bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 139: Transcriptional Regulation By Infliximab Therapy In Kawasaki Disease Patients With Immunoglobulin Resistance
Authors: Ogihara Yoshihito , Ogata Shohei , Ebato Takasuke , Takanashi Manabu , Honda Takashi , Kimura Sumito , Ishii Masahiro
Published: March 2022

Background:
Infliximab (IFX) is a known monoclonal antibody against TNF-α that is used to treat Kawasaki disease (KD) patients with intravenous immunoglobulin (IVIG) resistance. The transcriptional modulation of inflammation following IFX therapy has not been reported in KD patients.

Methods:
We investigated the transcript abundance profiles in whole blood obtained from eight IVIG-resistant KD subjects treated with IFX therapy using microarray platforms and compared them to those in initially IVIG-responsive subjects. A pathway analysis was performed using WikiPathways to search for the biological pathways of the transcript profiles. Four transcripts changed by IFX therapy were subsequently validated using RT-PCR.

Results:
The pathway analysis showed the reduced abundance of transcripts in the nucleotide-binding oligomerization domain, matrix metalloproteinase, and inflammatory cytokines pathways and the increased abundance of transcripts in the T cell receptor, apoptosis, TGF-β, and IL-2 pathways. Additionally, the levels of four transcripts (peptidase inhibitor-3, matrix metalloproteinase-8, chemokine receptor-2, pentraxin-3) related to KD vasculitis and IVIG resistance decreased after IFX therapy.

Conclusions:
The administration of IFX was associated with both the signaling pathways of KD inflammation and several transcripts related to IVIG resistance factors. These findings provide strong theoretical support for the use of IFX in KD patients with IVIG resistance.
Abstract 151: Optical Coherence Tomography post-processing towards an automated quantification of coronary artery wall alteration subsequent to Kawasaki Disease
Authors: Abdelali Maria , Cheriet Farida , Dionne Audrey , Dahdah Nagib
Published: March 2022

Introduction:
Statistical mathematical processing of medical imaging promotes operator-independent interpretation. We sought to identify discriminative image features for a histological disambiguation of KD related coronary (CA) lesions. The ultimate goal is to develop a fully automated algorithm for the quantification of the degradation/healing state of the CA wall structure post KD.

Methods:
We analyzed OCT CA recordings from two KD patients with (KD
+
AN
+
) and two patients with no history of CA aneurysm (KD
+
AN
[[Unable to Display Character: –]]
), vs a non KD patient (KD
[[Unable to Display Character: –]]
).

Results:
In KD
[[Unable to Display Character: –]]
, regardless of the radial region of interest (ROI) position in the image, the OCT mean signal intensity presents centrifugally two peaks corresponding to the intima and media, constantly separated (17.1± 2.0 pixels) (fig. 1A). In KD
+
AN
[[Unable to Display Character: –]]
the peaks may disappear (Fig. 1-B left medial hyperplasia) and the distance between remaining crests vary between ROIs (22.7±6.9 Pixels). In KD
+
AN
+
these peaks disappear (Figure1-C) and the signal intensity changes drastically between ROIs due to wall restructuration. Figure1-C shows a hatched signal that maybe that of a laminar structure. In this case the variation of gradient intensity may be a discriminative feature.

Conclusion:
Mathematical modeling of CA wall layers is feasible. While the consistency of the distance between media and intima peaks may discriminate KD
[[Unable to Display Character: –]]
from KD
+
and while the gradient intensity may detect restructuration in KD
+
AN
+
, ongoing investigation to discriminate CA lesions include signal homogeneity, energy and contrast. Texture analysis with anatomical correlates (e.g., calcium, fibrosis and clots) may allow automated diagnoses.
Abstract 155: Long-term Aortic Root Dilation in Kawasaki Disease with Coronary Aneurysm
Authors: Carr Michael , Schuette Caroline R , Pahl Elfriede
Published: March 2022

Introduction:
Aortic root dilation is a known finding in the acute/subacute phase of Kawasaki disease (KD). These changes may be inflammatory and related to the degree of coronary artery (CA) dilation, and may lag when compared to CA changes. Long-term changes in the aorta have not been previously reported.

Methods:
A retrospective review of patients with KD from our institution was conducted, identifying individuals with American Heart Association (AHA) Risk Level 3, 4 or 5 over a 20 year period (1994-2014). Aortic annular and root dimensions were measured at the most recent echocardiogram and converted to z-score measurements. When possible, ascending aorta dimensions were measured, and all studies were evaluated for the presence of aortic regurgitation. Time from KD diagnosis to the last echocardiogram was determined. Patients with disease processes predisposing to aortic dilation were excluded, as were those with duration of echocardiographic follow-up <1 year.

Results:
Fifty-three patients were identified, with a median age at diagnosis of 29 months (SD 42, 1.2-162 months). Twenty-seven (51%) were AHA Risk Level 3, 20 (38%) Risk Level 4 and 6 (11%) Risk Level 5. The mean time from diagnosis to latest echocardiogram was 7.3 years (1.4-17.3 years). Aortic annular and root dimensions were obtained in all patients (mean aortic annular z-score -0.06, mean aortic root z-score 0.67). Four patients (8%) had a dilated (z-score >2) aortic root, one also had a dilated annulus. Ten patients (19%) had borderline root dilation (z-score >1.5). Ascending aorta dimension measurements were possible in 72% (38/53) of the cohort, of which only 1 (3%) had a z-score >2 and 3 (8%) had a z-score >1.5. Importantly, no patients demonstrated aortic regurgitation.

Conclusion:
In patients with history of KD and significant coronary artery involvement, borderline/mild dilation of the aortic root is not uncommon at intermediate to long- term follow-up, suggesting the possibility of a higher degree of aortic involvement in the acute and subacute phase of the disease process. The ascending aorta appears to be less affected and there was no evidence of functional derangements of the aortic valve. Accurate measurement of the aortic root dimension at all stages of KD is warranted.
Abstract 165: Coronary Artery Dilatation in Kawasaki Disease is Associated with Anatomical Coronary Dominance: An Angiography-Based Study
Authors: Hanna Baher M , Lapierre Chantale , Trinh Tan Frédérick , Desjardins Larent , Fournier Anne , Dahdah Nagib
Published: March 2022

Introduction:
Coronary artery (CA) dilatation in Kawasaki disease (KD) is best determined by elevated Z-scores. Z-score equations, do not take into account anatomical CA dominance. We hypothesize that, except for CA aneurysms, CA dominance influences dilatation status in KD (Z-score > 2.5).

Material and Methods:
We retrospectively analyzed CA status in KD patients followed at our institution for persistent CA dilatation. All patients who had a diagnostic catheterization between 2002 and 2012 were considered. Serial echocardiographic dimensions of LCA, RCA, and LAD upon diagnosis, 1 week, 2 weeks, 4 weeks, 2 months, 3-6 months, and 9-12 months later were normalized to BSA using published CA Z-score equations. Data were contrasted with CA angiography description of CA dominance: right or left dominance was adopted when the respective CA supplies both diaphragmatic LV free wall and posterior inter ventricular septum (IVS); Co-dominance was when posterior IVS was supplied by RCA and diaphragmatic LV free wall by LCA.

Results:
Of 69 potential patients, 16 were excluded (9 never presented a CA dilatation and 7 had CA aneurysms). The interval between acute onset and selective CA angiography of the remaining 53 patients was 69.5±52.8months at 9.2±5.2years old. Of the latter, 20(37.7%) had LCA-dominance, 31(58.5%) RCA-dominance, and 2(3.8%) Co-dominance. Upon KD onset, the LCA-dominant subset had 14/20(70%) ipsilateral dilatation vs. 6/20(30%) contralateral dilatation. Similarly, RCA-dominant dilatation was ipsilateral in 21/31(68%) vs. 10/31(32%) contralateral dilatation (p=0.89). On late follow-up, persistent CA dilatation was similar between LCA-dominance 6/14(43%) and RCA-dominance 10/21(47%) (p=0.94). The interval between onset and normalizing CA Z-score was 1.16±1.65 vs. 2.45±3.6years in ispilateral vs. contralateral subsets (p=0.19). From the inflammatory perspective, serum albumin was significantly lower in patients with contralateral CA dilatation (p=0.02). Nevertheless, other inflammatory markers did not show a significant difference.

Conclusion:
Transitory CA dilatation following KD is closely related to anatomical dominance. This may be a reflection of vasodilation during immune carditis rather than coronary vasculitis.
Abstract 166: Reappraisal of Coronary Abnormalities Using Systemic Focused Coronary Echocardiographic Imaging in Kawasaki Disease
Authors: Hsieh Kai-Sheng , Lin Chu-Chuan , Wu Huang-Wei , Hong Yu-Ci
Published: March 2022

Background:
Coronary artery abnormalities (CAA) is an important complication in children with Kawasaki disease (KD). The incidence of CAA used to be around 5-10% after acute phase of KD. So far, there had been scanty information about the systemic approach to examine the status of coronary in children with KD. We thus developed a systemic focused coronary echocardiographic imaging (SFCEI) in Kawasaki disease.

Methods:
Between July 2013 and June 2014, a total of 35 patients with acute phase Kawasaki disease was enrolled in this study. Echocardiography of 100 normal pediatric patients was used for control. In this study, we employed the Siemens ACUSON SC2000 echocardiography system with 8V3 transducer (3-8MHz) for examination. All the patients was examined at diagnosis, 1 week, 2 weeks and repeating at 6-8 weeks after the onset of illness. Assessment of right coronary (proximal and distal portions), left main (middle portion), left anterior descending (proximal and distal portions) and circumflex arteries(proximal portion) was performed in each patients. Coronary abnormality is considered at the presence of any one of the following: 1) dilatation or aneurysm formation 2) lack of tapering 3) irregularity 4) intimal thickening(brightness)

Results:
Various coronary artery abnormalities were present in Kawasaki disease, include dilatation in 11(31%) patients, aneurysm formation in 2(6%) patients, lack of tapering in 13(37%) patients, irregularity in 12(34%) , and intimal thickening(brightness) in 23(65%) patients. Overall, coronary artery anomalies was present in 32(91%) of our patients in acute phase of disease.

Conclusion:
Our result showed that the incidence of coronary artery abnormalities in Kawasaki disease is higher than previously reported.

Echocardiography can provide an accurate and timely diagnosis regarding the presence of cardiac and coronary artery lesions in Kawasaki diseases. With our SFCEI method, more detailed and comprehensive features of coronary artery abnormalities other than coronary aneurysm and dilatation can be provided.
Abstract 167: CT Calcium Scoring Detects Coronary Artery Pathology In Patients With A Remote History Of Kawasaki Disease
Authors: Kahn Andrew M , Daniels Lori B , Gordon John B , Budoff Matthew J , Vejar Matthew , Burns Jane C
Published: March 2022

Background:
As a result of the acute vasculitis associated with Kawasaki disease (KD), subsets of patients with a remote history of KD have coronary artery aneurysms and may develop coronary artery stenoses with associated risks of late morbidity. Hence, there is a need for effective non-invasive testing to detect coronary artery pathology and risk stratify patients with a remote history of KD. In a pilot study we previously showed that computed tomography (CT) coronary artery calcium (CAC) scoring with relatively low radiation doses detects late CAC in patients with aneurysms and a remote history of KD.

Methods:
We performed CT calcium volume scoring in 166 subjects (median age 19.5 years) with a remote history of KD (median interval from onset of KD to CT 15.1 years). Coronary arteries were classified as normal (n = 100), transiently dilated (n = 23), persistently dilated (n = 10), resolved aneurysm (n = 9), or aneurysm (n = 24) based on the initial echocardiograms. We defined coronary artery pathology as the presence of a coronary artery aneurysm or stenosis.

Results:
All subjects with coronary arteries classified as normal, persistently dilated, or resolved aneurysm had zero CAC. All but one of the subjects with transiently dilated coronary arteries had zero CAC (the one subject with a CAC score of 666 mm
3
had a history of severe left main coronary artery stenosis requiring bypass surgery). Of the 24 subjects with coronary aneurysms, all but 5 had CAC (median volume score 542 mm
3
; range 17 mm
3
to 8,218 mm
3
). Four of the 5 subjects with aneurysms and no CAC were imaged within 6 years of their episode of acute KD. For subjects imaged 9 or more years after their acute KD (n=144), the presence of CAC on CT had a sensitivity of 95% and a specificity of 100% for detecting coronary artery pathology.

Conclusions:
For patients with a remote history of KD, CT calcium scoring is a sensitive and specific test for detecting coronary artery pathology. Patients with coronary artery aneurysms secondary to KD develop late CAC, which may be severe. The pathophysiology and clinical significance of this calcification are currently unknown.
Abstract 17: Environmental Epidemiology of Kawasaki Disease
Authors: O’Shea Sunita , Manlhiot Cedric , Labelle Michael , Bai Heming , Bernknopf Bailey , Chahal Nita , Birken Catherine S , McCrindle Brian W
Published: March 2022

Background:
The etiology of Kawasaki disease (KD) is commonly described as an exaggerated immune response to an environmental or infectious trigger in developmentally, immunologically and genetically susceptible children. The trigger for KD has not yet been identified.

Methods:
Patients with newly diagnosed KD (n=73) were enrolled within 6 weeks of KD diagnosis. Control subjects (n=65) were enrolled during pediatric annual visits and from friends of enrolled KD patients. All participants completed an extensive questionnaire about medical history, family and environment. Geographic localisation software characterized the participants’ neighborhoods. A hypothetical scenario was used for control patients to simulate similar recall bias to that of the KD patients.

Results:
There were no differences in age, gender, allergies, child and family medical history or recent vaccination. Children with KD were more likely to be unwell prior to KD symptom onset than controls, including fever, stomach pain, lethargy, jaundice, loss of appetite and irritability, but not infectious disease symptoms (16% vs. 21%, p=0.49). Infectious symptomatology developed concurrently to classic KD symptoms. Children with KD had less exposure to environmental allergens and were more likely to be exposed to chemical irritants.

Conclusions:
The presence of symptoms for up to 1 month before onset of KD may suggest that a preceding illness/environmental agents may alter barriers to entry/exposure or prime an immunologic reaction to an etiologic trigger. Children with fewer allergen/infectious exposures and chronic chemical exposure may be immunologically more susceptible.
Abstract 174: Relationship between Kawasaki Disease Related-Angiopathy and Pressure Wave Reflection in the Arterial System
Authors: Shimizu Yo , Nakamura Tsuneyuki , Ko Giyo , Akita Chisato , Saikawa Yutaka
Published: March 2022

Background:
Recently we reported that the carotid arteries of Kawasaki disease (KD) appear to develop mild sclerotic changes shortly after onset using the speckle tracking echocardiography. However, it remains to be elucidated what factors hemodynamically may induce these sclerotic changes.

Objectives:
The aim of this study was to investigate the relationship between KD related-angiopathy and arterial pressure wave reflection using the two-dimensional speckle tracking echocardiography and radial augmentation index (AIx).

Subjects & Methods:
We studied a cohort of children with history of KD. The subjects were 87 KD patients (age, 9.7±2.9 years) and 93 healthy controls (11.3±3.2 years). As for our methodology, the two regions of interest (ROI) for speckle tracking were manually positioned at near and far carotid arterial walls using a Philips iE33. Continuously, we examined the following strain values: (A) peak strain in expansion phase, (B) peak strain before aortic valve closure, and (C) strain value at aortic valve closure (Figure 1). Also, we examined two ratios, B/A and C/A, for emphasizing recoil function. Concurrently, the radial AIx were obtained.

Results:
KD patients had significantly the lower A values, the higher B/A, and the higher radial AIx, compared with controls. Furthermore, there was good correlation between B/A and radial AIx in KD.

Conclusions:
It is well known that a higher AIx results from earlier arrival of reflected pressure waves and an early return of reflected waves is closely correlated with peripheral stiffness. Therefore, these results indicate that peripheral angiopathy may induce sclerotic changes of carotid arteries in KD patients.
Abstract 176: Persistent Peripheral Arteritis Long After Kawasaki Disease - Another Documentation Of Ongoing Vascular Inflammation -
Authors: Suda Kenji , Tahara Nobuhiro , Honda Akihiro , Iemura Motofumi , Yoshimoto Hironaga , Kishimoto Shintaro , Kudo Yoshiyuki , Tanaka Hiroyuki , Kaida Hayato , Abe Toshi , Ueno Takafumi , Fukumoto Yoshihiro
Published: March 2022

A 22-year-old male patient, who was suffered from Kawasaki disease (KD) at 1 year and 1 month of age and left with bilateral axillary arterial aneurysms (AAA) and regressed coronary aneurysm, visited us because of left hand edema and itchiness. He has been taking aspirin for thromboprophylaxis of AAA and well without any vascular event for these 20 years and does not have any sign of inflammatory disease. Digital subtraction angiography of bilateral arms revealed complete occlusion of left AAA with multiple collateral arteries supplying blood flow to the distal arm and persistent giant right AAA with 12 mm in diameter with only mild stenosis proximal to this AAA. To determine if the active inflammatory process is going on the axillary artery wall, the patient underwent positron emission tomography (PET) using fluorodeoxyglucose (FDG) with co-registration of multi-detector x-ray computed tomography, PET indeed showed significant FDG uptake inside and part of the outer wall of the left AAA and only minimum FDG uptake at the right AAA. For left arm ischemia, he underwent resection of the left AAA and successful axilla-brachial artery bypass surgery using a reversed autologous saphenous vein graft that relieved his symptoms. Histological examination of the resected wall of AAA showed significant intimal thickening and the immunohistochemistry study labeling CD68, as the marker of macrophages, showed relatively dense staining of the intimal thickening of left AAA wall compatible with FDG uptake. This is the first documentation of persistent inflammation of peripheral arterial wall long after KD using FDG-PET that must have resulted in peripheral arterial remodeling.
Abstract 177: Follow-up Study of Thrombus in Coronary Aneurysms due to Kawasaki Disease.
Authors: Suzuki Atsuko
Published: March 2022

The features of MR coronary angiography (MRCA) are able to detect arterial walls and thrombus in aneurysms clearly by using the sequences of black blood methods.

Up to now 262 patients have been followed up by MRCA(the average 3.5 times ±2.3 times), The duration of the follow up is 4.7years±3.3years, During the periods, the coronary arterial lesions have changed as follows; decreased size of aneurysms in 116 patients out of the 262 (44.3%), enlargement of aneurysm in 2 (0.8%), newly appeared or progressed degree of localized stenosis in 26 (9.9%), appearance of occlusion in 5 (1.9%), recanalized vessels in 20 (7.6%). These changes are related to thrombus formation, thrombolysis and thickening of arterial walls.

The thrombus often change their locations in the aneurysm, sizes, even disappear and some of them develop to recanalized vessels.

Thin membranes in aneurismal lumen and tiny polyps on the intima were often detected (Fig),These constructions and thrombus in aneurysms are observed to be still changeable even more than 2 decades after the onset of Kawasaki disease.

Therefore, MRCA is the most convenient for following up CAL frequently and noninvasively.
Abstract 181: Kawasaki Disease in Children Six Months and Below - Clinical Experience from Chandigarh, North India
Authors: Agarwal Sikha , Gupta Anju , Rohit Manojkumar , Suri Deepti , Rawat Amit , Singh Surjit
Published: March 2022

Kawasaki disease (KD) is a medium vessel vasculitis of childhood. Clinical presentation in infancy is often characterized by paucity of symptoms. We report our experience of managing 15 children with KD aged 6 months and below at the Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. To the best of our knowledge there are no data on this aspect of KD from any developing country.

Objective:
To describe the clinical and laboratory profile of children with KD aged 6 months and below in our cohort

Methods:
Records of Pediatric Rheumatology Clinic from 1994 - 2014 were analyzed. Fifteen of the 415 children with KD, diagnosed on the basis of American Heart Association criteria, were aged 6 months and below. Fourteen children were given intravenous immunoglobulin and 3 also received infliximab.

Results:
Incomplete KD was present in 13 children (87%). Mucosal changes were present in 11 (73%); extremity changes in 10 (66%); rash in 9 (60%); conjunctival injection in 8 (53%) and lymphadenopathy in 3 (20%) children. Irritability at presentation was noted in 13 (87%); 4 (26%) had respiratory symptoms and 2 (13%) children had BCG scar reactivation. Eleven patients were diagnosed beyond day 10 of illness. Of 12 patients, in whom C-reactive protein was estimated, 11 had raised levels. Thrombocytopenia was seen in 3 patients - one of these developed scrotal gangrene. Coronary artery abnormalities were present in 5 (33%) patients. Two children died from disease related complications - one of these had giant coronary artery aneurysm.

Conclusions:
Incomplete forms of KD are commonly seen in children below 6 months of age. This may result in delayed diagnosis.
Abstract 185: Is Lymph-Node-First Kawasaki Disease a High-risk Group for Coronary Aneurysm?
Authors: Chang Jeng-Sheng , Huang Yu-Chih
Published: March 2022

Cervical lymphadenopathy (CLA) is the least common main feature in patients with Kawasaki disease (KD), comprising only 42%-65% of all diagnoses. Nonetheless, several studies have shown that KD patients who first present with remarkable CLA and fever (NF-KD) are older in age and exhibit stronger inflammation than that of typical KD (tKD) patients. Therefore, whether NF-KD patients are also a high-risk group for intravenous immunoglobulin resistance (rIVIG) and coronary arterial aneurysm (CAA), and whether tKD with CLA (tKD-CLA) is associated with higher inflammatory indices than tKD without CLA warrants investigation. Previous retrospective (R) and prospective (P) studies have shown varied results (Table). In this study, we reviewed 10 years of medical records from a tertiary referral hospital and identified 42 NF-KD patients. These NF-KD patients were then compared with 113 tKD-CLA and 105 tKD patients from the same database over the same period. Significant trends of increasing values were noted in age, neutrophils, CRP, ESR, GOT, and doses of IVIG among these 3 groups of patients (
p
= 0.03 to < 0.0001). NF-KD patients presented with larger cervical LN (3.7 ± 7.0 cm) complicated by higher CAA (12/42 vs. 25/218,
p
= 0.008) and by moderate to extremely high CAA (6/42 vs. 4/218,
p
= 0.002), and suffered more CHF or shock at the acute stage (6/42 vs. 6/218,
p
< 0.001) than all of the tKD patients. The size of LN did not correlate with CAA occurrence, but the presence of bilateral CLA showed a higher risk for CAA than unilateral CLA did (6/10 vs. 6/32,
p
= 0.02). Author(Hospital No.) Method NF-KD tKD-CLA tKD LN(cm) CAA rIVIG Nomura Y (1) R 16 106 65 > 1.5 + + Kanegaye JT (1) P 53 . 287 3.0 ± 1.0 - - Kubota M (1) R 29 62 107 > 1.5 - - Sung RYT (14) R . 170 526 > 1.5 - - Chang JS (1) R 42 113 105 3.7 ± 7.0 + + This study showed that NF-KD patients, particularly those with larger lymph nodes, are a high risk group for CAA complications. The tKD-CLA patients also exhibited a tendency for higher inflammation. Previous pathological studies of swollen CLA have reported tissue edema in the sinus and paracortical areas of LN, as well as vessel thrombi in severe cases. Further study of swollen CLA is warranted to determine the pathological correlation between CLA severity and CAA complications in KD patients.
Abstract 188: Carotid Artery Strain in Young Adults with a History of Kawasaki Disease
Authors: Daniels Lori B , Vejar Matthew , Kahn Andrew M , Gordon John B , Maurice Roch L , Burns Jane C , Dahdah Nagib
Published: March 2022

Background:
Measuring carotid strain is a noninvasive way to assess the mechanical properties of the arterial wall. Whether there is an association between carotid strain and coronary artery status after Kawasaki disease (KD) is unknown.

Methods:
We enrolled 82 young adults, ages 15 to 30 yrs, with a history of KD (58% male), as well as 16 healthy controls (HC) of similar age (56% male). Carotid wall strain was measured from cine loops of common carotid artery B-mode ultrasound data using an offline optical flow analysis algorithm. Strain was normalized for age (Z-score) using a regression equation derived from a separate series of healthy young adults. Subjects were categorized based on their worst coronary artery status (normal, transiently dilated, aneurysm).

Results:
The mean age of KD subjects and HC at the time of carotid measurements was 25 ± 8 and 28 ± 8 years, respectively (p=0.30). Mean time since onset of KD was 20 ± 8 yrs. KD subjects with transiently dilated coronary arteries had significantly higher carotid strain compared to those with normal coronaries (p=0.002) and to HC (p=0.01) (Figure); those with CAA had a nonsignificant trend toward lower carotid strain compared to other groups. KD subjects with normal coronaries had carotid strain similar to HC.

Conclusion:
Young adults with a history of KD with normal coronary arteries also have normal carotid artery strain. Individuals with a history of transiently dilated coronary arteries had a paradoxical trend toward higher carotid strain. Thus, KD patients whose dilated coronary arteries return to normal may have healthier vasculature compared to other KD patients. The significance of this finding merits further study.
Abstract 194: Neurological Prognosis Of Infliximab Therapy Against Immunoglobulin Refractory Kawasaki Disease
Authors: Katsumata Nobuyuki , Kaga Yoshimi , Koizumi Keiichi , Toda Takako , Kise Hiroaki , Hasebe Youhei , Sugita Kanji , Hoshiai Minako
Published: March 2022

Background:
Infliximab (IFX) which is an anti-TNFα monoclonal antibody is effective in the treatment of gamma globulin treatment (IVIG) resistance Kawasaki disease (KD) . It has been reported that TNFα adjusts the gene expression of myelin protein components and cause demyelination. Furthermore, at IFX treatment, the possibility of onset of the demyelinating disease in rheumatic diseases, and the exacerbation of the underlying disease in demyelinating disease have been suggested.

Objective:
To evaluate the neurological prognosis in pediatric cases who underwent treatment with IFX against IVIG resistant KD, were examined for the presence or absence of demyelination and delayed myelination.

Methods:
It is targeted for the 10 cases of IVIG refractory KD patients who received IFX 5mg/kg administration. Informed consent was obtained from the parents of all participants. We evaluated the candidate child’s mental development by the intelligence test (WISC-IV) and investigated the presence of demyelination and delayed myelination by brain MRI.

Results:
All cases were above 6 years old, and more than a year had passed since they received medication of IFX. In all cases, abnormalities of neurological findings and psychomotor developmental delay after treatment were not observed. There was no obvious abnormality in eight cases (boys of 5 cases, girls of 3 cases, 6-11 years of age at the investigation) who underwent the WISC- IV; Full Scale IQ 97.4 ± 12.5, Verbal Comprehension Index 92.8 ± 11.9, Perceptual Reasoning Index 103.9 ± 17.9, Working Memory Index 97.1 ± 15.5, Processing Speed Index 100.9 ± 9.7. In addition, in nine cases (boys of 4 cases, girls of 5 cases, 6-16 years of age at the investigation) who underwent brain MRI, there was no evidence of demyelination and delayed myelination.

Conclusion:
In this study, there were not existed the findings of demyelination, delayed myelination, and mental retardation in IFX administration cases. However, it is necessary to repeat examination how the IFX medication to children make adverse effects on central nervous system.
Abstract 2: Historical Trends in Kawasaki Disease over Three Decades in a Single Institution
Authors: Baker Annette L , Gauvreau Kimberly , Tang Alexander , de Ferranti Sarah D , Friedman Kevin G , Fulton David R , Newburger Jane W
Published: March 2022

Purpose:
Kawasaki disease (KD) awareness and therapy have evolved since its description in 1967. We explored historical trends since 1984 in patients (pts) treated for KD at a single institution.

Methods:
Inclusion criteria were 1) first episode of KD, and 2) treated with IVIG within 3 weeks of illness onset. Exclusion criteria were 1) evaluation solely for a second opinion, and 2) presence of congenital heart disease. We reviewed age at diagnosis, sex, race, presence of complete vs. incomplete (fever + <4 clinical criteria), days of fever at initial IVIG treatment, and incidence of retreatment. Changes in pt characteristics over time were evaluated using tests of trends.

Results:
Of 1739 pts, 1133 met eligibility criteria. Race included 61% White, 10% Black, 11% Asian: 6% other, and 12% unknown. At diagnosis, 16% were age <1 years (yrs), 58% were 1<5 yrs, 24% were 5<12 yrs, and 2% were ≥12 yrs. The median age at fever onset was 3 yrs and has not changed significantly over time. Male to female ratio was 59% to 41% and was stable over time. Median fever duration before IVIG treatment in the whole cohort was 7 days. Within the complete vs. incomplete KD groups, illness day at treatment was stable over time. However, median days of fever before IVIG treatment were lower in pts with complete vs. incomplete criteria (6 vs. 8 days, respectively, p<.001). The % of pts treated with IVIG for incomplete KD increased significantly over time. Before 1989, only 1 pt (2%) was treated with IVIG for incomplete KD. From 1990-1994, 11 pts (15%) pts had incomplete criteria, whereas from 2010-2014, 45 pts (27%) received IVIG treatment with incomplete clinical criteria (p=.001). The incidence of retreatment with IVIG also increased, from 9% (1984-1989) to 23% (2010-2014, p<.001). The use of adjunctive therapies (i.e., steroids, cyclosporine, cytoxan, abciximab and/or infliximab) were documented in 104/1133 pts (9%) and increased over time (p<.001).

Conclusions:
At a single center over 3 decades, treatment of incomplete KD, as well as retreatment with IVIG and use of adjunctive therapies have become increasingly common. Pts who had incomplete diagnostic criteria received IVIG later in their illness. Future studies should assess whether these secular trends have improved outcomes in pts with KD.
Abstract 207: Relationship between patients with Kawasaki disease and the role of Parents Association Kawasaki Disease (Parents Association)
Authors: Okamoto Shigeru
Published: March 2022

Katayama et al. indicated that the Parents Association for children with Kawasaki disease plays a significant role through four phases of “the psychological development process over 10 years in mothers with children with Kawasaki disease.” In the first phase, parents are bewildered, persistently worrying about their child’s poor physical condition with no clear cause. In the second phase, parents are confused by the diagnosis of Kawasaki disease and feel panicked not knowing what to do. In the third phase, they reexamine their attitudes as parents and alter their consciousness through an encounter with the Parents Association. In the fourth phase, parents begin to act proactively with the growth and development of children, facing the reality and future as the parents of children with Kawaski disease. However, no detailed analysis has been reported regarding the significance of the Parents Association itself. Therefore, we analyzed the entire content of Parents Association newsletters from No. 1 through No. 192. Here we report the reevaluated significance of the Parents Association.
Abstract 213: Caracteristics of Kawasaki Disease in Chile: Temuco′s experience
Authors: Soza Guillermo , Cerda Carolina , Berkhoff Andreas , Lozano Claudia , Salgado Andrea
Published: March 2022

Kawasaki Disease (KD) is a vasculitis mainly affecting children under two years old and harms arterial vessels (especially coronary) causing dilatation, aneurysms and eventual myocardial complications. Though etiology is unknown, a relationship with an infectious agent is suspected.

Diagnosis is doing by clinical criteria and laboratory support. KD cases reported in Latin America go along abscence of management protocols and it is not considered notifiable disease. In order to contribute to a greater understanding of this disease, a retrospective - descriptive analysis of 75 patients diagnosed with KD at the time of discharge was carried out from January 2005 to August 2014 at Hospital Dr.Hernán Henríquez Aravena, Temuco, Chile. Information was tabulated in Microsof Office Excel 2007 and a statical analysis were performed using STATA 11.0 program.

Average age 2 years 7 months (range 2 months to 17 years). Sex Male/Female 49%/51%. Prior consultations 85% (64/75). Initial diagnosis KD 51% (38/75). Fever 100% (75/75), 64%(48/75) about 39 ° C. Eye involvement 68% (51/75). Oropharyngeal erythema 87% (55/75). Strawberry tongue 40% (30/75). BCG erythema 19% (14/75). Rash 83% (62/75). Erythema/oedema of hands and foots 73% (55/75). Cervical adenopathy 41% (31/75). Irritability 55% (41/75). Leukocytosis 36% (27/75). Plaquetosis 69%(52/75) and periungual descamation 39% (29/75). Echocardiogram abnormal at startup 28% (21/75), (6/75)8% prior application of IVGG and 5%(4/75)remained with coronary involvement. A single dose of 2g/kg of Intravenous Gamma Globuline (IVGG) was administrated to 97%(73/75). Aspirin 50 mg/kg initial and 5 mg/kg during the following. A second dose of IVGG was required in 13% (10/75). Two patients were treated with anticoagulant for giant aneurysms and in one case, bilateral brachial aneurysms. Tipycal KD in 73% (55/75) and 27%(20/75) incomplete.

Further clinical suspicion is needed, because a high percentage of patients had coronary involvement at diagnosis. Those who received early IVGG coronary involvement were lower. Prominent among coronary involvement factors are extreme age, atypical or incomplete forms and high RCP. Needed be considered KD as a notifiable disease, considering the economic and social implications.
Abstract 216: Natural History of Kawasaki Disease with Medium-sized Coronary Aneurysm: Long-term Follow-up in a Tertiary Medical Center
Authors: Wu Pei-Yuan , Sun Li-Chuan , Lin Ming-Tai , Chen Chun-An , Chiu Shuenn-Nan , Lu Chun-Wei , Wang Jou-Kou , Wu Mei-Hwan
Published: March 2022

Objectives:
Patients with coronary artery aneurysms are at risk for thrombotic and stenotic complications later in their lives. The longitudinal changes of medium-sized coronary aneurysms caused by Kawasaki disease (KD) and their long-term outcome are still unclear in Taiwan.

Methods:
We retrospectively reviewed medical records of KD patients with medium-sized coronary aneurysms (4-8mm). The longitudinal change of coronary diameters were re-evaluated by domestic coronary z score calculator. The coronary artery diametes were transformed to standard deviation units from the mean (Z-score) normalized for body surface area. We also look for the potential risk factors for the persistence of coronary lesions.

Results:
Between 1983 and 2012, 56 KD patients suffered from medium aneurysms. The male to female ratio was 41:15. The mean age of disease onset was 2.13 years old, and 39.3% (22 of 56) was diagnosed at below 1 year old. The mean follow up duration was 8.2 years. No death occurred in this group of patient, and only one patient with persistent coronary aneurysm and stenosis/calcification had clinical evidence of myocardial ischemia. However, coronary aneurysms persisted in 24 (42.8%) patients and were associated with stenosis in 8 patients (14.3%), and calcification in 4 patients (7.1%). The coronary aneurysm persistence-free survival rates at 6 months, and 1, 2, 5 years after KD onset were 81%, 69%, 52%, 43%, respectively. Chi-square analysis revealed KD patients with history of ever deterioration of coronary Z score were significantly associated with the persistence of coronary aneurysms ( P = 0.0125). However, the initial aneurysm Z score (+4.43 vs +4.49), male gender or IVIG use were not risk factors to the persistence of coronary aneurysms.

Conclusion:
The prognosis of Kawasaki disease patient who developed medium size coronary aneurysm was good. However, those with ever deterioration of coronary Z scores were high risk group to have persistent coronary aneurysms. Specific therapies to promote vascular health in these patients should be advocated.
Abstract 32: Improper Histone Modification Of Gene Expression In Kawasaki Disease May Influence Both Its Development And Outcome
Authors: Yeter Deniz , Kuo Ho-Chang
Published: March 2022

Kawasaki disease (KD) is characterized by development of an autoimmune vasculitis and potential coronary artery lesions (CAL). Patients present with significantly marked expression of various immune cells and the inflammatory cells that they produce, recruit, or secrete, particularly cytokines. Concurrently, regulatory immune cells that suppress immune and inflammatory cells are significantly reduced in KD, particularly regulatory T cells (Tregs) such as CD4+CD25+FOXP3+ Tregs. Therefore, the clinical picture results from an unchecked, marked increase of immune and inflammatory cells infiltrating passed activated endothelial cells and into the vascular wall. This appears to largely be a consequence of amplified cell signaling via the Ca2+/NFAT pathway in KD, which is involved in targeted gene expression. As a result, we hypothesized that epigenetic control of gene expression through histone modifications may play a leading role in development of KD, its complications, and recovery. A previous study found significant DNA hypomethylation of CpG sites for the SOCS1 gene in KD patients (n=32), which was higher in patients without CAL. We conducted a preliminary study to widely examine epigenetic changes in DNA methylation of CpG sites before and after IVIG treatment in KD patients (n=9) using age-matched febrile controls (n=8). Our results demonstrated ≥10% differences in DNA methylation rates for 67 genes in KD patients, in addition to 10 genes with ≥15% methylation difference. Larger studies are required to accurately determine the role of epigenomic changes in KD development, in addition to investigations of the methylation reactions which regulate them (see Figure 1).
Abstract 39: Human Oral, Gut, and Blood Microbiota in Patients with Kawasaki Disease
Authors: Abe Jun , Ebata Ryouta , Saito Naoki , Okunushi Kentaro , Nakabayashi Kazuhiko , Kuroda Makoto
Published: March 2022

Objective:
We studied microbiome of throat swab, rectal swab, and venous blood obtained from patients with Kawasaki disease (KD) to determine whether bacterial nuclei are detectable in circulating blood of KD patients and whether the microbial composition resembles to that of oral cavity or gut.

Methods:
We initially studied 7 patients (4 males and 3 females, 20-59 months) and obtained swabs and blood samples before IVIG treatment (day 4-5) to prepare DNA and cDNA library. Next, we studied 14 patients (8 males and 6 females, 2-47 months) and prepared blood cDNA library before IVIG treatment (day 2-8) and before discharge (day 10-15). Samples were sequenced by Illumina HiSeq2000 and the results were analyzed using MePIC for human genome subtraction and megablast search, followed by taxonomic analysis with MEGAN viewer.

Results:
The number of sequences homologous to bacterial genome per swab sample obtained from DNA or cDNA libraries varied 20,000~4,700,000 or 500,000~2,400,000, respectively. In most of the throat samples, the sequences were classified in descending order of phyla, Firmicutes > Proteobacteria > Bacteroidetes > Actinobacteria. In rectal samples, Proteobacteria and Bacteroidetes were more abundantly and Firmicutes was less abundantly represented than throat samples. The total number of sequences per blood sample was 30,000,000~70,000,000 and 99.0~99.9% of them were homologous to human genome. The number of sequences homologous to bacterial genome per DNA or cDNA library was 221-286 or 125-593, respectively. In blood samples, the frequencies of phyla were arranged in descending order, Proteobacteria = Actinobacteria > Firmicutes >> Bacteroides. The sequences homologous to Burkholderia, Streptococcus and Neisseria, the indigenous bacteria in the oral cavity, were present in most of the patients. Among them, the abundance of Streptococcus was significantly (p=0.03) reduced in the cDNA libraries during convalescence.

Conclusion:
A variety of sequences homologous to bacterial genome were detected from the venous blood obtained from KD patients during the acute as well as the convalescent phase. Further study is necessary to investigate the specificity and the characteristics of these sequences in patients with KD.
Abstract 40: A Prospective Study on the Association of Kawasaki Disease and Mycoplasma pneumoniae Infection
Authors: Choi Jong-Woon , Cha Min-Ah
Published: March 2022

Objective:
The etiology of Kawasaki disease(KD) remains unknown, and several infectious agents have been proposed as the etiology of KD. There have been some studies, stating that KD and Mycoplasma pneumoniae(M. pneumoniae) infection are linked. So authors performed a prospective study to elucidate whether there is association between KD and M. pneumoniae infection.

Subjects and Methods:
Subjects are 36 patients with KD who admitted to Bundang Jesaeng General Hospital from January 2013 through August 2014. Patients were assigned to the M. pneumoniae group and the control group according to anti-mycoplasmal IgM antibody(AMA) titers. Clinical features, laboratory findings, courses and outcomes were compared between two groups.

Results:
AMA were positive or indeterminate in 11 patients(30.6%; M. pneumoniae group) and were negative in 25 patients(69.4%; control group). There were no significant differences between two groups in age and sex distributions, duration of fever, laboratory findings(WBC counts, ESR, CRP, AST, ALT, bilirubin), chest X-ray findings, and echocardiographic abnormalities(coronary arterial lesion, pericardial effusion, valvular regurgitation, LV dysfunction). AMA titers were rechecked in 6 patients, of whom 5(83.3%) showed decreased titers and 1(16.7%) showed an increased titer. All of patients were treated successfully with intravenous immunoglobulin and oral aspirin.

Conclusion:
Although AMA was detected in some patients with KD, it did not affect clinical features, laboratory findings, courses and outcomes of KD. In most cases AMA titers were decreased in the second examinations, so authors think that M. pneumoniae infection was a previous infection rather than a concurrent infection in some patients with KD and it did not act as a causative agent of KD.
Abstract 42: Simultaneous development of Kawasaki Disease associated with adenovirus infection in identical twins
Authors: Fukuda Sayaka , Fujiwara Maya , Ito Shuichi , Abe Jun , Hanaoka Nozumu , Fujimoto Tsuguto , Katsumori Hiroshi
Published: March 2022

Background:
The cause of Kawasaki disease (KD) remains unknown. However, many studies have suggested that specific genetic factors and some infectious agents could be associated with the onset of KD. Human adenovirus (AdV) infection is one of the triggering events in KD. We experienced identical twins who sequentially developed KD in conjunction with AdV infection.

Patients:
The patients were 4-year-old identical twin boys. The elder brother developed a high fever and was diagnosed with AdV infection by an immunochromatographic kit for AdV (IC-kit). He was transferred to our institute after persistence of fever for 7 days. On admission, he already fulfilled all of the diagnostic criteria of KD. The laboratory data were as follows: WBC, 9700/μl; CRP, 2.42 mg/dl; IFN-γ, 99.8 pg/ml; and TNF-α, 10.9 pg/ml. He received intravenous immunoglobulin (IVIG) and aspirin, and responded well without coronary artery abnormalities. The younger brother, who was also IC-kit-positive, was hospitalized on the same day as his elder brother after persistence of fever for 3 days. The data on admission were as follows: WBC, 12,600/μl; CRP, 5.54 mg/dl; IFN-γ, 105.0 pg/ml; and TNF-α, 33.6 pg/ml. Although he developed all of the KD symptoms by the 4th day, his fever spontaneously subsided on the 6th day without IVIG or aspirin. He developed dilation of the coronary artery on the 10th day at the left circumflex artery bifurcation area. This disappeared after 3 months with antiplatelet therapy. AdV type 3 (AdV3) DNA was detected in both of the patients’ stool samples by PCR, and AdV3 was isolated from the younger brother’s stool sample. Moreover, serum neutralizing antibody to AdV3 was greatly elevated in both of the patients.

Discussion:
Identical twins who simultaneously develop KD are rare. Both of the twin brothers were infected with AdV3 immediately before they developed symptoms of KD. The combined condition of genetic susceptibility and an infection could be an essential trigger in development of KD.
Abstract 45: Incomplete Kawasaki Disease followed by Systemic Onset Juvenile Idiopathic Arthritis
Authors: Jo Jeong-hyun , Kim Na-yeon , Ryoo Eell
Published: March 2022

Incomplete Kawasaki disease (KD) is second most common systemic vasculitis presented with persistent fever in childhood. Systemic onset juvenile idiopathic arthritis (SoJIA) is a rare rheumatic arthritis characterized with spiking fever for more than 6 weeks with prominent painful joint swelling. KD may trigger or prodrome of SoJIA. Both diseases have overlapping clinical features and laboratory findings including fever, rash, lymphadenitis, thrombocytosis, arthralgia and coronary artery dilatation so that they could hardly be distinguished. We present 4 years old girl and 30 months old girl who presented with persistent fever, rash and arthralgia. They were initially diagnosed with incomplete KD and treated with intravenous immunoglobulin and steroids. Spiking fever and painful swelling of bilateral knee joints were noticed after 25days and 40days of illness. They were diagnosed with SoJIA followed by incomplete KD and treated with NSAIDs and MTX in addition. Neither coronary complication nor joint complication was noticed. Careful follow up is needed for patients with KD and arthralgia.