bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 103: Incomplete Kawasaki Disease - Patients With ≦ 5 Days Of Fever Successfully Treated By Antibiotics But Left With Coronary Aneurysms -
Authors: Suda Kenji , Nishino Hiroshi , Kudo Yoshiyuki , Yoshimoto Hironaga , Kishimoto Shintaro , Iemura Motofumi , Iwamoto Jiro , Nishihara Shigetaka , Gotou Yoshitaka , Nishibatake Makoto , Matsuishi Toyojiro
Published: July 2021

Objective:
We report four patients with incomplete Kawasaki disease (KD) successfully treated by antibiotics without intravenous immunoglobulin (IVIG) treatment with ≦ 5 days of fever but left with coronary artery lesion.

Result:
The patients were 2 babies and 2 young children age ranged from 2 months to 2 years old and 9 months. They showed fever and other signs of KD, but did not fulfill diagnostic criteria. The numbers of symptoms compatible with KD were 2 or 3 and included conjunctival injection, oral or lip injection, and eruption. Within 5 days, they became afebrile by antibiotics without IVIG treatment. However, they were noted to have coronary artery aneurysm (CAA) on day from 7 to 33 of illness. All patients had been placed on antithrombotic treatment including aspirin or aspirin plus warfarin and, fortunately, showed regression of CAA within 2 years.

Conclusions:
This case series indicates that there are patients with incomplete KD successfully treated by antibiotics without IVIG but left with CAA. These cases must be underdiagnosed if intentional echocardiographic examination are scheduled and might be left without appropriate treatment, antithrombotic treatment. Further collection of data of these patients is indispensable.
Abstract 110: Histologic Assessment of a Case of Likely Kawasaki Disease in 1870 London
Authors: Shulman Standford T , Rowley Anne , Orenstein Jan
Published: July 2021

William Shrosbree, a 7 yo boy, died in 1870 at St. Bartholomew’s Hospital in London, England, “in consequence of scarlatinal dropsy” after a 2 d hospitalization. His case was cryptically reported briefly by Dr. Samuel Gee in 1871, who found 3 epicardial coronary artery (CA) aneurysms at autopsy, each containing “small recent clots, quite loose.” Two aneurysms were “pea-sized” at the apex close to the tip of the right auricular appendage, while the 3
rd
was the size of a “horse bean” and located in the sulcus at the posterior base of the ventricles. “Specks of atheroma” were described in the aorta “near the valves” and on the aortic cusp of the mitral valve. The heart was reported to be of normal size, and the valves were healthy. We have had the opportunity to study a limited number of CA photomicrographs of this specimen.

Overall, the vasculopathy in this case is highly compatible with our recent description of pathognomonic histologic features in 41 fatal or transplanted KD cases with severe disease (PLoS One, 2012). Of the 3 characteristic linked pathologic processes we reported, the limited number of sections do not show acute self-limiting necrotizing arteritis, which is relatively rare. Areas of subacute/chronic (SA/C) vasculitis containing barely recognizable lymphocytes, variably damaged media and prominent fibrotic adventitial fibrosis are seen. Very little of the internal and external elastic lanima could be seen in EVG and methylene blue stained sections. The most characteristic of the 3 processes, luminal myofibroblastic proliferation (LMP), is variable in prominence. The medium power magnification, H+E and methylene blue stained sections show a relatively uniform circumferential luminal layer thicker than the normal media. A higher magnification H+E section shows up to 100% LMP narrowing of the lumen involving about half the vessel, containing relatively prominent pleomorphic cells that may be myofibroblasts. The lumen in another section shows total obliteration by LMP with similar myofibroblasts and half of the media replaced by LMP.

The gross and histologic features of the CA of the child who died in 1870 in London are highly compatible with the changes noted in severe KD, suggesting that this illness was present as early as the 19
th
Century.
Abstract 13: Elevated Atmospheric Levels of Environmental Allergens Might be Associated with Decreased Risk of an Immunologic Reaction to an Etiologic Trigger in Kawasaki Disease
Authors: Manlhiot Cedric , O’Shea Sunita , Bernknopf Bailey , Chahal Nita , McCrindle Brian W
Published: July 2021

Introduction:
There is considerable interest in identifying potential etiologic and/or triggering agents for the severe immune response associated with Kawasaki disease (KD). The presence of environmental allergens might modulate the odds of triggering such a response despite those allergens not being direct etiologic agents.

Methods:
We queried the Canadian hospital discharge database (Canadian Institute for Health Information) for hospital admissions associated with a discharge diagnosis of KD in 2011 in the Greater Toronto Area. Atmospheric levels of pollens (35 species), spores (24 species) and fungi (27 species) were measured by Aerobiology Research Laboratories (Nepean, Ontario). A number of separate models were tested using theoretical incubation periods of 0, 7, 14 or 21 days. Correlation between KD cases and atmospheric levels of environmental allergens were assessed in linear regression models.

Results:
n=145 patients with KD were included. The highest levels of environmental allergens were in summer months. Overall atmospheric pollens levels were not associated with the KD cases (total pollen count r=0.04, p=0.54); there was no consistent pattern of association with specific pollens. . However, higher levels of spores were associated with a decreased prevalence of KD for all spore species (r=-0.23, p<0.001). Associations were observed for 6 of 19 specific species detected (p<0.001), including
leptosphaeria, ascospores, oospore, coprinus/coprinellus, basidiospores,
and
uredinales
. The same pattern was observed for all fungi species (r=-0.17, p=0.009). Associations were observed for 5 of 26 specific fungal species (p=0.002), including
alternaria, cladosporium, epicoccum, fusarium,
and
fungi imperfecti
. There were no discernable patterns regarding a potential incubation period.

Conclusions:
High levels of environmental allergens, particularly fungus and spores, were associated with lower incidence of KD. These results suggest that environmental allergens, even if they are not etiologic agents for KD, might modulate the threshold necessary for the actual etiologic/triggering agent. Atmospheric levels of environmental allergens might be partly responsible for the KD seasonality patterns observed in Canada.
Abstract 141: A Case of Kawasaki Disease with Re-dilatation of a Coronary Artery Aneurysm after Regression
Authors: Oka Kensuke , Minami Takaomi , Anzai Tatsuya , Furui Sadahiro , Yokomizo Akiko , Ishii Tomoyuki , Sato Tomoyuki , Kataoka Koichi , Yamagata Takanori
Published: July 2021

Background:
In patients with Kawasaki disease (KD), re-dilatation of coronary artery lesions (CAL) after regression is very rare. Here we report a case of KD with CAL re-dilatation after regression.

Case report:
A 15-year-old boy was diagnosed with KD at 1 year of age and was treated with intravenous immunoglobulin (IVIG, 400 mg/kg х 5 days). On day 14, echocardiography revealed CAL on the right coronary artery (RCA) and left coronary artery (LCA). Coronary arteriographic findings were as follows: segment 1, 3 mm in diameter; segment 6, 5 mm in diameter. He was prescribed aspirin, ticlopidine, and warfarin for 3 years. When he was 3 years old, coronary angiography showed complete CAL regression. His medications were discontinued and he underwent routine follow-up by echocardiography on which the CAL were not seen. At 14 years of age, coronary CT revealed re-dilatation of the LCA. Coronary angiography showed the same findings: 7 mm in diameter at the bifurcation between the LAD and the left circumflex artery, while the other regions were intact. He restarted aspirin and warfarin.

The mechanism of CAL re-dilatation remains unclear; however, it is very important to follow patients carefully and routinely using echocardiography and/or coronary computed tomography, especially in cases with a history of CAL.
Abstract 144: Lung Parenchymal Consolidation during typical Kawasaki Disease
Authors: Sato Seiichi
Published: July 2021

Introduction:
Kawasaki disease (KD) is a systemic vasculitis of childhood throughout the body. We report a patient who complicated by severe pneumonia of lung parenchymal consolidation (LPC) during typical KD clinical course.

Case reports:
A 7-yr-old male who had a past history of KD at 3-yr-old, visited a general practitioner with fever, sore throat and neck pain. Three days later, after being treated with CTRX/TBPMPI, he was transferred to our hospital because of bilateral lymph nodes swelling and a generalized erythema and rash.

On admission he was still febrile and had bilateral conjunctival injections, cervical and axillary lymphadenopathy and markedly reddened pharynx, without edema. We diagnosed him as KD and treated him with aspirin and IVIG at a dose of 2.0g/kg, but the condition worsened; he developed dyspnea and dry cough. Crackles were noted on rt-lung auscultation, along with rt-basal dullness to percussion of the thorax.

Chest radiography and a subsequent computed tomography scan revealed disseminated patchy infiltrates and ground-glass alterations with massive pleural effusions on rt-lung, and enlarged axillary and mediastinal lymph nodes.

Some kinds of microbiology (including Mycoplasma) and virology (Epstein-Barr virus, cytomegalovirus, parvovirus B19), from all sampled sites (pleural effusion, blood, pharyngeal swab and cerebrospinal fluid), were negative for pathogenic specimens.

So we treated him as intractable KD with second-IVIG and m-PSL, which led to the quick resolution of fever and progressive amelioration of pneumonia. Echocardiography showed normal ventricular size and function without coronary artery lesion (CAL). Thereafter, he was finally afebrile. At the first follow-up visit, 1 month after discharge, he had fully recovered. Clinically, echocardiographically and radiographically, no residues were noted.

Conclusion:
Several manifestations of broncho-pulmonary involvement in KD have been described. But there are very few case of LPC. We should consider the possibility that LPC were secondary to pulmonary arteritis.
Abstract 15: Multicenter Kawasaki Disease Study In Children Of Argentina
Authors: Melonari Pablo A ,   Working group, Llano Lopez Luis H , Olguín Marisa , Albano Anahí , Gajo Gané Andrea , Bellone Luciana , Aletti Alicia , Ellis Alejandro , Calvari Miriam , Cancellara Aldo , de Carli Norberto , Euliarte Cristina , Bonardo Virginia , Leonardo Mannino , Alejandra Gaiano , Mariana Brusadín , Alejandro Santillán , Ivana Tonetto , Petricca Juan , Gustavo Lazarte , Luis Flynn , Collia Adrián , Iris Vilca , Cristina Battagliotti , Apaz María T , Cutica Rubén , Abate Héctor J , Melonari Pablo A
Published: July 2021

Introduction:
Kawasaki disease (KD) is a vasculitis that affects vessels of small and medium caliber.

Objectives:
1 Determine clinical and epidemiology of KD in children in 22 pediatric referral centers in Argentina. 2 Identify risk factors for coronary complications (CC).

Material and Methods:
A retrospective and analytical study from 01/01/2010 to 31/12/2013. Variables: age, sex, heart rate (HR), clinic features, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), leukocytes (Gb), neutrophils, hemoglobin (Hb) and CC. Color Doppler echocardiography: acute phase and 4-6 weeks.

Results:
Subjects: 191, age (Md) 29 months (R: 2-144) .Ratio v / m: 1.8 / 1. Clinical: fever 100% (191/191) more frequent and adenopatía: 57% (110/191) less frequent. CC: 15.7% (30/191). Mortality: 0.52% (1/191 cases). Increased risk of CC: leukocytosis> 20,000 / mm3 Odds ratio (OR) = 4.235 (95% CI 1704-10529). Hematocrit <30, OR = 6.042. (95% CI 2469-14782) p <0.0002; Hb <10 OR = 5.056 (95% CI 2163-11814) p 100 mm / 1h OR = 3.725 (95% CI 1642-8447) p 100 mg / dl OR = 6.417. (95% CI 2441-16869) p <0.0002 and other heart affections.OR = 7.964. (95% CI 2459-25794) p <0.0010. Children from the West of the country have 2.7 times greater risk of CC OR = 2.714 (95% CI: 1228-5997) p <0.019 compared to the rest.

Conclusions:
Increased frequency in males. Increased risk of CHD in subjects from western Argentina. Low mortality. Increased risk of CC: low hematocrit and hemoglobin; leukocytes, neutrophils, ESR, CRP, FC, high, Presence of other heart alterations and more days of fever at the time of establishing of treatment. Risk factors for coronary involvement
Abstract 169: Impact of Resistance to Intravenous Immune Globulin on Changes of Left Ventricular Myocardial Deformation Over Time in Children with Kawasaki Disease
Authors: Kang Soo Jung , Yon Dong Keon
Published: July 2021

Introduction:
This study aimed to assess the impact of resistance to intravenous immune globulin(IVIG) on left ventricular(LV) myocardial deformation in children with Kawasaki disease(KD) during the acute and convalescent phases of illness. Few studies have elucidated the impact of resistance to IVIG on the progressive changes of myocardial mechanics over time in patients with KD.

Methods:
We studied 26 patients with KD and 8 normal control subjects. Of the 26 patients, 16 were IVIG non-responders. Echocardiograms were obtained during the acute and convalescent phases of KD. Standard echocardiographic data and peak systolic global LV longitudinal strain[strain(ε)] were obtained using vector velocity imaging.

Results:
During the acute phase of KD, peak systolic global LV longitudinal ε decreased significantly in both IVIG non-responders(-21.18 % ± 3.97) and responders(-20.94 % ± 3.15) compared to controls(-24.99 % ± 2.23). Although in the acute phase, LV ejection fraction(EF) was significantly higher in the IVIG non-responders(55.38 % ± 5.14) compared to the responders(50.2 % ± 6.53), peak systolic global LV longitudinal ε was not significantly higher in the IVIG non-responders compared to the responders. During the convalescent phase, peak systolic global LV longitudinal ε tended to increase in non-responders(-21.62% ± 3.98) and responders(-21.83% ± 2.61) compared to the acute phase, but remained significantly decreased in both groups compared to controls. The increment of peak systolic global LV longitudinal ε from acute to convalescent phase tended to be smaller in the IVIG non-responders compared to the responders. The proportion of patients with coronary dilatations in both IVIG non-responders(4 of 16) and IVIG responders(2 of 10) did not differ significantly.

Conclusions:
The increment of peak systolic global LV longitudinal ε over time tended to be smaller in the IVIG non-responders compared to the IVIG responders. Resistance to IVIG may delay normalization of myocardial mechanics in IVIG non-responders. Further studies with larger number of patients, as well as long-term follow-up of myocardial deformation in KD are necessary.
Abstract 20: Kawasaki Disease In France: Incomplete Forms Are Frequent And Associated With A High Frequency Of Cardiac Complications
Authors: Piram Maryam , Darce Bello Martha , Tellier Stéphanie , Merlin Etienne , Launay Elise , Faye Albert , Boralevi Franck , Di Filippo Sylvie , Bosdure Emmanuelle , Armengaud Jean-Baptiste , Arnoux Armelle , Coutard Laure , Koné-Paut Isabelle ,   Kawanet Group
Published: July 2021

KD is the main vasculitis affecting children < 5 years and the leading cause of acquired heart disease in children. Its epidemiology is few reported in France. Even if IVIG is still the standard treatment; the management of patients at risk for cardiac complications may change toward reinforced (and new) therapeutic approaches. Kawanet is a clinical and biological data repository aimed to define the epidemiological characteristics of KD in France.

Methods:
Institutional physicians received information on a national registry for KD. All patients suspected with KD and seen since 2011 were eligible to enter the study. An eCRF was implemented in a web database.The included patients without the AHA international criteria were reviewed by an experts' committee.

Results:
468 cases were entered by 84 physicians from 65 centers. The AHA classification gave: 280 complete KD, and 73 incomplete KD. An expert consensus classified 48 other patients as probable leading to 401 patients considered as KD (M229/F72). 67 were excluded (incomplete data or doubful). The median age at diagnosis was 3.1y (2m-14y). Their ethnical backgrounds were: European Caucasian 67%, Eastern Caucasian/North African 15%, afro-Caribbean 13%, Asian 4% and mixed ancestry 1%. The clinical symptoms were (%): conjunctivitis 84, cheilitis 82, diffuse exanthema 74, modification of the extremities 73, oral erythema 66, cervical adenopathy 52, raspberry tongue 49, seat erythema 26, perineal desquamation 18 and BCG erythema 5. The cardiac complications were: coronary dilatation 30%, pericarditis 15%, coronary aneurysm 4%, and myocarditis 3% (1 death). 392/401 (98%) patients received IVIG, 64 (21%) and 5 required 2 and 3 courses. The mean treatment delay was 6 days. The factors associated with the coronary abnormalities were: male gender (p=0.01), young KD onset age (p=0.03), and resistance to IVIG (p=0.03).

conclusion:
KD diagnosis remains challenging and overdiagnosis represents at least 10% of cases in this registry. Incomplete forms of KD account for 37 % and are associated with coronary dilatation/aneurysm (34%; p<0.01) and a high rate of IVIG resistance. Unlike previous studies, our population is very mixed with 28 % of children from the Middle East and Africa, in whom KD is still few reported.
Abstract 219: Long - Term Prognosis Of Patients With Kawasaki Disease Complicated By Significant Coronary Aneurysm (diameter ≥ 6 mm)
Authors: Bang Ji Seok , Kim Gi Beom , Kwon Bo Sang , Bae Eun Jung , Noh Chung Il , Choi Jung Yun
Published: July 2021

Background:
Some patients with Kawasaki disease (KD) develop large coronary aneurysms (diameter ≥ 6mm) and coronary stenosis, leading to ischemic heart disease. This study determined the long-term outcome for patients with Kawasaki disease complicated by significant coronary aneurysm.

Methods and Results:
From the database in Seoul National University Children’s Hospital between December 1986 and December 2013, medical records of 83 patients (61 men and 22 women) with large coronary aneurysms (diameter ≥ 6mm) were retrospectively reviewed. Information on patient demographics, catheter or surgical interventions, and most recent status was collected. From these data, we calculated the survival rate, cumulative coronary intervention rate, coronary artery bypass graft surgery rate. The mean age at onset was 4.28 ± 2.62 years, and the mean observational period was 13.2 ± 6.5 years. The maximum coronary artery internal diameter ranged from 6.1 to 25mm (median 9mm). Giant coronary aneurysm was 57 patients (68.7%) and large coronary aneurysm (6-8mm) was 26 patients (31.3%). Coronary aneurysms had progressed to coronary artery stenosis and/or complete occlusion in 42 patients (50.6%). The overall freedom from coronary intervention, coronary artery bypass surgery, or coronary thrombi was respectively 85.5%, 85.5%, and 90.3%. Catheter and surgical coronary interventions (median 1 intervention; range 1 to 5 interventions) were performed in 20 patients (24.1%) at 9 month to 18 years after onset, resulting in 33.7% cumulative coronary intervention rates at 20 years after onset. There were no differences in cumulative coronary intervention rates between two coronary aneurysm groups (6-8mm vs ≥8mm). Myocardial infarction occurred in 8 (8.98 %) patients. During this study period, 1 patient died and 98% survival rates was seen in our patients group.

Conclusion:
The long-term survival of patients with Kawasaki disease complicated by large coronary aneurysm is good even though a fourth of patients underwent multiple catheter or surgical interventions. Further research should focus on the indications for and effectiveness of percutaneous and surgical coronary interventions in large coronary aneurysm (≥ 6mm).
Abstract 225: Variations in Pharmacological Management of Children with Coronary Artery Aneurysms after Kawasaki Disease: A Study from the North American Kawasaki Disease Registry
Authors: Selamet Tierney Elif Seda , Mackie Andrew S , McCrindle Brian W , Mathew Mathew , Armstrong Kathryn R , Williams Emily , Thacker Deepika , Neufeld Madisen , Nourse Susan , Manlhiot Cedric , Raghuveer Geetha ,   North American Kawasaki Disease Registry
Published: July 2021

Background:
The pharmacological management of coronary artery aneurysms (CAA) associated with Kawasaki disease (KD) is based on imperfect evidence, which may lead to considerable practice variation.

Methods:
Pharmacological management of patients included in the North American Kawasaki Disease Registry was reviewed. The Registry included data for 621 patients with CAA after KD (280 patients with maximum CAA z-score between 2.5-5.0, 139 with z-score 5.0-10.0 and 202 with z-score >10.0) followed at 20 medical centers. Practice variation regarding acute treatment, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy and anticoagulation were assessed.

Results:
Considerable practice variation existed between centers. During the acute phase, 93% of patients received at least one dose of IVIG (range: 80-100%), with 23% (range: 12-50%) receiving additional immunomodulatory treatment (22% additional IVIG, 17% steroids, 4% infliximab). Use of a 3
rd
course of IVIG was infrequent (2%). All centers reported using additional IVIG or steroids for IVIG-resistant patients, but only 6 centres reported any experience with infliximab (2 commonly, 4 infrequent). Routine use of non-steroidal anti-inflammatory agents was limited to 2 centres, with 4 additional sites reporting infrequent use (10% of patients). Statins (5%), beta blockers (4%) and abciximab (3%) were mostly used by a single centre and was limited to patients with giant CAAs. Aspirin was the primary antiplatelet modality for 97% of patients, clopidogrel (10% of all patients, 23% in giant CAA) was routinely prescribed to patients with giant CAAs at 6 centres, with 2 more centres reporting infrequent use and the remainder not reporting any use. For patients with giant CAA (z-score>10.0), 46% were maintained on an antiplatelet agent alone, 17% additionally were on low molecular weight heparin(LMWH), 12% on warfarin and 25% had initially received LMWH and were later switched to warfarin.

Conclusions:
Given the important variations in management between centres and the poor evidence base, randomized controlled trials examining outcomes and nested in a high-quality collaborative registry may be an efficient strategy to address this gap.
Abstract 61: Anti-inflammatory Effect Of Resveratrol In Human Coronary Arterial Endothelial Cells Via Autophagy: Implication For The Treatment Of Kawasaki Disease
Authors: Huang Fu-Chen Huang , Kuo Ho-Chang , Yu Hong-Ren
Published: July 2021

Kawasaki disease (KD) is an acute febrile vasculitis of childhood and is the leading cause of acquired heart disease in children in the developed world. If untreated, KD can result in coronary aneurysms in 25% of patients, who are at risk of myocardial infarction, sudden death, and congestive heart failure. Despite the success, 10-20% of children will have persistent or recrudescent fever after their first infusion of IVIG. These patients are at increased risk of developing coronary artery abnormalities. Additional therapies should be explored to decrease the incidence of coronary arteritis complication and improve the prognosis in Kawasaki disease. Induced autophagy with resveratrol confers cardioprotection during ischemia and reperfusion in rats.

KD is associated with elevated production of inflammatory cytokines, causing damage to the coronary arteries. Serum TNF-alpha levels are elevated in KD, which was supposed to activate the endothelial cells. As a result, adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1(VCAM-1) are expressed in the endothelial cells, and leucocytes adhere firmly to endothelial cells. The leucocytes then damage the endothelial cells and smooth muscle cells and cause vasculitis.

In this study, we examined the anti-inflammatory effects of resveratrol on TNF-alpha-induced adhesion molecule expression (VCAM-1 and ICAM-1) and cytokine production (interleukin (IL)-1beta, IL-6 and IL-8) in HCAECs. Pretreatment with resveratrol significantly inhibited TNF-alpha-induced adhesion molecules and cytokines production in HCAECs via the activation of autophagy. Our results suggest that adjunctive resveratrol therapy may modulate the inflammatory response during KD vasculitis and explore the role of autophagy in the pathogenesis of the complication and the promising therapy.
Abstract 62: Functional mechanism of cyclosporin A therapy for immunoglobulin-resistant Kawasaki disease
Authors: Kakimoto Nobuyuki , Suzuki Hiroyuki , Suenaga Tomohiro , Takeuchi Takashi , Shibuta Shoichi , Abe Jun , Yoshikawa Norishige
Published: July 2021

Background:
We have reported that cyclosporin A (CsA) therapy may be a promising and safe option for patients with Kawasaki disease (KD) resistant to initial and additional intravenous immunoglobulin (IVIG). Up to now, it has been considered that CsA exerts effects on the intracellular phosphatase calcineurin, and subsequently inhibits activation of nuclear factor of activated T cells (NFAT). However, the functional mechanism of CsA therapy in KD patients has remained unclear.

Methods:
The KD patients enrolled in this study were treated with CsA between April 2012 and December 2013. In accordance with our treatment protocol, KD patients are initially treated with IVIG and aspirin. If there is no response, a further course of IVIG is given, and if there is no response to this additional IVIG, the patients are treated with CsA. Peripheral blood samples were obtained just before and after the initial course of IVIG, additional IVIG, and CsA therapy. To evaluate the NFAT pathway and activation of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, we examined the gene expression of cytokines and intracellular signal transducers using real-time RT-PCR and phospho-STAT3 (pSTAT3) and STAT5 (pSTAT5) using flow cytometry.

Results:
Thirty-six KD patients were divided into three groups: responsive to initial IVIG (n=19), responsive to additional IVIG (n=7), and treated with CsA group (n=10). In the CsA group, expression of mRNAs for interleukin (IL)-2, NFATc1 and NFATc2 was significantly increased, whereas the mean fluorescence intensity (MFI) of pSTAT3 (CD3+ T cell) and pSTAT3 (CD16b+ granulocyte) was decreased after CsA treatment. In the group responsive to initial IVIG, the expression of mRNAs for IL-2, IL-6, NFATc1 and NFATc2 was significantly increased, whereas that for STAT3, 5A, 5B was decreased after IVIG treatment; on the other hand, the MFI of pSTAT3 (CD3+ T cell) and pSTAT3 (CD16b+ granulocyte) was decreased, and that of pSTAT5 (CD16b+ granulocyte) was increased, after IVIG.

Conclusion:
In patients with refractory KD, CsA exerts effects on the activity of the NFAT and JAK-STAT pathways. However, our results suggest that in patients with immunoglobulin-resistant KD, CsA may act through a mechanism other than the NFAT pathway.
Abstract 9: The Japan Environment and Children’s Study and Kawasaki disease
Authors: Ito Shuichi , Yamamoto Kiwako , Ishizuka Kimie , Komuro Hisako , Mezawa Hidetoshi , Masuda Hiroshi , Abe Jun , Ono Masashi , Ohya Yukihiro
Published: July 2021

Background:
The Japan Environment and Children’s Study (JECS) is a nation-wide birth cohort study involving 100,000 parent-child pairs that was conducted by the Japanese Ministry of the Environment. This study was started in 2011 to evaluate the effect of various environmental factors on children’s health and development. Health outcomes and exposure measurements will continue until the participating children become 13 years old.

Method:
Exposure to environmental factors was assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environmental measurements, and computational simulations using monitoring data, as well as questionnaires. The JECS’s priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, including Kawasaki disease (KD), and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, history of infection, and lifestyle factors were also examined as covariates and potential confounders.

Results:
Some of the questionnaires for children under 2 years old have already been collected. The numbers of patients with KD according to age were as follows: 14/71,133 (0.02%) between 0-6 months old, 102/51,351 (0.2%) between 6-12 months old, 71/34,595 (0.21%) between 12-18 months old, and 20/20,995 (0.1%) between 18-24 months old. According to these results, the estimated incidence of KD in children younger than 2 years old could reach more than 0.5%, but this number may increase after further collection of questionnaires. We also conducted a secondary survey regarding KD patients, including family history, clinical symptoms, laboratory data, treatment, and outcome.

Conclusion:
Recently, similar birth cohorts to JECS were already initiated in many countries, but this is the first large-scale birth cohort focusing KD. The results of this cohort may shed new light on the environmental pathogenesis of KD.
Abstract O.05: The Incidence and Outcome of Kawasaki Shock Syndrome:2003-2013
Authors: Sexson Tejtel Sara K , Ramirez Andrea A , Seery Thomas , Liou Amy , Canter Debra , DeGuzman Marietta , Altman Caroly A
Published: July 2021

Kawasaki disease (KD) is the leading cause of acquired heart disease in children with a subset presenting in shock. We sought to describe the incidence and outcomes of KD shock in the US.

Methods:
The Pediatric Health Information Systems (PHIS), 1/2004-12/2013, dataset including all hospitalizations at 44 of the largest freestanding children’s hospitals in the US was used. We assumed KD shock patients were admitted to the ICU.

Results:
KD admissions included 16,417 patients, 1,179 requiring ICU care, KD shock, with an annual incidence of 8 - 13%, Figure 1.

Among KD shock admissions (versus non-ICU KD), the length of stay (10 vs 4 days, P<0.001) and mortality (10 vs 1 death) is higher in the shock group. The rate of coronary artery (CA) changes during initial admission for KD shock was higher than non-shock, Figure 2 (P<0.001).

Conclusions:
KD shock may not be an uncommon presentation given 8-13% of KD admissions required ICU care. KD shock patients are more likely to have complications including coronary artery changes, mechanical ventilation, ECMO, and longer hospitalizations than non-ICU admissions.
Abstract O.24: Gut Microflora Influences Pathology in the Kawasaki Disease Vasculitis Mouse Model
Authors: Wakita Daiko , Kurashima Yosuke , Takasato Yoshihiro , Lee Youngho , Shimada Kenichi , Chen Shuang , Crother Timothy R , Fishbein Michael C , Lehman Thomas J , Kiyono Hiroshi , Arditi Moshe
Published: July 2021

Background:
Kawasaki Disease (KD) is the leading cause of acquired heart disease in the US. We have demonstrated the critical role of innate immune responses via IL-1R/MyD88 signaling in the Lactobacillus casei cell wall extract (LCWE)-induced KD mouse model. The diversity and composition of microflora (both bacterial and fungal) have been associated with the regulation and alterations of immune responses and various pathologies. However, the role of gut microbiota in immunopathology of KD has not been investigated.

Objective:
To evaluate the role of gut microflora in development of coronary arteritis, and vascular abnormalities in KD mouse model.

Methods and Results:
We investigated the role of gut microflora in the LCWE-induced KD mouse model, using Specific-Pathogen Free (SPF) and Germ Free (GF) mice (C57BL/6). GF mice showed a significant decrease of KD lesions, including coronary arteritis compared with SPF mice. The development of LCWE-induced AAA, which we recently discovered in this mouse model, was also markedly diminished in GF mice. In addition to GF mice, we also investigated the specific role of commensal fungi, and determined whether altered fungal burden in this KD mouse model contributes to disease severity. To deplete fungi in the gut microflora, we exposed pregnant SPF mice and their offspring to fluconazole (antifungal) in their drinking water for 5 wks and induced KD. The fluconazole treated mice had significantly reduced coronary arteritis, and AAA compared to controls. Since Dectin-1 has emerged as a key receptor that recognizes β-1,3-glucans found in the cell wall of nearly all fungi, we next induced KD in Dectin-1 deficient mice. Dectin-1 deficient mice also had significantly reduced KD lesions such as coronary arteritis compared with WT mice.

Conclusions:
We demonstrate here that gut microflora play a critical role in the development of KD vasculitis in LCWE-induced mouse model. Our results suggest that fungi in the intestinal microbiota may specifically control the induction and severity of KD vasculitis, which may be mediated by Dectin-1. These findings provide a new perspective on the potential role of the microbiome in KD pathogenesis and may offer new diagnostic and therapeutic strategies for KD patients.
Abstract O.37: Coronary Artery Dilatation in Viral Myocarditis Mimics Coronary Artery Findings In Kawasaki Disease
Authors: Rached-d'Astous Soha , Boukas Ibtissama , Fournier Anne , Raboisson Marie-Josée , Dahdah Nagib
Published: July 2021

Background:
Coronary artery dilatations are almost always secondary to Kawasaki disease in the pediatric population. The presence of CA involvement is used as a criterion to diagnose incomplete KD disease, which may be challenging. It has been recently demonstrated that febrile patients had larger CA size than non-febrile children in a pilot study. As there is almost always a myocarditis in the acute phase of KD disease we sought to investigate whether viral myocarditis may cause CA dilatations.

Method:
This retrospective study reviewed 14 consecutive patients with a diagnosis of viral myocarditis at Saint-Justine Hospital, Montreal, from April 2000 trough December 2010. Kawasaki disease was excluded in all patients. All echocardiogram studies were reviewed by an independent experienced technician for CA size and function parameters. Patients were classified in three categories: definite CA dilatation (Z-score ≥ 2.5 in one or more CA), occult CA dilatation (Z score variation ≥ 2 for the same CA on 2 different echogrardiograms, but absolute Z score always < 2.5) and normal coronary artery. Demographics, laboratory values, microbial etiology testing, diagnostic studies were also collected.

Results:
Mean age at presentation was 1.67 ± 3.22 years, the majority < 2 years old, and 11 (78%) were girls. Of the 14 patients 8 (57.1%) had normal CA, 3 (21.4%) had occult CA dilatation and 3 (21.4%) had definite CA dilatation. When present, CA dilatation was detected within the first 8 days of presentation. Eleven (78%) patients presented with acute onset features and the remaining 3 presented with subacute characteristics. There was no correlation between CA involvement and the intensity of LV dysfunction however (p = 0.84).

Conclusion:
Patients with viral myocarditis can present CA dilatation during the acute phase of the illness. This finding should be taken into account when diagnosing patients with incomplete KD on the basis of the CA involvement as the two illnesses may present with similar features.
Abstract O.52: Infliximab Use And Cardiac Outcome in Infants ≤ 6 Months Old: A Two Center Retrospective Study
Authors: Tremoulet Adriana , Salgado Andrea , Ashouri Negar , Berry Erika , Jain Sonia , Sun Xiaoying , Burns Jane C
Published: July 2021

Background:
Incomplete KD, as well as a higher incidence of CAA, has been reported to occur more commonly in infants ≤ 6 months (mos), but only small case series have been published. We characterized the KD course in infants ≤6 mos and compared to outcomes in KD pts >6 mos.

Methods:
We retrospectively reviewed the course of 88 subjects ≤ 6 mos diagnosed with KD between January 2004 and December 2013 at Children’s Orange County (CHOC) and Rady Children’s Hospital San Diego (RCHSD) and compared to 632 subjects >6 mos at RCHSD. Complete and incomplete KD cases were defined based on the 2004 AHA guidelines. Subjects were classified by coronary artery (CA) status (normal, dilated, or aneurysmal CA based on RCA and LAD measurements) and by Z-score (RCHSD only). IVIG resistance was defined as fever ≥38C at least 36 hours after completion of IVIG. Fisher’s Exact test was used for comparisons.

Results:
Of the 88 infants, 62 (70.4%) were male and 76 (86.3%) were treated at ≤ 10 days of illness. Treatments in the 88 pts were as follows: IVIG responder: 55(62.5%); IVIG resistant: 13(14.7%); infliximab for cardiac indications: 16 (18.2%); late treatment >10days: 2 (2.3%); not treated: 2 (2.3%). Infliximab was administered to a total of 27 pts (30.7%) and was well-tolerated with rash as the only adverse event in 1 pt. Worst CA status was “normal” in 37 (42.1%), dilated in 29 (32.9%), aneurysm in 15 (17.1%) and giant aneurysm in 7 (7.9%) pts. Of the 48 pts at RCHSD who presented within the first 10 days of illness, only 26 (54.2%) had a Z-score <2.5. Of these 26 pts, 7(26.9%) went on to have a subsequent Z score ≥ 2.5. Comparing the ≤6 mos vs. > 6 mos RCHSD cohorts, there were no significant differences in number of pts treated within the first 10 days of illness (48/53, 90.5% vs. 545/632, 86.2%) or pts having incomplete presentations (12/53, 22.6% vs. 106/632, 16.8%).

Conclusions:
There were no significant differences in the rate of incomplete KD or rate of diagnosis within the first 10 days of illness in children ≤6 mos vs. >6 mos. Infliximab use in 30.7% of the ≤6 mos old pts was safe. Infants ≤6 mos had a high rate of aneurysms (22/88, 25%) despite timely diagnosis and treatment. Better treatments are needed for this high risk group of KD pts.
Abstract O.58: Medium-term Outcomes of Coronary Artery Aneurysms after Kawasaki Disease: A Study from the North American Kawasaki Disease Registry
Authors: McCrindle Brian W , Manlhiot Cedric , Sexson Kristen , Jone Pei-Ni , Mathew Mathew , Norozi Kambiz , Harris Kevin C , Hughes Alana , Ferris Anne , Dallaire Frederic , Crean Andrew M , Dahdah Nagib ,   North American Kawasaki Disease Registry
Published: July 2021

Background:
One of the main impediments to conceiving and planning studies in children with coronary artery aneurysms (CAA) after Kawasaki disease (KD) is the lack of normative data regarding the prevalence of outcomes over time and risk factors.

Methods:
The North American Kawasaki Disease Registry was used to determine the prevalence of multiple clinically important outcomes of CAA after KD. All analyses were stratified by severity of CAA (small CAA with z-score = 2.5-5, medium with z-score = 5-10 and giant with z-score >10). All analyses were performed using non-parametric survival analysis.

Results:
n=621 patients submitted to the Registry had complete follow-up data and were included in the analysis (280 [45%] small CAA, 139 [22%] medium and 202 [33%] giant). Time-related freedom from multiple outcomes stratified by type of CAA are reported in the Table. Reduction in z-scores was strongly associated with the initial size of the lesion, with smaller lesions being more likely to decrease to a normal dimension over time. Thrombosis and stenosis were infrequent in patients without giant CAA. For those patients with giant CAA, the risk of thrombosis, myocardial infarction, angiographically-confirmed stenosis and revascularization was substantial and persisted up to 10 years after diagnosis. In addition to larger luminal diameter, other factors associated with increased risk of adverse outcomes included larger CAA longitudinal area and complex CAA (vs. isolated lesions).

Conclusions:
Only patients with giant CAA are at substantial risk of adverse clinical outcomes; future trials of pharmacological therapy targeting thrombosis and stenosis risk should focus on these patients.
Abstract O.69: Coronary Vessel Wall Imaging By Using Multi-detector Computed Tomography And Outcomes In Patients Long After Kawasaki Disease: Potential For Risk Stratification
Authors: Ohashi Hiroyuki , Kitagawa Kakuya , Sawada Hirohumi , Hayakawa Hidetoshi , Otsuki Shoichiro , Yodoya Noriko , Sakuma Hajime , Komada Yoshihiro , Mitani Yoshihide
Published: July 2021

Background:
In acute coronary syndrome (ACS) in adults after Kawasaki disease (KD), acute thrombosis occurs in culprit lesions with calcified intima even in the absence of giant aneurysms (AN) or severe stenosis. Recently, multi-detector computed tomography (MDCT), a non-invasive modality, was shown to have good diagnostic accuracy of detecting IVUS-defined intimal thickening and calcification. We investigated whether MDCT-derived vessel wall lesions are associated with coronary artery lesions (CAL) and outcomes in patients long after KD. Methods: MDCT was performed and analyzed (Vitrea fX, vs2.0, VITAL) in patients ≥10 years after KD, in which CAL were determined by ultrasound (US) during acute KD and serial CAG (if CAL was detected by US). Any discernible structure under the luminal surface with the CT density with or without areas ≥ 130 Hounsfield units, was defined as a calcified or noncalcified intima. Results: A total of 42 patients (median age 19.7 yo, male 64%, median interval after KD 17.5 y) were recruited and followed-up for 4.0 years (median) (range 0.1-5.5): 23 (55%) patients have any CAL in any segments, including regressed AN in 42 segments, persistent AN in 27 segments, localized stenosis (LS) in 7 segments; normal coronary artery from the onset was found in 225 segments in total patients. MDCT findings revealed no intimal lesions in 271 segments, 6 non-calcified intima, and 24 calcified intima; Mean (range) value of Agatston calcium score was 140 (0-2247) with zero value in 29 (69%). Normal segments from the onset exhibited no intimal lesions (225/225, 100%); regressed AN exhibited no intima (35/42, 83%), non-calcified intima (2/42, 5%), and calcified intima (5/42, 12%); persistent AN exhibited no intima (11/27, 41%), noncalcified intima (4/27, 15%), and calcified intima (12/27, 44%); all the LSs exhibited calcified intima (7/7, 100%). In the follow-up after MDCT, a 23 year-old patient (calcium score 17) had ACS at the culprit lesion with LS <50% and calcified intima; another 16 year-old patient (calcium score 545) had asymptomatic myocardial infarction at the culprit lesion with persistent aneurysm and calcified intima. Conclusions: Coronary vessel wall imaging by using MDCT may have a potential role for risk stratification of adults after KD.
Abstract O.71: Thrombosis and Thromboprophylaxis for Patients with Giant Coronary Artery Aneurysms after Kawasaki Disease: A Study from the North American Kawasaki Disease Registry
Authors: Manlhiot Cedric , Mahle William T , Hill Kevin D , Li Jennifer S , Tucker Dawn , Kulkarni Ashwini , Lai Lillian S , Anderson Brett , Olson Aaron K , McCrindle Brian W ,   North American Kawasaki Disease Registry
Published: July 2021

Background:
Children with giant coronary artery aneurysms (CAA) after Kawasaki disease (KD) are at substantial risk of thrombosis. There are currently no evidence-based guidelines for optimal thromboprophylactic therapy in these children.

Methods:
The North American Kawasaki Disease Registry was queried to identify all patients with giant CAA (maximum coronary artery z-score >10) and their antithrombotic therapy. Freedom from thrombosis was modelled using the Kaplan-Meier method; thrombotic complication rate was calculated per patient-year/month of follow-up.

Results:
n=202 patients with giant CAA were included, of whom 28 (14%) experienced either coronary artery thrombosis with or without myocardial infarction. Freedom from thrombotic complications was 92%, 85% and 79% at 3 months, 5 and 10 years after diagnosis, respectively. Non-pharmacological factors associated with increased risk of thrombotic complications included higher maximum coronary artery z-scores (HR: 1.7/+10 SD, p<0.001), higher number of coronary artery branches with giant CAA (HR: 2.6/branch, p<0.001), higher number of discrete CAA (HR: 1.4/aneurysm, p=0.001) and presence of complex CAA (involving the bifurcation or non-discrete; HR: 3.0, p=0.05). A total of 982 patient-years of follow-up were available for analysis (11% low molecular weight heparin (LMWH), 32% warfarin, 57% antiplatelet alone). All patients were maintained on ASA, with 47 patients (23%) also receiving clopidogrel. Patients while on LMWH had the highest event rate, at 1 event per 13 patient-years, compared to 1 per 39 on warfarin and 1 per 33 on no anticoagulant. However, LMWH was predominantly prescribed immediately after the acute phase, which is also the highest risk phase for thrombosis. When limiting analysis to events within 3 months of the acute phase, patients on LMWH had the lowest event rate at 1 per 46 patient-months, compared to 1 per 27 on warfarin and 1 per 33 on no anticoagulant (p=NS).

Conclusions:
Current thromboprophylaxis strategies in patients with giant CAA have suboptimal efficacy, and residual thrombosis risk persists. New anticoagulants/antiplatelet agents should be assessed in this population to determine if they provide better, safer and more tolerable thromboprophylaxis.
Abstract 10128: The Impact of Replacing the Pooled Cohort Equation With Other CVD Risk Scores on Atherosclerosis Cardiovascular Disease Risk Assessment: MESA
Authors: Qureshi Waqas , Flueckiger Peter , Blaha Michael , Michos Erin D , Sandfort Veit , Herrington David M , Burke Gregory , Yeboah Joseph
Published: July 2021

Introduction:
The increase in statin eligibility by the new cholesterol guidelines is mostly driven by the Pooled Cohort Equation (PCE) criterion (≥ 7.5% 10yr. PCE). The impact of replacing the PCE with either the modified Framingham risk score (FRS) or the Systematic COronary Risk Evaluation (SCORE) on ASCVD risk assessment and statin eligibility remains unknown. We assessed the comparative benefits of using the PCE, FRS and SCORE for ASCVD risk assessment in the Multi Ethnic Study of Atherosclerosis (MESA).

Methods:
: 4632 out of 6814 participants (mean age 60±10 years, 47% males, 39% whites, 27% blacks) were included in analysis. Area under the curve (AUC) and decision curve analysis (DCA) were used to compare the three risk scores. [DCA is the plot of net benefit versus probability thresholds; Net Benefit = true positive rate - (false positive rate x weighting factor). Weighting factor = Threshold probability/1-threshold probability].

Results:
After a median of 10.2 years, 347 (7.5%) ASCVD events (MI, CHD death, fatal or non-fatal stroke) occurred. All three risk scores had acceptable discriminative ability for incident ASCVD events [(AUC (95% CI) PCE: 0.748(0.722-0.774); FRS: 0.732(0.703-0.761) and SCORE: 0.790(0.764-0.816)]. The SCORE had the best net benefit compared with PCE or FRS across all the probability thresholds considered (0-20%). At the 7.5% probability threshold adopted by the new cholesterol guidelines, SCORE identifies 7 additional people not eligible for statins out of 100 persons eligible under the “treating all” approach compared with PCE (43/100 for SCORE vs. 36/100 for PCE; hence 19% reduction) without missing any true high risk person.

Conclusions:
At the ACC/AHA recommended 7.5% ASCVD risk threshold, SCORE reduced statin eligibility by 19% compared with the PCE without missing any true high risk person. Validation of our findings in other cohort is needed.