki disease （KD） in Chinese children were investigated by using Meta-analysis. We searched documents published from January 1997 to December 2009 from medical electronic databases. According to inclusion and exclusion criteria, eligible full-text papers were identified. We conducted a comprehensive quantitative analysis by using Stata10.0 statistical software package to assess the heterogeneity among the documents, calculated the summary effect and analyze publication bias and sensitivity. A total of 92 documents and 16 biomarkers were identified. All documents were case-control studies, and included 2398 patients in CAL group and 5932 patients in non-CAL （NCAL） group. The Meta-analysis showed that the levels of platelet count, platelet hematocrit （PCT）, neutrophils count, platelet distribution width （PDW）, mean platelet volume （MPV）, erythrocyte sedimentation rate （ESR）, cardiac troponin Ⅰ （cTnI）, and endothelin-1 （ET-1） in CAL group were significantly higher than those in NCAL group, and serum albumin （Alb） and hemoglobin （Hb） levels were significantly lower in CAL group （all P〈0.05）. White blood cell （WBC） count, serum sodium, matrix metalloproteinase 9 （MMP-9）, total cholesterol （TC）, hematocrit （HCT） and CD3＋T lymphocytes percentage had no statistically significant difference between the two groups. In conclusion, our results indicated that the 10 biomarkers including platelet count, neutrophils count, PCT, PDW, MPV, ESR, cTnI, ET-1, Alb and Hb were associated with CAL, and may be involved in the pathogenesis of CAL. The biomarkers of WBC count, serum sodium, MMP-9, TC, HCT, and CD3＋T lymphocytes percentage bore no relationship with the development of CAL among Chinese children with KD.展开更多
Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This stu...Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 （MMP-9） and on the underlying mechanisms in tumor necrosis factor-α （TNF-α）-activated human coronary artery endothelial cells （HCAECs）,a cell model of Kawasaki disease.Methods：HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time points.The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,respectively.Nuclear factor-κB （NF-κB） activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot assay.Protein expression levels of mitogen-activated protein kinase （c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38） were determined by Western blot assay.Results：After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity.Furthermore,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min.In addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.Conclusions：The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.展开更多
Background Cardiovascular complications of Kawasaki disease （KD） are a common cause of heart disease in pediatric populations.Previous studies have suggested a role for endothelial progenitor cells （EPCs） in coron...Background Cardiovascular complications of Kawasaki disease （KD） are a common cause of heart disease in pediatric populations.Previous studies have suggested a role for endothelial progenitor cells （EPCs） in coronary artery lesions associated with KD.However,long-term observations of EPCs during the natural progression of this disorder are lacking.Using an experimental model of KD,we aimed to determine whether the coronary artery lesions are associated with down-regulation of EPCs.Methods To induce KD,C57BL/6 mice were administered an intraperitoneal injection of Lactobacillus casei cell wall extract （LCWE; phosphate buffered saline used as control vehicle）.Study groups included：group A （14 days following LCWE injection）,group B （56 days following LCWE injection） and group C （controls）.Numbers of circulating EPCs （positively staining for both CD34 and FIk-1 while staining negative for CD45） were evaluated using flow cytometry.Bone marrow mononuclear cells were cultured in vitro to expand EPCs for functional analysis.In vitro EPC proliferation,adhesion and migration were assessed.Results The model was shown to exhibit similar coronary artery lesions to KD patients with coronary aneurysms.Numbers of circulating EPCs decreased significantly in the KD models （groups A and B） compared to controls （（0.017±0.008）% VS.（0.028±0.007）%,P〈0.05 and （0.016±0.007）% vs.（0.028±0.007）%,P 〈0.05）.Proliferative,adhesive and migratory properties of EPCs were markedly impaired in groups A and B.Conclusion Coronary artery lesions in KD occur as a consequence of impaired vascular injury repair,resulting from excess consumption of EPCs together with a functional impairment of bone marrow EPCs and their precursors.展开更多
Kawasaki disease shock syndrome （KDSS） refers to Kawasaki disease （KD） patients who present more than 20% decrease in systolic blood pressure compared to healthy individuals of the same age, or to those patients w...Kawasaki disease shock syndrome （KDSS） refers to Kawasaki disease （KD） patients who present more than 20% decrease in systolic blood pressure compared to healthy individuals of the same age, or to those patients who show peripheral blood circulation perfusion disorder. KDSS may have varied clinical courses and could be easily ignored and misdiagnosed. Yet, this syndrome could be deleterious, especially when combined with coronary artery injury or multiple organ dysfunctions. Therefore, early diagnosis of KDSS through specific clinical manifestations is critical. This manuscript summarizes the clinical features and treatment methods of 11 children with KDSS who were able to fully recover in our hospital. The results shed lights on understanding the early identification of KDSS and could assist in reducing the complications of KD and improving the quality of life in KDSS patients.展开更多
Background Coronary artery damage from Kawasaki disease （KD） is closely linked to the dysfunction of endothelial progenitor cells （EPCs）. The aim of the present study was to evaluate the therapeutic effect of EPCs...Background Coronary artery damage from Kawasaki disease （KD） is closely linked to the dysfunction of endothelial progenitor cells （EPCs）. The aim of the present study was to evaluate the therapeutic effect of EPCs transplantation in KD model. Methods Lactobacillus casei cell wall extract （LCWE）-induced KD model in C57BL/6 mice was established. The model mice were injected intravenously with bone marrow-derived in vitro expanded EPCs. Histological evaluation, number of circulating EPCs and the function of bone marrow EPCs were examined at day 56. Results Inflammation was found around the coronary artery of the model mice after 14 days, Elastin breakdown was observed after 56 days. CM-Dil labeled EPCs incorporated into vessel repairing foci was found. At day 56, the number of peripheral EPCs in the KD model group was lower than in EPCs transplanted and control group. The functional index of bone marrow EPCs from the KD model group decreased in proliferation, adhesion and migration. Increased number of circulating EPCs and improved function were observed on the EPCs transplanted group compared with model group. Conclusion Exogenously administered EPCs, which represent a novel strategy could prevent the dysfunction of EPCs, accelerate the repair of coronary artery endothelium lesion and decrease the occurrence of aneurysm.展开更多
Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistentl...Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistently found in patients with KD,usually in 2nd to 3rd week of illness.Thrombocytopenia has occasionally been reported in the acute phase of KD.An increase or decrease in platelet number in patients with KD was initially considered to be a benign phenomenon.However,recent literature on platelet biology in KD has suggested that platelets are not only increasing but are rather activated.This phenomenon has been found to increase the risk of thrombosis in these patients.Similarly a fall in platelet counts during acute stage of KD has also been found to be associated with increased severity of disease.In this review,we update on the current best understanding about pathogenic role of platelets in patients with KD.展开更多
Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A ...Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018.Eighty patients with MAS were enrolled,including 53 cases with systemic juvenile idiopathic arthritis(SJIA-MAS),10 cases of Kawasaki disease(KD-MAS),and 17 cases of connective tissue disease(CTD-MAS).The clinical and laboratory data were collected before(pre-),at onset,and during full-blown stages of MAS.We compared the data among the SJIA-MAS,KD-MAS,and CTD-MAS subjects.Results 51.2%of patients developed MAS when the underlying disease was first diagnosed.In patients with SJIA,22.6%(12/53)were found to have hypotension before the onset of SJIA-MAS.These patients were also found to have significantly increased aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as decreased albumin(P<0.05),but no difference in alanine aminotransferase,ferdtin,and ratio of ferritin/erythrocyte sedimentation rate(ESR)at onset of MAS when compared to pre-MAS stages of the disease.In addition,ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage.Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD.Receiver-operating characteristic analysis showed that 12,217.5μg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity(80.0%and 90.5%)and specificity(88.2%and 86.7%),respectively,for predicting full-blown SJIA-MAS.The majority of the patients received corticosteroids(79/80),while biologic agents were used in 12.5%(10/80)of cases.Tocilizumab was the most commonly selected biologic agent.The overall mortality rate was 7.5%.Conclusions About half of MAS occurred when the underlying autoimmune diseases(SJIA,KD,and CTD)were first diagnosed.Hypotension could be an importa展开更多
Background：Coronary artery lesions （CALs） are known to be the main complication in children with Kawasaki disease （KD）.Instead of intravenous immunoglobulin （IVIG）,corticosteroid therapy has been accepted to be...Background：Coronary artery lesions （CALs） are known to be the main complication in children with Kawasaki disease （KD）.Instead of intravenous immunoglobulin （IVIG）,corticosteroid therapy has been accepted to be used for children with KD who are unresponsive to IVIG.This study aimed to evaluate risk factors for CALs in children with KD.Methods：We retrospectively reviewed the clinical records of 2331 children with KD from January 2005 to December 2014.To identify the independent risk factors for CALs,multivariable logistic regression models were constructed using significant variables identified from univariate logistic regression analysis.Results：The incidence of CALs was 36.0% （840 of 2331）,including 625 （26.8%） coronary artery dilations and 215 （9.2%） coronary artery aneurysms （CAAs）.Multivariable logistic regression analysis identified that male,incomplete KD,longer fever duration,and C-reactive protein （CRP） 〉 100 mg/L were independent risk factors for coronary artery dilatations.On the other hand,male,incomplete KD,longer fever duration,prolonged days of illness at the initial treatment,corticosteroid therapy,sodium ≤133 mmol/L,and albumin 〈35 g/L were the independent risk factors for CAAs.In addition,corticosteroid therapy,prolonged days of illness at the initial treatment,and albumin 〈35 g/L were the independent risk factors for giant CAAs.Conclusions：CALs might be associated with male sex,incomplete KD,longer fever duration,prolonged days of illness at the initial treatment,albumin 〈35 g/L,sodium ≤ 133 mmol/L,CRP 〉 100 mg/L,and corticosteroid therapy.Corticosteroid therapy was an independent risk factor for CAAs and giant CAAs.Thus,corticosteroids should be used with caution in the treatment of KD with the risk for CALs.展开更多
Background Cardiac involvement is the most common complication of Kawasaki disease （KD）; however, the underlying mechanisms are not understood. The present study was designed to investigate changes in plasma hydrog...Background Cardiac involvement is the most common complication of Kawasaki disease （KD）; however, the underlying mechanisms are not understood. The present study was designed to investigate changes in plasma hydrogen sulfide （H2S） and nitric oxide （NO） levels in the acute and recovery stages of KD children and to examine their clinical significance. Methods Thirty-five KD patients and 32 healthy children were enrolled in the study. KD patients were divided into two subgroups： a non-cardiac involvement group and a cardiac involvement group. Plasma H2S levels were measured using the sulfur-sensitive electrode method and plasma NO levels and NO synthase activity were determined using the nitrate reductase method both before and after intravenous immune globulin （IVIG） therapy. Results Plasma H2S levels significantly decreased in KD patients during the acute phase of the disease and NO levels were significantly increased, compared with the control group （P 〈0.01）. After treatment with IVIG, both plasma H2S and NO levels significantly increased （P 〈0.01）. The plasma levels of H2S were significantly lower in the cardiac involvement group compared with the non-cardiac involvement group （P 〈0.05）. Conclusion H2S and NO may play a role in the pathophysiological process of inflammation during the acute phase of KD. Endogenous H2S may exert protective effects with respect to cardiac complications in KD.展开更多
Background Doppler color echocardiography is a common method for detecting coronary artery lesions in patients with Kawasaki disease（KD）.However,the diagnostic accuracy for the whole coronary artery lesions is limit...Background Doppler color echocardiography is a common method for detecting coronary artery lesions in patients with Kawasaki disease（KD）.However,the diagnostic accuracy for the whole coronary artery lesions is limited.The purpose of this study was to compare the diagnostic value of dual-source computed tomography （DSCT） and Doppler color echocardiography for the assessment of coronary artery lesions caused by KD.Methods Sixteen patients,12 with typical KD and 4 with atypical KD,underwent DSCT and Doppler color echocardiography.The position and internal diameter of each coronary artery lesion was measured.Correlation analysis was used to compare the diagnostic value of the two imaging modalities.Results ln the typical KD group, seven patients did not have any coronary artery Iesion as confirmed by both DSCT scans and Doppler color echocardiography;in four patients proximal coronary artery injuries were identified by both modalities;in one patient an aneurysm in the middle and distal segments of the coronary artery was detected by DSCT but was negative in Doppler color echocardiography.In the atypical KD group,three cases showed the same results with both modalities,while one case with coronary artery stenosis in the middle segment was identified by DSCT but not detected by Doppler color echocardiography.There was a good correlation between the two imaging modalities（Kappa value,0.768（≥0.75））.Conclusion DSCT coronary artery angiography is an accurate,non-invasive,and valuable technique for detecting and following up coronary artery lesions in patients with KD.展开更多
Background Macrophage activation syndrome(MAS)is a rare,life-threatening complication of Kawasaki disease(KD).Early recognition and treatment of MAS are very important,but sometimes it is difficult to distinguish MAS ...Background Macrophage activation syndrome(MAS)is a rare,life-threatening complication of Kawasaki disease(KD).Early recognition and treatment of MAS are very important,but sometimes it is difficult to distinguish MAS from a severe form of KD.Data sources A PubMed search was performed in Clinical Queries using the key terms“macrophage activation syndrome or secondary hemophagocytic lymphohistiocytosis(HLH)”and“Kawasaki disease”.Results KD patients with MAS show high intravenous immunoglobulin(IVIG)resistance and coronary complications.Mortality is also as high as MAS in other diseases.Persistent fever greater than 10 days is highly associated with development of MAS in KD.Splenomegaly is observed in more than two-thirds of KD patients with MAS.Thrombocytopenia is often the earliest laboratory finding of MAS.Hyperferritinemia is highly specific and sensitive for detecting MAS in KD;so,ferritin levels should be checked if there are unexplained clinical exacerbations in KD patients.Given the under-recognition of MAS in KD,it is prudent to consider resistant KD as occult/subclinical MAS.Many KD patients with MAS have good outcomes on immune modulators.However,if KD patients fulfill the HLH-2004 diagnostic criteria,they may undergo longer and more intensive treatment than needed.Conclusions The possible existence of MAS should be taken into account when a KD patient shows persistent fever,splenomegaly,thrombocytopenia,hyperferritinemia,or IVIG resistance.The under-diagnosis of MAS in patients with KD is an important issue to be addressed.Therapeutically,however,there is a possibility of over-treatment of MAS in patients with KD.展开更多
文摘Background The epidemiologic pictures of Kawasaki disease （KD） in Shanghai from 1998 through 2002 were reported while the current status of KD in the following five years remains unknown. Methods A questionnaire form and diagnostic guidelines for KD were sent to 50 hospitals providing pediatric medical care in Shanghai, China. All patients with KD diagnosed during January 2003 through December 2007 were recruited. Results In total, 1187 cases of KD were enrolled. The incidence of KD was 36.78 to 53.28 （mean 46.32±6.51） per 100 000 children under the age of 5 years between 2003 and 2007, which was higher than the year from 1998 to 2002 of （27.32±7.11） per 100 000, （t=4.406, P=0.002）. Ages at onset ranged from 12 days to 13.6 years （median 1.8 years）. It occurred more frequently in summer and spring. Coronary arterial lesions （CAL）, defined as ectasia or aneurysm, accounted for 19.8% （232 cases）. Flattened or inverted T wave was the most frequent finding （194 cases, 20.5%） by electrocardiogram. Intravenous gamma-globulin was administrated to 1028 cases （86.6%）. The occurrence of CAL seemed less frequent in the patients received gamma-globulin from day 5 to day 9 after the onset with the regimen of 1000 mg/kg once or 1000 mg/kg twice. Conclusions The incidence of KD was increasing in Shanghai. Treatment with intravenous gamma-globulin from day 5 to day 9 after the onset with the regimen of 1000 mg/kg once or 1000 mg/kg twice resulted in less coronary seauelae.
文摘Kawasaki disease(KD) is a common medium vessel systemic vasculitis that usually occurs in small children. It has a predilection for the coronary arteries, but other medium sized arteries can also be involved. The etiology of this disorder remains a mystery. Though typical presentation of KD is quite characteristic, it may also present as incomplete or atypical disease in which case the diagnosis can be very challenging. As both incomplete and atypical forms of KD can be associated with serious coronary artery complications, the pediatrician can ill afford to miss these diagnoses. The American Heart Association has enunciated consensus guidelines to facilitate the clinical diagnosis and treatment of this condition. However, there are still several issues that remain controversial. Intravenous immunoglobulin remains the cornerstone of management but several other treatment modalities, especially glucocorticoids, are increasingly finding favour. We review here some of the contemporary issues, and the controversies thereon, pertaining to management of KD.
基金This work was supported,in part,by grants from The National Natural Science Foundation of China(81670251).
文摘Background Currently,there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease.Methods A total of 300 patients with Kawasaki disease were studied retrospectively.Laboratory data were compared between the intravenous immunoglobulin resistant (29 patients) and responsive groups,and between the groups with coronary artery lesions (48 patients) and without coronary artery lesions.Results The intravenous immunoglobulin resistant group had significantly higher D-dimer,globulin,interleukin-6 and serum ferritin levels in comparison to the intravenous immunoglobulin responder group.D-dimer level had a sensitivity of 87.0% and a specificity of 56.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 1.09 mg/L.Globulin had a sensitivity of 62.1% and a specificity of 82.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 34.7 g/L.Serum ferritin level had a sensitivity of 42.9% and a specificity of 88.8% for predicting intravenous immunoglobulin resistance at a cutoff point of 269.7 ng/mL.The patients with coronary artery lesions had higher D-dimer and tumor necrosis factor-α level.D-dimer level had a sensitivity of 50% and a specificity of 78.6% for predicting coronary artery lesions at a cutoff point of 1.84 mg/L.Based on analysis by multivariate logistic regression,serum ferritin and globulin were independent risks for intravenous immunoglobulin resistance,D-dimer was independent risk for coronary artery lesions.Conclusions Elevated serum ferritin,globulin and D-dimer levels are significantly associated with intravenous immunoglobulin resistance in Kawasaki disease.Moreover,serum D-dimer is significantly increased in Kawasaki disease with coronary artery lesions.
文摘The biomarkers associated with coronary artery lesions （CAL） secondary to Kawasaki disease （KD） in Chinese children were investigated by using Meta-analysis. We searched documents published from January 1997 to December 2009 from medical electronic databases. According to inclusion and exclusion criteria, eligible full-text papers were identified. We conducted a comprehensive quantitative analysis by using Stata10.0 statistical software package to assess the heterogeneity among the documents, calculated the summary effect and analyze publication bias and sensitivity. A total of 92 documents and 16 biomarkers were identified. All documents were case-control studies, and included 2398 patients in CAL group and 5932 patients in non-CAL （NCAL） group. The Meta-analysis showed that the levels of platelet count, platelet hematocrit （PCT）, neutrophils count, platelet distribution width （PDW）, mean platelet volume （MPV）, erythrocyte sedimentation rate （ESR）, cardiac troponin Ⅰ （cTnI）, and endothelin-1 （ET-1） in CAL group were significantly higher than those in NCAL group, and serum albumin （Alb） and hemoglobin （Hb） levels were significantly lower in CAL group （all P〈0.05）. White blood cell （WBC） count, serum sodium, matrix metalloproteinase 9 （MMP-9）, total cholesterol （TC）, hematocrit （HCT） and CD3＋T lymphocytes percentage had no statistically significant difference between the two groups. In conclusion, our results indicated that the 10 biomarkers including platelet count, neutrophils count, PCT, PDW, MPV, ESR, cTnI, ET-1, Alb and Hb were associated with CAL, and may be involved in the pathogenesis of CAL. The biomarkers of WBC count, serum sodium, MMP-9, TC, HCT, and CD3＋T lymphocytes percentage bore no relationship with the development of CAL among Chinese children with KD.
基金Acknowledgments We thank Medjaden and Editage for its linguistic assistance during the preparation of this manuscript. Financial support and sponsorship This study was supported by the grants from National Natural Science Foundation of China （No. 81274109, 30973238）, Key Research Project of Beijing Natural Science Foundation （B）/Beijing Education Committee （No. KZ201010025024）, and Project for Science and Technology Innovation, Beijing Education Committee （No. PXM2011 014226 07 000085）.
文摘Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 （MMP-9） and on the underlying mechanisms in tumor necrosis factor-α （TNF-α）-activated human coronary artery endothelial cells （HCAECs）,a cell model of Kawasaki disease.Methods：HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time points.The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,respectively.Nuclear factor-κB （NF-κB） activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot assay.Protein expression levels of mitogen-activated protein kinase （c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38） were determined by Western blot assay.Results：After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity.Furthermore,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min.In addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.Conclusions：The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.
基金This study was supported by the grants from National Natural Science Foundation of China（No.30973238）,Beijing Natural Science Foundation （No.7092032）,Key Research Project of Beijing Natural Science Foundation （B）/Beijing Education Committee （No.KZ201010025024） and Beijing ＂215＂ Medical Professional Project （No.2009-3-38）.
文摘Background Cardiovascular complications of Kawasaki disease （KD） are a common cause of heart disease in pediatric populations.Previous studies have suggested a role for endothelial progenitor cells （EPCs） in coronary artery lesions associated with KD.However,long-term observations of EPCs during the natural progression of this disorder are lacking.Using an experimental model of KD,we aimed to determine whether the coronary artery lesions are associated with down-regulation of EPCs.Methods To induce KD,C57BL/6 mice were administered an intraperitoneal injection of Lactobacillus casei cell wall extract （LCWE; phosphate buffered saline used as control vehicle）.Study groups included：group A （14 days following LCWE injection）,group B （56 days following LCWE injection） and group C （controls）.Numbers of circulating EPCs （positively staining for both CD34 and FIk-1 while staining negative for CD45） were evaluated using flow cytometry.Bone marrow mononuclear cells were cultured in vitro to expand EPCs for functional analysis.In vitro EPC proliferation,adhesion and migration were assessed.Results The model was shown to exhibit similar coronary artery lesions to KD patients with coronary aneurysms.Numbers of circulating EPCs decreased significantly in the KD models （groups A and B） compared to controls （（0.017±0.008）% VS.（0.028±0.007）%,P〈0.05 and （0.016±0.007）% vs.（0.028±0.007）%,P 〈0.05）.Proliferative,adhesive and migratory properties of EPCs were markedly impaired in groups A and B.Conclusion Coronary artery lesions in KD occur as a consequence of impaired vascular injury repair,resulting from excess consumption of EPCs together with a functional impairment of bone marrow EPCs and their precursors.
文摘Kawasaki disease shock syndrome （KDSS） refers to Kawasaki disease （KD） patients who present more than 20% decrease in systolic blood pressure compared to healthy individuals of the same age, or to those patients who show peripheral blood circulation perfusion disorder. KDSS may have varied clinical courses and could be easily ignored and misdiagnosed. Yet, this syndrome could be deleterious, especially when combined with coronary artery injury or multiple organ dysfunctions. Therefore, early diagnosis of KDSS through specific clinical manifestations is critical. This manuscript summarizes the clinical features and treatment methods of 11 children with KDSS who were able to fully recover in our hospital. The results shed lights on understanding the early identification of KDSS and could assist in reducing the complications of KD and improving the quality of life in KDSS patients.
基金This study was supported by the grants from National Natural Science Foundation of China （No. 30973238）, Beijing Natural Science Foundation （No.7092032）, Key Research Project of Beijing Natural Science Foundation （B）/Beijing Education Committee （No. KZ201010025024） and Beijing ＂215＂ Medical Professional Project Fund （No. 2009-3-38）.
文摘Background Coronary artery damage from Kawasaki disease （KD） is closely linked to the dysfunction of endothelial progenitor cells （EPCs）. The aim of the present study was to evaluate the therapeutic effect of EPCs transplantation in KD model. Methods Lactobacillus casei cell wall extract （LCWE）-induced KD model in C57BL/6 mice was established. The model mice were injected intravenously with bone marrow-derived in vitro expanded EPCs. Histological evaluation, number of circulating EPCs and the function of bone marrow EPCs were examined at day 56. Results Inflammation was found around the coronary artery of the model mice after 14 days, Elastin breakdown was observed after 56 days. CM-Dil labeled EPCs incorporated into vessel repairing foci was found. At day 56, the number of peripheral EPCs in the KD model group was lower than in EPCs transplanted and control group. The functional index of bone marrow EPCs from the KD model group decreased in proliferation, adhesion and migration. Increased number of circulating EPCs and improved function were observed on the EPCs transplanted group compared with model group. Conclusion Exogenously administered EPCs, which represent a novel strategy could prevent the dysfunction of EPCs, accelerate the repair of coronary artery endothelium lesion and decrease the occurrence of aneurysm.
文摘Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistently found in patients with KD,usually in 2nd to 3rd week of illness.Thrombocytopenia has occasionally been reported in the acute phase of KD.An increase or decrease in platelet number in patients with KD was initially considered to be a benign phenomenon.However,recent literature on platelet biology in KD has suggested that platelets are not only increasing but are rather activated.This phenomenon has been found to increase the risk of thrombosis in these patients.Similarly a fall in platelet counts during acute stage of KD has also been found to be associated with increased severity of disease.In this review,we update on the current best understanding about pathogenic role of platelets in patients with KD.
基金This study is funded by Zhejiang Basic Public Welfare Research Project(LGF19H100002).
文摘Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018.Eighty patients with MAS were enrolled,including 53 cases with systemic juvenile idiopathic arthritis(SJIA-MAS),10 cases of Kawasaki disease(KD-MAS),and 17 cases of connective tissue disease(CTD-MAS).The clinical and laboratory data were collected before(pre-),at onset,and during full-blown stages of MAS.We compared the data among the SJIA-MAS,KD-MAS,and CTD-MAS subjects.Results 51.2%of patients developed MAS when the underlying disease was first diagnosed.In patients with SJIA,22.6%(12/53)were found to have hypotension before the onset of SJIA-MAS.These patients were also found to have significantly increased aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as decreased albumin(P<0.05),but no difference in alanine aminotransferase,ferdtin,and ratio of ferritin/erythrocyte sedimentation rate(ESR)at onset of MAS when compared to pre-MAS stages of the disease.In addition,ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage.Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD.Receiver-operating characteristic analysis showed that 12,217.5μg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity(80.0%and 90.5%)and specificity(88.2%and 86.7%),respectively,for predicting full-blown SJIA-MAS.The majority of the patients received corticosteroids(79/80),while biologic agents were used in 12.5%(10/80)of cases.Tocilizumab was the most commonly selected biologic agent.The overall mortality rate was 7.5%.Conclusions About half of MAS occurred when the underlying autoimmune diseases(SJIA,KD,and CTD)were first diagnosed.Hypotension could be an importa
基金This study was supported by grants from National Natural Science Foundation of China，Key Research Project of Beijing Natural Science Foundation (B)/Beijing Education Committee，Project for Science and Technology Innovation,Beijing Education Committee
文摘Background：Coronary artery lesions （CALs） are known to be the main complication in children with Kawasaki disease （KD）.Instead of intravenous immunoglobulin （IVIG）,corticosteroid therapy has been accepted to be used for children with KD who are unresponsive to IVIG.This study aimed to evaluate risk factors for CALs in children with KD.Methods：We retrospectively reviewed the clinical records of 2331 children with KD from January 2005 to December 2014.To identify the independent risk factors for CALs,multivariable logistic regression models were constructed using significant variables identified from univariate logistic regression analysis.Results：The incidence of CALs was 36.0% （840 of 2331）,including 625 （26.8%） coronary artery dilations and 215 （9.2%） coronary artery aneurysms （CAAs）.Multivariable logistic regression analysis identified that male,incomplete KD,longer fever duration,and C-reactive protein （CRP） 〉 100 mg/L were independent risk factors for coronary artery dilatations.On the other hand,male,incomplete KD,longer fever duration,prolonged days of illness at the initial treatment,corticosteroid therapy,sodium ≤133 mmol/L,and albumin 〈35 g/L were the independent risk factors for CAAs.In addition,corticosteroid therapy,prolonged days of illness at the initial treatment,and albumin 〈35 g/L were the independent risk factors for giant CAAs.Conclusions：CALs might be associated with male sex,incomplete KD,longer fever duration,prolonged days of illness at the initial treatment,albumin 〈35 g/L,sodium ≤ 133 mmol/L,CRP 〉 100 mg/L,and corticosteroid therapy.Corticosteroid therapy was an independent risk factor for CAAs and giant CAAs.Thus,corticosteroids should be used with caution in the treatment of KD with the risk for CALs.
文摘Background Cardiac involvement is the most common complication of Kawasaki disease （KD）; however, the underlying mechanisms are not understood. The present study was designed to investigate changes in plasma hydrogen sulfide （H2S） and nitric oxide （NO） levels in the acute and recovery stages of KD children and to examine their clinical significance. Methods Thirty-five KD patients and 32 healthy children were enrolled in the study. KD patients were divided into two subgroups： a non-cardiac involvement group and a cardiac involvement group. Plasma H2S levels were measured using the sulfur-sensitive electrode method and plasma NO levels and NO synthase activity were determined using the nitrate reductase method both before and after intravenous immune globulin （IVIG） therapy. Results Plasma H2S levels significantly decreased in KD patients during the acute phase of the disease and NO levels were significantly increased, compared with the control group （P 〈0.01）. After treatment with IVIG, both plasma H2S and NO levels significantly increased （P 〈0.01）. The plasma levels of H2S were significantly lower in the cardiac involvement group compared with the non-cardiac involvement group （P 〈0.05）. Conclusion H2S and NO may play a role in the pathophysiological process of inflammation during the acute phase of KD. Endogenous H2S may exert protective effects with respect to cardiac complications in KD.
文摘Background Doppler color echocardiography is a common method for detecting coronary artery lesions in patients with Kawasaki disease（KD）.However,the diagnostic accuracy for the whole coronary artery lesions is limited.The purpose of this study was to compare the diagnostic value of dual-source computed tomography （DSCT） and Doppler color echocardiography for the assessment of coronary artery lesions caused by KD.Methods Sixteen patients,12 with typical KD and 4 with atypical KD,underwent DSCT and Doppler color echocardiography.The position and internal diameter of each coronary artery lesion was measured.Correlation analysis was used to compare the diagnostic value of the two imaging modalities.Results ln the typical KD group, seven patients did not have any coronary artery Iesion as confirmed by both DSCT scans and Doppler color echocardiography;in four patients proximal coronary artery injuries were identified by both modalities;in one patient an aneurysm in the middle and distal segments of the coronary artery was detected by DSCT but was negative in Doppler color echocardiography.In the atypical KD group,three cases showed the same results with both modalities,while one case with coronary artery stenosis in the middle segment was identified by DSCT but not detected by Doppler color echocardiography.There was a good correlation between the two imaging modalities（Kappa value,0.768（≥0.75））.Conclusion DSCT coronary artery angiography is an accurate,non-invasive,and valuable technique for detecting and following up coronary artery lesions in patients with KD.
文摘Background Macrophage activation syndrome(MAS)is a rare,life-threatening complication of Kawasaki disease(KD).Early recognition and treatment of MAS are very important,but sometimes it is difficult to distinguish MAS from a severe form of KD.Data sources A PubMed search was performed in Clinical Queries using the key terms“macrophage activation syndrome or secondary hemophagocytic lymphohistiocytosis(HLH)”and“Kawasaki disease”.Results KD patients with MAS show high intravenous immunoglobulin(IVIG)resistance and coronary complications.Mortality is also as high as MAS in other diseases.Persistent fever greater than 10 days is highly associated with development of MAS in KD.Splenomegaly is observed in more than two-thirds of KD patients with MAS.Thrombocytopenia is often the earliest laboratory finding of MAS.Hyperferritinemia is highly specific and sensitive for detecting MAS in KD;so,ferritin levels should be checked if there are unexplained clinical exacerbations in KD patients.Given the under-recognition of MAS in KD,it is prudent to consider resistant KD as occult/subclinical MAS.Many KD patients with MAS have good outcomes on immune modulators.However,if KD patients fulfill the HLH-2004 diagnostic criteria,they may undergo longer and more intensive treatment than needed.Conclusions The possible existence of MAS should be taken into account when a KD patient shows persistent fever,splenomegaly,thrombocytopenia,hyperferritinemia,or IVIG resistance.The under-diagnosis of MAS in patients with KD is an important issue to be addressed.Therapeutically,however,there is a possibility of over-treatment of MAS in patients with KD.
