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1.
Zhonghua Er Ke Za Zhi ; 59(2): 95-100, 2021 Feb 02.
Artigo em Chinês | MEDLINE | ID: mdl-33548954

RESUMO

Objective: To investigate the safety of warfarin for Kawasaki disease (KD) with coronary artery aneurysm (CAA) and its prognosis. Methods: Twenty one children with KD complicated with giant CAA, multiple CAA in one coronary artery or thrombosis in coronary artery were enrolled in this prospective study. Warfarin was used to control the goal international normalized ratio (INR) ranging from 2.0 to 3.0. The CAA diameter, number, location and thrombus in coronary artery were recorded at the beginning of treatment, 1, 2, 3, 4 weeks and 2, 3, 6, 12 months after treatment, as well as the influence on INR, electrocaroliogram, creatine kinase-MB (CK-MB), troponin I. Standardized warfarin bleeding risk training and management was implemented. Children were divided into implementation group and non-implementation group according to the status of actual implementation of their parents. The incidence of bleeding events was compared between the two groups. Comparisons between groups were performed using a Rank sum test and a Fisher exact test. Results: In the 21 patients (15 males and 6 females), the age of onset ranged from 2 months to 6 years. There were 4 cases with grade Ⅱ, 7 cases with grade Ⅲ, 7 cases with grade Ⅳ and 3 cases with grade Ⅴ according to the severity of coronary arterial lesions before treatment. The time of clinical detection of thrombus in 10 children with thrombosis ranged from the fourth day to the fourth month. The dose distribution of warfarin was 0.06-0.10 mg/(kg·d), and the INR was 1.80-2.59. Among the 10 cases with thrombus, 8 cases had disappearance of thrombi and 2 cases with grade Ⅴ had thrombus organization to different degree. After treatment, the coronary artery ectasia of the 4 cases with grade Ⅱ all returned to normal. Among the 7 cases with grade Ⅲ, 3 cases of coronary artery aneurysms returned to normal, and 4 cases did not change. Among the 7 cases with grade Ⅳ , 5 cases of coronary artery aneurysms shrank to grade Ⅲ, and 2 cases remained unchanged. Three cases with grade Ⅴ lesions had no changes in aneurysm. Neither new thrombus nor new CAA was detected during the treatment. There was no significant change in electrocardiogram before and after treatment. No statistically significant difference was found regarding the troponin I (0.07 (0-3.01) vs. 0.04 (0-0.29) µg/L, Z=0.932, P>0.05) and CK-MB (20.6 (11.2-58.2) vs. 29.0 (16.7-47.0) U/L, Z=1.906, P>0.05) before and after treatment. The incidence of bleeding events in the implementation group was significantly lower than that in the non-implementation group (2/15 vs. 4/6, Fisher=5.689, P=0.031). Conclusions: The application of goal INR of 2.0-3.0 and adjustment of warfarin dose according to the severity of CAA combined with standardized and strict warfarin bleeding risk training and management, can increase the safety of warfarin therapy in children with KD, improve the prognosis of coronary artery lesions, promote the dissolution of thrombi, prevent new thrombosis, and effectively reduce the incidence of bleeding complication.


Assuntos
Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Anticoagulantes/efeitos adversos , Criança , Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/etiologia , Feminino , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Estudos Prospectivos , Varfarina/efeitos adversos
2.
Clin Drug Investig ; 41(1): 77-88, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33341911

RESUMO

BACKGROUND AND OBJECTIVES: Intravenous immunoglobulin (IVIG) therapy for acute-stage Kawasaki disease (KD) is the first-line treatment for preventing the development of coronary artery aneurysms (CAA). Corticosteroids (prednisolone) and infliximab are often used in patients at a high risk of CAA or those with CAA at diagnosis; however, there are only a few reports of non-responders to corticosteroids as an adjuvant therapy or rescue alternative to IVIG. In this study, we compared the therapeutic effects of primary and secondary prednisolone with IVIG for KD. METHODS: We established the following three protocols: A was a secondary rescue prednisolone protocol; B was no prednisolone and second-line infliximab protocol, and C was the primary prednisolone protocol. The indication for prednisolone administration was based on the following: primary prednisolone administration, Kobayashi score; and secondary administration, Shizuoka score. RESULTS: Four hundred and sixty-nine patients were enrolled in the three protocols. A comparison between primary and secondary prednisolone and IVIG, as the first-line therapy revealed that the number of first non-responders in C group was 7 (8.3%), which was significantly lower than the 50 (20.9%) in A group. There was a significant difference in the first and second non-responders among the three groups, and the number of non-responders in A group was 6 (2.5%), which was significantly lower than the 13 (9.9%) in B group (p < 0.001, by Bonferroni test). The multivariate logistic regression analysis showed that IVIG non-responders among the protocol groups had an adjusted odds ratio of 6.47. Fifteen IVIG non-responders were administered infliximab as a second-line therapy, and of them, 9 (60%) showed therapy resistance. CAA occurred in 21 patients (4.6%). There was no significant difference among each protocol group. CONCLUSIONS: The number of IVIG non-responders in the group with prednisolone administration was lower than that in the group without prednisolone administration. Secondary rescue infliximab therapy for IVIG non-responders resulted in a lower defervescence effect than the secondary rescue IVIG with prednisolone administration. Further prospective randomized studies are needed to identify factors useful for preventing IVIG non-responders and determine the optimal rescue therapy for preventing CAA.


Assuntos
Imunoglobulinas Intravenosas/administração & dosagem , Infliximab/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Prednisolona/administração & dosagem , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Estudos Prospectivos
3.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334773

RESUMO

The aetiology of febrile exanthems in children is often difficult to distinguish clinically. A diagnosis of Kawasaki disease (KD) should be considered in infants with exanthematous fever. More perplexing is the increasing incidence of an atypical form of KD. Pathogenesis of KD remains unclear even though an aberrant response of the immune system to an unidentified pathogen is often hypothesised. A 30-fold increase in the incidence of KD in Italy during the SARS-CoV-2 pandemic suggests an immune response to a viral trigger. We report an infant clinically diagnosed with high probability as incomplete KD, who presented with reactivation of the BCG injection site even though fever with rash was only less than 3 days duration. Echocardiography confirmed coronary artery abnormalities and prompt treatment with intravenous immunoglobulin facilitated rapid recovery. Physicians should consider a diagnosis of KD if BCG site reactivation is noted in children presenting with febrile exanthema.


Assuntos
Exantema/etiologia , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Vacina BCG/administração & dosagem , Febre , Humanos , Fatores Imunológicos/uso terapêutico , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Vacinação/efeitos adversos , gama-Globulinas/uso terapêutico
4.
Medicine (Baltimore) ; 99(52): e23714, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350751

RESUMO

INTRODUCTION: Kawasaki disease (KD) is the leading cause of acquired heart abnormalities during childhood. The infiltration of CD8+ T cells plays an essential role in the formation of coronary aneurysms. Follicular cytotoxic T (Tfc) cells are a newly defined subset of CD8+ T cells that express CXC-chemokine receptor 5. The role of Tfc cells in KD is unclear. However, in this report, we present 2 KD children with sustained coronary artery aneurysms (CAA), and we found that their peripheral C-X-C Chemokine Receptor 5+ T cells contained quite amounts of CD4 negative cells. Importantly, these cells have never been reported in KD. PATIENTS CONCERNS: Case 1 was a 3-year-old boy with a complaint of continuous fever for 6 days and conjunctival injection for 3 days. Case 2 was a 6-month-old boy who was hospitalized because of persistent fever for 5 days, rashes and conjunctival injection for 1 day. DIAGNOSIS: Case 1 was diagnosed with KD according to typical symptoms and signs including fever over 5 days, conjunctival injection, rashes, swelling cervical lymph nodes and a strawberry tongue. Case 2 had atypical symptoms including persistent fever for 5 days, rashes and conjunctival injection, and he was diagnosed with KD based on the echocardiographic findings. INTERVENTION: Both the 2 patients received intravenous immunoglobulin and oral aspirin. Besides, case 1 was given the second infusion of intravenous immunoglobulin, intravenous prednisolone and low-molecular-weight heparin. OUTCOMES: The CAA of case 1 did not regress until the 12th month after disease onset. The CAA of patient 2 began to regress at the third month after disease onset. During the months from disease onset to the recent follow-up, no cardiovascular events had occurred. CONCLUSIONS: We speculate that Tfc cells may be associated with the formation of CAA. Further studies with larger sample size and functional analysis of these cells are needed.


Assuntos
Aneurisma Coronário/diagnóstico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Administração Oral , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Pré-Escolar , Aneurisma Coronário/complicações , Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/metabolismo , Diagnóstico Diferencial , Febre/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/metabolismo , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Linfócitos T Citotóxicos/metabolismo
5.
J Biol Regul Homeost Agents ; 34(4 Suppl. 2): 47-53, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33000600

RESUMO

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. It has a self-limiting course and so far, represents the most common cause of coronary heart disease acquired in children aged between 6 months and 5 years. The inflammatory process can involve the coronary arteries with the formation of aneurysms and thrombotic occlusions with the risk of sudden death, especially in infants. Myocardial inflammation and abnormalities of cardiac contractility can occur acutely or many years after the disease onset. Therapy must be started within 10 days after the onset of symptoms to reduce the risk of heart complications. Immunoglobulin and aspirin treatment are effective in reducing heart complications. Recent studies have shown new therapeutic strategies (corticosteroids, immunosuppressive and biological drugs) in case of ineffectiveness of treatment with immunoglobulins.


Assuntos
Cardiopatias , Síndrome de Linfonodos Mucocutâneos , Pré-Escolar , Vasos Coronários , Cardiopatias/etiologia , Humanos , Lactente , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico
6.
PLoS One ; 15(8): e0237321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853226

RESUMO

Kawasaki disease is the leading cause of pediatric acquired heart disease. Coronary artery abnormalities are the main complication of Kawasaki disease. Kawasaki disease patients with intravenous immunoglobulin resistance are at a greater risk of developing coronary artery abnormalities. Several scoring models have been established to predict resistance to intravenous immunoglobulin, but clinicians usually do not apply those models in patients because of their poor performance. To find a better model, we retrospectively collected data including 753 observations and 82 variables. A total of 644 observations were included in the analysis, and 124 of the patients observed were intravenous immunoglobulin resistant (19.25%). We considered 7 different linear and nonlinear machine learning algorithms, including logistic regression (L1 and L1 regularized), decision tree, random forest, AdaBoost, gradient boosting machine (GBM), and lightGBM, to predict the class of intravenous immunoglobulin resistance (binary classification). Data from patients who were discharged before Sep 2018 were included in the training set (n = 497), while all the data collected after 9/1/2018 were included in the test set (n = 147). We used the area under the ROC curve, accuracy, sensitivity, and specificity to evaluate the performances of each model. The gradient GBM had the best performance (area under the ROC curve 0.7423, accuracy 0.8844, sensitivity 0.3043, specificity 0.9919). Additionally, the feature importance was evaluated with SHapley Additive exPlanation (SHAP) values, and the clinical utility was assessed with decision curve analysis. We also compared our model with the Kobayashi score, Egami score, Formosa score and Kawamura score. Our machine learning model outperformed all of the aforementioned four scoring models. Our study demonstrates a novel and robust machine learning method to predict intravenous immunoglobulin resistance in Kawasaki disease patients. We believe this approach could be implemented in an electronic health record system as a form of clinical decision support in the near future.


Assuntos
Resistência a Medicamentos , Imunoglobulinas Intravenosas/farmacologia , Aprendizado de Máquina , Modelos Biológicos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Pré-Escolar , China , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/prevenção & controle , Estudos de Viabilidade , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Modelos Logísticos , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/imunologia , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
7.
Lancet Infect Dis ; 20(11): e276-e288, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32818434

RESUMO

As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions. However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown. We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19. We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill. These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development. TRANSLATIONS: For the French, Chinese, Arabic, Spanish and Russian translations of the abstract see Supplementary Materials section.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/uso terapêutico , Criança , Pré-Escolar , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Recém-Nascido , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/imunologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Fatores de Risco , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/virologia , Adulto Jovem
8.
J Clin Invest ; 130(11): 5942-5950, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32701511

RESUMO

BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center.


Assuntos
Corticosteroides/administração & dosagem , Betacoronavirus/metabolismo , Imunoglobulinas Intravenosas/administração & dosagem , Imunomodulação , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Síndrome de Resposta Inflamatória Sistêmica , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Lactente , Interleucina-10/sangue , Interleucina-6/sangue , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/tratamento farmacológico , Síndrome de Ativação Macrofágica/imunologia , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/imunologia , Peptídeo Natriurético Encefálico/sangue , Estudos Retrospectivos , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/imunologia
10.
Phytomedicine ; 70: 153208, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32283413

RESUMO

Background: Kawasaki disease (KD) is a self-limiting acute systemic vasculitis occur mainly in infants and young children under 5 years old. Although the use of acetylsalicylic acid (AAS) in combination with intravenous immunoglobulin (IVIG) remains the standard therapy to KD, the etiology, genetic susceptibility genes and pathogenic factors of KD are still un-elucidated. Purpose: Current obstacles in the treatment of KD include the lack of standard clinical and genetic markers for early diagnosis, possible severe side effect of AAS (Reye's syndrome), and the refractory KD cases with resistance to IVIG therapy, therefore, this review has focused on introducing the current advances in the identification of genetic susceptibility genes, environmental factors, diagnostic markers and adjuvant pharmacological intervention for KD. Results: With an overall update in the development of KD from different aspects, our current bioinformatics data has suggested CASP3, CD40 and TLR4 as the possible pathogenic factors or diagnostic markers of KD. Besides, a list of herbal medicines which may work as the adjunct therapy for KD via targeting different proposed molecular targets of KD have also been summarized. Conclusion: With the aid of modern pharmacological research and technology, it is anticipated that novel therapeutic remedies, especially active herbal chemicals targeting precise clinical markers of KD could be developed for accurate diagnosis and treatment of the disease.


Assuntos
Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/genética , Fitoterapia/métodos , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes Farmacêuticos/uso terapêutico , Aspirina/uso terapêutico , Antígenos CD40/genética , Caspase 3/genética , Criança , Pré-Escolar , Marcadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Japão/epidemiologia , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Receptor 4 Toll-Like/genética
11.
Cardiovasc Ther ; 2020: 3568608, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256707

RESUMO

Children with Kawasaki disease (KD) resistant to intravenous immunoglobulin (IVIG) have a higher incidence of coronary artery lesions (CAL). Despite the association between Purinergic receptor P2Y12 (P2RY12) polymorphism, KD genetic susceptibility, and CAL complications being proved, few studies have assessed the relationship between P2RY12 polymorphisms and IVIG resistance in patients with KD. We recruited 148 KD patients with IVIG resistance and 611 with IVIG sensitivity and selected five P2RY12 polymorphisms: rs9859538, rs1491974, rs7637803, rs6809699, and rs2046934. A significant difference in the genotype distributions between patients was only observed for the rs6809699 A > C polymorphism (AC vs. AA: adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.27-0.84, P=0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27-0.83, P=0.0084). After adjusting for age and gender, the carriers of the rs6809699 C allele had OR of 0.44 to 0.49 for IVIG sensitivity (AC vs. AA: adjusted OR = 0.48, 95% confidence interval (CI) = 0.27-0.84, P=0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27-0.83, P=0.0084) compared to the carriers of a rs6809699 AA genotype, suggesting the protective effect of this SNP against IVIG resistance. Moreover, individuals with all five protective polymorphisms experienced a significantly decreased IVIG resistance compared to that of individuals with up to three protective polymorphisms (adjusted OR = 0.27, 95% CI = 0.13-0.57, P=0.0006). Our results suggest that the P2RY12 rs6809699 polymorphism could be used as a biomarker to predict IVIG resistance in KD patients.


Assuntos
Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/prevenção & controle , Resistência a Medicamentos/genética , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Receptores Purinérgicos P2Y12/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Tomada de Decisão Clínica , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/imunologia , Feminino , Frequência do Gene , Heterozigoto , Homozigoto , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/imunologia , Seleção de Pacientes , Testes Farmacogenômicos , Valor Preditivo dos Testes , Fatores de Risco
13.
Medicine (Baltimore) ; 99(6): e18535, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32028387

RESUMO

BACKGROUND: In recent years, many studies focused on the association between the neutrophil-to-lymphocyte ratio (NLR) and the risk of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (rKD), with inconsistent results. Therefore, we aimed to investigate the role of NLR as a biomarker in detecting rKD. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through May 18th, 2019. Meta-disc 1.4 and STATA 15.1 were used to perform this metaanalysis in a fixed/random-effect model. RESULTS: A total of 7 relevant studies were eligible to analyze pooled accuracy. The overall performance of NLR detection was: pooled sensitivity, 0.66 (95% confidence interval [CI], 0.63 - 0.70); pooled specificity, 0.71 (95%CI, 0.69 - 0.73); and area under the summary receiver operating characteristic curves value (SROC), 0.7956. The meta-regression analysis showed that the type of samples was the sources of heterogeneity. The subgroup analysis suggested that NLR detection after the initial treatment of IVIG had the largest area under curve of SROC in all the subgroups: pooled sensitivity, 0.58 (95%CI, 0.53 - 0.63); pooled specificity, 0.77 (95%CI, 0.75 - 0.79); and SROC, 0.8440. CONCLUSIONS: This is the first meta-analysis demonstrated that NLR might be a biomarker for detecting rKD, especially NLR value after the initial treatment of IVIG. More well-designed researches need to be done to launch the application of NLR for predicting rKD in the clinic.


Assuntos
Resistência a Medicamentos , Imunoglobulinas Intravenosas/uso terapêutico , Linfócitos/citologia , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Neutrófilos/citologia , Biomarcadores/sangue , Humanos , Síndrome de Linfonodos Mucocutâneos/sangue
15.
Vascul Pharmacol ; 127: 106660, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32070767

RESUMO

Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis especially in coronary arteries. Berberine (BBR) shows several beneficial effects on cardiovascular system. The present study is to investigate whether BBR exerts protective effect against KD-induced damage of human coronary artery endothelial cell (HCAECs) and the underlying mechanisms. HCAECs exposed to medium with 15% serum from KD patients or healthy volunteers for 24 h. Stimulated HCAECs were treated with vehicle (without BBR) and BBR (20 µM) for 24 h, the cell apoptosis, cell cycle, induction of intracellular reactive oxygen species (ROS) and protein expression were examined by flow cytometry and western blot. The KD-induced differentially expressed proteins in HCAECs were determined by quantitative proteomics. BBR inhibited HCAECs from apoptosis and arrested cell cycle at G0/G1 stage. BBR protected HCAECs from injury by inhibiting expression of THBD, vWF and EDN1. Bioinformatics analysis suggested that the oxidative and ER stress were involved in KD-induced damage in HCAECs. ROS production and the protein expression of ATF4, p-EIF2α, p-PERK, XBP1, p-IRE1, HSP90B1, HSPG2, DNAJC3, P4HB and VCP were increased by serum from KD patients and decreased by BBR treatment. BBR exerts its protective effects on KD-induced damage of HCAECs through its inhibitory effects on oxidative and ER stress indicating BBR as a therapeutic candidate for KD.


Assuntos
Antioxidantes/farmacologia , Berberina/farmacologia , Doença da Artéria Coronariana/prevenção & controle , Vasos Coronários/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Células Cultivadas , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/metabolismo , Síndrome de Linfonodos Mucocutâneos/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
16.
Pediatr Infect Dis J ; 39(3): 229-231, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31917754

RESUMO

The evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for intravenous immunoglobulin resistance prediction was prospectively performed in a large cohort of Kawasaki disease patients. It was found that the predictive values of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, alone or combined, were not good enough although they were identified as independent risk factors for intravenous immunoglobulin resistance.


Assuntos
Resistência a Medicamentos , Imunoglobulinas Intravenosas/uso terapêutico , Contagem de Leucócitos , Linfócitos , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Neutrófilos , Biomarcadores , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Contagem de Linfócitos , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Prognóstico , Sensibilidade e Especificidade , Resultado do Tratamento
17.
J Hum Genet ; 65(4): 421-426, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31965063

RESUMO

Kawasaki disease (KD) is an acute, self-limited vasculitis, mainly affecting children younger than 5 years old, with accompanying fever and signs of mucocutaneous inflammation. Intravenous immunoglobulin (IVIG) is the standard treatment for KD; however, ~15% of patients are resistant to IVIG treatment. To identify protein coding genetic variants influencing IVIG resistance, we re-analyzed our previous genome-wide association study (GWAS) data from 296 patients with KD, including 101 IVIG non-responders and 195 IVIG responders. Five nonsynonymous SNPs (nsSNPs) in five immune-related genes, including a previously reported SAMD9L nsSNP (rs10488532; p.Val266Ile), were associated with IVIG non-response (odds ratio [OR] = 1.89-3.46, P = 0.0109-0.0035). In a replication study of the four newly-identified nsSNPs, only one in the interleukin 16 (IL16) gene (rs11556218, p.Asn1147Lys) showed a trend of association with IVIG non-response (OR = 1.54, P = 0.0078). The same IL16 nsSNP was more significantly associated with IVIG non-response in combined analysis of all data (OR = 1.64, P = 1.25 × 10-4). Furthermore, risk allele combination of the IL16 CT and SAMD9L TT nsSNP genotypes exhibited a very strong effect size (OR = 9.19, P = 3.63 × 10-4). These results implicate IL16 as involved in the mechanism of IVIG resistance in KD.


Assuntos
Resistência a Medicamentos/genética , Imunoglobulinas Intravenosas/administração & dosagem , Interleucina-16/genética , Síndrome de Linfonodos Mucocutâneos , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/genética
18.
Arterioscler Thromb Vasc Biol ; 40(3): 802-818, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31996019

RESUMO

OBJECTIVE: Kawasaki disease (KD) is the leading cause of acute vasculitis and acquired heart disease in children in developed countries. Notably, KD is more prevalent in males than females. We previously established a key role for IL (interleukin)-1 signaling in KD pathogenesis, but whether this pathway underlies the sex-based difference in susceptibility is unknown. Approach and Results: The role of IL-1 signaling was investigated in the Lactobacillus casei cell wall extract-induced experimental mouse model of KD vasculitis. Five-week-old male and female mice were injected intraperitoneally with PBS, Lactobacillus caseicell wall extract, or a combination of Lactobacillus caseicell wall extract and the IL-1 receptor antagonist Anakinra. Aortitis, coronary arteritis inflammation score and abdominal aorta dilatation, and aneurysm development were assessed. mRNA-seq (messenger RNA sequencing) analysis was performed on abdominal aorta tissue. Publicly available human transcriptomics data from patients with KD was analyzed to identify sex differences and disease-associated genes. Male mice displayed enhanced aortitis and coronary arteritis as well as increased incidence and severity of abdominal aorta dilatation and aneurysm, recapitulating the increased incidence in males that is observed in human KD. Gene expression data from patients with KD and abdominal aorta tissue of Lactobacillus caseicell wall extract-injected mice showed enhanced Il1b expression and IL-1 signaling genes in males. Although the more severe IL-1ß-mediated disease phenotype observed in male mice was ameliorated by Anakinra treatment, the milder disease phenotype in female mice failed to respond. CONCLUSIONS: IL-1ß may play a central role in mediating sex-based differences in KD, with important implications for the use of anti-IL-1ß therapies to treat male and female patients with KD.


Assuntos
Aorta Abdominal/metabolismo , Interleucina-1beta/metabolismo , Síndrome de Linfonodos Mucocutâneos/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Aorta Abdominal/imunologia , Estudos de Casos e Controles , Modelos Animais de Doenças , Resistência a Medicamentos , Feminino , Disparidades nos Níveis de Saúde , Humanos , Incidência , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1beta/genética , Lactobacillus casei , Masculino , Camundongos Endogâmicos C57BL , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/microbiologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Transdução de Sinais
19.
JAMA Netw Open ; 3(1): e1918565, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899532

RESUMO

Importance: Timely initiation of intravenous immunoglobulin plus aspirin is necessary for decreasing the risk of recrudescent fever and coronary artery abnormalities in children with Kawasaki disease (KD). The optimal dose of aspirin, however, remains unclear. Objective: To evaluate whether initial treatment with low-dose compared with high-dose aspirin in children with KD is associated with an increase in fever recrudescence. Design, Setting, and Participants: A retrospective cohort study of 260 children with KD at Riley Hospital for Children, Indianapolis, Indiana, between January 1, 2007, and December 31, 2018, was conducted. Children aged 0 to 18 years with a first episode of KD, identified by International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes treated within 10 days of symptom onset with high-dose intravenous immunoglobulin plus aspirin were eligible. Patients who received an alternative diagnosis, experienced a second episode of KD, did not receive intravenous immunoglobulin plus aspirin for initial treatment, were not treated within 10 days of symptoms, or had incomplete records were excluded. Exposures: High-dose (≥10 mg/kg/d) or low-dose (<10 mg/kg/d) aspirin therapy. Main Outcomes and Measures: The primary outcome was recrudescent fever necessitating retreatment of KD. The secondary outcomes were coronary artery abnormalities and hospital length of stay. Results: Among the 260 patients included, the median (interquartile range) age was 2.5 (1.6-4.3) years, 103 (39.6%) were girls, 166 (63.8%) were non-Hispanic white, 57 (21.9%) were African American, 22 (8.5%) were Asian, 11 (4.2%) were Hispanic, and 4 (1.5%) were of unknown race/ethnicity. One hundred-forty-two patients (54.6%) were treated with low-dose aspirin. There was no association between recrudescent fever and aspirin dose, with 39 children (27.5%) having recrudescent fever in the low-dose group compared with 26 children (22.0%) in the high-dose group (odds ratio [OR], 1.34; 95% CI, 0.76-2.37; P = .31), with similar results after adjusting for potential confounding variables (OR, 1.63; 95% CI, 0.89-2.97; P = .11). In a subset analysis of 167 children with complete KD, however, there was nearly a 2-fold difference in the odds of recrudescent fever with low-dose aspirin (OR, 1.87; 95% CI, 0.82-4.23; P = .14), although this difference did not reach statistical significance. In addition, no association was identified between treatment group and coronary artery abnormalities (low-dose, 7.4% vs high-dose, 9.4%; OR, 0.86; 95% CI, 0.48-1.55; P = .62) or median (interquartile range) length of stay (3 [3-5] days for both groups; P = .27). Conclusions and Relevance: In this study, low-dose aspirin for the initial treatment of children with KD was not associated with fever recrudescence or coronary artery abnormalities. Given the potential benefits, further study of low-dose aspirin to detect potentially clinically relevant outcome differences is warranted to inform treatment decisions and guideline development.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Febre/prevenção & controle , Imunoglobulinas Intravenosas/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/prevenção & controle , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Febre/epidemiologia , Febre/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
Pediatr Int ; 62(3): 363-370, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31657491

RESUMO

BACKGROUND: The precise mechanism of hyponatremia in Kawasaki disease (KD) remains elusive because assessment of volume status based on serial changes in body weight is lacking in previous reports. METHODS: Seventeen patients who were diagnosed with KD and hyponatremia (serum sodium levels <135 mmol/L) were analyzed. Volume status was assessed based on serial changes in body weight. Plasma arginine vasopressin (ADH), urine electrolytes, and serum cytokine levels were measured on diagnosis of hyponatremia. An increase in body weight by >3% was defined as hypervolemia and a decrease in body weight by >3% was defined as hypovolemia. RESULTS: The volume status was hypervolemic in three patients (18%), euvolemic in 14 (82%), and hypovolemic in none (0%). Five (29%) patients were diagnosed with "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH) and no patients were diagnosed with hypotonic dehydration. The contribution of decreased total exchangeable cations (salt loss) to hyponatremia (5.9% [interquartile range, 4.3%, 6.7%]) was significantly larger than that of increased total body water (-0.7% [-1.8%, 3.1%]) (P = 0.004). Serum interleukin-6 levels were elevated in all of the nine patients who were evaluated. Among the 12 (71%) patients who did not meet the criteria of SIADH and hypotonic dehydration, plasma ADH levels were inappropriately high in ten patients. These patients were also characterized by euvolemic or hypervolemic hyponatremia and salt loss, which might be compatible with a diagnosis of SIADH. CONCLUSIONS: Our study shows that hyponatremia in KD is euvolemic or hypervolemic and is associated with nonosmotic secretion of ADH and salt loss in the majority of patients.


Assuntos
Arginina Vasopressina/metabolismo , Hiponatremia/etiologia , Síndrome de Linfonodos Mucocutâneos/complicações , Arginina Vasopressina/sangue , Água Corporal , Pré-Escolar , Feminino , Humanos , Hiponatremia/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Secreção Inadequada de HAD/complicações , Síndrome de Secreção Inadequada de HAD/tratamento farmacológico , Lactente , Interleucina-6/sangue , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Sódio/sangue , Sódio/urina , Resultado do Tratamento
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