bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12: Wind Patterns are not Associated with Kawasaki Disease in Canada
Authors: Manlhiot Cedric , O’Shea Sunita , Bernknopf Bailey , Chahal Nita , McCrindle Brian W
Published: March 2022

Introduction:
Previous wind pattern studies have suggested that the etiologic and/or triggering agent for Kawasaki disease (KD) originates from Central Asia and that westward tropospheric winds are associated with the incidence pattern in Japan. This hypothesis has not been formally tested elsewhere. Should it be correct, it follows that incidence patterns should be similarly associated with North/North-West winds in Canada.

Methods:
We queried the Canadian hospital discharge database (Canadian Institute for Health Information) for hospital admissions associated with a discharge diagnosis of KD from 2004 through 2011; only acute admissions were included. Hourly weather data, including wind direction, was obtained from 9 weather stations across Canada situated closest to clusters of cases. The number of new KD admissions per day and per weather station was calculated. Wind direction was divided in 8 different quadrants covering 45° regions starting with 0°. A Poisson regression model for count data, adjusted for repeated measures (9 measures per day) was used to determine whether wind patterns were associated with incident cases. A number of separate models were tested using theoretical incubation periods of 0, 7, 14 or 21 days.

Results:
A total of 3363 KD cases were assigned to one of 26,283 time/space periods for which wind direction was available. Wind direction was not associated with incidence patterns in any of the 4 incubation models: incubation time 0 day (global wind pattern effect chi-square: 4.28, p=0.75). 7 days (chi-square: 5.08, p=0.65), 14 days (chi-square: 7.32, p=0.29) or 21 days (chi-square: 4.74, p=0.69). Focusing on North/North-West wind patterns also failed to show a significant association in all models: incubation time 0 day (+0.0021 (0.0151) cases/day, p=0.89), 7 days (-0.0071 (0.0142) cases/day, p=0.62), 14 days (+0.0009 (0.0148) cases/day, p=0.95) or 21 days (+0.0073 (0.0156) cases/day, p=0.64). Results were similar when stratifying Eastern vs. Western Canada and when each weather station was considered separately.

Conclusions:
Wind patterns were not found to be associated with incident KD cases in Canada. It is unclear if the reported association is specific to Japan or an ecologic fallacy.
Abstract 134: Early Immunoglogulin Therapy and Outcomes of Kawasaki Disease
Authors: Lin Ming-Chih , Ho Chi-Lin , Fu Yun-Ching
Published: March 2022

Background and Objectives:
Kawasaki disease is the leading cause of acquired heart disease among children in most industrialized countries.However, only few descriptive studies discussed the pros and cons of early immunoglobulin therapy. The aim of this study isto see the effect of early immunoglobulin therapy on Kawasaki disease outcomes.

Methods:
This study enrolled patients who received immunoglobulin therapy for the first time. Basic data was analyzed for descriptive epidemiology. Clinical risk factors of acute coronary aneurysm, chronic coronary aneurysm and recurrence rate were analyzed.

Results:
Totally 5235 patients of first attack of Kawasaki disease were enrolled. Among them, 1156 children were classified as early immunoglobulin therapy. The odds ratio for acute aneurysm and needing long-term anti-coagulant therapy were 0.94 (95% CI, 0.77~1.16) and 1.01 (95% CI, 0.77~1.32) respectively. The recurrence rate was higher for early immunoglobulin therapy group. The adjusted odds ratio was 1.86 (95% CI, 1.07~3.23).

Conclusions:
Early immunoglobulin therapy might not benefit the coronary outcomes for children of Kawasaki disease. On the contrary, it might be associated with higher recurrence rate.
Abstract 157: Functional and Structural Intermediate Vascular Phenotypes Relating to Long-Term Cardiovascular Risk in Kawasaki Disease
Authors: Chen Katherine Y , Dahdah Nagib , Maurice Roch L , Miller Jessica , Curtis Nigel , Cheung Michael , Burgner David
Published: March 2022

Background:
It is uncertain whether Kawasaki disease (KD) increases overall long term cardiovascular risk, especially in those without demonstrable coronary artery lesions. Data from non-invasive vascular assessment, extrapolated from studies of subclinical atherosclerosis, are conflicting.

Methods:
Patients at least 2 years post-KD and healthy controls had fasting plasma glucose, lipid profile, high sensitivity C-reactive protein, carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (cIMT), abdominal aorta intima-media thickness (aIMT), retinal vascular calibre, carotid and aortic elastography performed.

Results:
37 controls and 45 patients with KD (21 with regressed or persistent coronary artery changes) were studied at mean ± sd of 10.5 ± 5.7 years following KD. Compared to controls, KD patients did not have increased traditional cardiovascular risk factors; blood pressure, body mass index, waist-to-hip ratio, glucose, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride and smoking history.

Of the cohort, 26 patients (age 15.38 ± 6.19 years) and 27 controls (age 18.7 ± 7.11 years) have had cIMT, aIMT and carotid elastography analysed. The maximum aIMT in KD patients was 0.65 ± 0.15 mm, compared to 0.63 ± 0.13 mm in controls, with the most marked difference in those with coronary artery changes at 0.68 ± 0.14 mm. After adjusting for age, sex, systolic blood pressure, aortic diastolic diameter and high sensitivity C- reactive protein, the average maximum aIMT in all KD patients was 0.071mm larger (95% CI -0.005, 0.147) than controls. Aortic elastography and Doppler pulse wave analysis are underway. Otherwise, there are no detectible differences in PWV, cIMT, carotid elastography, or retinal vascular calibre between KD patients and controls.

Conclusion:
Compared to carotid artery characteristics, changes in the abdominal aorta may be more discriminative markers of long-term cardiovascular risk in KD. Focus on large arteries in longitudinal KD vascular studies are warranted. Recruitment and analysis are ongoing and further results will be presented.
Abstract 160: Angiography Based Comparison of Echocardiography Z-value Equations for the Case Definition of Coronary Artery Dilatation Following Kawasaki Disease
Authors: Dahdah Nagib , Tan Frederick Trinh , Lapierre Chantale , Miro Joaquim , Fournier Anne
Published: March 2022

Introduction:
Echo-based coronary artery (CA) Z-value is the current standard for the case definition of CA dilatation (Z>2.5) in KD. Extrapolating Z-value equations to selective angiography has not been evaluated. CA to aortic valve (AV) ratio is stable versus BSA (Figure).

Methods:
CA measurements from selective angiography were compared to echo measurements within 3 months interval, late after KD. Measurements were performed 3-5 mm from CA ostium for patients without aneurysms, and proximal to the aneurysm for the remainder. The AV was measured in the echo long axis and the angio frontal views. Z-values and CA/AV ratios were compared between angio and echo measurements.

Results:
There were 22 cases with and 55 without CA sequelae. Echo measurements overestimated the smallest CA segments (intercept 0.75 mm), with an error attenuation for larger coronaries (slope 0.74, r
2
0.45). In contrast, CA/AV ratio had a better correlation for all CA size range (intercept 0.04, slope 0.87, r2 0.55). There was a disagreement between echo and angio for the case definition of coronary dilatation for the Z-value equations (p value 0.02 and 0.04), but not for the CA/AV ratio (p value 0.1 and 0.27). The best sensitivity and specificity of echo to predict angio-based CA status were obtained with the CA/AV (100 and 93 percent for the right and 50 and 87 percent for the left coronary, versus 36 and 93 percent and 44 and 87 percent, respectively).

Conclusion:
CA/AV is a better representative of the angiographic CA status compared to echocardiography based Z-value calculations.
Abstract 164: Thrombotic Risk Assessment in Kawasaki Disease Patients with Coronary Artery Aneurysms using Transluminal Attenuation Gradient Analysis
Authors: Grande Gutierrez Noelia , Kahn Andrew M , Shirinsky Olga , Lyskina Galina A , Fukazawa Ryuji , Ogawa Shunichi , Burns Jane C , Marsden Alison L
Published: March 2022

Background:
Coronary artery aneurysms (CAA) put patients (pts) at risk for thrombosis and myocardial infarction. Clinical guidelines recommend systemic anticoagulation for giant CAA, diameter ≥ 8mm. Pt-specific modeling and computer simulations in KD pts suggest that hemodynamic data can predict regions with increased risk of thrombus formation and may be superior to simple assessment of the geometry of the aneurysm. Specifically, regions with high Particle Residence Time gradients (PRTg) have correlated with regions of thrombus formation.

Methods:
Transluminal Attenuation Gradient (TAG) is determined from the change in radiological attenuation on CT angiography (CTA) images in Hounsfield units per vessel length. TAG analysis has been used for characterizing coronary artery stenoses; however this approach has not been used for CAA. We analyzed the correlation between TAG and PRTg in KD pts with CAA and evaluated TAG for prediction of thrombotic risk.

Results:
Pt-specific anatomic models for flow simulations were constructed from CTA image data from 6 KD pts with CAA and one normal control. TAG was calculated for all aneurysmal vessels and one control vessel. TAG values for the CAA were markedly lower than for the non-aneurysmal vessel (mean -23.76 vs. -2.21). In addition, TAG values were compared to PRTg and other hemodynamic data obtained for each pt.

Conclusion:
TAG analysis is a new technique that can be applied to pt data obtained non-invasively through CTA. Thrombotic risk stratification for CAA and decisions about whether to start systemic anticoagulation may be improved by incorporating TAG and should be evaluated in future prospective studies.
Abstract 183: Mortality in children with Kawasaki disease: 20 years of experience from a tertiary care centre in North India.
Authors: Bhattad Sagar B , Gupta Anju , Rohit Manojkumar , Suri Deepti , Rawat Amit , Singh Surjit
Published: March 2022

Background:
Kawasaki disease (KD) is a common vasculitic disorder of childhood. Reported mortality in KD in the West is 0.08 %. We report clinical profile of 4 children who succumbed to KD during 1994-2014 at Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research Centre, Chandigarh, India. To the best of our knowledge, this is the first report on mortality in KD from any developing nation.

Objectives:
To study the clinical and laboratory profile of 4 children with KD who died at our centre.

Methods:
During the period 1994-2014, a total of 415 children were diagnosed to have KD based on American Heart Association criteria. M:F ratio was 1.9:1 and 96 children were aged 2 years or less. Children with KD received 2 g/kg of intravenous immunoglobulin (IVIg) and 50-80 mg/kg/day of aspirin initially and 3-5 mg/kg/day later. 2-D echocardiography was done once during the acute phase and then 6-8 weeks later on follow up. 4 amongst these died and their details were analysed by study of clinical records.

Results:
We report 4 deaths (2 boys, 2 girls) in this cohort of 415 children with KD. All 4 were below 2 years of age and had had significant delays in diagnosis and referral (Table). Symptomatic myocarditis was noted in 2 children, while 2 of them had thrombocytopenia.

Conclusion:
We report a mortality of about 1% in children with KD. Delays in diagnosis and referral contributed significantly to this mortality.
Abstract 191: Atherosclerosis risk and Carotid Intima-Media Thickness after Kawasaki Disease in Mexican Children
Authors: Garrido-Garcia Luis M , Solorzano Sara , Espinosa-Rosales Francisco J , Garcia-De La Puente Silvestre
Published: March 2022

Background:
Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis of unknown etiology. Recent studies have shown that even after resolution of the disease, endothelial dysfunction persists and may progress to premature atherosclerosis. Carotid intima-media thickness (cIMT) is a well-established indicator for atherosclerosis in both pediatric an adult patients.

Objective:
To assess whether patients after Kawasaki disease (KD) have increased risk factors and abnormalities suggestive of premature atherosclerosis by measuring the cIMT compared with healthy control subjects.

Material and Methods:
One hundred and three patients with KD aged 102.12 ± 41.82 months (61.94 ± 33.23 after the acute episode) and 83 age-matched healthy control subjects were examined for family, medical and dietary history, serum markers of atherosclerotic risk and inflammation and carotid intimal-medial thickness (CIMT) with vascular ultrasound scanning.

Results:
Patients and control subjects were similar in age, gender, family and dietary history, body mass index and blood pressure. We found no difference in the levels of triglycerides and glucose. And the levels of total cholesterol (162 ± 39.2 vs 150 ± 37.4), low-density lipoprotein cholesterol (102.57 ± 32.3 vs 89.6 ± 33.5), and high-density lipoprotein cholesterol (47.38 ± 17.65 vs 39.5 ± 17.54) were slightly higher with no statistical significance. The cIMT was slightly higher in the KD group (0.48 ± 0.1 vs 0.45 ± 0.15) We did found higher levels in the lipid profile and in the cIMT in children with or with regression of coronary aneurysms compared with children without coronary aneurysms.

Conclusions:
There is no clear evidence of increased atherosclerosis in Mexican children with KD, but there is evidence of an altered lipid profile and in the cIMT in patients with KD with coronary lesions compared with children with KD without coronary lesions the warrant further study
Abstract 197: Coronary Aneurysm and Ectasia In Adults
Authors: Kim Nam Su , Hwang Jae-kyoon
Published: March 2022

Background:
We investigate the status of coronary aneurysm or ectasia in adults.

Methods:
We retrospectively reviewed all coronary angiograms and coronary computed tomography angiograms (CT) performed at Hanyang University Hospital between January 2011 and August 2014.

Results:
Coronary angiography was performed in 4383 patients. Coronary CT was performed in 4099 patients. Coronary aneurysm or ectasia was detected in 28 patients (0.63%) on coronary angiography and in 21 patients (0.51%) on coronary CT angiography. Mean age of patient with coronary aneurysm or ectasia on angiography or coronary CT is 60.5(SD 14.7) or 58.0(SD 11.2). Mean age of patient without coronary aneurysm or ectasia on angiography or coronary CT is 63.2(SD 12.7) or 57.2(SD 12.0).

For 28 patients with coronary aneurysm or ectasia on coronary angiography, male and female ratio was 16:12. Age was for 57.6(SD 11.9) for male and 64.5(SD 17.6) for female. For 21 patients with coronary aneurysm or ectasia on CT angiography, male and female ratio was 14:7. Age was for 53.9(SD 8.3) for male and 66.1(SD 13.4) for female. The age gap between male and female was increased for patients with coronary aneurysm or ectasia on both studies. These suggest adult with coronary aneurysm or ectasia might have Kawasaki disease in young age.

Conclusions:
The mean age of male patients with coronary aneurysm or ectasia was lower than that of female patients without coronary aneurysm or ectasia. This indicates adult with coronary aneurysm or ectasia might have Kawasaki disease in young age.
Abstract 204: Risk factors for development of coronary artery aneurysms in Kawasaki disease in Mexican Children
Authors: MORALES-GARNICA GABRIELA A , MELGAR.CRUZ GUSTAVO A , SOTO-BLANQUEL JUAN L , ESPINOSA-ROSALES FRANCISCO J , GONZALEZ-GARAY ALEJANDRO , GARRIDO-GARCIA LUIS M
Published: March 2022

Background:
Kawasaki Disease (KD) is an acute febrile illness characterized by systemic vasculitis of unknown etiology. Cardiac sequelae, such as coronary artery aneurysms (CAA), are one of the most important aspects of this disease. Actually, it is the major cause of acquired heart disease in developed countries but its frequency in Mexico is still unknown.

Objective:
To establish the risk factors for development of coronary artery lesions in children with KD who were treated at the Instituto Nacional de Pediatria in Mexico City.

Material and Methods:
An observational, comparative, retrospective case-control study of all patients diagnosed with KD in our Institution from August 1995 to May 2014. We reviewed the medical records and analyzed gender, age, weight, height, clinical manifestations, time from the onset of the symptoms to diagnosis, hemoglobin, leucocyte count, platelet count, ESR, C-RP, albumin, sodium, AST ASL, treatment used and the development of coronary artery aneurysms.

Results:
We studied 384 cases of KD, 68% were male with a mean age at diagnosis of 39.02 ± 36.55 months. The mean duration of fever from the onset of the symptoms to diagnosis was 9.4 ± 5.79. An incomplete form of KD was diagnosed in 69 patients (19.4%). 150 patients developed CAA (39%). Multivariate analysis for CAA showed that younger age (p < 0.028) prolonged time to diagnosis (p < 0.001), central nervous system manifestations (p < 0.008) anemia (p < 0.001) leukocytosis (p < 0.005), thrombocytosis (p < 0.041) and elevated C-RP (p < 0.022) were the most important risk factors for development of CAA in our patients.

Conclusions:
This is the largest series of KD in Mexico, with more cases diagnosed in recent years, so it appear that the disease is more common than initially thought. Also, the frequency of CAA is greater than the reported in the literature, but it appears that is related to a delayed diagnosis and treatment.
Abstract 218: Weekly Exercise Increases Coronary Artery Diameter: A Case Report
Authors: Akimoto Katsumi , Nakamura Asuka , Harada Mana , Shigemitsu Sachie , Fukunaga Hideo , Furukawa Takeshi , Ohtsuki Masahiro , Takahashi Ken , Kishiro Masahiko , Shimizu Toshiaki
Published: March 2022

Background:
Studies have reported that heparin and exercise may alleviate myocardial ischemia in patients with Kawasaki disease (KD).Moreover, exercise alone can alleviate ischemic heart disease, e.g., cardiac rehabilitation in adult coronary disease. Exercise induces secretion of some growth factors and improves endothelial function. We found that exercise may play a role in physiologically increasing the diameter of the coronary artery(CA) in KD patients with history of coronary aneurysm.

Clinical course:
We report the case of a 9-year-old boy who had been admitted to our hospital at 6 months of age. He had long-term fever, rash, peripheral edema, conjunctivitis, and strawberry tongue and was diagnosed with KD. We treated him with a high dose of gamma globulin and pulse therapy. Despite these treatments, he developed coronary aneurysms on both sides. In the left descending artery (LAD), the aneurysmal diameter was 8 mm. We initiated treatment with warfarin and aspirin and performed angiography twice in the acute phase and at one year after admission, followed by magnetic resonance coronary angiography every 6 months. At 6 years of age, the aneurysmal changes disappeared. We stopped warfarin and started regular exercise on a weekly basis (1 hour of running and 2 hours of baseball). After initiation of exercise,echocardiography showed that LAD diameter increased from 2.8 mm to 3.5 mm. At 9 years of age, we performed angiography and intravascular ultrasound (IVUS) to determine whether this increase in diameter was due to recurrent aneurysmal change or physiological change. The diameter of the LAD was 3.5 mm (>+2 SD of normal). IVUS showed that there was a small amount of endothelial hypertrophy but no irregularity, calcification, or thrombus. Thus, we concluded that this dilatation was not an inflammatory change but a physiological change.

Conclusion:
Regular exercise may play a role in improving CA lesions through arterial dilatation and improvement of endothelial function.
Abstract 30: Are Man-made Pollutants Originating From China, Central Asia One Of The Windborne Mystery Infections Of Kawasaki Disease Carried Across The Pacific?
Authors: Yeter Deniz , Deth Richard , Kuo Ho-Chang
Published: March 2022

Kawasaki disease (KD) is an acute febrile illness predominately affecting children (75-80%) that is classified as an autoimmune vasculitis of small- to medium-sized arteries. KD is generally self-limited, although serious cardiac lesions develop in 25-30% of cases. Despite over four decades of extensive international investigation, no cause of KD has been confirmed. Significantly higher rates of concurrent viral infections were recently observed in patients during acute KD, while another study found significantly greater risk of early hospitalization for bacterial infections before KD onset. Several recent large investigations appear to confirm that patients are significantly more likely to develop asthma or common allergies such as acute rhinitis and atopic dermatitis both before and after KD. Seasonal shifts in large-scale wind currents originating from heavily polluted regions in China and Central Asia are significantly associated with the occurrence of KD cases in Japan, Hawaii, and San Diego. Recently, it appears these authors discovered that marked candida pollution from the soil of heavy agricultural and industrial areas in Northeastern China is significantly associated with the occurrence of KD in Japan. There is extensive precedent for trans-ocean wind transport of industrial pollutants, including across the Pacific. China now accounts for more than 50% of the world’s total anthropogenic emissions and is responsible for 20-29% of total air pollution in the United States, particularly as a result of its rapid industrialization and heavy reliance upon coal-fired power plants. Significantly higher consumption of seafood contaminated with methylmercury, PCBs, and dioxins may account for the disproportionate rates of KD in East Asian populations. In Japan, the appearance of KD during the 1950s and 1960s coincides with outbreaks of Minamata disease during this same period, which resulted from an unprecedented increase in mercury pollution and the contamination of seafood. Lastly, industrialization and subsequent pre- and postnatal exposure to various irritants are significantly associated with the development of asthma and common allergies during early childhood, which suggests a potential common link to KD that deserves scrutiny.
Abstract 37: Consortium-Based Genetic Studies of Kawasaki Disease in Korea: Overview of Korean Kawasaki Disease Genetics Consortium
Authors: Lee Jong-Keuk , Hong Young Mi , Jang Gi Young , Yun Sin Weon , Yu Jeong Jin , Yoon Kyung Lim , Lee Kyung-Yil , Kil Hong-Rang , Kim Gi Beom ,   The Korean Kawasaki Disease Genetics Consortium
Published: March 2022

In order to perform large-scale genetic studies of Kawasaki disease (KD) in Korea, the Korean Kawasaki Disease Genetics Consortium (KKDGC) was formed in 2008 with 10 hospitals. Since the establishment of KKDGC, we have collected a total of 1,198 patients’ clinical data and approximately 5 ml of blood samples per patient (for genomic DNA and plasma isolation) using standard clinical data collection forms and nation-wide networking system for blood sample pick-up. In our previous clinical risk factor analysis using collected clinical data of 478 KD patients, we found that incomplete KD, intravenous immunoglobulin (IVIG) non-responsiveness, long febrile days are major risk factors for coronary artery lesions (CALs) development, whereas low serum albumin concentration is an independent risk factor for IVIG non-responsiveness. Recently, we are re-analyzing the clinical data of all collected KD patients to evaluate the effect of age, gender, family history status, recurrence status, KD types on clinical features of KD. In addition, in our previous genome-wide association studies (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls, we identified a Kawasaki disease susceptibility locus at 1p31. We also identified significant associations of coronary artery aneurysm with a variant located in KCNN2 gene and common variants in CRP gene promoter with the increased CRP levels in KD patients. Furthermore, to identify new KD susceptibility and subphenotype loci, we are performing another GWAS using Illumina Human Omni1 SNP chip with approximately 300 KD cases containing 16 cases with family history, 46 cases with recurrence, 119 cases with IVIG non-responsiveness, 52 cases with CALs (diameter >5mm). Multiple subsets of KD cases will be very useful to detect loci associated with the subphenotypes of KD in GWAS data analysis. We also performed DNA microarray analysis to determine differential gene expression by
in vitro
immunoglobulin treatment using patient-derived B cell lines (IVIG-responders vs. IVIG-non-responders). However, we could not find any difference between B cell lines. Furthermore, a pilot study of exome sequencing of 12 KD cases was not successful in identifying causal KD susceptibility genes.
Abstract 4: Analysis of West Coast Atmospheric Circulation Patterns and Kawasaki Disease “Dry Spells”
Authors: Burns Jane C , Tyree Mary , Berry Erika K , Rodó Xavier , Cayan Daniel R , Berger Shaun S , Bruce Margaret , Daru Jennifer , Everhart Jennifer L , Gilbert Michael J , Guzman-Cottrill Judith , Hindo Heather , Kosut Jessica S , Kurio Gregory H , Lee Nathan C , Mao Chad Y , Melish Marian E , Michalik David E , Pathare Sameer , Portman Michael , Schultz Heather , Trost Margaret , Yee-Guardino Stephanie A
Published: March 2022

Background:
Tropospheric winds from northeastern China have been linked to fluctuations in Kawasaki disease (KD) cases in Japan. These winds may carry aerosols that trigger KD in genetically susceptible children. We investigated whether reduced numbers of KD cases were linked to large scale circulation patterns affecting the U.S. West Coast.

Methods:
KD cases with either date of onset of fever or date of hospitalization (PHIS, Pediatric Health Information System) were obtained from 5 sites from Seattle to San Diego from 1995-2014. Six days were subtracted from date of hospitalization to approximate date of onset. For each site, periods from December-March were identified for which there were no KD cases for an interval of ≥10 days, called “KD dry spells”. Daily NCEP-NCAR atmospheric Reanalysis 700hPa height anomalies were used to represent the atmospheric circulation.

Results:
From 27-48 dry spells were defined for each site. Composites of atmospheric circulation from Day -20 to Day +10 relative to first day of a dry spell were created for each study site. The atmospheric circulation preceding the KD dry spell featured a higher than normal pressure center (results in weakened onshore flow) either offshore over the North Pacific or directly over the site. The circulation anomalies were statistically significant, and unlikely to have occurred by chance. The dry spell pattern intensified and persisted over several days. The strongest anomalous atmospheric circulation (and associated blocked wind flow) occurred between Day -6 to -1 relative to the start of the dry spell. A similar pattern was shared by 4 of the 5 sites. One site featured strong high pressure anomalies > 6 days before the KD dry spells, but only a weak anomaly in the Day -6 to-1 interval preceding the dry spell.

Conclusion:
This analysis reinforces results from previous studies of KD case fluctuations in Japan wherein anomalous KD activity was associated with particular wind flow patterns. The circulation patterns associated with the West Coast KD “dry spells” suggest that reduced wind flow from the North Pacific results in reduced KD occurrences. These results support the hypothesis that a KD agent is transported by winds, possibly from a shared source region with transport of the agent across the Pacific.
Abstract 48: Small Arteritis is the Basic Pathology of Kawasaki Disease
Authors: Onouchi Zenshiro , Okamoto Akiko , Suzuki Chinatsu , Hamaoka Kenji
Published: March 2022

Introduction:
Pathologic processes of two features in Kawasaki disease (KD) have not been elucidated. The one is the preponderance of aneurysms in the main coronary artery. The other is the discontinuity in the process of the vasculitis between those of microvessels and small arteries, and those of medium-sized to large arteries.

Hypothesis:
We assessed the hypothesis that arteritis of the vasa vasorum, which we described for the first time, plays a key role in the preponderance of aneurysms in the main coronary artery in KD.

Methods:
We examined the relationship between patient age at onset of KD and the distance ratio of the aneurysm in the left main coronary artery (LMCA) to clarify the role of arteritis of the coronary vasa vasorum, originated from the atrial and ventricular branches of the peripheral coronary artery, in the ischemia at the media of LMCA. The distance ratio Y was defined as D1/D2 х 100, where D1 and D2 are the distances from the left coronary ostium to the proximal point of the aneurysm and to the bifurcation into the left anterior descending and left circumflex artery, respectively. We then studied the relations between cardiogenic shock and extracardiac aneurysm, and coronary aneurysm in our cases and those of literatures.

Results:
The mean distance ratio of 56 aneurysms correlated with age, similar to the development of the coronary vasa vasorum: Y = 49.75383 - 3.3739X, P = 0.002987, R = 0.356. Cardiogenic shock which indicates severe interstitial myocarditis and severe arteritis of the coronary vasa vasorum occurs in the 1st week of the illness and is followed by aneurysm formation in LMCA. Extracardiac aneurysm due to severe arteritis of its vasa vasorum associates with severe arteritis of the coronary vasa vasorum originated from the aorta which may induce dilatation at the proximal portion of LMCA. Thus, aneurysm in LMCA complicated with extracardiac aneurysm reveals its proximal extension. In conclusion, these findings may contribute to understand morphogenesis and to investigate the treatment on KD.
Abstract 56: Increased Neutrophil Counts and Serum Transforming Growth Factor-beta 1 Levels in an Infant With Autoimmune Neutropenia Who Recovered From Kawasaki Disease
Authors: Okada Seigo , Hasegawa Shunji , Suzuki Yasuo , Wakabayashi Midori , Ichimura Takuya , Kaneyasu Hidenobu , Shimomura Maiko , Nakamura Kazuhiro , Kobayashi Masao , Ohga Shouichi
Published: March 2022

Kawasaki disease (KD) is an acute, febrile, and systemic vasculitis that primarily occurs in infants and young children. Although the aetiology is unknown, it is considered that abnormal activation of monocytes/macrophages but not lymphocytes could occur during the acute phase of KD. Neutrophils may have a pivotal role in the pathogenesis of KD as well as the formation of coronary artery lesions (CAL). Primary autoimmune neutropenia (AIN) is a common form of chronic benign neutropenias of childhood. AIN, occuring in infancy, is characterised by persistent severe neutropenia (<500/μL of absolute neutrophil counts [ANC]), detection of the autoantibodies against neutrophil-specific antigens, and 95% of resolution before 4 years of age. There has been only one report on a patient with AIN who developed severe KD after the administration of granulocyte colony-stimulating factor. Here, we describe a 21-month-old female with AIN who developed full-blown KD on severe neutropenia remained. Single dose intravenous immunoglobulin led to a prompt response with defervescence. During the convalescent phase of KD, the patient showed a rapid increase and the following recovery of ANC in concert with the elevated levels of serum transforming growth factor-beta 1, that is one of the representative immunoregulatory cytokines. During hospitalization, echocardiography indicated no evidence of CAL. The pathophysiology of KD and the resolution of autoimmunity were discussed with special reference to the cytokine profiles.
Abstract 66: High-dose IgG Completely Inhibited TNF-α-induced, But Not IL-1β-induced, G-CSF Expression By Human Coronary Artery Endothelial Cells
Authors: Matsuda Akio , Motomura Kenichiro , Saito Hirohisa , Matsumoto Kenji , Abe Jun
Published: March 2022

High-dose intravenous IgG (IVIG) is a well-established standard therapy for Kawasaki Diseases (KD) that effectively reduces both systemic inflammation and the risk of developing coronary artery aneurysms, in approximately 80% of KD. However, some patients do not respond to IVIG and the cause of their unresponsiveness remains unclear. We previously reported that high-dose IgG specifically and completely inhibited accelerated expression of KD-related cytokines, including G-CSF, by human coronary artery endothelial cells (HCAEC) in response to TNF-α. The suppression of these cytokine genes correlated closely with functional inhibition of a transcription factor, C/EBPδ. Here we show that IL-1β-induced expression of the KD-related cytokines by HCAEC was never inhibited by high-dose IgG treatment. Furthermore, although TNF-α-induced C/EBPδ activities, as measured by gel shift assay, were completely inhibited after high-dose IgG treatment, those induced by IL-1β were not inhibited at all. Our findings suggest that C/EBPδ may play a pivotal role in the clinical effectiveness of IVIG in patients with KD. Greater understanding of the precise underlying mechanisms of IVIG on coronary artery endothelial cells may contribute to the development of novel therapeutic strategies for current IVIG-resistant patients with KD.
Abstract 67: Peroral Administration Of Extract Of Candida Albicans Induce Kawasaki Disease-like Vasculitis In Mice
Authors: Oharaseki Toshiaki , Yokouchi Yuki , Enomoto Yasunori , Yamada Hitomi , Miura Noriko , Ohno Naohito , Takahashi Kei
Published: March 2022

Background:
The cause of Kawasaki disease (KD) has been still unknown though the intestinal flora was reported as one of the candidate etiology of KD. Candida is known as one of the intestinal flora. Intraperitoneal injection of Candida albicans water-soluble fractions (CAWS) that compose of polysaccharide of cell wall of the yeast can induce systemic vasculitis in mice. It is evaluated as animal model of Kawasaki disease vasculitis because this experimental vasculitis is similar to those observed in KD patients. However it is uncertain whether or not oral administration of CAWS can induce vasculitis in mice.

Aim:
The present study aimed to elucidate whether or not oral administration of CAWS can induce vasculitis.

Materials and methods:
Mice, DBA/2, male, 4 weeks of age were used. CAWS suspended in PBS was administered perorally to mice for 28 consecutive days. As a priming agent, 20 micrograms of LPS was injected to mice intraperitoneally before administration of CAWS. Experimental groups are as follows. Group-I : Peroral administration of 800 micrograms of CAWS with LPS, Group-II: Peroral administration of 800 micrograms of CAWS without LPS, Group-III : Peroral administration of 250 micrograms of CAWS with LPS. Mice injected CAWS intraperitoneally (conventional procedure) were used as control group. Vasculitis was evaluated by routine histological techniques. This study conformed with regulations of position of the American Heart Association on research animal use and Toho University’s Animal Ethics Committee.

Result:
The incidence of vasculitis in each group were as follows : Group-I : 1/6, Group-II:0/6, Group-III:1/6, Control : 3/3. Dense infiltration of neutrophils and macrophages was observed in coronary artery and/or aortic root. Severity of inflammatory cell infiltration and extent of the lesion in Group-I and Group-III were milder and smaller than those of control.

Conclusion:
Present study revealed that peroral administration of CAWS could induce vasculitis in mice though the incidence of vasculitis was lower than that of control. This model is considered to be useful to clarify the relation between intestinal immunity and vasculitis. We should clarify the mechanism that oral administration of CAWS induced vasculitis.
Abstract 73: A Case Of Fatal Kawasaki Disease Associated With Fulminant Myocarditis
Authors: Azumagawa Kohji , Katayama Hiroshi , Horiuchi Tsuyoshi , Yamamoto Shinji , Tanaka Keiko , Morinobu Wakaba , Ohta Yoshio
Published: March 2022

Introduction:
Acute phase Kawasaki disease (KD) is often associated with myocarditis. In most cases, such myocarditis is self-limiting. Fulminant myocarditis is rare as a cause of death for acute KD. We report a case of fatal KD associated with fulminant myocarditis.

Case:
A 4-year-old boy presented high fever and consulted family doctors for the second successive day. Although he received antibiotics, high fever persisted. He consulted to our hospital on the 4th day of illness. At the initial visit, conjunctival congestion, redness of pharyngeal and lip, bilateral cervical lymphadenitis and erythema on neck, palms and abdomen were observed. Initial laboratory data were shown as follows: WBC count 20,800 / μL, CRP 14.18 mg / dL. He was hospitalized with the diagnosis of acute febrile disease including KD. At first he was prescribed acetylsalicyclic acid and intravenous infusion of antibiotics, however high fever still persisted. On the 6th day of illness, immunoglobulin (IG) and prednisolone were administered intravenously because he was anticipated to be refractory to IG. On echocardiography, left ventricular contraction was normal. There were no findings of coronary artery abnormalities or pericardial effusion. After the first administration of IVIG, high fever persisted. Inflammatory markers on blood examination exacerbated. Laboratory data on the 8th day of illness were as follows: WBC 23,500 / μL, CRP 27.35 mg / dL, CPK 1,451 IU / L (MB 2%). Therefore, we added the second IVIG, steroid pulse therapy and urinastatine. On the next day (9th day), however, he suddenly suffered from cardiopulmonary arrest and deceased.

Pathological findings revealed scattered myocardial necrosis on both ventricles. The CD 3, CD 8 positive T lymphocytes were infiltrated around myocytes. There were no findings of coronary artery aneurysms or thromboembolisms. These findings were compatible with fulminant myocarditis.

Discussion:
Recent advances in therapy for acute KD significantly reduce coronary artery lesions and subsequent mortality. However, clinical feature of KD has a lot of variety. Although fulminant myocarditis associated with KD in early acute phase is extremely rare, we should prepare for refractory KD and its abrupt change.
Abstract 75: High Sensitivity C Reactive Protein in Adolescent and Young Adult Patients with Kawasaki Disease Late After Onset
Authors: Chen Yung-Chuan , Huang Yi-Ling , Shen Ching-Tsuen , Wang Nan-Koong , Chiu Shuenn-Nan , Chen Chun-An , Wang Jou-Kou , Wu Mei-Hwan , Lin Ming-Tai
Published: March 2022

Background:
In children with history of Kawasaki disease (KD), low grade inflammation was ever reported to be associated with persistent coronary artery lesions (CAL). However, this issue had rarely been checked in adolescents and young adults (10-25 years old).

Methods and Results:
The study cohort was comprised of 104 subjects: 22 KD patients with angiography-confirmed CAL, which persisted at an average of 12.5 years after onset of KD, 38 KD patients with regressed aneurysms, 44 KD patients without any coronary complications from the disease onset and 31 age-matched (18.7 ± 1.88 years old) healthy controls. Plasma levels of high-sensitivity C reactive protein (hs-CRP) were measured for all participants with a commercially available high-sensitivity method (Immulite, Simens, USA). Plasma levels of hs-CRP were significantly higher in KD patients, regardless of the severity of coronary artery involvement, than controls. However, there was no difference of hs-CRP level between each KD patient groups including any severity of coronary artery lesions. After adjustment for confounding factors such as body mass index, gender and levels of HDL-c, linear regression analysis showed the only independent predictor of logarithmically transformed hs-CRP levels was BMI (β=0.32, p=0.007), rather than patient grouping (p=0.126).

Conclusion:
Levels of hs-CRP are significantly higher in adolescent and young adult KD patients than age-matched controls. However, we failed to detect significant difference among patients with different severities of CAL. The results implied, in Taiwan, low grade inflammation might play a minor role on the persistence of coronary lesions in KD.
Abstract 77: Association of Sodium and Coronary Arteriopathy in Acute Phase of Kawasaki Disease
Authors: Eun Lucy Y , Park Sora , Sung Mindong , Jung Se Yong , Jung Jo Won , Choi Jae Young
Published: March 2022

Background:
Kawasaki disease(KD) is an immune related multisystemic inflammatory vasculitis in children, especially ensues coronary artery lesions. Several cardiovascular diseases are known to be correlated with sodium level. In this study, we examined the association between serum sodium levels and the severity of coronary artery lesion in acute phase of Kawasaki disease.

Objective:
The purpose of this study was to determine the association of serum sodium level for predicting cardiac events in Kawasaki disease (KD) patients especially in coronary artery lesions (CALs).

Methods:
We conducted a retrospective review of the medical records of 158 Kawasaki disease patients from June 2013 to August 2014. We devided the subjects into two groups regarding to the serum sodium level. Various laboratory tests and echocardiographic data were analyzed. Student t-tests were carried out to analyze the significance of the difference in each group.

Results:
ESR, CRP, BNP, and liver enzymes were significantly greater in lower sodium group. Echocardiographic diastolic marker of mitral E and E/E’ measurement were statistically different. Coronary arterial changes were significant in lower sodium group as well.

Conclusions:
The lower sodium group demonstrated significant increase of various inflammatory markers and coronary arterial lesions. The sodium level might be associated with the severity of coronary vessel and cardiac inflammation in acute phase of Kawasaki disease.
Abstract 81: A retrospective analysis of 274 cases of Kawasaki disease
Authors: Goto Kenjiro
Published: March 2022

Purpose:
Haematological, biochemical and clinical parameters were retrospectively analysed in a group of patients with Kawasaki disease, to determine predictive variables on the effect of intravenous immunoglobulin (IVIG) therapy.

Methods:
We studied 274 cases of Kawasaki disease between October 2006 and September 2013 at a single centre (Kawasaki Municipal Tama Hospital, Japan). These cases were analysed on the basis of:

(1) Requirement of additional therapy post IVIG (41 cases vs 200 cases not requiring additional therapy)

(2) Presence of coronary artery lesions (CAL: Z score≧2.5) within a month (15 cases with CAL, 220 cases without CAL)

Haematological, biochemical and clinical parameters including white blood cell, percentage of neutrophils, platelet, total-bilirubin, AST, ALT, Albumin, Sodium, C-reaction protein, Fibrinogen and D-dimmer as well as time to first post-IVIG treatment were compared in the categories shown above. Statistical analysis was performed with Mann-Whitney U test. Differences were considered to be significant when the two-tailed p-value was < 0.05.

Results:
The percentage of neutrophils, total-bilirubin, AST, ALT, Albumin, Sodium, C-reaction protein, D-dimmer and time to first treatment show significant difference between the groups stratified on the requirement of post-IVIG therapy. In the stratification based on acute CAL- AST, ALT, Albumin and Sodium show significant difference between the groups.

Conclusion:
We suggest that ratio of neutrophil, total-bilirubin, AST, ALT, Albumin, Sodium, C-reaction protein, D-dimmer and time to first treatment are predictive factors of resistance to single IVIG therapy. Similarly, levels of AST, ALT, Albumin and Sodium are predictive factors of acute coronary artery lesions in Kawasaki disease.
Abstract 88: Pentraxin 3 in Coronary Artery Lesions in Kawasaki Disease
Authors: Kitoh Toshiyuki , Kitagawa Yoshiro , Baba Reizo , Kaneko Atsushi , Shimizu Masaki , Yachie Akihoro , Kume Noriaki , Hamakubo Takao
Published: March 2022

Although vascular inflammation is an important feature of Kawasaki disease (KD), the usefulness of local inflammatory markers as biomarkers for KD is unknown. Pentraxin 3 (PTX3), soluble lectin-like oxidized low density lipoprotein receptor 1 (sLOX-1) and matrix metraloproteinase-9 (MMP-9) are biomarkers of inflammation of vascular components. Objective: We tested whether plasma concentrations of PTX3, sLOX-1 or MMP-9 would be a useful biomarker for detecting high risk patient of coronary artery aneurysm (CAA) in KD and compared with serum level of interleukin-6 (IL-6) and IL-18. The ability of the assays to identify KD patients at risk for CAA was analyzed. Methods: PTX3, sLOX-1, MMP-9, IL-6 and IL-18 concentrations of 50 KD patients at different four clinical points were analyzed. Point A represented on admission; B, pre-IVIG; A+B, before IVIG; C, after IVIG; D, after fever resolution. Each concentration was compared with the rate of occurrence of CAA and IVIG unresponsiveness. Results: Each value was evaluated in 50 KD patients (2 with CAA, 48 without CAA). Three patients were treated without IVIG, 17 with one course of IVIG, and six with two IVIGs, two with three IVIGs, respectively. At the points A+B, C, D means for PTX3 were; 33.4, 11.7, 9.00 ng/ml, mean for MMP-9; 34.6, 19.2, 24.2 ng/ml, mean for sLOX-1; 3.82, 2.33, 2.25 ng/ml, respectively. Levels of PTX3 (p<0.001) and MMP-9 (p<0.05) were significantly higher in before IVIG than after IVIG; whereas levels of sLOX-1, as well as those of IL-6 and IL-18 were comparable between before and after IVIG. PTX3 were well correlated with IL-6 level (R2=0.73). Both cases with extraordinary high PTX3 levels at admission of 91.8 and 65.3 ng/ml were complicated with coronary artery aneurysms, even though they were treated by three courses of IVIG. The level of plasma PTX3 was significant related with the course numbers of IVIG (p<0.05). Conclusion: Levels of PTX3 and MMP-9 appear to be associated with clinical course of KD. Levels of PTX3 were correlated with the severity of disease; how many doses of IVIG enough to resolve fever. An extraordinary high PTX3 level might be suggestive of the existence of CAA. These data suggest that PTX3 can be a candidate biomarker for prediction of unresponsiveness and CAA formation in patients with KD.