bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 209: Kawasaki Disease In Infants. Experience in a Third Level Facility in Mexico City
Authors: RAMIREZ-PEREA ANA I , GARRIDO-GARCIA LUIS M
Published: March 2022

Background:
Kawasaki disease (KD) is an acute febrile vasculitis of unknown origin. KD represents the most common cause of acquired heart disease in children in developed countries. Worldwide KD is uncommon in infants (younger than 3 months of age), and in Mexico there are few reports of KD in this group of age.

Objective:
To describe the clinical features, laboratory parameters, the incidence of coronary aneurysms, treatment employed and the outcome of infants with KD in a third level facility in Mexico City

Methods:
A retrospective and descriptive study was performed on children younger than 3 months of age with KD from August 1995 to August 2014. We analyzed gender, age, clinical manifestations, hemoglobin levels, leucocyte count, platelet count, ESR, CRP, albumin, sodium, potassium, AST, ASL, time from the onset of the symptoms to diagnosis, treatment used, the development of CAA and outcome in the acute phase of the disease.

Results:
Eight infants were diagnosed with KD during the study period. The median age at diagnosis was 2.5 months (range 2-3 months). Five patients were male (62.5%). The median from the onset of the clinical manifestations to diagnosis of KD was 14 days (range 4 to 26 days). All patients received medical consultations (range 1 to 7) prior to diagnosis. An incomplete form of KD was present in 4 patients. Five patients (62.5%) received IVIG. Four patients (40%) received steroids and low dose aspirin. Five of our patients developed coronary aneurysms, all of them were categorized as giant aneurysms (Z-Score > 10); one of these patients died of cardiogenic shock in the acute phase of the disease.

Conclusions:
In Latin American countries are few reports of KD in infants. We present our experience in infants with KD. Near two thirds of our patients developed coronary aneurisms; most of the patients with coronary aneurisms were associated with late diagnosis and therefore late onset treatment.
Abstract 223: Surgical Resolution of Coronary Artery Obstruction in Incomplete Kawasaki Disease
Authors: Rodriguez Andres N , Maldonado Maria Del Rocio , Faugier Enrique , Tomala Javier E , Flores Angel D , Salinas Diego , Garcia Fernando , Lara Paola B
Published: March 2022

Case Report 8 months old male, who presented with 7 days fever, hematuria, conjunctival injection and limb edema; treated as a post infectious glomerulonephritis. Twenty days later, desquamation at the tip of the fingers and in palms and soles plus thrombocytosis were found. Considering Kawasaki disease (KD), an echocardiogram was performed, finding a 5mm aneurysm in right coronary artery and 4mm ectasia in the left coronary artery. The patient was on the subacute therefore IVIG was not administered; aspirin however in antiplatelet dose range was begun. He continued on surveillance by Cardiology Department without signs of cardiac malfunction. At two years follow up a new echocardiogram was performed, showing a left coronary aneurism of 6mm and a right coronary artery of 2.0mm which was difficult to identify. Left ventricular function was preserved with an ejection fraction of 72%. Four years later, posterior myocardial necrosis, without acute ischemia on electrocardiography was found. A perfusion myocardial scan showed an uptake defect in apical region, both during stress and rest phase, suggesting an old apical infarction. Cardiac catheterization reported a tortuous right coronary artery with diffuse obstruction and left coronary artery aneurysm of 6.1mm. Due to findings above, heart transplant was considered. On a second perfusion scan a large perfusion defect on the inferior and septal wall, which improved during the rest phase was seen. The finding above correlates with inferior and septal myocardial infarction and residual ischemia. The PET-CT scan showed viable tissue in the left ventricle wall. Recently, the patient underwent revascularization surgery of right coronary artery with coronary artery bypass graft. Postsurgical echocardiogram reported a left coronary giant aneurysm of 8mm, ejection fraction of 40%, and a compromised posterior and inferior left ventricular wall function. We report the first case of surgical resolution of a coronary artery obstruction due to KD in our medical center. Because of patient’s age and coronary arteries abnormalities, a surgically intervention was the best approach in order to preserve patient’s life, cardiac function, improve the prognosis and mainly to gain time for future treatment decisions.
Abstract 31: Acute Febrile Acrodynia (1781-1966): Historical Cases Of Kawasaki Disease Before Kawasaki?
Authors: Yeter Deniz , Kuo Ho-Chang
Published: March 2022

Infantile acrodynia is a mercurial reaction that can mimic the complete clinical picture of Kawasaki disease (KD), and is therefore considered a differential diagnosis for KD. Before the 1950s, acrodynia affected 1 in 500 children in industrialized nations. The recently formed pediatric community was fascinated by this new disease since the late 1800s, resulting from the child’s extreme irritability along with striking mucocutaneous changes such as the bright red, swollen hands and feet. Parents would initially report their child suffered from a sudden fever caused by an undetermined infection. Children were not typically seen in hospital until their case became protracted and the insidious symptoms of advanced acrodynia were apparent weeks later. In the 1950s, it was discovered that mercurial remedies such as teething powders were a cause of acrodynia, leading to their removal from the market. Physicians in the British Isles first reported acrodynia in the medical literature after the use of mercurials were extended from adult syphilitic patients to the generalized patient population in the late 1700s. Previously, these acute febrile mercurial reactions were mistaken as a form of secondary syphilis. During the early to mid-1900s, it was noted that syphilitic patients undergoing mercurial or arsenical treatment were more likely to develop arterial thromboses, particularly of the coronary arteries, leading to diagnoses of a unique polyarteritis nodosa. Sudden death in infantile acrodynia often results from secondary infections, arterial thromboses, and cardiac failure. Shortly after acrodynia became a rare pediatric ailment, KD was first observed by Kawasaki in 1961 and reported in 1967. This coincides with unprecedented increases of mercury pollution and seafood contamination in East Asia, resulting in Minamata disease outbreaks during the 1950s and 1960s in Japan. Outbreaks of Minamata disease have been observed among indigenous populations in Canada since the 1970s, while Canada has the highest rates of KD outside of East Asia or Hawaii. Temporal associations are seen with increases and reductions of thimerosal from routine pediatric vaccines and KD outbreaks in the US and Japan. KD may in part represent a modern re-emergence of infantile acrodynia.
Abstract 46: Effect Of Infliximab And Plasma Exchange Therapy On Activated Monocytes/macrophages In Kawasaki Disease Intractable To IVIG.
Authors: Koizumi Keiichi , Katsumata Nobuyuki , Toda Takako , Kise Hiroaki , Hasebe Yohei , Sugita Kanji , Hosiai Minako
Published: March 2022

Background:
Kawasaki disease (KD) is a generalized vasculitis of unknown etiology that occurs predominantly in infant and children. KD has been reported as one of the cytokine-induced disease. The monocyte / macrophage is thought to the subject of proinflammatory cytokines sources. It has been reported that IVIG therapy in KD normalizes the increased numbers of activated CD14 + CD16 + monocyte / macrophage. We examined the effect of the infliximab (IFX) and plasma exchange (PE) therapy on the peripheral blood cells, especially the monocyte / macrophage in KD intractable to intravenous immunoglobulin (IVIG).

Patients:
We studied 9 patients with KD intractable to IVIG (2g/kg/dose), seven with IFX therapy (5mg/kg/dose), four with PE therapy (including two patients of refractory to IFX therapy), who were seen at our hospital. The median age and body weight were 3.3 years (range, 0.5 to 5.5 years) and 13.0kg (range, 6.1 to 20.3kg), respectively. White blood cell count and differentiation were compared before with after the treatment.

Results:
IFX group: White blood cell count was significantly decreased to 11640 ± 3509 from 14141 ± 4673/μl. The neutrophil count was decreased and the lymphocyte count was increased. Both the counts were normalized. CD14 + monocyte / macrophage count (normal value: 339 ± 91/μl) was significantly decreased to 488 ± 195 from 999 ± 528/μl. Especially, the activated CD14 + CD16 + monocyte / macrophage count (normal value: 35 ± 18/μl) was significantly decreased to 69 ± 45 from 176 ± 164/μl.

PE group: White blood cell count was decreased to 10683 ± 4665 from 16810 ± 2527/μl. Neutrophil count was decreased, but the lymphocyte count was no changed. CD14 + monocytes / macrophage count was decreased to 401 ± 278 from 1402 ± 1286/μl. The activated CD14 + CD16 + monocyte / macrophage count was decreased to 24 ± 9 from 243 ± 364/μl.

Conclusion:
In KD intractable to IVIG, the CD14 + CD16 + monocyte / macrophage count of prior to the treatment was increased. Both IFX and PE therapy has the effects of decreasing the CD14 + CD16 + monocyte / macrophage count which involved in the pathogenesis of KD.
Abstract 51: Kawasaki disease in a patient with Acute Myeloid Leukemia and Candida infection
Authors: Yamazaki-Nakashimada Marco , Rivas-Larrauri Francisco , Sorcia-Ramirez Giovanni , Zapata Marta , Garrido-García Martín
Published: March 2022

Though the causative agent of Kawasaki disese (KD) remains unclear, an infectious agent is thought to trigger the disease. KD has been described associated with immunodeficiency disorders including HIV. We report a patient with Acute Myeloid Leukemia (AML) who developed KD in an early course of the disease.

A 4 year-old boy was diagnosed as AML and received treatment with daunorubicin, etoposide and Ara-C. Eleven days later he started presenting fever, diarrhea and abdominal pain. A diagnosis of neutropenic colitis was made and treatment with vancomycin and cefepime was started. He continued having fever and polymorphic eruption was added, with prominent perineal erythema. Later he presented redness of the lips, hands and feet edema, erythema in the palms and soles and conjuctival erythema. The diagnosis of KD was established and treatment with IVIG and low-dose prednisone was administered. Echocardiogram revealed left coronary aneurysm and pericardial effusion. Abdominal-ultrasound showed gallbladder hydrops. Candida grew in blood culture and treatment with amphotericin-B was started.

Akita et al. reported one previous case of leukemia associated with KD. As the previous reported case, our case developed the disease in the induction therapy for the AML. Interestingly, infection with Candida was documented in our patient. Administration of Candida cell Wall-antigens induced KD-like coronary vasculitis in mice. C. abicans colonizes the intestinal tract and causes invasive deep micosis in an immune-compromised host. Beta-glucan from the fungus stimulates the host immune system inducing an inflammatory response. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, provide support for the feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD. To our knowledge this is the second case of KD associated with leukemia. Chemotherapy-induced immunosuppresion could have a role in the genesis of KD in our patient and possibly triggered by a Candida infection.
Abstract 53: Tenascin-C Expression in Cardiovascular Lesion of Kawasaki disease.
Authors: Yokouchi Yuki , Oharaseki Toshiaki , Enomoto Yasunori , Naoe Shiro , Imanaka-Yoshida Kyoko , Takahashi Kei
Published: March 2022

Background:
Tenascin-C (TN-C) is an extracellular matrix that is closely associated with tissue remodeling and inflammation. It is expressed under pathological condition such as myocarditis, myocardial infarction, atherosclerosis and aneurysm. However, examination of TN-C expression in Kawasaki disease (KD) has not been yet performed.

Materials and methods:
The tissue samples of myocardium and coronary arteries were obtained from 25 autopsy cases of KD(age: 3 months to 20 years old, sex: 18 males and 7 females, duration of the illness: 6 days to 17 years). Histological findings of the myocardium and coronary artery were analyzed and correlated with TN-C expression by immunohistochemistry.

Results:
1) Myocardium: Myocarditis was observed in 8 KD patients who died within 33 days after the onset. On the other hand, chronic persistent myocarditis and post-inflammatory myocardial fibrosis were not seen in the patients who died after 33th day of the disease. Myocardial infarction was observed in 9 patients who died in the convalescent and remote phases of KD. Expression of TN-C in the myocardium corresponded to the area with inflammatory cell infiltration and granulation tissue. The degree of expression correlated with the severity of the inflammation.

2) Coronary artery: Intense TN-C expression was observed at the site of active inflammation of coronary arteries in acute stage. Regarding convalescent period (27 to 57 days after the onset) when the inflammation began to disappear, the TN-C expression still remained in the intima and media but weakened in the adventitia and surrounding connective tissue. In remote phase, TN-C expression was limited to the neovascular vessels in the thickened intima and recanalized vessels.

Conclusion:
The results of this histological study demonstrate that TN-C may be a useful biomarker for indicating in KD cardiovascular lesions.
Abstract 6: Coronary Artery Involvement In Children With Kawasaki Disease In A Northern Region Of Italy In 13 Years
Authors: Fabi Marianna , Pierantoni Luca , Mazzoni Elisa , Landini Chiara , Lami Francesca , Di Fazzio Giorgia , Casadei Maria Chiara , Bigucci Barbara , Testa Gabriella , Palladini Alessia , Cicero Cristina , Sogno Vallin Paola , Corinaldesi Elena
Published: March 2022

Objective:
to evaluate the incidence of coronary anomalies (CAA) and risk factors for coronary involvement in children with KD from 2000 through 2013 in Emilia-Romagna.

Design:
an 11-centers retrospective study was conducted using data from 132 patients diagnosed with KD.

Results:
during the acute phase, CAA developed in 13/132 pts (9.8%): 2 pts had isolated ectasia of right coronary artery (RCA), 10 pts had ectasia of left anterior descending CA (LAD), 1 pt had aneurysm of LAD, 1 pt had ectasia of circonflex CA (CX). During the subacute phase 14/117 pts (11.9%) presented CAA: 3 had aneurysm of LAD, 1 had aneurysm of LAD and RCA, 1 had isolated ectasia of RCA, 9 had ectasia of LAD. During the convalescent phase CAA were detected in 18/83 pts (21%): 3 had aneurysm of LAD and RCA, 2 isolated aneurysm of LAD, 1 had aneurysm of RCA, 12 ectasia of LAD. 3 out of 6 aneurysms detected in theconvalescent phase developed in the subacute stage. Univariate analyses identified WBC and RBC in the subacute phase, and PLT in chronic phase as predictors of chronic CAA (respectively p 0.04, 0.013 and 0.002). A multivariate logistic regression analysis revealed that only PLT of the chronic stage was predictor for chronic CAA. ROC curve for PLT identified a value superior to 652000/mm3 to be the cut off value for CAA, with an 72% sensitvity and 87% specificity. Incomplete or atipical clinical presentation was correlated with CAA (p 0.02). Younger age (< 1 yr) at diagnosis, seasonal distribution, IVIG responsivness, race, elevation of ALT, percentage of neutrophil, hemoglobin, CRP and ESR, albumin and sodium were not correlated with risk for CAL.

Conclusions:
atipical/incomplete clinical presentation, higher WBC and RBC in the subacute phase and PLT of the convalescent phase were predictors of CAA in our region, while blood exams of the acute stage, IVIG responsivness, sex and younger age were not.
Abstract 98: Tenascin-C as a Novel Biomarker for Predicting Therapeutic Effect in Kawasaki Disease
Authors: Okuma Yoshiaki , Imanaka-Yoshida Kyoko , Hiroe Michiaki , Matsushita Takeji , Abe Jun , Ichida Fukiko , Saji Tsutomu , Takahashi Kei , Shiraishi Isao , Suda Kenji , Takeda Atsuhito , Mitani Yoshihide , Yoshikane Yukako
Published: March 2022

Background:
In acute stage of Kawasaki disease (KD), patients who are unresponsive to initial therapy are immediately administered additional therapy to prevent the development of coronary artery abnormalities (CAAs). Although failure to respond is defined as persistent or recrudescent fever after treatment, it is difficult to recognize the presence of fever because steroids are administered with intravenous immunoglobulin (IVIG) in severe KD patients in Japan. In addition, inflammatory markers such as CRP usually decrease after initial therapy in patients who are unresponsive to initial therapy and there is no biomarker for monitoring treatment effect. Tenascin-C (TN-C) is an extracellular matrix protein specifically upregulated in response to tissue injury and inflammation.

Methods:
We recruited 174 patients (male 102, female 72) from August 2011 to April 2014, from fourteen institutions in Japan. Serum levels of TN-C (sTN-C) were examined using ELISA before and after initial treatment. The initial treatments consisted of: 30 aspirin only, 111 IVIG + aspirin, and 33 IVIG + aspirin + prednisolone. We compared patients who responded to initial therapy (R group; n = 134) with those who did not respond (NR group; n = 40) regarding patient profile and laboratory data.

Results:
Patients in NR group had higher % neutrophil (p = 0.004), CRP (p = 0.012) and sTN-C (p = 0.049) than in R group before treatment. After initial therapy, WBC, % neutrophil and CRP significantly decreased in both groups (p < 0.001), but sTN-C did not significantly decrease in NR group (p = 0.485). When sTN-C after initial therapy was used to predict unresponsiveness of initial therapy, sensitivity, specificity and AUC were 85%, 55%, and 0.745 respectively. Especially in patients who were administered steroids with IVIG as initial therapy, the accuracy of predictive model using sTN-C after initial therapy was high (AUC 0.812, sensitivity 71%, specificity 81%). The incidence of CAAs tends to be higher in NR group than in R group (12.5 vs. 3.7 %, p = 0.051).

Conclusions:
TN-C is a potential biomarker in predicting the need for additional therapy. Especially in KD patients who are treated by steroids with IVIG, TN-C may be useful.
Abstract O.01: Epidemiology of Kawasaki disease in South Korea, 2009-2011
Authors: Kim Gi Beom , Han Ji Whan , Park Yong Won , Song Min Seob , Hong Young Mi , Cha Sung Ho , Kim Dong Soo
Published: March 2022

We assessed the recent epidemiologic features of Kawasaki disease in South Korea from the nationwide survey conducted between 2009 and 2011. We collected data regarding the incidence, symptoms, treatment, and coronary complications associated with acute Kawasaki disease by sending questionnaires to the 100 hospitals that have pediatric residency programs. We received complete responses from 73 hospitals and partial responses from 14 hospitals. A total of 13,031 cases of Kawasaki disease were reported from the 87 hospitals (3,941 in 2009, 4,635 in 2010, and 4,455 in 2011). The male to female ratio was 1.44:1, and the median age at diagnosis was 28 months. From the questionnaires with complete responses, we noted that the incidence of Kawasaki disease per 100,000 children less than 5 years of age was 115.4 in 2009, 132.9 in 2010, and 134.4 in 2011 (average rate, 127.7). Kawasaki disease occurred more frequently during summer (June, July, and August) and during winter (December and January). The recurrence rate was 3.83% (387 of 10,100). The mean total duration of fever was 5.6 ± 2.4 days. The most common symptom was conjunctival injection (88.2%). The standard dose of intravenous immunoglobulin was administered to 93.6% (9,453 of 10,097), and non-responder rate was 11.6%. Coronary aneurysm occurred in 1.9% (180 of 9,028) though giant aneurysm developed in 0.26% (26 of 9,882) of patients over 3 years. Two patients had myocardial infarction. No mortality was reported during this period. In conclusion, the average annual incidence of Kawasaki disease in South Korea has continuously increased to 134.4 per 100,000 children less than 5 years of age in 2011, which is the second highest incidence of Kawasaki disease worldwide, following its incidence in Japan.
Abstract O.04: Kawasaki Disease With Down Syndrome:low Risk For Ivig Resistance And Coronary Artery Abnormalities
Authors: Takatsuki Shinichi , Yokozawa Masato , Ono Masae , Fujiwara Masako , Ida Horoyuki , Motomura Hideki , Moriuchi Horoyuki , Taketazu Mio , Oki Junichi , Nonoyama Shigeaki , Kawano Tatsuya , Ihara Kenji , Kido Sachiko , Shiono Junko , Tsuchiya Shiro , Tsuchiya Keiji , Goushi Teruhumi , Ogata Shuhei , Ishii Masahiro , Ichida Fukiko , Saji Tsutomu
Published: March 2022

Background:
Japanese nationwide survey reported that Down syndrome (DS) is less-frequently occurring comorbidity in Kawasaki disease (KD). Thus, no studies have focused treatment response and risk for coronary artery abnormalities (CAAs) in KD with DS. The aim of this study was to evaluate clinical manifestations, treatment response and incidence of CAAs in KD with DS.

Methods:
We retrospectively reviewed the medical records of KD with DS from 2005 through 2012. Data were collected according to survey questionnaires from 16 hospitals.

Results:
The response rate was 80% and the survey questionnaires from 16 KD patients (11 boys and 5 girls) with DS were collected. Age at diagnosis was 3 years (8 months to 12 years). Eight children (50%) were diagnosed incomplete KD. Five children had previous history of repaired congenital heart disease (AVSD 2, VSD+ASD 1, ASD 2, PDA 1). Of all, 8 children were classified as high risk group based on Kobayashi score. Twelve children received IVIG and 3 children were treated with only high dose aspirin. All 15 children were responded to initial treatment. In the remaining one girl with incomplete KD, the clinical symptoms spontaneously resolved. CAAs were not detected by echocardiography during follow-up.

Conclusions:
All DS children with KD were responded to initial IVIG or aspirin therapy despite the high risk of IVIG resistance and none of children had CAAs. Therefore, our finding suggested DS is not a risk factor for IVIG resistance and developing CAAs in KD.
Abstract O.42: Efficacy And Safety Of Treatment With Immunoglobulin Plus Steroid For Kawasaki Disease: A Prospective Observational Study
Authors: Miyata Koichi , Fukushima Naoya , Morikawa Yoshihiko , Okuma Yoshiaki , Misawa Masahiro , Hara Mitsuhiko , Yamagishi Hiroyuki , Miura Masaru
Published: March 2022

Background:
Non-responders to primary intravenous immunoglobulin (IVIG) therapy with aspirin are at risk of coronary artery lesions in Kawasaki disease (KD). A randomized controlled trial (the RAISE study) indicated that prednisolone + primary IVIG improves responsiveness to treatment and coronary artery outcomes in non-responders to IVIG predicted on the basis of Kobayashi score. The present study aimed to verify the efficacy and safety of prednisolone + primary IVIG in predicted non-responders to IVIG.

Methods:
We conducted a multicenter, prospective cohort study at 30 hospitals in Japan from July 2012. All KD patients received primary IVIG therapy (2 g/kg/24 h) and, if febrile at diagnosis, oral aspirin (30 mg/kg/day) and were stratified by Kobayashi score into non-responders (score [[Unable to Display Character: ]]5) and responders (score ≤4). The required sample size to reach statistical significance was 1,500 for KD patients and 500 for non-responders.

Results:
We enrolled 868 patients with KD by the end of 2013, including 545 (63%) predicted responders and 323 (37%) predicted non-responders. Within the non-responder group, 256 patients received IVIG + prednisolone and 67 patients IVIG alone. The non-response rate to IVIG was significantly lower (17% vs. 55%, p<0.001) and the incidence of coronary artery lesions (Japanese criteria; 5% vs. 11%, p=0.06) non-significantly lower in the IVIG + prednisolone group than the IVIG alone group. These results are similar to those of the RAISE study (non-response rate of 13% and coronary artery lesion rate in non-responders of 3%). There were 10 severe adverse events (i.e., aseptic meningitis 2, liver dysfunction 2, anaphylaxis 1, hypertension 1, ventricular tachycardia 1, bacteremia 1, drug eruption 1, and gait disorder 1) and no significant between-group difference in event rate.

Conclusion:
Like the RAISE study, our study suggests that prednisolone added to IVIG therapy with oral aspirin reduces the non-response rate and incidence of coronary artery lesions in predicted non-responders to IVIG with KD.
Abstract O.45: Kawasaki Disease Refractory To Primary IVIG Treatment - Use Of Scoring Systems And Predictive Modelling Based On Data From Singapore Children
Authors: Quek Swee Chye , Leow Yao Guang , Rajgor Dimple D , Lim Terence , Heng Chew Kiat , Grignani Robert
Published: March 2022

Objectives:
Although first-line treatment for Kawasaki Disease (KD) is IVIG, some children may not respond, requiring repeat IVIG or another second-line therapy. It is important to predict non-responders for timely management decisions in this group of patients. The objective of our study was to assess the predictive value of the currently available scoring systems and propose an improved model for predicting refractory KD, based on data from KD patients in Singapore.

Method:
We performed a retrospective review of the medical records (2001-2014) of 180 children with KD and identified 17 refractory cases. The 4 scoring systems; Egami, Kobayashi, Sano and Fukunishi; were applied to the data of refractory KD cohort to determine their predictive value based on sensitivities (SN) and specificities (SP). A logistic regression model was built using 5 predictors (age, AST, CRP, Hb, platelet and duration of illness) which were common among the existing models to propose a new scoring system based on our data -. The formula used was 1/(1+e^(-(-5.642839-0.192452*(zHb)-0.011597*(Age)+0.003756*(PLT)+0.009441*(CRP)+0.006015*(AST)+0.084408*(Days).

Results:
The SN and SP obtained were; (1) Egami: SN 35.3%, SP 73.9% (original SN 78% and SP 76%) (2) Kobayashi: SN 23.5%, SP 67.5% (original SN 86% and SP 68%) (3) Sano: SN 18.8% and SP 88.2% (original SN 77% and SP 86%) (4) Fukunishi: SN 53.3% and SP 76.0% (original 84.6% and 87.0%). As the existing scoring systems proved less predictive in our population, we used logistic regression model to derive a formula incorporating the common variables to predict the likelihood of non-responders. This model attained an SN of 80% and SP of 80%.

Conclusion:
The proposed model should be validated prospectively in our local population for predicting unresponsiveness, and the formula can be applied to different datasets from other KD populations to test its robustness.
Abstract O.51: Effects of Anti-TNF-alpha Antibody Therapy on IVIG-resistant Patients with Kawasaki Disease
Authors: Masuda Hiroshi , Abe Jun , Oana Shinji , Ishiguro Akira , Tsuchida Nao , Sakai Hirokazu , Ito Shuichi , Ono Hiroshi , Kato Hitoshi
Published: March 2022

Background:
Kawasaki disease (KD) patients who do not respond to initial intravenous immunoglobulin (IVIG) therapy have a higher risk of developing coronary artery lesions (CALs). Infliximab (IFX) has been reported to be effective in alleviating fever in these patients and has been increasingly used. However, little is known about how IFX suppresses inflammation in KD. We analyzed immunological parameters in KD patients who responded to IFX, as well as those who did not, after the initial IVIG therapy.

Methods:
Twenty-six KD patients hospitalized and treated with IFX after initial IVIG and aspirin between August 2009 and July 2014 were enrolled in this study. We analyzed electronic medical records of baseline characteristics and laboratory data (WBC, neutrophil, lymphocyte and platelet counts, levels of GOT, GPT, Alb, Na, CRP and D-dimer), and measured plasma levels of cytokines (G-CSF, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-γ, sIL-2R, sTNFR1 and sTNFR2) before and after IFX. We defined responders as patients who became afebrile within two days after IFX treatment.

Results:
The median age of 17 responders (11 males and 6 females) and 9 non-responders (5 males and 4 females) was 31 mo (9-84 mo) and 39 mo (16-64 mo), respectively (p=0.65). The initiation of IFX treatment after the onset of fever was compatible in both the group (day 9 vs day 9 in medians) (p=0.85). The incidence of CALs one month after onset was 0% (0/17) and 22% (2/9), respectively (p=0.11). Observed only in responders, WBC and neutrophil counts, and the levels of CRP, D-dimer, G-CSF, IL-6, sIL-2Rα, TNF-α, sTNFR-1 and sTNFR-2 decreased remarkably after IFX (p<0.01). In non-responders, serum level of Na was significantly lower (p=0.04) before IFX, while WBC (p=0.04) and neutrophil (p=0.01) counts, and the levels of CRP (p=0.02), IL-6 (p=0.01), IL-10 (p=0.03) were higher. After IFX, the level of Alb (p=0.02) was lower.

Conclusions:
After IFX, the level of TNF-α, together with many pro- and anti-inflammatory mediators, decreased in responders but not in non-responders. In particular, suppression of IL-6 and IL-10 was insufficient in non-responders, suggesting that inflammation mechanisms other than the TNF-α axis would be important in KD patients who are unresponsive to IFX.
Abstract O.70: Safey and Efficacy of Warfarin Therapy in Kawasaki Disease
Authors: Baker Annette L , Murray Jenna , Newburger Jane W
Published: March 2022

Purpose:
Giant aneurysms are managed with combined anticoagulation and anti-platelet therapy, heightening risk of bleeding complications. We sought to describe the safety and efficacy of warfarin for Kawasaki disease (KD) patients (pts) with giant coronary artery aneurysms (CAA, ≥8 mm).

Methods:
We reviewed the % time in therapeutic range (%TTR); % of INR’s in range; bleeding events, categorized as major bleeding, clinically-relevant non-major bleeding, and minor bleeding; clotting events; INRs ≥5; and INRs <1.5.

Results:
Our anticoagulation service managed 9 KD pts (5 male), median age 13.2 y (range 7-22 y). INR testing was prescribed weekly to monthly and was done by home monitor (n=6) or lab (n=3). Median length of warfarin therapy was 6.5 y (1.6-12.5). Goal INR was 2.0-3.0 (n=6) or 2.5-3.5 (n=3), based on CAA size and history of CAA thrombosis. All pts were treated with aspirin; 1 was on triple therapy with warfarin, aspirin, and clopidogrel. From 6/2011-6/2014, the median %INRs in range was 62% (34-93%), and median %TTR was 68%(53-92%). INRs >6 occurred in 2 pts (2 events); INRs
5
<6 in 5 pts (9 events); and INRs <1.5 in 5 pts (21 events)
.
During warfarin therapy, 3
major bleeding
events occurred in 3 pts: 1 hemorrhage in calf muscle with compartment syndrome requiring surgical clot evacuation (INR 2.5); 1 hemorrhagic ovarian cyst needing hospitalization and Vit K (INR 5.2); and 1 hemopericardium (INR 2.8) 9 days post CABG requiring readmission to the hospital, pericardiocentesis and blood transfusion. There were 2
clinically-relevant non-major bleeding events
in 2 pts: 1 hospitalized for bleeding 1 wk after wisdom teeth extraction (INR 6.1) and 1 requiring cauterization for nose bleeds.
Minor bleeding
events
included: a) severe recurrent nosebleeds in 3 pts, causing 4 ER visits (2 pts) and Hgb fall to 7 mg/dL (1 pt, Fe treatment); and b) heavy menses in the 2 post-pubertal females, both treated with oral contraceptives. Four of 9 pts had no bleeding events, and no pt had new CAA thrombosis.

Conclusions:
Bleeding complications are common in pts on warfarin and aspirin. Despite management by a hospital anticoagulation service, INRs were in range only 2/3 of the time. Studies on oral Factor Xa inhibitors as an alternative to warfarin are needed in this at-risk population.
Abstract 15933: Scn5a Gating Pore Current Causes Cardiac Arrhythmias Associated With Dilated Cardiomyopathy
Authors: Moreau Adrien , Mercier Aurélie , Gosselin-Badaroudine Pascal , Burger Bettina , Keller Dagmar I , Chahine Mohamed
Published: March 2022

Dilated cardiomyopathy (DCM) is a structural heart disease that causes dilatation of cardiac chambers, impairs cardiac contractility and systolic function leading to heart failure. SCN5A gene encodes the cardiac sodium channel (Nav1.5) in which mutations have been identified in patients with arrhythmic disorders associated with DCM. However, it is not understood how a dysfunction in SCN5A may cause very atypical cardiac arrhythmias associated with dilatation remodeling of the heart.

We generated control and patient specific human induced pluripotent cells (hiPS) carrying the Nav1.5/R219H mutation. hiPS were differentiated to obtain cardiomyocytes derived from hiPS (hiPS-CM). Molecular dynamic simulations experiments revealed that the R219H mutation opens up a pathway directly through the voltage sensitive domain (VSD) of Nav1.5 channels. We hypothesized that such a proton leak through the VSD caused by the R219H mutation may be responsible for the clinical phenotypes observed in our index patient. We unraveled the underlying mechanism responsible for the association of SCN5A and DCM. Indeed, the data shows the presence of a gating pore or omega current that is responsible of the observed abnormal ionic homeostasis, absent in control hiPS-CM. Action potential recordings showed abnormal electrical activities in both atrial and ventricular hiPS-CM. Myocytes stemmed from the index patient exhibited dilatation. Single cardiomyocytes contractility probed using atomic force microscopy revealed a higher frequency of contractility with reduced force compared to control myocytes. This could be attributed to the observed contractile protein dysfunction uncovered using immunofluorescence.

Overall, the results support the hypothesis that the Nav1.5/R219H mutation creates a proton leak. This leak then causes electrical, structural and contractile disturbances that may explain the related cardiac arrhythmias associated with myocytes dilatation.

We concluded that gating pore current, a novel cardiac channelopathy is directly related to the association of SCN5A and DCM. We suggest that this aberrant leak current should be investigated to characterize similar SCN5A mutations with similar clinical phenotypes.
Abstract 15947: Machine Learning to Predict Rapid Progression of Carotid Atherosclerosis in Patients With Impaired Glucose Tolerance in the ACT NOW Study
Authors: Hu Xia , Abbasi Ali , Saremi Aramesh , Liu Huan , Reaven Peter , Migrino Raymond Q ,   ACT NOW Investigators
Published: March 2022

Impaired glucose tolerance (IGT) is associated with increased cardiovascular disease. Identifying IGT patients with rapid atherosclerosis progression will help in early risk-stratification. Machine learning (ML) involves algorithms that can learn complex relationships from data to make accurate predictions. Unlike traditional low-dimensional statistical approaches, ML can handle high dimensional datasets to make accurate predictions.

Aim:
To test the performance of ML in identifying IGT patients who will develop rapid carotid plaque progression.

Methods:
In the ACT NOW study (IGT patients were randomized to receive either pioglitazone or placebo), 382 subjects had carotid intima-media thickness (IMT) measured at baseline and at 15-18 months. Patients with IMT change in the top 10 percentile (n=39) were classified as rapid progressors (RP) and the rest (n=343) considered non-rapid progressors (NRP). ML using Naïve Bayes model was performed using 115 clinical/laboratory variables to develop a model to fit the true value of the class label (RP, NRP). Experiments were conducted with 10-fold cross validation in training/validation sets. Class prediction was also performed using traditional logistic regression model using 5 variables found different between RP and NRP by univariate analyses. Model performance was assessed using area under receiver operating characteristic curve.

Results:
Mean±SD IMT change was 0.011±0.026 mm overall; 0.058±0.018 for RP and 0.006±0.02 for NRP. Area under the curve (AUC) for ML (0.855) was higher versus traditional logistic regression model (0.73) (Fig.). ML correctly classified 78% of instances with κ statistic of 0.32.

Conclusions:
ML using naïve Bayes method provided good predictive ability in identifying IGT patients who had the most rapid plaque progression. ML may improve clinical prediction over traditional low-dimensional biostatistical approaches.
Abstract 15951: Psychosocial Wellbeing Does Not Affect Muscle Pain and Quality of Life During Atorvastatin Treatment
Authors: Zaleski Amanda L , Taylor Beth A , Pescatello Linda S , Panza Gregory A , Capizzi Jeffrey A , Grimaldi Adam , White Charles M , Thompson Paul D
Published: March 2022

Introduction:
HMG-CoA reductase inhibitors (statins) are generally well-tolerated, although muscle weakness and pain have been reported in ~10% of statin users. However, many self-reported muscle side effects are non-specific. As mental health influences self-perception of pain, we sought to assess the effect of baseline well-being and depression on self-reported muscle pain and quality of life (QOL) after 6 months of atorvastatin (ATORVA) 80 mg/d or placebo in healthy, statin-naïve adults. Hypothesis: We hypothesized that lower levels of well-being and higher levels of depression would result in higher self-reported pain that interferes with QOL after statin therapy.

Methods:
The Psychological General Well-Being Index (Well-Being; n=82) and Beck Depression Inventory (Depression; n=55) were administered at baseline in subjects (aged 59.5+1.2 yrs) from STOMP (Effect of Statins on Skeletal Muscle Performance; Clinical Trials #NCT00609063). Muscle pain (Short-Form McGill Pain Questionnaire [SF-MPG]) and pain that interferes with QOL (Brief Pain Inventory [BPI]), were also measured before and after drug treatment.

Results:
At baseline, there were no group differences in Well-Being, Depression, or pain measures between groups (ps ≥0.05). Baseline Well-Being correlated with baseline BPI pain severity (r=-0.309, p<0.01) and BPI pain interference with QOL (r=-0.271, p<0.05); including both affective and activity subcomponents (ps<0.05). Baseline Depression correlated with baseline pain (r=0.313, p<0.05). Pain severity and interference with QOL scores were not different between statin users and controls after 6 mo of ATORVA (ps≥0.05). Baseline Well-Being and Depression were not significant predictors of pain after 6 mo of ATORVA (ps≥0.05 for overall effects and interactions). Conclusions: Lower levels of psychosocial well-being and higher levels of depression are associated with greater non-specific muscle pain, however, they are not associated with statin-associated muscle side effects or QOL after 6 mo of ATORVA in otherwise healthy adults. Trial Registration: NCT00609063
Abstract 15960: Engineered Vascular Construct via the Ring Stacking Method
Authors: Pinnock Cameron B , Lam Mai T
Published: March 2022

Introduction:
Treatments for arteriosclerosis such as bypass surgery use vessel grafts that can cause infections in patients, with more than 50% of these grafts failing within 10 years. Discovering different methods to create vascular replacements in vitro has become one of the major focuses of tissue engineering.

Material and Methods:
Utilizing a novel approach termed the “Ring Stacking Method” we will create tissue resembling that of a blood vessel. With the aid of a 3D-printed PLA tubular scaffold placed in the center of a 35mm plate, we are able to create two cell ring layers. The ring layers are composed of smooth muscle cells and fibroblasts seeded onto fibrin gel, composed of 40μL of 100U/mL thrombin and 160μL of 20mg/mL fibrinogen, which have rolled towards the PLA scaffold.

Results and Discussion:
To evaluate our proposed technique of the Ring Stacking Method, we began by attempting to fabricate the smooth muscle layer. We used a human aortic smooth muscle cell line for relevance to cardiac bypass surgery application. The contractile properties of smooth muscle cells make them an ideal candidate for our ring formation methods. The SMC rings were subsequently stacked on top of one another using a plastic tube as an internal guide to keep the ring stack initially in place (
Fig. 1A
). The tubular SMC construct contained six ring segments and was about 10 mm in length (
Fig. 1B
). Remarkably, the lumen of the preliminary vascular construct had the ability to hold itself open, displaying structural integrity (
Fig. 1C
, white arrow).

Conclusion:
Creation of engineered vascular replacements could eventually lead to decreased dependence on auto-graft harvesting from other parts of the body. Replacement vessels have potential to integrate into the pre-existing native tissue and promote healing and reestablishment of function of the region. The vascular construct could be applied to other ischemia disease and tissue engineering problems.
Abstract 15978: The Lifestyle Physical Activity for Sedentary Older Women (LPAW) Study: Primary Outcomes From a Randomized Controlled Clinical Trial
Authors: Lefler Leanne L , McSweeney Jean C , Lensing Shelly Y , Garner Kimberly K , Dubbert Patricia K , Packard Kathy A
Published: March 2022

Introduction:
Evidence is clear that a physically active lifestyle reduces the human and economic cost of heart disease in a dose-response relationship; but current efforts to increase long-term physical activity (PA) are inadequate.

Purpose/hypothesis:
To test whether a parsimonious and tailored motivational interviewing (MInt) intervention would increase home-based PA.

Methods:
We conducted a single-blinded randomized controlled study of sedentary women aged 60 years and older to test a MInt counseling intervention for PA. Lifestyle physical activity was promoted by 2 one-on-one counseling sessions and coaching telephone calls tapering in frequency over 6 months. Women wore Triaxial accelerometers for 7 days to collect data at 0-, 3-, and 6-months to include vector magnitude activity counts, time spent in sedentary, light, moderate and vigorous activity, time spent in lifestyle PA bouts, sedentary time and daily energy expenditure.

Results:
123 older women (mean age 69; 64% White; 34% African American) without significant functional or cognitive impairment were randomized to the MInt intervention or PA information/attention control groups. Risk factor profiles designated participants at high-risk for coronary heart disease (70% hypertensive, 48% hyperlipidemic, 25% diabetic, mean BMI 31). At baseline (Time 0) PA was similar; at Time 3 and 6 months the MInt group increased step counts per day (0=3.3K vrs 3.7K; 3=4.2K vrs 3.8K; 6= 4.0K vrs 3.5K) vector magnitude activity counts (0=322K vrs 335K; 3=370K vrs 336K; 6=344K vrs 318K), time in moderate to vigorous activity (0=225 minutes/week vrs 244; 3=288 vrs 247; 6= 261 vrs 225) significantly greater when compared to Control (all with p < .05). PA bouts remained greater and overall sedentary behavior was reduced in the MInt group and maintained over time.

Conclusions:
The LPAW intervention was successful in improving home-based PA over 6 months and should be tested broadly in other populations.
Abstract 15989: Exercise Training Improves Aerobic Capacity and Right Ventricular Function in a Rat Model of Chronic Pulmonary Embolism
Authors: Neto-Neves Evandro M , Brown Mary B , Kline Jeffrey A
Published: March 2022

Introduction:
Right ventricular (RV) dysfunction worsens outcome after pulmonary embolism. This study investigated whether aerobic exercise training may induce salutary RV adaptations to improve RV contractility and exercise capacity in a rat model of chronic PE (CPE).

Methods:
Male Sprague-Dawley rats (350-400g) received a single dose of polystyrene microspheres (221.000/100g, 85 μm, jugular vein) and SU 5416 (20mg/kg, s.c.) to produce CPE with pulmonary hypertension (CPE, n=6), or vehicle (Sham, n=4). A subgroup of Sham and CPE (Sham+EXE and CPE+EXE, n=4-6) underwent 6 weeks of treadmill training at mild relative intensity (50% of VO
2
max), 60 min, 5x/wk. Sedentary counterparts were placed on a stationary treadmill (Sham+SED and CPE+SED, n=4-6). VO
2
max was assessed via analysis of expired gases at three time points: pre-CPE, 3 days and 6 weeks after CPE induction. Echocardiography and in-vivo RV cannulation were performed during the 6
th
week. Hearts were extirpated and perfused via the aorta using Langendorff’s technique.

Results:
CPE+SED had lower (p<0.05) VO
2
max (in ml/kg/hr) at 3 days (2491±250), and 6 weeks (2791±121) post-CPE, vs. Sham+SED (3 days: 3407±151; 6 weeks: 3876±68). Exercise training attenuated CPE-induced decrement in VO
2
max (CPE+EXE, 3087±93 ml/kg/hr, p<0.05 vs. CPE+SED). Echocardiography indicated increased RV wall thickness and RV/LV ratio, and reduced RV fractional shortening, following CPE (CPE+SED vs. SHAM+SED, p<0.05), the last two were improved by exercise training (CPE+EXE vs. CPE+SED, p<0.05). In vivo measures of RV systolic pressure and dP/dtmax increased following CPE (85±10 mmHg and 3317±599 mmHg/s for CPE+SED vs 24±01 mmHg and 1312±68 mmHg/s for SHAM+SED, p<0.05), and were not affected by exercise (p>0.05 vs. CPE+EXE). When adjusted for RV mass, RV contractile function decreased significantly post-CPE, CPE+SED (100±7.7 mm Hg/g) vs SHAM+SED (322±19, p<0.05) and tended to be improved by exercise (CPE+EXE 137±5.5, p>0.05).

Conclusion:
In rats with CPE and severe pulmonary hypertension, mild exercise training improved aerobic capacity coincident with a trend toward improved RV contractility. These data suggest salutary effects of exercise in chronic thromboembolic pulmonary hypertension.