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1.
J Pediatr Hematol Oncol ; 45(6): 356-359, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37314881

RESUMO

Giant or large coronary artery aneurysms (CAA) are rare in children, most often secondary to Kawasaki disease, and anticoagulation is recommended to prevent thromboembolism. There are no published pediatric reports on the use of a direct oral anticoagulant for this indication. We describe the anticoagulation management of an 8-year-old boy with a dilated right CAA secondary to Kawasaki disease that has remained stable on rivaroxaban and aspirin, following bleeding complications on enoxaparin and challenges on warfarin. The use of rivaroxaban appears to be safe and effective in the prevention of thrombosis in a pediatric patient with CAA.


Assuntos
Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Tromboembolia Venosa , Masculino , Humanos , Criança , Rivaroxabana/uso terapêutico , Anticoagulantes/uso terapêutico , Vasos Coronários , Síndrome de Linfonodos Mucocutâneos/complicações , Tromboembolia Venosa/tratamento farmacológico , Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/etiologia , Aneurisma Coronário/prevenção & controle
2.
Arch Dis Child ; 108(10): 833-838, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37258054

RESUMO

OBJECTIVE: Children with Kawasaki disease (KD) and an initial echocardiogram that demonstrates coronary artery aneurysms (CAAs, Z score ≥2.5) are at high risk for severe cardiovascular complications. We sought to determine if primary adjunctive infliximab treatment at a dose of either 5 or 10 mg/kg, compared with intravenous immunoglobulin (IVIG) alone, is associated with a greater likelihood of CAA regression in patients with KD with CAA at the time of diagnosis. DESIGN AND SETTING: Single-centre observational study. PATIENTS: Children with acute KD and Z score ≥2.5 at baseline. INTERVENTIONS: Primary adjunctive infliximab (5 or 10 mg/kg) within 48 hours of initiating IVIG 2 g/kg. MAIN OUTCOME MEASURES: Incidence of CAA regression to Zmax <2 within 2 months of disease onset. RESULTS: Of the 168 patients with KD, 111 received IVIG alone and 57 received primary adjunctive infliximab therapy: 39 received 5 mg/kg and 18 received 10 mg/kg. Incidence of CAA regression to Zmax <2 within 2 months was statistically significant at 52%, 62% and 83% in the IVIG alone, IVIG+infliximab 5 mg/kg and IVIG+infliximab 10 mg/kg, respectively. The multivariable logistic regression model adjusting for age, sex, baseline Zmax and bilateral CAA at baseline showed that IVIG plus 10 mg/kg infliximab was significantly associated with a greater likelihood of CAA regression (adjusted OR: 4.45, 95% CI 1.17 to 16.89, p=0.028) compared with IVIG alone. The difference between IVIG+infliximab 5 mg/kg and IVIG alone was not significant. CONCLUSIONS: Primary adjunctive high-dose 10 mg/kg infliximab treatment was associated with a greater likelihood of CAA regression in patients with CAA at the time of diagnosis.


Assuntos
Aneurisma Coronário , Doença da Artéria Coronariana , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Lactente , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Infliximab/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Vasos Coronários , Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/etiologia , Aneurisma Coronário/diagnóstico , Estudos Retrospectivos , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/etiologia
3.
J Pediatr ; 263: 113346, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36775190

RESUMO

OBJECTIVES: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). STUDY DESIGN: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). RESULTS: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). CONCLUSION: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD.


Assuntos
Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Aneurisma Coronário/epidemiologia , Aneurisma Coronário/etiologia , Aneurisma Coronário/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , América Latina/epidemiologia , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Estudos Retrospectivos
4.
Cardiol Young ; 33(4): 613-618, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35545881

RESUMO

BACKGROUND: The Etanercept as Adjunctive Treatment for Acute Kawasaki Disease, a phase-3 clinical trial, showed that etanercept reduced the prevalence of IVIg resistance in acute Kawasaki disease. In patients who presented with coronary artery involvement, it reduced the maximal size and short-term progression of coronary artery dilation. Following up with this patient group, we evaluated the potential long-term benefit of etanercept for coronary disease. METHODS: Patients were followed for at least 1 year after the trial. The size of dilated arteries (z-score ≥ 2.5) was measured at each follow-up visit. The z-score and size change from baseline were evaluated at each visit and compared between patients who received etanercept versus placebo at the initial trial. RESULTS: Forty patients who received etanercept (22) or placebo (18) in the Etanercept as Adjunctive Treatment for Acute Kawasaki Disease trial were included. All patients showed a persistent decrease in coronary artery size measurement: 23.3 versus 5.9% at the 6-month visit, 24 versus 13.1% at the 1-year visit, and 20.8 versus 19.3% at the ≥ 2-year visit for etanercept or placebo, respectively, with similar results for decrease in coronary artery z-scores. In a multivariate analysis, correcting for patients' growth, a greater size reduction for patients on the etanercept arm versus placebo was proved significant for the 6-month (p = 0.005) and the 1-year visits (p = 0.019) with a similar end outcome at the ≥ 2-year visit. DISCUSSION: Primary adjunctive therapy with etanercept for children with acute Kawasaki disease does not change the end outcome of coronary artery disease but may promote earlier resolution of artery dilation.


Assuntos
Aneurisma Coronário , Doença da Artéria Coronariana , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Lactente , Imunoglobulinas Intravenosas/uso terapêutico , Etanercepte/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Seguimentos , Doença Aguda , Doença da Artéria Coronariana/tratamento farmacológico , Aneurisma Coronário/tratamento farmacológico
5.
BMJ Case Rep ; 15(6)2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35680277

RESUMO

Multisystem inflammatory syndrome in children (MIS-C) is a newly described syndrome related to the COVID-19, resembling other known aetiologies, including Kawasaki disease. Cardiovascular involvement is common; left ventricle dysfunction and coronary artery aneurysm (CAA) are also observed. Many treatment guidelines recommend using intravenous immunoglobulin (IVIG) alone or with glucocorticoids as the first-line therapy. Biological agents, such as anakinra, are recommended for refractory cases, but the evidence is still accumulating. Moreover, the use of other treatment agents can be beneficial, especially when anakinra is unavailable. Here, we report the case of a 9-year-old girl who presented with MIS-C with CAAs. She received cyclosporine because two rounds of IVIG treatment were ineffective and the use of anakinra is not approved in Japan. Her cytokine profile showed that cyclosporine prevented exacerbation. The case highlights that cyclosporine therapy can be an option for the treatment of refractory MIS-C with CAA.


Assuntos
COVID-19 , Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , COVID-19/complicações , Criança , Aneurisma Coronário/complicações , Aneurisma Coronário/tratamento farmacológico , Vasos Coronários , Ciclosporina/uso terapêutico , Feminino , Humanos , Imunoglobulinas Intravenosas , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(4): 399-404, 2022 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-35527415

RESUMO

OBJECTIVES: To examine the association between duration of fever before intravenous immunoglobulin (IVIG) treatment and IVIG resistance in children with Kawasaki disease (KD). METHODS: A retrospective analysis was performed on the medical data of 317 children with KD who were admitted from January 2018 to December 2020. According to the duration of fever before IVIG treatment, they were divided into two groups: short fever duration group (≤4 days) with 92 children and long fever duration group (>4 days) with 225 children. According to the presence or absence of IVIG resistance, each group was further divided into a drug-resistance group and a non-drug-resistance group. Baseline data and laboratory results were compared between groups. A multivariate logistic regression analysis was used to identify the influencing factors for IVIG resistance. RESULTS: In the short fever duration group, 19 children (20.7%) had IVIG resistance and 5 children (5.4%) had coronary artery aneurysm, and in the long fever duration group, 22 children (9.8%) had IVIG resistance and 19 children (8.4%) had coronary artery aneurysm, suggesting that the short fever duration group had a significantly higher rate of IVIG resistance than the long fever duration group (P<0.05), while there was no significant difference in the incidence rate of coronary artery aneurysm between the two groups (P>0.05). In the short fever duration group, compared with the children without drug resistance, the children with drug resistance had a significantly lower level of blood sodium and significantly higher levels of procalcitonin, C-reactive protein, and N-terminal B-type natriuretic peptide before treatment (P<0.05). In the long fever duration group, the children with drug resistance had significantly lower levels of blood sodium and creatine kinase before treatment than those without drug resistance (P<0.05). The multivariate logistic regression analysis showed that a reduction in blood sodium level was associated with IVIG resistance in the long fever duration group (P<0.05). CONCLUSIONS: IVIG resistance in children with KD varies with the duration of fever before treatment. A reduction in blood sodium is associated with IVIG resistance in KD children with a duration of fever of >4 days before treatment.


Assuntos
Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Criança , Aneurisma Coronário/tratamento farmacológico , Febre/complicações , Febre/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Estudos Retrospectivos , Sódio/uso terapêutico
8.
Zhonghua Er Ke Za Zhi ; 60(1): 14-19, 2022 Jan 02.
Artigo em Chinês | MEDLINE | ID: mdl-34986617

RESUMO

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.


Assuntos
Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Criança , Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/etiologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Infliximab/efeitos adversos , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Estudos Retrospectivos
9.
Pediatr Res ; 91(6): 1542-1550, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34021270

RESUMO

BACKGROUND: The use of corticosteroids in Kawasaki disease (KD) is still controversial. The aim of this study was to investigate the safety and effectiveness of modified methylprednisolone (mPSL) regimen as an initial treatment for refractory KD. METHODS: This is a real-world observational study. We identified refractory KD with a self-developed scoring system. Patients were divided into the intravenous immunoglobulin (IVIG) + mPSL group and the IVIG group. Clinical outcomes and changes in coronary arteries after the treatment during a 12-week period were observed. Propensity-score matching was used to analyze those patients with similar baseline characteristics. RESULTS: Of a total of 168 patients, 104 patients were assigned into the IVIG group and 64 patients into the IVIG + mPSL group. The therapeutic response rate of the IVIG + mPSL group was significantly higher than that of the IVIG group (98.4 vs 76.0%, P < 0.05). The IVIG + mPSL group had a shorter duration of fever and a higher rate of C-reactive protein decline than the IVIG group (1.17 ± 0.64 vs 1.81 ± 1.16 days; 88.1 vs 83.5%; P < 0.05). The luminal diameter and Z-score of the left circumflex coronary artery (LCX) were significantly smaller and lower in the IVIG + mPSL group than that in the IVIG group at weeks 2 and 12. CONCLUSIONS: Modified mPSL regimen has minimal side effects. It might improve the initial response to IVIG and decrease the dilation of LCX for refractory KD. IMPACT: Modified mPSL regimen (2-4 mg/kg/day, divided into 2-3 doses for 3-5 days, then 1 mg/kg/day, once a day for 3-5 days, then oral prednisone was tapered over 3-5 weeks in 5-7 days steps) as an intensive initial treatment can decrease LCX dilation in high-risk IVIG-resistant KD patients. Our self-developed scoring system has been proven validated and can be used to identify high-risk IVIG-resistant KD patients in North China. The present study provides an alternative therapeutic regimen for high-risk refractory KD patients.


Assuntos
Aneurisma Coronário , Doença da Artéria Coronariana , Síndrome de Linfonodos Mucocutâneos , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/tratamento farmacológico , Doença da Artéria Coronariana/tratamento farmacológico , Dilatação , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Metilprednisolona/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Estudos Retrospectivos
10.
J Pediatr ; 243: 173-180.e8, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34953816

RESUMO

OBJECTIVES: To determine the safety, pharmacokinetics, and immunomodulatory effects of 2-6 weeks of anakinra therapy in patients with acute Kawasaki disease with a coronary artery aneurysm (CAA). STUDY DESIGN: We performed a Phase I/IIa dose-escalation study of anakinra (2-11 mg/kg/day) in 22 patients with acute Kawasaki disease with CAA. We measured interleukin (IL)-1RA concentrations after the first dose and trough levels up to study week 6. Markers of inflammation and coronary artery z-scores were assessed pretreatment and at 48 hours, 2 weeks, and 6 weeks after initiation of therapy. RESULTS: Up to 6 weeks of anakinra (up to 11 mg/kg/day) was safe and well tolerated by the 22 participants (median age, 1.1 years), with no serious adverse events attributable to the study drug. All participants were treated with intravenous immunoglobulin (IVIG), and 20 also received infliximab (10 mg/kg) before initiation of anakinra. Serum levels of IL-6, IL-8, and tumor necrosis factor α decreased similarly in patients with Kawasaki disease treated with IVIG, infliximab, and anakinra compared with age- and sex-matched patients with Kawasaki disease treated only with IVIG and infliximab. Anakinra clearance increased with illness day at diagnosis. Simulations demonstrated that more frequent intravenous (IV) dosing may result in more sustained concentrations without significantly increasing the peak concentration compared with subcutaneous (SC) dosing. CONCLUSIONS: Both IV and SC anakinra are safe in infants and children with acute Kawasaki disease and CAA. IV dosing every 8-12 hours during the acute hospitalization of patients with Kawasaki disease may result in a sustained concentration while avoiding frequent SC injections. The efficacy of a short course of IV therapy during hospitalization should be studied. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT02179853.


Assuntos
Aneurisma Coronário , Proteína Antagonista do Receptor de Interleucina 1 , Síndrome de Linfonodos Mucocutâneos , Doença Aguda , Aneurisma Coronário/complicações , Aneurisma Coronário/tratamento farmacológico , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Infliximab/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico
12.
Pediatr Rheumatol Online J ; 19(1): 31, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731148

RESUMO

BACKGROUND: Despite timely administration of IVIG, some patients with Kawasaki disease (KD) develop rapidly progressive or giant coronary artery aneurysms (CAA). CASE PRESENTATION: We describe our experience using cyclophosphamide (CYC) for the treatment of such cases as well as a review of the literature on the use of CYC in KD. Through a retrospective chart review of our KD population, we identified ten children treated for KD with intravenous CYC (10 mg/kg/dose) for one or two doses. Seven patients were male, the median age was 2.0 years (range 4 months - 5 years). All patients received initial IVIG between day 4-10 of illness. Other anti-inflammatory treatments administered before CYC included second IVIG (n = 9), corticosteroids (n = 10), infliximab (n = 4), cyclosporine (n = 2), and anakinra (n = 1). Median illness day at administration of the first CYC dose was 22.5 days (range:10-36 days). The primary indication for treatment with CYC for all patients was large or giant CAA and/or rapid progression of CAA. Three patients received a second dose of CYC (10 mg/kg) for progressively enlarging CAA. CAA did not progress after final CYC treatment. One patient with a history of neutropenia in infancy developed severe neutropenia 9 days after treatment with CYC, which recovered without intervention or complications. No patient developed infections or other serious toxicity from CYC. CONCLUSION: In KD patients with severe and progressive enlargement of CAA despite anti-inflammatory therapy, CYC seemed to arrest further dilation and was well-tolerated. Future multicenter studies are needed to confirm our findings in this subgroup of KD patients.


Assuntos
Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/etiologia , Ciclofosfamida/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
13.
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
15.
Arch Dis Child ; 106(3): 247-252, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32943389

RESUMO

OBJECTIVE: Patients with Kawasaki disease (KD) with coronary artery enlargement at diagnosis are at the highest risk for persistent coronary artery aneurysms (CAAs) and may benefit from primary adjunctive anti-inflammatory therapy beyond intravenous immunoglobulin (IVIG). We evaluate the effect of primary adjunctive corticosteroid therapy on outcomes in patients with CAA at diagnosis. DESIGN: Single-centre, retrospective review. PATIENTS: Patients with KD diagnosed within 10 days of fever onset and with baseline CA z-score ≥2.5. INTERVENTIONS: Primary treatment with IVIG (n=162) versus IVIG plus corticosteroids (n=48). MAIN OUTCOME MEASURES: Treatment resistance (persistent fever >36 hours after initial treatment), CAA regression rate. RESULTS: Of the 92 patients with KD who received corticosteroids at our institution from 2012 to 2019, 48 met the inclusion criteria for primary adjunctive therapy. The corticosteroid group was younger and had larger baseline CAAs compared with historical controls. Demographics and laboratory values were otherwise similar between groups. The corticosteroid group had a less treatment resistance (4% vs 30%, p=0.003) and a greater improvement in C reactive protein. After adjusting for baseline CA z-score, age and baseline bilateral versus unilateral CAA, the corticosteroid group had a higher odds of (OR 2.77 (1.04, 7.42), p=0.042) and a shorter time to CAA regression (HR 1.94 (1.27, 2.96), p=0.002). CONCLUSION: Primary adjunctive corticosteroid therapy is associated with decreased initial treatment resistance, greater improvement in inflammatory markers and higher likelihood of CAA regression in patients who have CAA at diagnosis. Multi-centre, randomised controlled trials are needed to confirm the benefits of corticosteroids in patients with CAA at diagnosis and to compare corticosteroids with other adjunctive therapies.


Assuntos
Corticosteroides/uso terapêutico , Aneurisma Coronário/diagnóstico , Febre/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Corticosteroides/administração & dosagem , Proteína C-Reativa/efeitos dos fármacos , Estudos de Casos e Controles , Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/etiologia , Anomalias dos Vasos Coronários/patologia , Quimioterapia Combinada , Feminino , Febre/complicações , Febre/epidemiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
16.
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 Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/uso terapêutico , Linfócitos T Citotóxicos/metabolismo
17.
Can J Cardiol ; 36(10): 1598-1607, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32621885

RESUMO

BACKGROUND: The substantial risk of thrombosis in large coronary artery aneurysms (CAAs) (maximum z-score ≥ 10) after Kawasaki disease (KD) mandates effective thromboprophylaxis. We sought to determine the effectiveness of anticoagulation (low-molecular-weight heparin [LMWH] or warfarin) for thromboprophylaxis in large CAAs. METHODS: Data from 383 patients enrolled in the International KD Registry (IKDR) were used. Time-to-event analysis was used to account for differences in treatment duration and follow-up. RESULTS: From diagnosis onward (96% received acetylsalicylic acid concomitantly), 114 patients received LMWH (median duration 6.2 months, interquartile range [IQR] 2.5-12.7), 80 warfarin (median duration 2.2 years, IQR 0.9-7.1), and 189 no anticoagulation. Cumulative incidence of coronary artery thrombosis with LMWH was 5.7 ± 3.0%, with warfarin 6.7 ± 3.7%, and with no anticoagulation 20.6 ± 3.0% (P < 0.001) at 2.5 years after the start of thromboprophylaxis (LMWH vs warfarin HR 1.5, 95% confidence interval [CI] 0.4-5.1; P = 0.56). A total of 51/63 patients with coronary artery thrombosis received secondary thromboprophylaxis (ie, thromboprophylaxis after a previous thrombus): 27 LMWH, 24 warfarin. There were no differences in incidence of further coronary artery thrombosis between strategies (HR 2.9, 95% CI 0.6-13.5; P = 0.19). Severe bleeding complications were generally rare (1.6 events per 100 patient-years) and were noted equally for patients on LMWH and warfarin (HR 2.3, 95% CI 0.6-8.9; P = 0.25). CONCLUSIONS: LMWH and warfarin appear to have equivalent effectiveness for preventing thrombosis in large CAAs after KD, although event rates for secondary thromboprophylaxis and safety outcomes were low. Based on our findings, all patients with CAA z-score ≥ 10 should receive anticoagulation, but the choice of agent might be informed by secondary risk factors and patient preferences.


Assuntos
Quimioprevenção , Aneurisma Coronário , Heparina de Baixo Peso Molecular , Síndrome de Linfonodos Mucocutâneos , Trombose , Varfarina , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Canadá/epidemiologia , Quimioprevenção/métodos , Quimioprevenção/estatística & dados numéricos , Pré-Escolar , Aneurisma Coronário/complicações , Aneurisma Coronário/tratamento farmacológico , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Incidência , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Sistema de Registros/estatística & dados numéricos , Risco Ajustado , Trombose/epidemiologia , Trombose/etiologia , Trombose/prevenção & controle , Estados Unidos/epidemiologia , Varfarina/administração & dosagem , Varfarina/efeitos adversos
18.
Can J Cardiol ; 36(6): 967.e1-967.e3, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32407676

RESUMO

Coronary stent infection is considered to be a rare but catastrophic complication of percutaneous coronary intervention. In this report, we present a 72-year-old man who developed a coronary stent infection complicated by coronary aneurysm and purulent pericarditis. Coronary artery aneurysm resolved over a period of 8 months following the successful management of infection with intensive antibiotic therapy alone. This case suggests that conservative therapy can be a therapeutic option in patients with high operative risks.


Assuntos
Antibacterianos/administração & dosagem , Aneurisma Coronário , Doença das Coronárias/cirurgia , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea , Pericardite , Infecções Relacionadas à Prótese , Idoso , Angiografia por Tomografia Computadorizada , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/etiologia , Duração da Terapia , Eletrocardiografia/métodos , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Pericardite/diagnóstico , Pericardite/tratamento farmacológico , Pericardite/etiologia , Infecções Relacionadas à Prótese/complicações , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/fisiopatologia , Risco Ajustado/métodos , Staphylococcus aureus , Resultado do Tratamento
19.
Int Heart J ; 61(3): 601-605, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32350203

RESUMO

Giant coronary artery aneurysm (CAA) is a rare disorder, defined as coronary artery dilatation, in which the diameter of the coronary artery exceeds more than 1.5 times of its normal size. The most common cause of CAA is coronary atherosclerosis for adults and Kawasaki disease (KD) for children and adolescents (especially for the giant CAA that occurred in adolescence). CAA complications include thrombus, acute myocardial infarction (AMI), vasospasm, rupture, ischemia, heart failure, and arrhythmia. So, antithrombotic therapy is crucial for patients with giant CAA.Although giant CAA has been reported in some cases before, few of these cases described antithrombotic therapy particularly, let alone informed direct oral anticoagulant (DOAC) use in these patients. Here, we report a case of a young patient with acute coronary artery disease caused by huge CAA. Rivaroxaban combined with clopidogrel was used for his antithrombotic therapy. Moreover, we reviewed the existing reports to provide an overview of antithrombotic treatment in patients with giant CAA.


Assuntos
Clopidogrel/uso terapêutico , Aneurisma Coronário/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/uso terapêutico , Humanos , Masculino , Adulto Jovem
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