bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 47: Expression of Galectin-3 in the Myocardium and Arterial Walls of Kawasaki Disease Patients
Authors: Numano Fujito , Shimizu Chisato , Jimenez-Fernandez Susan , Vejar Matthew , Oharaseki Toshiaki , Takahashi Kei , Salgado Andrea , Tremoulet Adriana H , Gordon John B , Daniels Lori B , Burns Jane C
Published: March 2022

Background:
Although coronary artery aneurysms are the most significant complication of Kawasaki Disease (KD), histologic examination has revealed myocarditis and myocardial fibrosis (MF) in most cases. Galectin-3 (Gal-3) is a matricellular protein that plays a multifunctional role in inflammation, fibrosis, and cell differentiation. It is a prognostic indicator of heart failure and cardiovascular events. Gal-3 plays a role in adhesion and migration of inflammatory and fibroblastic cells. We previously reported that plasma Gal-3 levels were elevated in acute pediatric KD and adult KD with giant aneurysms (GA). We postulated that Gal-3 may be involved in both acute inflammation and convalescent fibrosis in KD.

Methods:
Conventional H&E staining, Trichrome staining and immunohistochemical analysis for Gal-3 were performed on 1 acute stage KD subject and 10 convalescent stage KD hearts including 6 from subjects with GA and 4 from subjects without aneurysms who died of non-cardiovascular causes.

Results:
In the acute KD myocardium, round inflammatory cells were seen infiltrating the myocardium and positive staining for Gal-3 was noted. In the myocardium of convalescent KD with GA, widespread cardiomyocyte degeneration and necrosis with extensive bridging fibrosis were observed but inflammatory cells were not detected; spindle-shaped cells expressing Gal-3 in the cytoplasm were observed between cardiomyocytes. Myocardial fibrosis and Gal-3 expression were not observed in the myocardium of KD subjects without aneurysms. In the acute KD coronary arteries, Gal-3 positive inflammatory cells were observed in all layers, and the intima was already thickened by illness day 7. Destruction of the internal elastic lamina and intimal thickening with Gal-3-positive spindle-shaped cells were observed in coronary and systemic arteries of convalescent KD subjects.

Conclusion:
Gal-3 expression was related to inflammation in acute KD and tissue fibrosis in late convalescent KD with GA. Elevated levels of Gal-3 should raise concern for MF in KD patients with GA. However, in KD without aneurysms, myocardial fibrosis and Gal-3 expression were not observed; therefore myocarditis in KD patients with normal coronary arteries may improve without progression to MF.
Abstract 58: Magnetographic Recognition Of Abnormal Depolarization And Repolarization In Patients With Coronary Artery Lesions Caused By Kawasaki Disease
Authors: Tamaki Wataru
Published: March 2022

Background:
Noninvasive recognition of abnormalities of depolarization (DE) and repolarization (RE) in patients with coronary artery disease is difficult.

Purpose:
Our aim was to identify abnormalities of DE and RE in patients with coronary artery lesions (CAL) due to Kawasaki disease (KD) using magnetocardiography (MCG).

Methods:
We evaluated sixty one pts (48 males and 13 females) with CAL due to KD, The age at MCG ranged from 11 months to 38 years (median 15 years). Eleven pts had had previous myocardial infarction (MI), and 22 pts had had at least an occlusion of a major coronary artery branch. MCG was performed at rest with a multichannel superconducting quantum interference device system. The integral value was computed for each channel and isointegral maps were constructed during DE and RE. We analyzed abnormalities of DE and RE depending on occlusion of coronary arteries (OC) or a history of MI. Univariate analysis was performed on respective factors for DE and RE.

Results:
In the MI group, the number of abnormal DE and RE, abnormal DE and abnormal RE were 3 , 1 and 3, respectively. In OC group, the number of abnormalities of DE and RE was 2, and abnormality of RE was 9. In the non-OC group, the number of abnormal DE and RE was 2, and abnormal RE was 5. The factor of MI was significantly related on abnormal DE and abnormal RE (p<0.05). On the other hand, the factor of OC was significantly related to abnormality of RE (p<0.05).

Conclusion:
Although symptomatic coronary occlusion affects both DE and RE, occlusion of coronary artery only affects RE. MCG is useful to detect changes in DE and RE.
Abstract 59: New findings implicated in Coronary calcification in Chronic phase Kawasaki disease
Authors: Yahata Tomoyo , Ikeda Kazuyuki , Hamaoka Akiko , Suzuki Chinatsu , Yoshioka Ayako , Kuchitsu Yuki , Hamaoka Kenji
Published: March 2022

Background:
Kawasaki disease (KD) is a systemic vasculitis prevalent in infants and sometimes complicates coronary artery lesions (CALs). It has been well known that CALs gradually develop endothelial dysfunction, post-inflammatory arteriosclerotic changes, and finally coronary calcification. It has been also reported, recently, that vascular calcification is an active cell-driven process characterized by osteogenic differentiation of vascular smooth muscle cells, relating to the chronic inflammation and oxidative stress. In this study, in KD, we evaluated the possible implication of significant calcification prevalent in CALs to the long-term prognosis.

Methods:
We included 42 patients with a history of KD (age:18.3±6.7 year-old). The breakdown was 17 patients without CALs and 25 with CALs; 12 without calcification and 13 with calcification on multi-detector computed tomography. We measured %FMD as an endothelial function marker and hs-CRPs as an inflammatory marker, serum hydroperoxide and urinary 8-OHdG as oxidative stress markers, and the bone mineral density (BMD). Patients in CALs(-) group took no medicine and those in CALs(+) group were under antiplatelet and/or anticoagulant therapy, particularly, those with calcification were additionally administrated statin or ARB.

Results:
Values of %FMD in CALs(+) group were significantly lower compared with those in CALs(-) (p<0.05), and values in those with calcification were still lower than those without calcification (p<0.05). Values of hs-CRPs in CALs(+) group were significantly lower than those in CALs (p<0.05). 8-OHdG values as oxidative stress marker in CALs(+) group were significantly lower than those in CALs(-) (p<0.05). The BMD in CALs(+) group tended to be lower compared with the age-matched reference values (88.9±7.0% of normal).

Conclusions:
In KD chronic stage, the decreased %FMD may be an essential condition to occur coronary calcification. Decreased BMD in patients with coronary calcification suggested the possible existence of the skeletal and the vascular system in KD, similar to the mechanism of common vascular calcification.
Abstract 60: FcR
+
CD4
+
T Cells as a Specific Subset of IL-17-producing Cells Controlled by BATF/IRF8: Novel Insights Into Etiology of Kawasaki Disease
Authors: Chang Chia-Jung , Ko Tai-Ming , Chen Chien-Hsiun , Wu Jer-Yuarn , Chen Yuan-Tsong
Published: March 2022

Kawasaki disease (KD) is an acute vasculitis primarily involved coronary arteries of infants and children. Although more than 40 years have passed since the first description of the disease, its etiology remains unclear. Circulating interleukin 17 is increased in the acute stage of KD and expressed in the damaged coronary arterial wall from autopsies of children after KD. The aim of this study was to elucidate the involvement of IL-17 in the pathogenesis of KD. In this study, we identified a specific subset of CD4
+
T cell expressing Fc receptor which existed high percentage in acute stage of KD than in recover stage. In addition, FcR
+
CD4
+
T cell in acute stage expressed higher level of IL-17 than in recover stage. Therefore, we suggest this IL-17-producing FcR
+
CD4
+
T cell may be a critical regulator of immunity in Kawasaki disease. In order to investigate the detail mechanism that FcR
+
CD4
+
T cell subset expressed higher amount of IL-17 in KD, we isolated FcR
-
CD4
+
and FcR
+
CD4
+
T cells from adult healthy donors and stimulated with anti-CD3/CD28 beads only. We found that FcR
+
CD4
+
T cells produced much higher IL-17 than FcR
-
CD4
+
T cells without the need of Th17-differentiation cytokine. Furthermore, FcR
+
CD4
+
T cells expressed higher IL-17-related transcriptional activator, BATF and lower level of transcriptional repress, IRF8 than FcR
-
CD4
+
T cells. Knockdown of BATF and IRF8 could reduce and increase IL-17 production, respectively. These findings define BATF and IRF8 as the intrinsic transcriptional regulators in IL-17 production from FcR
+
CD4
+
T cells. Collectively, our results suggest that IL-17-producing FcR
+
CD4
+
T cells are the novel subset of IL-17-producing cells and important pathogenic immune cells in KD. Inhibition of IL-17 production from FcR
+
CD4
+
T cells has great potential to be as a therapeutic strategy for Kawasaki disease and other FcR
+
CD4
+
T cell-driven autoimmune diseases.
Abstract 80: Correlation of N-terminal pro-BNP Release with Myocardial Involvement in Acute Kawasaki Disease
Authors: Fournier Anne , Desjardins Laurent , Dahdah Nagib
Published: March 2022

N-terminal pro-BNP (NT-proBNP) is elevated at the onset of Kawasaki Disease (KD). This is based on the hypothesis of immune myocardial inflammation. We sought to study the relationship between NT-proBNP and cardiac function in KD.

Parameters of myocardial involvement determined by ECG (PR and QTc intervals, QT dispersion, R-T axis) and by echocardiogram (systole and diastole) were correlated with levels of NT-proBNP in the acute (1 week), sub-acute (2-3 months) and chronic (6 months to 1 year) phases of KD. KD patients were compared to a febrile group. KD patients were further subdivided into 2 groups according to the levels of NT-proBNP; normal NT-proBNP (NT-proBNP Z-score < 2), or elevated NT-proBNP (Z-score ≥ 2).

There were 56 subjects (14 controls, 19 KD-1 and 23 KD-2 patients), with similar age at assessment (3.8±4.3 vs. 3.3±2.3 years-old, p=0.609). Myocardial contractility was significantly lower in KD patients in the acute phase with an ejection fraction of 57.4±7.5% compared to CTL 61.9±6.5%; p=0.049). Myocardial dysfunction was more significant in KD with high NT-proBNP compared to those with normal NT-proBNP, (shortening fraction Z-score of-1.6±1.5 versus -0.5±1.5; p=0.025) QTc interval was longer in KD compared to febrile CTL (412.3±21.0 mS vs. 390.6±14.6 mS, respectively; p=0.009). In contrast, there were no significant differences for left ventricular mass index (p=0.935) or LV end-diastolic diameter (p=0.565). Likewise, there were no significant differences for the PR interval (p=0.344), QT dispersion (p=0.288) or R-T axis (p=0.577). Otherwise, there was a significant correlation between coronary artery involvement (CA z-score ≥ 2.5) and the likelihood of lower LV ejection fraction (p=0.049) and higher NT-proBNP z-score (p=0.043), but no correlation with normalized LV shortening fraction (p=0.16) or QTc (p=0.14). The anomalous findings disappear in the sub-acute phase. On the other hand, a lengthening of QTc interval in the acute phase, irrespective of NT-proBNP status, resolves after 2-3 months.

In acute KD, there is a reduction in myocardial function, to a higher extent in cases with elevated NT-proBNP. This correlates with coronary artery involvement. KD patients with elevated NT-proBNP z-score may warrant careful follow-up.
Abstract 84: The Circulating MicroRNA Study for Children with Acute stage of Kawasaki disease
Authors: Jan Sheng L , Tsai Chi R , Chan Sheng C , Fu Yun C , Lin Ming C
Published: March 2022

Background:
Kawasaki disease (KD) is a systemic vasculitis syndrome related to immune dysregulation. MicroRNAs (miRNAs) can regulate the expression of protein-coding genes, and have been used as a biomarker for the diagnosis of various diseases. This study was designed to identify plasma miRNAs changed in patients with acute stage of KD and to identify candidate miRNAs.

Methods:
A total of ten children, ranged from 9 months to 5 years old, with acute stage of KD were enrolled. The profiles of plasma miRNAs were analyzed by miRNA arrays. The miRNAs of interest identified by array were confirmed by reverse transcription-quantitative PCR (qRT-PCR).

Results:
In comparison with the convalescent stage, plasma miR-10a (ten of ten) and miR-155 (eight of ten) were significantly down-regulated during the acute stage of KD. Pathway analysis of the combinatorial effects of these two microRNAs (DIANA miRPath) indicated the genes involved in the T-cell receptor signaling pathway (p.= 2.604015e-05), the MAPK signaling pathway (p.=4.541392e-05) and the Toll-like receptor signaling pathway (p.= 0.0001528698) that were highly co-regulated by these two miRNAs.

Conclusions:
This is the first report of uncovering circulating miRNAs involved in patients with acute stage of KD. The results of this study indicated that the miRNAs might play a crucial role in the immune dysregulation of acute KD. Further studies and more KD patients should be investigated to elucidate the roles and as biomarkers of these miRNAs for early diagnosis of acute KD.

Keywords:
Biomarker, Children, Kawasaki Disease, MicroRNAs
Abstract 85: Early Detection of Kawasaki Disease in Infants
Authors: Kang Ji Hae , Lee Dong-Seok , Seo In Ae , Kwak Min Ha , Choi Sung Min , Kim Doo Kwon , Cho Seung Man
Published: March 2022

Background and Objective:
This study was aimed to investigate clinical characteristics of infantile Kawasaki disease (KD), and to evaluate early diagnostic features of KD in febrile infants.

Subjects and Methods:
We retrospectively reviewed the medical records of 66 patients with KD who were admitted to Dongguk University Gyeongju Hospital, between January 2010 and August 2014. The clinical, laboratory data between infants and children were analyzed. And the clinical and laboratory data of infantile KD patients were compared with 18 infants who were admitted for other acute febrile disease during same period as above.

Results:
A total of 66 patients were identified; 21(31.8%) were infants; 45(68.2%) were > 1 year old children. Incomplete KD was much more common in infants (n=15, 71.4%) than in children group (n=14, 31.1%) (P = 0.002). The infants group was characterized by significantly higher rates of inflammatory changes at the Bacille Calmett-Guerin (BCG) inoculation site (P<0.001), but lower rates of changes in the cervical lymphadenopathy (P=0.005), conjunctival injection (P=0.047). The serum levels of hemoglobin were lower (P<0.001), and platelet (P=0.029), C-reactive protein (P=0.042), N-terminal pro-brain natriuretic peptide (NT-proBNP) (P=0.042) was higher in the infants group significantly. Pyuria was also significantly higher in the infants group (P=0.017). Between infants with KD and with other acute febrile diseases, there were significantly higher serum levels of ESR (P<0.001), CRP (P=0.009) and NT-proBNP (P=0.002) in the infantile KD.

Conclusion:
Because incomplete KD was much more in infants, the diagnosis of infantile KD can be difficult. The BCGitis and higher level of NT-proBNP can help to early diagnosis of incomplete KD in infants, and may be a good predictor of KD in acute febrile infants combined with other acute phase reactants.
Abstract 87: Urinary LDH activities in patients with Kawasaki disease
Authors: Kawamura Yoichi , Kanai Takashi , Tsujita Yuki , Takeshita Seiichiro , Nonoyama Shigeaki
Published: March 2022

Background:
Kawasaki disease (KD) is a systemic vasculitis with unknown origin. KD patients often have leukocytes in urine as well as urinary tract infection (UTI). The aim of this study is to evaluate urinary LDH and its isozyme, which is useful in diagnosis with UTI, in patients with KD.

Patients and methods:
158 patients with KD (including 4 with incomplete KD) and 52 patients with febrile sickness were enrolled as control group in this study. Urine samples were obtained at least one point.

Results:
Total level of urinary LDH in patients with KD was significantly higher than that in control group. Urinary LDH level in the acute phase was significantly higher than that with convalescent phase in patients with KD. Urinary LDH isozyme showed predominant elevations of LDH1 and LDH2. Some patients showed the elevation of urinary LDH level before the clinical criteria of KD were fulfilled. There was no correlation between urinary LDH concentration and pyuria.

Conclusion:
The levels of LDH isozyme (LDH4 and LDH5) in urine is known to increase in patients with acute upper urinary tract infection, while the level of its isozyme (LDH1 and LDH2) increased in acute phase of KD. The elevated levels of total urinary LDH and its isozyme (LDH1 and LDH2) may be useful for early diagnosis of KD and also for diagnosis of incomplete KD.
Abstract 89: Reducing Overdiagnosis and Miss Rates of Kawasaki Disease at First Contact Setting
Authors: Kua Jade , Choo Jonathan , Lin Wenyun , Loh Ann , Tan Ze Lei , Tan Teng Hong
Published: March 2022

Background:
Kawasaki Disease(KD) is a challenging diagnosis at first presentation. Diagnosis relies on the 1993 American Heart Association(AHA) criteria of ≥5 days of fever with ≥4 of the following features: mucositis, cervical lymphadenopathy, non-suppurative conjunctivitis, swollen or desquamating extremities, polymorphous rash. Many present atypically and are not easily identified by the Emergency Department(ED) physician. This leads to delays in diagnosis and treatment of KD.

Aim:
To reduce miss rates and overdiagnosis in the ED through identifying early clinical predictors for KD, within and out of the AHA criteria.

Methods:
Retrospective case-controlled study on patients discharged with a diagnosis of KD at KK Women’s and Children’s Hospital (KKH) from April 2007 - December 2010. Patients admitted from the ED over the same period with initial diagnoses of KD, but with discharge diagnoses that stated otherwise formed the control group. We analysed the presentation patterns in both groups. Using multivariate logistic regression, we identified significant clinical predictors of KD.

Results:
The diagnostic guidelines in the ED were neither specific nor sensitive, resulting in high overdiagnosis and miss rates, respectively. Of the patients admitted with the initial diagnosis of KD, 59.2% did not have KD. 44.3% and 29.1% of KD diagnoses were missed at first visit and during reattendences respectively. Miss rates were higher in infants than in older children(≥1 year old).

In older children, lymphadenopathy (OR1.79, p=0.013), non-suppurative conjunctivitis (OR2.22; p=0.001), irritability (OR2.24, p=0.005) and age (OR0.75, p<0.0001) were early predictors for true KD. With reattendances, lymphadenopathy (OR2.23, p=0.002), conjunctivitis (OR3.02, p<0.0001), irritability (OR1.86, p=0.040) and age (OR0.75, p<0.0001) remained significant, while changes in extremities (OR1.93, p=0.008) emerges as a useful predictor. No significant predictors were found for infants.

Conclusion:
ED physicians should be aware of early predictors of KD. We advocate incorporating irritability into diagnostic guidelines for older children. These measures would reduce overdiagnosis and miss rates, permitting appropriate institution of early treatment.
Abstract 99: Retrospective Analysis of Kawasaki Disease Patients Resistant to Second Intravenous Immunoglobulin
Authors: Ono Minako , Miyamoto Tomoyuki , Nagamoto Tetsuharu , Sumi Kataharu , Murashima Yoshinori , Sato Ryusuke , Iwaoka Ari , Santo Yoko , Mouri Yoko , Mouri Takeshi
Published: March 2022

Objective:
This retrospective analysis aimed to identify the risk factors of Kawasaki disease (KD) resistant to second intravenous immunoglobulin ( IVIG) and design the score system discerning IVIG resistant patients in acute phase.

Materials and Methods:
A retrospective chart review of pediatric patients admitted to Children’s Medical Center, Yokosuka General Hospital Uwamachi with the diagnosis of KD during 2011 to 2013. In total 127 patients, 116 patients received IVIG and of 92 patients were respondent for initial course of IVIG. Rest of 17 patients received second course of IVIG and of 7 patients were resistant to second course of IVIG.

Results:
Logistic regression analysis showed that serum sodium concentration <131 mEq/L (odds ratio[OR]=7.43, 95% confidence interval [CI]=1.470-37.564), serum albumin concentration <3.0 g/dl (OR=7.00, 95% CI=1.109-44.195), age less than six months (OR=8.25, 95% CI=1.615-42.146), and white blood cell count <9000/μ (OR=6.29, 95% CI=1.309-30.191) were associated with risk factors of resistant to second IVIG. Designed the score system on the basis of these four factors, we could estimate the failure to second IVIG and its accuracy was 95.3%.

Conclusion:
The score system based on easy and simple clinical factors might be useful for estimating the patients resistant to second IVIG and improve those patients’ further treatment.
Abstract O.03: Monitoring the Occurrence of Kawasaki Syndrome in the United States
Authors: Maddox Ryan A , Person Marissa K , Joseph Lindsay J , Haberling Dana L , Steiner Claudia A , Schonberger Lawrence B , Belay Ermias D
Published: March 2022

Objectives:
To describe the occurrence of Kawasaki syndrome (KS) in the United States.

Methods:
The Kids’ Inpatient Database (KID; 2003, 2006, 2009, 2012) and the Nationwide Inpatient Sample (NIS; 2001-2011) were analyzed to determine KS-associated hospitalization rates and trends; the United States Centers for Disease Control and Prevention (CDC; 2010-July 2014) passive KS surveillance database was analyzed to assess the frequency of coronary artery abnormalities (CAAs) among reported KS cases meeting the CDC KS case definition.

Results:
The KS-associated hospitalization rate for children <5 years of age using the KID was 18.1 (95% CI: 16.0-20.2) per 100,000 children in 2012, 20.0 (95% CI: 17.8-22.2) in 2009, 21.3 (95% CI: 18.9-23.7) in 2006, and 19.7 (95% CI: 17.7-21.7) in 2003. The 2012 KS-associated hospitalization rate was 21.0 (95% CI: 18.6-23.4) among males <5 years of age and 15.0 (95% CI: 13.0-17.0) among females. Asians/Pacific Islanders had the highest rate among all racial groups, 29.8 (95% CI: 22.2-37.4). The average annual KS-associated hospitalization rate for children <5 years of age using the NIS was constant from 2001-2011 at 18.8 per 100,000 per year (95% CI: 17.3-20.3; p=0.16) with peaks in 2005 (27.0 per 100,000; 95% CI: 19.3-34.7) and, to a lesser extent, in 2010 (22.6 per 100,000; 95% CI: 16.6-28.5). The CDC surveillance database included 497 physician-diagnosed KS cases <18 years of age reported with onset occurring January 1, 2010 through July 31, 2014; about three-quarters (n=372) of the cases met the CDC KS case definition. Among KS cases meeting this definition that also contained complication data, 18.7% (69/369) had CAAs reported; among Asian/Pacific Islander children, 24.7% (18/73) had CAAs reported. Almost all KS cases in the database (98.1%, 363/370) were treated with intravenous immunoglobulin.

Conclusions:
Analyses of KID and NIS data did not indicate any increase in KS-associated hospitalization rates for children <5 years of age in the United States through 2012. CAAs continue to occur at a comparable rate with past reports.
Abstract O.10: Risk Factors Associated with Recurrence of Kawasaki Disease in Mexican Children
Authors: Sorcia-Ramirez Giovanni , Garrido-Garcia Luis M
Published: March 2022

Background:
Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis. Recurrences of KD (defined as at least three clinical signs of KD in addition to fever ≥ 5 days), presenting ≥ 14 days after the return to baseline from the index episode is reported in approximately 3-4% of all cases in Japan.

Objective:
To assess the frequency and determined the risk factors associated with recurrences of KD in patients treated at the Instituto Nacional de Pediatría in Mexico City.

Material and Methods:
An observational, comparative, retrospective and case-control study of all patients diagnosed with recurrent KD in our Institution from August 1995 and May 2014 was performed. The clinical presentation, laboratory results, treatment used and coronary artery abnormalities in the recurrent-KD and non-recurrent KD groups were analyzed and compared.

Results:
We included 371 patients with KD diagnosed at our institution; we had 19 recurrences of KD (5.1%), 16 patients had one recurrence, 1 patient had 2 recurrences and 1 patient had 3 recurrences of KD. 17 cases or our cases were male (89.4%) with mean age at diagnosis of the first episode of 31.63 ± 36.40 months and with a median of 16 months of the new event after the initial episode (1 to 60 mo.) In bivariate analysis, male gender (p < 0.037), central nervous system manifestations in the acute phase of KD (p < 0.053) and coronary aneurysms at diagnosis (p < 0.05) showed statistical significance. There were no factors associated with recurrence in a multivariate analysis.

Conclusions:
This is a very small series of KD with a slightly increased rate of recurrence compared with the rate of recurrences reported in the literature. But to allow an early recognition of a new event, a previous history of KD should be considered to initiate treatment and to achieve better outcomes in the recurrent cases.
Abstract O.12: Update of 2011-2014 Kawasaki Disease Surveillance in Emilia Romagna, a Northern region of Italy.
Authors: Corinaldesi Elena , difazzio giorgia , Mazzoni Elisa , landini chiara , bigucci barbara , casadei maria chiara , testa gabriella , cicero cristina , Palladini Alessia , pierantoni luca , Sogno Vallin Paola , lami francesca , fabi marianna
Published: March 2022

We updated our regional database for KD patients from 2011 to 2014 to investigate differences in epidemiological, clinical and outcome data between 2011-2014 pts and those diagnosed between 2000-2010 in Emilia Romagna. We had 77 KD patients during last 4 years ( vs 81 pts during 2000-2010), mean age at diagnosis 40 months+- 36,4 (vs 31,2 mths ), 10% were younger than 6 months at diagnosis (vs 14%), male were 60 % (vs 59%). Seasonality was as follows: spring 27 (% vs 33%), winter 25% (vs 28%), autumn 25% (vs 26%), summer 23% (vs 14%). Clinical presentation was complete in 69 % (vs vs 74%), incomplete in 30% (vs 26%), atipical 1 % (vs 0%). IVIG responder were 77% (vs 67%), non responders 16 % (vs 12%), late treatment 2 % (vs 12% P 0.002), not treated with IVIG 5 % (vs 9%). 18/77 pts ( vs 7 of 2000-2010,P 0.004 ) had alteration of ALT ( v> 45 U/) and AST ( v > 55 U/l) and among those with transminases alteration 8 ( vs 4 pts) had cholestasis. Coronary arteries anomalies (CAA) were present in 15% ( 9 % ectasia and 6% (vs 2 %) aneurysms ( mean age 12,6 months, 2 pts non responders to standard therapy, 1 pts with late treatment, 1 pts not treated, and 1 pts well treated. The 2 patients who developed giant aneurysms were both non responder to standard therapy, 1 pts had associated cholestasis.

Conclusion:
during the last four years we observed an higher number of diagnosis of KD than 2000-2010; incomplete and atipical cases, and non-responder pts were more frequent but we noted a decreased of pts not treated or delayed treated; more cases of cholestasis associated to KD and an increased number of patients with aneurysms.
Abstract O.14: Incidence rate of recurrent Kawasaki disease in Japan (2003-2012)
Authors: Sudo Daisuke , Nakamura Yosikazu
Published: March 2022

To investigate the incidence of recurrent Kawasaki disease, data of nationwide surveys of Kawasaki disease in Japan from January 2003

(18th survey) to December 2012 (22th survey) are analyzed. Our group previously reported the incidence rate of recurrent Kawasaki disease (Nakamura et al., 1994 and Hirata et al., 2001). In the current study, 104,751 patients with 498,388.9 person-years are observed to calculate the rate of recurrence. The incidence rate of recurrence is 4.14 per 1,000 person-years, with a high incidence within the 12 months from the first episode. The observed person-year categorized by some variables is calculated, such as sex, age at first episode, period of time after the initial episode, presence of cardiac sequelae in the acute (within 2 months) and late (after 2 months) stage, exposure to intravenous gamma globulin (IVGG) therapy, presence of additional IVGG administration, and exposure to steroid therapy. Using those data, incidence rate of recurrent Kawasaki disease and incidence rate ratio are calculated according to such variables, and potential risk factors for recurrence of Kawasaki disease are discussed.
Abstract O.26: Angiotensin Receptor Blocker, Losartan suppresses coronary arteritis in a Murine Model of Kawasaki Disease. -Effectiveness of IVIG versus Losartan-
Authors: Suganuma Eisuke
Published: March 2022

Background:
Although intravenous immunoglobulin (IVIG) is an established treatment for Kawasaki disease (KD), 5 % of KD patients treated with IVIG still have coronary involvement. Angiotensin receptor blockers (ARBs), beside their antihypertensive effects, also suppress cell infiltration in atherosclerosis. However, the efficacy of ARB for KD has not been established.

Objective:
We aimed to elucidate if ARB ameliorates coronary arteritis (CA) in a murine model of KD, introduced by Lactobacillus casei wall extract (LCWE). We also aimed to verify whether ARB’s effects are different from those of IVIG.

Method:
4-week-old male mice were intraperitoneally injected with LCWE (L, n=15) or PBS (P, n=15). 5 days later, those mice were given IVIG (1g/kg, L+IVIG, n=8), or ARB (losartan 100mg/L in drinking water for 2 wks, L+ARB, n=18). 2 weeks after LCWE injection, histological assessment of the heart and measurement of plasma cytokine levels were performed. IL-6 and mannose receptor (MR) mRNA expressions in the aortic root were studied (n=5 each group) in an additional experiment.

Results:
CA score was significantly increased by LCWE (L: 8.3±0.5 vs. P: 2.9±0.5, p<0.0001). ARB significantly ameliorated CA (L+ARB: 5.1±0.7 vs. L, p=0.008). The effect of IVIG on CA was milder and not significant (L+IVIG: 6.0±0.9 vs. L). Of note, macrophage infiltration was dramatically decreased by ARB but not by IVIG. IVIG treatment ameliorated serum levels of IL-1β, IL-10 and TNF-α in a milder fashion than ARB. Interestingly, serum IL-6 level was suppressed by ARB, but not by IVIG. Locally up-regulated mRNAs of IL-6 and MR were significantly ameliorated by ARB, with milder effects by IVIG.

Conclusions:
ARB, rather than IVIG, exerts powerful anti-CA effects with suppressing local macrophage infiltration and systemic/local inflammatory cytokines. Thus, ARB potentially exerts additive anti-CA effects in KD under IVIG treatment.
Abstract O.32: An Improved Point-of-care Differentiation Of Kawasaki Disease From Other Febrile Illnesses
Authors: Hao Shiying , Jin Bo , Tan Zhou , Li Zhen , Ji Jun , Tremoulet Adriana , Burns Jane C , Cohen Harvey J , Ling Xuefeng B
Published: March 2022

Background:
Kawasaki disease (KD) shares many clinical features with other pediatric febrile illnesses (FC). Clinical confusion can lead to a missed or delayed diagnosis that increases the risk of coronary artery damage. In the present study, we improved our previous KD diagnostic algorithm for point-of-care diagnosis.

Methods and Results:
We reviewed clinical records of 534 acute KD and 318 FC patients (development dataset) and subsequent 268 acute KD and 161 FC patients (validation dataset). KD subjects met the American Heart Association definition. Using clinical data and lab test results, we integrated our previously developed linear discriminant analysis (LDA)-based clinical model with a newly developed decision tree-based algorithm to improve KD diagnosis. To train the decision trees, sub cohorts were constructed based upon the 5 KD classic criteria. Our 1
st
clinical model (LDA) stratified the subjects into FC (FC diagnosis, negative predictive value NPV >=95%), undecided (88/802 KD, 167/479 FC), and KD (KD diagnosis, positive predictive value PPV >=95%) subgroups. The subsequent 2
nd
clinical model (decision trees) further classified the undecided group into FC, undecided, and KD subgroups, resulting in a much-improved algorithm with only 59/479 FC (Specificity>76%) and 26/802 KD (Sensitivity>95%) undetermined.

Conclusions:
Our computer-based algorithm that incorporates only clinical findings and readily available clinical laboratory data now has sufficient sensitivity and specificity in distinguishing acute KD from FC patients that a multicenter, prospective clinical trial is warranted to test the performance of the diagnostic algorithm against the gold standard of expert clinical opinion.
Abstract O.35: BCGits as a Clinical Diagnosis Marker in Mexican Children with Kawasaki Disease
Authors: Castillo-Moguel Jose A , Ynga-Duran Mario A , Galvez-Cuitiva Eduardo , Carrasco Cesar , Sorcia-Ramirez Giovanni , Garrido-Garcia Luis M
Published: March 2022

Background:
Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis of unknown etiology. A BCG reactivation (BCGitis) is not included in the classical clinical criteria for KD. BCGitis recently has been recognized as a clinical marker of incomplete KS in younger children in countries where BCG vaccination is mandatory.

Objectives:
To assess the frequency of BCGitis in the clinical profile of patients diagnosed with KD in a Mexican third level Children’s Hospital and its association with the presence of coronary artery abnormalities. (CAA)

Material and Methods:
An observational, comparative, retrospective and case control study of all patients diagnosed with KD at our Institution between August 1995 and May 2014 was performed. The clinical presentation, laboratory results, treatment used and coronary artery abnormalities in the BCG-reactive [BCG(+)] and BCG-nonreactive [BCG(-)] groups were analyzed and compared.

Results:
We included 356 patients with KD diagnosed at our institution; 83 had BCGitis. (23.3%) The BCG(+) group was younger than the BCG(-) group, 21.2 ± 22.51 vs 44.33 ± 38.85 months (p < 0.00001) There were 17 (20.48%) incomplete cases in the BCG(+) group compared with 52 (19.11%) in the BCG(-) group without statistical significance. The BCG(+) group had a slightly shorter fever duration before IVGG treatment than the BCG(-) group. Laboratory results showed lower hemoglobin counts, higher white blood cell counts, platelet counts, CRP counts, and ALT counts in the BCG(+) group. The BCG+ group developed CAA in 29 cases and the BCG- group developed CAA in 110 cases without statistical significance. Multivariate analysis showed that younger age at diagnosis (< 24 months) was the only factor significantly associated with a reaction at the BCG inoculation site in KD patients

Conclusions:
In Mexico, as a country with a National BCG Vaccination Program and a low incidence of KD, a reaction at the BCG inoculation site could be a useful and early diagnostic sign of KD among younger patients, especially those younger than 24 months of age.
Abstract O.57: Coronary Circulation Assessed by Transthoracic Echocardiography during Exercise Test is Impaired in Patients after Kawasaki Disease Even with Regressed Coronary Arterial Lesions
Authors: Toyono Manatomo , Yamada Shunsuke , Oyamada Jun , Shimada Shunsuke , Aoki-Okazaki Mieko , Harada Kenji , Takahashi Tsutomu
Published: March 2022

Background:
Coronary flow reserve (CFR) has important clinical implications for the evaluation of coronary circulation including Kawasaki disease (KD). Pharmacological vasodilation is generally used to induce hyperemia for the assessment of CFR; however, exercise test provides more physiological stress.

Objectives:
This study sought to assess CFR during exercise in patients after KD with regressed coronary arterial lesions (CALs) by transthoracic echocardiography (TTE).

Methods:
Twenty KD patients were studied, comprising 8 patients with regressed CALs in the left anterior descending coronary artery (LAD) and 12 patients without CALs (median ages; 10 and 9 years, respectively). Fourteen age-matched healthy subjects were also studied as controls. We obtained peak diastolic coronary flow velocity (CFV) of the LAD by pulsed-Doppler TTE at rest and at submaximal exercise on supine ergometer. CFR was calculated as the ratio of exercise to rest CFVs.

Results:
The CFV measurements were obtained in all the subjects. There was no significant difference in the CFVs among the patients with regressed CALs, those without CALs and the controls (30 ± 7 vs. 31 ± 10 vs. 28 ± 8 cm/s, respectively). The CFVs increased during exercise in the patients without CALs and the controls (51 ± 11 and 49 ± 10 cm/s, respectively, both p <0.05). In consequence, the CFR was lower in the patients with regressed CALs compared with those without CALs and the controls (1.3 ± 0.2 vs. 1.7 ± 0.2 and 1.7 ± 0.2, respectively, p <0.05).

Conclusions:
Exercise test demonstrated impaired CFR in KD patients with regressed CALs. It suggests that these patients have risk of future myocardial ischemic events.
Abstract O.64: Characteristics and Fate of Systemic Artery Aneurysm caused by Kawasaki disease
Authors: Hoshino Shinsuke , Tsuda Etsuko , Yamada Osamu
Published: March 2022

Background:
The long-term outcome of Systemic artery aneurysms (SAA) caused by Kawasaki disease (KD) remains unknown. SAA refers to aneurysms developing anywhere in the arterial system other than the coronary circulation. SAA included peripheral artery aneurysm (PAN) and aortic artery aneurysm.

Methods:
We investigated the characteristics and the fate of SAA in 20 patients (14 males and 6 females) from their medical records and angiograms. The onset age of KD ranged from 1 to 20 months with a median of 6 months. The interval from the onset of KD to the latest angiogram ranged from 16 months to 24 years (median 18 years). The residual rate of PAN and the incidence of stenotic lesions were analyzed by the Kaplan-Meier method in 11 pts, who had undergone initial angiograms within 4 months.

Results:
The mean duration of fever was 24±12 days. All 20 patients had at least a symmetric pair of aneurysms in bilateral peripheral arteries and 16 pts (80%) had multiple PAN. The number of respective SAA was as follows, brachial artery 32, common iliac artery 20, internal iliac artery 21, abdominal aortic aneurysm 7, and others 30. The residual rates of PAN at 10 and 20 years after the onset of KD were 66% and 51%, respectively (n=42). The incidence of stenotic lesions at 10 and 20 years after the onset of KD was 6 % and 25 %, respectively. The diameter of PAN in the acute phase leading to stenotic lesions in the late period was more than 10.0mm.

Conclusions:
PAN occurred symmetrically and were multiple in younger infants and those with severe acute vasculitis. The fate of PAN resembles that of coronary artery aneurysms, and depends on its acute phase diameter. The larger PAN can lead to stenotic lesions in the late period.
Abstract O.65: Long-term Outcome of Patients with Giant Coronary Aneurysms caused by Kawasaki Disease: A 30-year Experience in a Single Center in Taiwan
Authors: Chih Wan-Ling , Lin Ming-Tai , Chang Ching-Hao , Chen Chun-An , Chiu Shuenn-Nan , Lu Chun-Wei , Wang Jou-Kou , Wu Mei-Hwan
Published: March 2022

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

Methods:
By retrospective chart review of patients diagnosed with Kawasaki disease complicated by giant coronary aneurysms, we analyze incidence of ischemic event, survival rates, and related risk factors.

Results:
Between 1984 and 2012, 28 patients (24 male and 4 female) developed giant aneurysms. The mean age at onset and observe period was 3.8 years (range from 0.41 - 10.3 years) and 12 years (0 to 36.8 years), respectively. The initial median coronary Z-score was +5.75 (+0.62 to +19.06) in left main coronary artery, +4.49 (-0.18 to +11.19) in left anterior descending artery, +6.71 (+1.79 to +14.46) in right coronary artery. None of the giant aneurysms regressed during follow-up. The 5- and 35-year survival rates were 0.92 and 0.69, respectively. Except the three deaths, four additional male patients were diagnosed with acute myocardial infarction (AMI), and 2 of these diagnoses occurred within 1 year of KD onset. The incidence of AMI or death in patients with giant aneurysms was 26%, and 67% of the AMI occurred within the first year of KD onset. Clinical evidence of ischemia as documented in nuclear medicine studies was also noted in a further 9 patients (33%), and only one was female. AMI/death-free survival rates were 76% and 69% at 10 and 20 years after KD onset, respectively. Ischemia event-free survival rates were 63% and 36% at 10 and 20 years after disease onset. Men tended to have AMI and ischemia, and only one ischemia patient was female. The hazard ratio of gender on the ischemia events was 2.70 (95% CI: 0.33 - 21.73,
P
= 0.38).

Conclusions:
The long-term survival of KD patients with giant coronary aneurysms is guarded. Ischemic heart disease is the major cause of morbidity and mortality. Male KD patients, once they had giant aneurysms, tend to have ischemic events. Other risk factors need to be validated in a larger cohort.
Abstract 15860: Arterial and Cardiac Hemodynamics in Advanced HF Patients Implanted With the C-Pulse Counterpulsation Device: Implications for Myocardial Recovery
Authors: Rame J. Eduardo , Georgakopoulos Dimitrios , Pomfret David , Atluri Pavan , Wiegn Phi , Segers Patrick , Abraham William T
Published: March 2022

Introduction:
Despite intensive medical and device therapy, many HF patients remain symptomatic with refractory NYHA class III/IV. Therapeutic options are limited in this population, with the goal being stabilization of HF progression. A novel approach is the use of an extra-aortic counterpulsation device, C-Pulse™, consisting of an extra-vascular balloon cuff wrapped around the ascending aorta. The C-Pulse operates on principle of counterpulsation however placement on the proximal aorta may afford unique hemodynamic advantages over traditional counterpulsation devices. We report for the first time hemodynamic effects from advanced HF patients implanted with C-Pulse.

Methods:
Radial tonometry and office BP were measured in successive patients (N=6) NYHA Class III/IV, 5M, EF 17.2±6.6%, age 67.8±9.7 years (mean±SD), during device optimization. Median time from implant was 180 days (range 1-1356 days). Waveforms and blood pressure were obtained after 5 minute steady state OFF period followed by device optimization (ON).

Results:
Systolic and diastolic BP were maintained with optimization (Table). Myocardial perfusion indexed by subendocardial viability ratio (SEVR) significantly increased primarily resulting from increase in diastolic area, Ad. Cardiac ejection was enhanced; increased forward wave amplitude, P1, and reduced time to peak pressure, P2. Late systolic load from wave reflections was also reduced assessed by augmentation index (Aix).

Conclusions:
In this small cohort, C-Pulse increased myocardial perfusion and reduced early and late components of cardiac load. Novel finding of reduced Aix may arise from aortic arch baroreceptor stimulation due to enhanced pulsatility or mechanical deformation from the balloon. These changes may translate into improved heart failure symptoms, cardiac reverse remodeling and possibly recovery.Further studies are needed to assess these mechanisms and their association with regression of heart failure.
Abstract 15881: Functional Benefits of CCN1-Collagen Matrix for the Treatment of Myocardial Infarction
Authors: McNeill Brian , Vulesevic Branka , Blackburn Nicholas , Ruel Marc , Suuronen Erik J
Published: March 2022

Background:
Matricellular proteins are non-structural ECM proteins with important wound healing effects. They regulate cell function through interactions with cell surface receptors, enzymes and structural proteins such as collagen. The aim of this study was to examine the effects of matricellular protein CCN1 delivery in a mouse myocardial infarction (MI) model using a collagen matrix. CCN1 is pro-angiogenic and restricts fibrosis, while the matrix promotes cell function and directly interacts with CCN1.

Methods/Results:
Experimental MI was induced by LAD ligation in mice. At 1wk post-MI mice were randomized to receive intramyocardial injection of PBS, CCN1, collagen matrix or CCN1-matrix. Cardiac function was assessed at 1 and 3 wk post-treatment. At 1wk, LVEF was superior in the CCN1 (48.1±3.3%) and CCN1-matrix (41.9±3.5%) groups compared to PBS (34.6±2.8%; p<0.03). At 4wk, LVEF of the CCN1-matrix treated hearts improved to 49.7±2.1%, while CCN1 (38.0±2.6%) and matrix (38.7±1.6%) were better than PBS (28.9±2.9%) but no better than at 1wk (p<0.01). In vitro, CCN1-matrix offered protective effects to cardiomyocytes as there was a 39.3% increase in their survival under stress conditions (serum and O2 deprivation) compared to matrix-cultured cells (p=0.02). Cardiac fibroblasts responded to culture on the CCN1-matrix with a 2.3±0.7 and 1.6±0.2 fold reduction in proliferation compared to TCPS (p=0.008) and matrix (p=0.03) culture, respectively. Furthermore, the collagenase activity of CCN1-matrix cultured fibroblasts was reduced compared to those cultured on TCPS or matrix. Circulating angiogenic cells (CACs), which play a role in neovascularization post-MI, responded to CCN1-matrix treatment with a 2.2±0.2 fold increase in proliferation (p=0.001), a 1.8±0.2 fold increase in migration towards VEGF (p=0.001) and promoted greater tubule network formation (5.1±0.6 fold; p=0.007) in an angiogenic assay compared to matrix-cultured CACs.

Conclusion:
We demonstrate a novel approach to treat MI using a CCN1-collagen matrix. CCN1 treatment improved LVEF at 1wk post-MI, but this persisted only when CCN1 was delivered with the matrix. These data suggest that CCN1 has a positive effect on the MI heart but required the matrix for sustained benefit.
Abstract 15896: Higher Baseline Body Mass Index Predicts Longitudinal Increase in C-Reactive Protein but not Vice Versa
Authors: Vaidya Dhananjay , Yanek Lisa R , Kral Brian G , Mathias Rasika A , Becker Lewis C , Becker Diane M
Published: March 2022

Introduction:
Basic research shows that adipose tissue is proinflammatory, and inflammation in turn may cause adipose tissue accumulation through insulin resistance. However, it is not well understood whether adiposity or inflammation, or equally both, are drivers of this vicious cycle. We examined this question through longitudinal structural equation modeling (SEM).

Methods:
We analyzed data from 869 GeneSTAR Study participants from 374 families who were free of clinical cardiovascular disease throughout the follow-up period, and had two study visits 2 to 8 years apart. Body Mass Index (BMI) was used as a measure of adiposity, and log transformed high sensitivity C-Reactive Protein (CRP) as a measure of inflammatory state. The crossed lag SEM for correlations is presented in the Figure, adjusting for demographic factors and smoking during the two visits. The predictive associations of follow-up BMI and CRP with baseline CRP and BMI, respectively, are adjusted for cross sectional correlations and longitudinal inertia of variables. We also estimated the beta coefficients of the crossed lag associations using generalized SEM, accounting for non-independence of families.

Results:
Baseline BMI was associated with follow-up CRP (3.6% increase/BMI unit, p<0.001), but baseline CRP was not associated with follow-up BMI (p = 0.66). The crossed lag correlations were significantly different (p < 0.001).

Conclusions:
Higher adiposity is the driver of its vicious cycle with inflammation. For future studies, we conjecture that weight control is likely to be more effective as compared to treatment of inflammation in improving the coupled metabolic and inflammatory profile over time.