bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P349: A Randomized Trial of a High Potassium Dietary Intervention to Lower Blood Pressure in Urban African Americans With Hypertension in the Primary Care Setting: The “Five Plus Nuts and Beans” Trial
Authors: Miller Edgar R , Cooper Lisa A , Carson Kathryn A , Wang Nae-Yuh , Appel Lawrence J , Gayles Debra , Charleston Jeanne , White Karen , Dalcin Arlene T , Martin-Daniels Michelle , Bates-Hopkins Barbara , Albert Michael , Yeh Hsin-Chieh
Published: July 2021

Background:
African Americans and persons with low income have greater exposure to poor food environments and are more likely to have deficiencies in micronutrients that lower blood pressure (BP).

Objective:
We conducted a 2-arm randomized trial to test the hypothesis that delivery of nutritional advice to adopt a diet rich in potassium, tailored to availability of foods from a local supermarket, relevant to patients’ preferences, and combined with provision of targeted foods by a food delivery system, will reduce BP in urban African Americans with hypertension.

Methods:
We recruited adults with controlled hypertension from an urban primary care clinic in Baltimore City, Maryland, and implemented the trial in partnership with a community supermarket and the Baltimore City Health Department. Participants in the DASH-Plus intervention group received 8 weeks of dietary advice and coach assistance with weekly online ordering of high potassium foods ($30/week) delivered by the supermarket to a neighborhood public library. Participants in the control group received a printed DASH diet brochure along with a debit account of equivalent value at the same supermarket. The primary outcome was BP.

Results:
We randomized 123 participants and had 100% follow-up. At baseline, mean (SD) age was 58.6 (9.5) years, 71% were women, median household income was $20K-$30K/yr, BMI was 34.5 (8.2) kg/m
2
, and 28% had diabetes. At follow-up, compared to the control group, there was no effect on SBP and DBP, but the intervention group had significant increases in self-reported fruit and vegetable consumption, dietary intake of potassium, and in measured urine potassium excretion, along with a significant decrease in urine sodium excretion (see table).

Conclusion:
Our intervention program in urban African Americans with controlled hypertension did not reduce BP, but improved dietary patterns. Limitations of this pragmatic trial approach included medication changes during the trial that affected BP and reliance on a single BP measurement at follow-up.
Abstract P361: The First Genome-Wide Association Study (GWAS) of GlycA, an NMR-Derived Marker of Inflammation, Reveals Associations With a Variant in the Intron of TXNL4B Across Two Cohorts
Authors: Frazier-Wood Alexis C , Aslibekyan Stella , Borecki Ingrid B , Ordovas Jose M , Rotter Jerome I , Tsai Michael Y , Arnett Donna K , Rich Stephen S
Published: July 2021

Markers of inflammation reflect metabolic dysfunction and may predict incident cardiovascular events. GlycA is a new NMR-derived plasma marker of inflammation. Our goal was to undertake first characterization of the genetic variants associated with fasting GlycA, to elucidate the pathways from genes to inflammation. We completed a GWAS in the Caucasian-ancestry population of The Multi-Ethnic Study of Atherosclerosis (MESA; N=2,520; 48% male, mean age 62.7 y). We specified linear regressions models with GlycA as the outcome, and ~2.5 million single nucleotide polymorphisms (SNPs) directly genotyped or imputed from HapMap as the predictors in separate models; all models additionally controlled for age, gender, alcohol intake (g/day), smoking status (yes / no) and 4 principal components of population structure. In MESA, 5 SNPs reached genome-wide levels of significance (P<10
-8
; Table 1). Forty six SNPs reached a ‘discovery threshold’ of P<10
-5
in MESA, but only one (rs217181; minor allele frequency = .18) replicated in the Genetics of Lipid Lowering Drug Network (GOLDN; N=817; 48% male, mean age=48.8 years) after an FDR multiple testing correction. Rs217181 is located in the intron of
TXNL4B
,
thioredoxin-like 4B,
and in close proximity to
HP
,
Haptoglobin
, and
HPR, Haptoglobin-related Protein
. Rs217181 has been validated as associating with levels of haptoglobin protein. Haptoglobin is released by the liver and reduces hemoglobin’s oxidative activity. Our data suggests that rs217181 is involved in inflammation status, and may be a risk factor for adverse cardiovascular events. We would encourage replication of these findings in other cohorts, and are undertaking examination of this association in non-Caucasian individuals.
Abstract P363: Circulating Soluble CD163 and Risk of Cardiovascular Disease and All-Cause Mortality in Older Persons: The Cardiovascular Heart Study (CHS)
Authors: Durda Jon P
Published: July 2021

Introduction:
Macrophages play important roles in atherosclerotic plaque formation and stability. CD163 is a macrophage specific receptor involved in the clearance and endocytosis of hemoglobin-haptoglobin complexes; soluble CD163 (sCD163) may be a useful biomarker to assess macrophage activation. We are not aware of epidemiologic studies of sCD163 levels and cardiovascular disease (CVD) risk. Also it is not known whether common genetic variants are associated with sCD163.

Methods:
We tested whether sCD163 was associated with carotid intima-media thickness (IMT) and incident clinical events (overall mortality, coronary heart disease [CHD], myocardial infarction [MI], stroke, and congestive heart failure [CHF]) in 4,577 Cardiovascular Health Study (CHS) participants (95% white, 5% black; age range 65-100 y). We used linear regression with adjustment for sex, age, race, study site, current smoking, BMI, hypertension status, systolic blood pressure (SBP) and LDL cholesterol to test for association between sCD163 and IMT. We used 2 Cox proportional hazards models for incident events analyses: (1) adjusting for sex, age, race, study site, and current smoking; (2) model 1 plus BMI, hypertension status, SBP, LDL-cholesterol, C-reactive protein (CRP), interleukin-6 (IL6), and fibrinogen. We also performed a genome-wide association study (GWAS) for sCD163 in 2,769 unrelated CHS white participants, using Hapmap 2 imputed SNPs.

Results:
sCD163 was positively associated with female sex, white race, age, BMI, SBP, CRP, IL6 and fibrinogen, negatively associated with current smoking status (p<0.0001), and not associated with LDL cholesterol or hypertension status. After adjustment for traditional CVD risk factors, sCD163 was positively associated with carotid IMT (p=0.027). In model 1, increased sCD163 levels were associated with overall mortality (p<0.0001), incident CHD (p=0.0034), incident stroke (p=0.016), and incident CHF (p<0.0001), but not incident MI (p=0.069). None of the model 2 analyses resulted in significant associations (all p>0.05). Five variants upstream of chromosome 2q gene MGAT5 (top result rs4954118, p=7.1x10-14) and a single variant (rs314253, p=6.0x10-13) on chromosome 17p between ASGR1 and DLG4 were significantly (p<5x10-8) associated with sCD163. The top result near the CD163 gene was for upstream variant rs6488429 (p=8.2x10-5).

Conclusions:
sCD163 was associated with carotid IMT after accounting for established CVD risk factors. There were associations of sCD163 with mortality and incident clinical CVD, although associations were attenuated after adjustment for other risk factors. Additional studies are needed to evaluate whether results are similar in younger age groups and other populations. The significant results in the GWAS for sCD163 implicate novel molecular pathways that warrant future fine-mapping and functional studies.
Abstract P366: Promoter Methylation of the Monoamine Oxidase a Gene is Associated With Fasting Plasma Glucose: A Monozygotic Twin Study
Authors: AN QIANG , Vaccarino Viola , Goldberg Jack , Zhao Jinying
Published: July 2021

Background:
Epigenetic factors play an important role in complex diseases including diabetes. The monoamine oxidase A (MAOA) gene codes for the enzyme MAOA that plays a key role in the metabolism of neurotransmitters including dopamine, norepinephrine, and serotonin. These neurotransmitters are known to be involved in the pathogenesis of diabetes. No study has examined the association of MAOA methylation with fasting plasma glucose (FPG), independent of genetic factors.

Objective:
To examine whether MAOA promoter methylation variation is associated with FPG, independent of familiar factors.

Methods:
We studied 69 middle-aged, male-male monozygotic twin pairs drawn from the Vietnam Era Twin Registry. All twins were free of overt diabetes. DNA methylation at seven CpG sites in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. To examine whether MAOA promoter methylation variation influences FPG, we first calculated the intra-pair difference, defined as the difference in DNA methylation level at each CpG site between members of a twin pair. The intra-pair differences in FPG and other potential confounding factors were similarly calculated. We then conducted a matched pair analysis by regressing the intra-pair difference in FPG (dependent variable) on the intra-pair difference in DNA methylation level at each CpG site (independent variable), adjusting for intra-pair differences in body mass index (BMI), smoking pack-years, physical activity and depressive symptoms assessed by beck depression inventory (BDI). Multiple testing was corrected by the FDR p-value (or q-value) with a significant threshold of q<0.05.

Results:
The mean age of the twins was 55 years old. DNA methylation at the seven examined CpG sites varied from 1.6% to 19.0% with a mean methylation level of 5.0%. Intra-pair difference in FPG was significantly and positively correlated with intra-pair difference in methylation level at 3 out of the 7 CpG sites (r2 ranges 0.10 to 0.18, all P<0.025) as well as the mean methylation level (r2=0.10, p=0.026). Matched-pair analysis showed that methylation variation at 3 CpG sites was significantly associated with FPG (β ranges 1.83 to 2.33, all P<0.015), independent of BMI, smoking, physical activity and depressive symptoms. On average, a 1% increase in the intra-pair difference in mean methylation level was associated with a 2.21 mg/dl increase in the intra-pair difference in FPG (P=0.015).

Conclusion:
Methylation variation in the MAOA gene promoter is associated with FPG, independent of genetic and other clinical factors. This finding suggests a novel mechanism through which MAOA methylation variation, and perhaps its resulting changes in neurotransmitters, may contribute to diabetes.
Abstract P368: Genome Wide Association Study Identifies Susceptibility Loci for Coronary Artery Calcium in Smokers
Authors: Lutz Sharon M , Cho Michael H , Kinney Gregory , Pratte Katherine , Casaburi Richard , Silverman Edwin , Budoff Matthew , Hokanson John E
Published: July 2021

Introduction:
Coronary artery calcium (CAC) is a measure of coronary atherosclerosis, which is strongly associated with the presence of coronary artery disease and predicts future coronary disease events and mortality. CAC is a heritable trait. Numerous candidate gene studies and more recently genome-wide association studies (GWAS) have identified susceptibility loci for CAC. In addition, cardiovascular disease risk factors such as smoking are associated with CAC.

Hypothesis:
We hypothesized that we would identify new genetic loci and replicate known genomic regions for CAC by performing a GWAS among heavy smokers in the COPDGene study, a multi-center observational study designed to identify genetic factors associated with risk of COPD.

Methods:
We conducted a GWAS of CAC in COPDGene, a study of 10,192 current and former smokers with at least 10 pack-years of smoking history. CAC was measured from chest CT scans using an established protocol and was available in 8,739 individuals (6,150 non-Hispanic Whites and 2,589 African Americans). The analysis was performed using PLINK v1.07 adjusting for genetic ancestry using principal components as well as and cardiovascular disease risk factors (age, gender, BMI, smoking status, pack-years of smoking history, diabetes, high blood pressure, steroid use, high cholesterol, and presence of a coronary stent).

Results:
Using the log transformation of CAC plus 1 as the outcome, there were 9 single nucleotide polymorphisms (SNPs) on chromosome 9 [CDKN2B-AS1] that reached genome wide significance in non-Hispanic Whites, with the most significant result being rs10757272 (p = 3.572e-11). Additional top loci that have been previously identified were rs9349379 on chromosome 6 [PHACTR1] (p =8.760e-08) and rs1263982 on chromosome 17 [CA10] (p =4.654e-06). Among African Americans, no genome-wide significant associations were identified; however, one of the top findings was rs7412 on chromosome 19 [APOE] (p = 1.597e-06).

Conclusions:
This study confirms genome wide significance for CAC for CDKN2B-AS1 on chromosome 9 among non-Hispanic Whites. This is the major GWAS signal for clinically manifested coronary artery disease. Among African Americans, we found a suggestive association signal in the APOE gene. In conclusion, genetic susceptibility for atherosclerosis is evident, even among individuals with a substantial smoking burden. This highlights the importance of both genetics and behavioral risk factors in the susceptibility to atherosclerosis.
Abstract P370: Cardiovascular Health Metrics, Lifetime Risks of Cardiovascular Disease and Chronic Disease Mortality, and Life Expectancy in Men and Women
Authors: Lee Chong
Published: July 2021

Whether cardiovascular health metrics relates to lifetime risks of cardiovascular disease (CVD) and chronic disease mortality and life expectancy in U.S. population remains less explored.

PURPOSE: We investigated the combined impact of 7 ideal cardiovascular health metrics on lifetime risks of CVD and chronic disease mortality and life expectancy in US men and women at 30 years of age.

METHODS:
Lifetime risks of CVD and chronic disease mortality to 80 years of age were estimated for men and women, with death free of chronic diseases as a competing event. We followed 11,341 men and women, aged 30 to 80 years, who participated in the Third National Health and Nutrition Examination Survey. All participants completed baseline lifestyle factors and lifestyle behavior questionnaires. The 7 ideal cardiovascular health metrics was defined as physically active, never smoking, a healthy diet, waist girth (<102/88 cm), untreated blood pressure (<120/80 mmHg), untreated total cholesterol (<200 mg/dL), and untreated fasting glucose (<100 mg/dL) defined by the American Heart Association Strategic Committee. They were further categorized as having 0, 1, 2, 3, 4, 5, 6 or 7 combined cardiovascular health metrics.

RESULTS:
During an average of 13.7 years of follow-up (155,726 person-years), there were a total of 1834 chronic disease deaths (945 CVD, 579 cancer, 217 respiratory disease, 93 diabetes mellitus). The lifetime risks of chronic disease mortality (at 30 years of age) across 0, 1, 2, 3, 4, 5, and 6 or 7 ideal health metrics were (95% CI) 46.2% (41.6, 50.7), 40.3% (36.9, 43.8), 33.1% (30, 36.1), 27.2% (23.9, 30.5), 25.8% (21, 30.5), 24.8% (16.8, 32.9), and 12.7% (1.2, 24.1), respectively. Men and women who had adopted increasing number ideal health metrics had a substantially lower lifetime risk of chronic disease mortality. The lifetime risks of CVD mortality across 7 ideal health metrics showed trends similar to chronic disease mortality. After adjustment for multiple risk factors, men and women with all 6 or 7 combined ideal health metrics had a 75% (95% CI: 51% to 88%) lower risk of chronic disease mortality and 93% (95% CI: 53% to 99%) lower risk of CVD mortality, respectively, when compared with men and women with zero ideal health metrics. Men and women with 0 compared with 6 or 7 combined ideal health metrics had a shorter life expectancy by 16 years (95% CI: 13 to 19.1 years). Approximately 63% (95% CI: 26% to 82%) of chronic disease deaths might have been avoided if men and women had maintained all 6 or 7 combined health factors and healthy lifestyle behaviors.

CONCLUSION:
Maintaining an ideal cardiovascular health metrics is associated with lower lifetime risks of CVD and chronic disease mortality in men and women.
Abstract P382: Fried Food Consumption is Associated with a Higher Risk of Heart Failure among US Male Physicians
Authors: Djousse Luc , Petrone Andrew , Gaziano John M
Published: July 2021

Background:
While previous studies have reported a positive relation of fried food consumption with type 2 diabetes, hypertension, and obesity, no previous study has examined the relation of total fried food intake with risk of heart failure (HF) in a prospective cohort.

Objective:
To test the hypothesis that fried food consumption is positively associated with risk of HF in male physicians.

Methods:
A prospective cohort of 19,968 participants from the Physicians’ Health Study. Frequency of fried food consumption was assessed between 1999 and 2002 using a food frequency questionnaire and HF was ascertained through annual follow-up questionnaires with validation in a subsample. We used Cox regression to estimate multivariable adjusted hazard ratios of HF.

Results:
During a median follow-up of 10.6 years, 862 cases of HF occurred. The mean age at baseline was 66.4 ± 9.2 years. Median frequency of fried food consumption was <1 time per week. Multivariable adjusted hazard ratios (95% CI) were: 1.0 (ref), 1.18 (1.01-1.37), 1.25 (1.02-1.54), and 1.68 (1.19-2.36) for fried food consumption of <1/week, 1-3/week, 4-6/week, and 7+/week, respectively (p for linear trend: 0.0004), after adjustment for age, alcohol use, smoking, exercise, and history of myocardial infarction, coronary artery bypass graph or angioplasty (Fig). Additional adjustment of total trans fats did not alter the findings. In a secondary analysis, body mass index did not modify the relation of fried foods with HF risk.

Conclusions:
Our data show a positive association between fried food intake and risk of HF in US male physicians.
Abstract 102: Midkine, A New Functional Cytokine, Increased After IVIG May Protects From Vascular Injury In Acute Kawasaki Disease
Authors: Saji Ben T , Takatsuki Shinichi , Kenmotsu Yasushi , Naoi Kazuyuki , Ikehara Satoshi , Nakayama Tomotaka , Matsuura Hiroyuki , Kusunoki Natsuko , Kawai Shinichi
Published: July 2021

Introduction:
Midkine(MDK), found in 1988, a heparin-binding low-molecular protein, is a member of growth factors or cytokines, activated in the process of inflammatory disorders like RA, cancer development, angiogenesis and wound healing etc. It also acts as protecting cell apoptosis, stimulating fibrinolysis on endothelial cells, inhibiting or suppressing the development of regulatory T cells, improving myocardial dysfunction, and promoting the survival of ischemic myocardium. But, little is known in vasculitis syndrome.

Methods:
Serum samples, clinical data and laboratory values from17 patients with acute KD patients in before, 1-2 days, and 7-10 days after IVIG. Serum samples were analysed for MDK concentrations by EIA with anti-human MDK antibody.

Results:
MDK values were significantly elevated in serum from 1-2d after IVIG; 1-2d after IVIG; mean=1291.6 ± 1119.0, compared with Pre-IVIG; mean=530.9±468.6(p<0.01), and rapidly decreased 7-10d after IVIG; mean=599.4±447.3 pg/ml(p<0.05)(healthy human cut off level; < 300pg/ml). CRP is significantly correlated with MDK (r=0.45, p<0.05). MDK of 2 patient with CAA was higher than that of no CAA.

Discussions and Conclusions:
Knockout mice deficient in the MDK gene poorly develop neointima when the artery is damaged by ischemic shock. Clinically, MDK increases in human carcinoma and play a central role in inflammatory pathway. It promotes the migration of inflammatory leucocytes, namely macrophages and neutrophils. Recently, it is becoming a molecular target for the treatment or prevention of inflammatory diseases.

Finally, this preliminary study suggests that MDK is a possible novel effector and may be relevant in the pathogenesis of arteritis in acute KD. IVIG may increase MDK levels and protect from inflammatory vascular damage.
Abstract 120: A Case With Left Ventricular Failure And Unconsciousness Treated With Plasma Exchange
Authors: Abe Yuriko , Ayusawa Mamoru , Kato Masataka , Cho Ami , Watanabe Hirohumi , Okuma Hiromi , Komori Akiko , Ichikawa Rie , Kamiyama Hiroshi , Takahashi Shori
Published: July 2021

Background:
Either encephalopathy or left ventricular (LV) failure complicated with Kawasaki disease (KD) is rare but occasionally fatal. We experienced a critical case simultaneously complicated with both of them and successfully rescued by plasma exchange (PE).

Case report:
A 4-year-old girl was hospitalized with a high fever lasting 7 days, conjunctival injection, reddened and swollen lips, cervical lymphadenopathy and erythema of the palms and soles. Laboratory tests revealed that her white blood cells count 35,400/μl, C-reactive protein was 35 mg/dl, N-terminal pro-brain natriuretic peptide was 15,317 pg/ml, and interleukin-6 reported afterward was 354 pg/ml. Echocardiography showed that LV ejection fraction was 40%. She was diagnosed as KD and was treated with 2g/kg of intravenous immunoglobulin (IVIG) and oral aspirin on the 7th day of illness. On the following day, however, her blood pressure declined to 80/40mmHg and LV function was becoming gradually poorer despite of intravenous injection of dobutamine. As her consciousness was unclear and electroencephalogram (EEG) indicated slow waves, she was additionally treated with D-mannitol. Infliximab is not indicated because of heart failure. Therefore, repetitive PE was started immediately after deep sedation with mechanical respiratory assist. Her fever, EEG and LV function began improving by PE consecutive 3 days, however, those findings recurrently worsened at every interval of PE. IVIG and steroid pulse therapy were added on the 12th day after PE. On the 13th day, she became defervescent and her consciousness became clear and EEG normalized. She returned to daily life without cardiac or neurologic abnormalities after discharge.

Conclusions:
PE is a rapid and sufficiently effective strategy for a critical KD case when infliximab is not indicated or immediate effectiveness of steroid including pulse therapy is not expected.
Abstract 129: Adaptation of Infliximab Therapy for Gamma Globulin Treatment Resistance Kawasaki Disease
Authors: Hoshiai Minako , Katsumata Nobuyuki , Hasebe Yohei , Koizumi Keiichi , Toda Takako , Kise Hiroaki , Sugita Kanji
Published: July 2021

Background:
Infliximab (IFX) which is an anti-TNFα monoclonal antibody is effective in the treatment of gamma globulin treatment (IVIG) resistance Kawasaki disease (KD) . On the other hand, plasma exchange therapy (PE) became insurance adaptation as treatment for IVIG-resistant KD in Japan. It is necessary to clarify the position of IFX as an additional treatment for IVIG-resistant KD.

Purpose:
We examined retrospectively the efficacy of IFX for IVIG-resistant KD and discussed its adaptation.

Method:
We studied 30 cases (boys 18 cases, 12 cases of girls) who underwent IFX treatment in our hospital because they were IVIG-resistant KD. Between the invalid group and the effective group of IFX treatment, we compared the age , gender, the time of administration, the sick days, CRP value and the presence or absence of coronary artery lesions (CAL) before the treatment in patients.

Result:
Clinical symptoms and laboratory data has improved in 22 cases of the 30 cases, but 8 cases underwent plasma exchange because IFX was invalid. Compared to the disabled group and effective group of IFX, the proportion with CAL was significantly higher in the disabled group (87.5% invalid group 40.9% vs effective group, p <0.05). There was no significant other factor between the two group.

Discussion:
We have to suppressed the inflammation in order to inhibit CAL. To do so, the enforcement period and selection of additional treatment are important. Because treatable facility is limited, PE is not able to carry out in all cases. In this study, the possibility that can predict efficacy of IFX by the presence or absence of CAL in the IVIG-resistant KD has been shown. we should clarify the adaptation of IFX by continuing further study to find the relevant factors.
Abstract 131: Retrospective Study of The Timing Of Additional Therapy For Severe Kawasaki Disease Before And After The Induction Of Raise Study Protocol
Authors: Katayama Hiroshi , Kishi Kanta , Noriyasu Ozaki , Odanaka Yutaka , Tamai Hiroshi
Published: July 2021

Background:
The RAISE study showed that combination therapy with intravenous immunoglobulin (IVIg) and prednisolone (PSL) improved coronary artery outcomes in patients with severe Kawasaki disease (KD). We encountered KD cases in which fever and findings such as WBC were masked by the steroid administration in combination therapy. We hypothesized that combination therapy might delay second- and third-line therapy for severe KD.

Purpose:
The goal of the study was to investigate whether combination therapy with IVIg and PSL might delay second- and third-line therapy for severe KD patients.

Methods:
We retrospectively investigated clinical data from acute KD patients admitted to our hospital from January 2011 to September 2014. We examined the following: 1) prediction score for refractory KD 2) first-line therapy for KD (IVIg group, n=10; IVIg/PSL group, n=11); 3) additional rescue therapy such as additional IVIg, steroid pulse therapy, plasma exchange, and so on 4) period from KD onset to end of main therapy for KD; 5) day of increased albumin from previous examination; and 6) day of CRP reaching <1.0 mg/l.

Results:
Seventy-four acute KD patients were admitted to our hospital during the study period. Only 1 KD patient had coronary artery lesions (CAL) at 1 month after onset. Detailed data were as follows: 1) Twenty-one patients were at high risk for refractory KD. 2) number of patients with additional IVIg (IVIg, 6/10; IVIg/PSL, 6/11); 3) number of patients with steroid pulse therapy (IVIg, 4/10; IVIg/PSL, 4/11); 4) period from KD onset to end of main therapy (IVIg, 8.3 days; IVIg/PSL, 8.7 days); 5) day of increased albumin (IVIg, 12.0 days; IVIg/PSL, 11.8 days); 6) day of CRP reaching <1.0 mg/l (IVIg, 13.7 days; IVIg/PSL, 11.4 days). No differences between IVIg and IVIg/PSL groups were seen for any factor.

Discussion and conclusion:
In this study, overall frequency of CAL was 1.3%, lower than that reported from nationwide surveillance in Japan. This study found no differences between groups in regard to frequency or timing of additional therapy and response. We concluded that combination therapy with IVIg and PSL did not delay the timing of additional therapy for acute KD. The cohort for this retrospective study was small, and further investigation is thus needed.
Abstract 135: Effectiveness Of Live Vaccines Following Intravenous Immune Globulin Therapy During The Convalescent Phase Of Kawasaki Disease Using The Schedule Recommended In Japan
Authors: Morikawa Yoshihiko , Miura Masaru , Sakakibara Hiroshi ,   Tokyo Pediatric Clinical Rsch Network
Published: July 2021

Background:
There are differences between Japan and the United States regarding recommended timing of live virus vaccinations after treatment of Kawasaki disease patients with intravenous immune globulin (IVIG): 6 months in Japan and 11 months in the U.S. The prevalence of antibodies to these vaccines using either vaccination schedule remains undetermined.

Objective:
The present study aimed to evaluate the effectiveness of the live virus vaccination schedule for Kawasaki disease recommended in Japan.

Methods:
This was a prospective observational study. Kawasaki disease patients aged 6 months and older without past history of or vaccination against measles, rubella, varicella-zoster (VZ), or mumps were enrolled. The children were vaccinated against measles, rubella, VZ, and mumps 6 months after IVIG. Serologic tests for IgG-class specific antibodies to each vaccine virus were performed prior to IVIG; 2 days, 3 months, and 6 months after IVIG, and 3 months after vaccination. The primary outcome was seroprevalence of positive antibodies, which was defined as serum concentration more than 4 IU/mL.

Results:
A total of 24 children (mean month age 16.8 ± 2.7 at vaccinations, 70.8% male) were enrolled. The rate of measles, rubella, VZ, and mumps seropositivity was 12.5% (3/24), 0% (0/24), 12.5% (3/24), and 0% (0/24), respectively, just before vaccination. The rate increased to 91.7% (22/24), 87.5% (21/24), 20.8% (5/24), and 8.3% (2/24), respectively, 3 months after vaccination. There were no serious adverse events.

Conclusions:
Use of the Japanese vaccination schedule led to extremely low seroprevalence of VZ and mumps antibodies but acceptable seroprevalence of measles and rubella antibodies. This study is ongoing and more cases (up to 30, the target sample size) are needed before the appropriateness of the timing of vaccination in Japan can be discussed.
Abstract 145: Long Term Follow-up Of Children With Kawasaki Disease (KD) Treated With Infliximab (IFX) - Our Experience At Chandigarh, North India
Authors: Sharma Dhrubajyoti , Gupta Anju , Rohit Manojkumar , Suri Deepti , Rawat Amit , Singh Surjit
Published: July 2021

Background:
Tuberculosis (TB) is endemic in India. Flare-up of TB is a concern in children treated with IFX.

Objective:
To report long-term follow-up of children with KD treated with IFX.

Patients and methods:
Study design: Review of records of 17 children with KD who had received IFX. Median age was 1.5 years (range 2 months to 6 years)

Study setting:
Pediatric Rheumatology Clinic, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, North India.

Study duration:
January 2007 to July 2014.

Patient group:
Patients with diagnosis of KD and given IFX were included and analyzed. 15 of these patients had received intravenous immunoglobulin (2g/kg) as first line therapy. Dose of IFX was 5-7 mg/kg given intravenously. Screening tests for TB (chest X-ray, tuberculin test) were not carried out prior to IFX infusion.

Duration of follow-up:6 -12 months in 6 patients;13-30 months in 5 patients;45-65 months in 5 patients and 80 months in 1 patient (mean follow-up 30.6 ± 24.4 months).

Results:
None of the patients had any significant adverse reactions during infusion of IFX. On follow-up none of these patients has developed TB or any other significant infection. Twelve (12)/17 patients showed coronary artery abnormalities (CAAs) (table). Post IFX, 66% (8 of 12) patients with KD showed improvement in CAAs on follow-up.

Conclusion:
In our experience use of IFX was not associated with flare-up of any significant bacterial infection (including TB) during follow-up. 8/12 patients with CAAs showed resolution.
Abstract 147: Coronary artery aneurysms on day 4 after onset of Kawasaki Disease: A Case report
Authors: Tatsuya Anzai , Minami Takaomi , Furui Sadahiro , Oka Kensuke , Yokomizo Akiko , Ishii Tomoyuki , Sato Tomoyuki , Kataoka Koichi , Yamagata Takanori
Published: July 2021

Background:
Coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD) almost always occurs after day 8, and the most early detection report of CAA was in an autopsy case on day 6 after onset. The possibility of CAA formation prior to day 6 has not been documented.

Case report:
A 10-month-old Japanese boy presented with a 4-day fever, conjunctival injection, erythema of the lips, erythema of the palms and soles, erythematous rush, and induration at a Bacillus Calmette-Guerin inoculation site. On day 4, echocardiography revealed coronary artery dilatation (right coronary artery [RCA], 4.6 mm; left main trunk [LMT], 4.6 mm; left anterior descending [LAD] artery, 3.4 mm). Laboratory data were as follows: white blood cell count, 19,400/μL; C-reactive protein, 15.2 mg/dL; albumin, 3.2 g/dL; high-density lipoprotein cholesterol, 20 mg/dL, and erythrocyte sedimentation rate, 48 mm/h. He was diagnosed with KD and treated with oral aspirin 30 mg/kg/day and intravenous immunoglobulin (IVIG) 2 g/kg. His fever subsided the next day. On day 17, periungual peeling of the fingers and toes was noted. His fever recurred and he treated with additional IVIG 1 g/kg, after which his fever subsided again. On day 20, the aneurysms had not increased in size (RCA, 3.3 mm; LMT, 3.6 mm; LAD, 2.4 mm). On day 44, although echocardiography showed a mild coronary artery dilatation, a coronary angiogram showed no apparent abnormality. He had no obvious fever or symptoms of KD prior to this course of KD. This case may help clarify the pathophysiology of CAA in patients with KD.
Abstract 152: Tri-Dimentional Fusion Image of Multidetector 64-Slice-Computed Tomography and Single-Photon Emission Computed Tomography enables us to Evaluate Complicated Hemodynamics in Patients with Coronary Artery Lesions after Kawasaki Disease
Authors: Abe Masanori , Watanabe Makoto , Fukazawa Ryuji , Ogawa Shunichi
Published: July 2021

Introduction:
An important complication of Kawasaki disease (KD) is myocardial ischemia and acute myocardial infarction which occurs by thrombosis in coronary aneurysms and severe stenosis. The most characteristic features of coronary artery lesions (CALs) are dilation or aneurysm in acute stage and stenosis after convalescence stage. As these lesions exist singly or multiply in one coronary branch or multiple branches, coronary hemodynamics can be complicated. Ordinal methods have less potential for detection of these diseased states. Recently, Fusion imaging from coronary CT angiography (CTA) /SPECT has been thought good method for evaluation of location and severity of myocardial damages in adults. Therefore, we evaluate CALs, ischemia, and infarction after KD by Fusion imaging.

Patients and Method:
Seventeen patients (16 males and 1 female, age10 to 34 y) were subject. Eight patients had coronary artery bypass grafting (CABG). These tests were performed 8 to 30 years after onset of KD.

CTA are performed by 64-slice-CT (LightSpeed VCT:GE Healthcare) ,and SPECT (Infinia:GE) by Tc-tetrofosmin was performed at rest and at stress after infusing adenosine. CTA and SPECT images were fused by the software (CardIQ Fusion:GE).

Results and findings:
In all cases, we had enough good images to detect the location of CALs and the area of ischemia.

1) Fusion images showed that no patient had significant stenotic findings at the anastomosis of bypass-graft at least several years after CABG.

2) Coronary native small branches arose from giant aneurysm were occluded by thrombosis and sub-aneurysmal lesions were infracted which were not detected by ordinal method.

3) Minimum sized myocardial ischemic lesions along to the normal visual epicardial coronary artery were detected and were suspected the existence of abnormal micro-coronary circulation caused by fibrous plaque or micro-thrombosis.

4) Collateral arteries at the stenotic and/or occluded lesions with or without ischemia were clearly detected by Fusion method.

conclusion:
Fusion images can visualize morphologically and functionally complicated CALs, myocardial ischemia ,and myocardial infarction after KD.

Also, we can realize that peripheral coronary vessels are damaged with myocardial ischemia.
Abstract 159: New Insight of Coronary Wall Structural Changes from an Optical Coherence Tomography (OCT) study Following Kawasaki Disease.
Authors: Dahdah Nagib , Dionne Audrey , Ibrahim Ragui , Gebhard Catherine , Fournier Anne
Published: July 2021

Background:
Coronary artery aneurysms (CAA) are a serious complication of Kawasaki disease (KD). Coronary imaging usually describes aneurysms, stenosis and dilatation. Optical coherence tomography (OCT) is a technique useful for intracoronary imaging and coronary wall structure characterization.

Method:
KD patients scheduled for routine coronary angiography underwent OCT imaging between June 2013 and August 2014. Subjects’ clinical courses with echocardiography and angiography were reviewed to contrast with OCT findings.

Results:
OCT was performed on 18 patients 9.0 ± 5.1 years after KD at 12.4 ± 5.5 yo (range 3.5-21 yo). Of those, 14 (77.7%) had a history of CAA (7 giant CAA, 7 regressed CAA at time of OCT). Prophylactic intracoronary nitroglycerin was given (88.4 ± 45.5 μg/m2). Total X-ray exposure was 10.9 mGy/kg. One patient had a transitory uneventful vasospasm at the site of a former CAA, otherwise no major complications occurred (such as dissection, thrombosis, ischemia, arrhythmia). OCT findings were intimal hyperplasia in 15/18 (83.3%) on aneurysmal and regressed aneurysm segments. Intimal hyperplasia measured 390.8 ± 166.0 μm for the affected segments, compared to 61.7 ± 17.0 μm for the unaffected segments (p<0.001). Destroyed media, fibrosis, calcifications, macrophage infiltration, neovascularization and white thrombus were also seen (Table 1). In two cases with previously implanted stent, the neo-intima was identified, measuring 80-160 μm.

Conclusion:
In our experience, OCT proved safe and insightful in the setting of KD. The observed coronary structural changes correspond to histological findings described in the literature late after KD.
Abstract 162: A Case of Fatal Kawasaki - Correlation Between Optical Coherence Tomography and Pathology
Authors: Dionne Audrey , Chami Rose , Morissette Geneviève , Dahdah Nagib
Published: July 2021

Background:
Coronary artery aneurysms (CAA) develop in up to 30% of untreated patients with Kawasaki disease (KD). This may lead to ischemic heart disease and sudden cardiac death, which is extremely rare nowadays.

Method:
A 3 mo infant presented with severe KD 27 days after onset of fever. He died few days later of multi vessel obstruction and aneurysms. OCT was performed post mortem and correlated with pathology findings.

Results:
The patient presented with shock, inferolateral ischemia on ECG and high Troponin-i (from 6.45 to 59 μg/L 2 days later). Echocardiography showed severe myocardial dysfunction with diffuse coronary dilation and right CAA. Arterial Doppler demonstrated thrombosis of aneurysmal axillary, subclavian and iliac arteries, which corroborated with clinically ischemic limbs. Withdrawal of support was implemented due to multiorgan failure.

OCT images from the proximal RCA, LAD, carotid and pulmonary arteries were obtained post mortem. The circumflex coronary could not be accessed by the OCT catheter, which was occluded on pathology exam. The carotid (figure TOP) and pulmonary arteries were normal on OCT and histology. RCA and LAD (figure BOTTOM) showed aneurysmal dilatation, with marked intimal hyperplasia and preserved media on OCT. Pathology confirmed these findings, with destruction of internal elastic lamina, luminal myofibroblastic proliferation, neovascularization, and attenuation of the media in some sections.

Conclusion:
This is the first report of pathologic correlation in a severe KD case with OCT imaging at the sub-acute stage, which adequately identified structural wall changes.
Abstract 170: Re-evaluation of Carotid Intima-Media Thickness by Z-score in Children and Adolescents After Kawasaki Disease
Authors: Noto Nobutaka , Kato Masataka , Abe Yuriko , Kamiyama Hiroshi , Karasawa Kensuke , Ayusawa Mamoru , Takahashi Shori
Published: July 2021

Objectives:
The carotid intima-media thickness (CIMT) is a reliable screening method for vascular alterations even in a pediatric cohort; however, reference values of CIMT established recently by LMS methods for childhood and adolescence are limited when comparing patients after Kawasaki disease (KD) and controls. We tested the hypothesis that there are significant differences between the values of CIMT expressed as absolute values and z-scores in children and adolescents after KD and controls.

Methods:
We reviewed 12 published articles regarding CIMT on patients after KD and controls. Absolute values (Ab) of the mean±1 SD of CIMT in patients after KD and controls were transformed to z-scores (Zs) using age-specific reference values established by Jourdan et al. (J: 247 Caucasian subjects aged 10-20 years) and our own data (O: 175 Asian subjects aged 6-20 years), and the results were compared between the two references. In this study, the mean age of the study population derived from each article was designated the representative age for transformation.

Results:
In either reference (J) or (O), there was no significant sex difference in CIMT at any given age. The mean CIMT of (Ab) and (Zs) transformed by (J) or (O) were significantly different between patients after KD and controls, at 41.6% (Ab), 66.6% (Zs) by (J), and 83.3% (Zs) by (O) among 12 articles, respectively. Therefore, patients after KD had significantly higher (Zs) by (O) than those of controls (0.66±0.71 vs. 0.03±0.68, p=0.006, respectively). Compared with reference values, the controls of (O) were within the normal range. However, there were no significant differences in (Zs) by (J) between the two groups (1.72±0.77 vs. 1.23±0.83, p=0.116, respectively). When we assessed 9 articles dealing with Asian subjects, the difference of (Zs) between the two groups remained significant only by (O) (p=0.015). In contrast, when we assessed 3 articles dealing with mainly Caucasian subjects, there was no significant difference in (Zs) between the two groups with both (J) and (O).

Conclusions:
These results indicate that age and race-specific reference values for CIMT are mandatory for performing an accurate assessment of the vascular status in healthy children and adolescents and particularly in those after KD.
Abstract 182: Proposal of Strategy for Threatened Rupture of Super-giant Coronary Aneurysm; Rare and Fatal Complication with Kawasaki disease
Authors: Ayusawa Mamoru , Kamiyama Hiroshi , Chou Ami , Kato Masataka , Watanabe Hirofumi , Komori Akiko , Abe Yuriko , Kawamura Yuki I , Takahashi Shori
Published: July 2021

Background:
Prognosis of Kawasaki disease and its main complications, coronary artery aneurysm (CAA) and myocardial ischemia were remarkably improved by intravenous immunoglobulin (IVIG) and other additional anti-inflammatory and anti-coagulation therapy. In contrast, rupture of coronary artery aneurysm is a rare, and still definitely fatal complication. Though approximately 10 cases were reported with sporadic occurrence in every three to four years in Japan, there is no patient whose life was saved. Case report: We experienced a 5-year-old boy who had already developed left CAA of 9 mm in diameter on the 7th day from onset of fever. Despite of repeated IVIG, left CAA was rapidly expanding day by day and finally the diameter became 18mm on the 12th day. Early in the next morning, sudden cardiac arrest was noted, but resuscitation was not effective. Autopsy revealed cardiac tamponade caused by rupture of very fragile wall of huge left CAA. Discussions: After this experience, we have tried to carry patients into the intensive care unit with deep sedation, if patient’s CAA is expanding more than 10mm within 2 weeks in acute stage of Kawasaki disease. Furthermore, we also recommend use of antihypertensive drugs such as calcium channel blocker and/or beta-blockers. We also have advised to colleagues in other hospitals to try in the same way when they asked for the management of similar cases. At least three patients with huge aneurysm were survived with this method in recent reports. If patient has strong inflammation sustaining with expanding huge aneurysm, plasma exchange and all possible anti-inflammatory agents including steroid or infliximab under the percutaneous cardiopulmonary support and surgeons' stand-by until inflammation will disappear. Following repair or platy of coronary aneurysm and coronary artery bypass surgery may be considered, but possibility and results are unknown. Conclusions: Because of its rarity, it is difficult to detect exact indication of deep sedation or intensive care, however, earlier and more cautious management will be safer for ‘super-giant’ aneurysm. Concerning to the sustaining inflammation with huge aneurysm, we would like to hear advices for this strategy from cardiac surgeons and pediatric intensivists.
Abstract 193: Hemophagocytic lymphohistiocytosis following kawasaki disease:Differential Diagnosis in IVIG Refractory Kawasaki Disease
Authors: Jun Hyun Ok , Cho Eun Kyung , Yu Jeong Jin , Kang So Yeon , Seo Chang Deok , Baek Jae Suk , Kim Young-Hwue , Ko Jae-Kon , Im Ho-Joon
Published: July 2021

Introduction:
Hemophagocytic lymphohistiocytosis(HLH) is a systemic inflammatory disorder characterized by uncontrolled histiocytic proliferation, hemophagocytosis and up-regulation of inflammatory cytokines. Thus, both HLH and Kawasaki disease(KD) are characterized by prolonged fever, and are diagnosed by a clinical and laboratory scoring system, concurrent manifestation of HLH and KD has been described in the literature. We describe two cases of children who diagnosed as KD initially, but after intravenous gamma globulin(IVIG) failed to produce clinical response, were found to have HLH.

Case report:
A 3-year-old boy who had previous KD history 5 months ago was admitted for 9day fever and skin rash. His symptoms were fulfilled KD criteria, and echocardiography showed dilated right coronary artery of 4.2mm. He was treated with 2 cycles of IVIG until fever subsided. However, 2 days later, he got fever again and cytopenia(Hb<9.0), hypertriglyceridemia, high level of ferritin was shown and had splenomegaly on physical examination. In the suspicion of HLH, bone marrow biopsy was done and revealed hemophagocytosis, consistent with HLH. A second case of 11-month-old boy admitted for 8-day fever with Kawasaki feature. Although, he showed incomplete feature(fever, skin rash, conjunctival injection, cervical lymphadenopathy), echocardiography showed dilated left main coronary artery(3.5mm) and treated with IVIG. However, 2days after IVIG administration, he was still pyrexial. The laboratory findings fulfilled 5 diagnostic criteria of HLH; bicytopenia(anemia, thrombocytopenia), hypofibrinogenemia, hyperferritinemia, hemophagocytosis in bone marrow, raised level of soluble IL-2 receptor. In both cases, the patients treated according to the HLH protocol 2004, and after that clinical symptoms and laboratory findings were improved. Several causes of febrile illness, EBV, CMV, rubella, parvo-viral infection, for example, were excluded.

Comment:
There is considerable overlap between the clinical syndromes of KD and HLH and early recognition and treatment of these two disease entity is imperative to avoid fatal outcomes in severe cases. Thus, these should both be considered and excluded in any child with unremitting fever and rash.