Analysis of Age, Sex, Lack of Response to Intravenous Immunoglobulin, and Development of Coronary Artery Abnormalities in Children With Kawasaki Disease in Japan.

Importance: Initial intravenous immunoglobulin (IVIG)-refractory status and prolonged fever are established risk factors for the development of coronary artery abnormalities (CAAs) among patients with acute-phase Kawasaki disease (KD). However, whether different risk factors exist for initial unresponsiveness to IVIG and CAA development remains unclear. Objective: To evaluate whether different risk factors exist for initial unresponsiveness to IVIG and CAA development among patients with KD (stratified by age at disease onset). Design, Setting, and Participants: This retrospective cohort study included a consecutive sample of 2414 patients from a database of patients with KD from October 1, 1999, to September 30, 2019. The data were based on annual surveys (response rate, 100%) using hospital medical records across Wakayama Prefecture, Japan. Data were analyzed from March 6 to March 26, 2022. Exposures: The patient's age and diagnosis of KD by board-certified pediatricians using the criteria established by the Japan KD Research Committee. Main Outcomes and Measures: Initial unresponsiveness to IVIG, defined as treatment with optional or advanced therapies, and development of CAAs. Echocardiograms performed 1 month after KD onset using the Japanese Ministry of Health criteria evaluated the presence or absence of CAAs. Odds ratios (ORs) with 95% CIs of patient age at KD onset for unresponsiveness to IVIG and developing CAAs were calculated using multivariable logistic regression models. Results: A total of 2414 patients (1403 male patients [58.1%]; median age at onset of KD, 25 months [range, 1-212 months]) were included in the study: 550 younger than 12 months, 1342 aged 12 to 47 months, and 522 older than 47 months. A total of 535 patients (22.2%) received optional or advanced treatment and 68 patients (2.8%) developed CAAs 1 month after disease onset. The sex-adjusted OR among patients younger than 12 months for unresponsiveness to IVIG was 0.77 (95% CI, 0.59-0.99) and for development of CAAs was 1.94 (95% CI, 1.07-3.52); among those older than 47 months, the OR for unresponsiveness to IVIG was 1.32 (95% CI, 1.05-1.67) and for development of CAAs was 2.47 (95% CI, 1.39-4.39). After adjusting for IVIG administration, ORs among boys older than 47 months for unresponsiveness to IVIG was 1.14 (95% CI, 0.84-1.56) and for development of CAAs was 2.15 (95% CI, 1.08-4.30); among girls younger than 12 months, the OR for unresponsiveness to IVIG was 1.02 (95% CI, 0.65-1.60) and for development of CAAs was 3.79 (95% CI, 1.21-11.90). Conclusions and Relevance: The results of this study suggest that risks of unresponsiveness to IVIG and the development of CAAs differ between infants with KD and older patients with KD. Residual risk factors for KD-related CAAs other than initial unresponsiveness to IVIG should be addressed, particularly in infants.

Seasonal Variation in Epidemiology of Kawasaki Disease-Related Coronary Artery Abnormalities in Japan, 1999-2017.

BACKGROUND: Epidemiological studies show a U-shaped tendency in Kawasaki disease (KD)-related coronary artery abnormalities (CAAs) across age categories. Since studies suggest seasonal variations in KD onset, this study aimed to clarify the epidemiologic features of CAAs, considering the seasons of KD-occurrence. METHODS: We analyzed 2,106 (males = 1,215, females = 891) consecutive KD cases from October 1999 through September 2017 using our electronic database of annual surveys, targeting all hospitals with pediatric departments across Wakayama, Japan. The primary outcome was the presence/absence of CAAs measured by echocardiography 1 month after KD onset. Odds ratios (ORs) and 95% confidence intervals (CIs) of combined patient age and sex for CAAs were calculated using logistic regression models adjusted for four seasons. RESULTS: The median age was 25 (range, 1-212) months. The proportion of males decreased with increasing age. The youngest age group (<6 months) showed an inverse summer/autumn to winter/spring ratio (>1.0) in KD-occurrence. CAAs were observed in 2.8% of cases (males = 3.4%, females = 2.1%), which significantly lessened in summer than in other seasons. Moreover, 50% (n = 4/8) of cases with giant aneurysms experienced KD in autumn. Adjusted ORs for CAAs among males aged ≥60 months (3.0; 95%, CI 1.2-7.5) and females aged <6 months (3.6; 95%, CI 1.1-11.8) were significantly higher than those among males aged 12-35 months. CONCLUSIONS: Cumulative 18-year data of consecutive KD cases from one area suggest the influence of interactions between patient age and sex on the development of KD-related CAAs. The season of KD-occurrence may reflect the diversity of agents.

Evaluation of the fatty acid composition of the seeds of Mangifera indica L. and their application.

Mango (Mangifera indica L.), an edible fruit, is one of the main agricultural products in many tropical regions. Mango varieties differ in not only fruit shape but also aroma, which is an important characteristic. Although the fruit has many uses, the seeds are discarded as waste. Therefore, this study aimed to estimate the fatty acid content of seed oil of mangoes from different cultivation areas (Miyazaki, Japan, and Taiwan), and to evaluate their application in cosmetics. Five fatty acids were identified in the mango seed oil. Oleic acid and stearic acid were the principal components of mango seed oil obtained from Miyazaki (46.1% and 39.8%, respectively) and Taiwan (43.7% and 40.1%, respectively). As a cosmetic ingredient, mango seed oil showed good deodorizing effect on both 2-nonenal and isovaleric acid. The results indicated the potential applications of mango seed oil in the cosmetic industry.

[Results of chemotherapy in head and neck cancer patients with residual or recurrent tumors after initial treatment].

A study of S-1 chemotherapy treatment of patients with head and neck cancer was conducted in 26 patients with residual or recurrent tumors after the initial treatment, i. e., chemoradiotherapy, radiotherapy and operation. The treatment courses consisted of oral administration of S-1 at a dose of 80 to 120 mg/day depending on the body surface area, for 14 consecutive days followed by a 7-day rest period. The response rate in all patients was 34.6%(9/26). In patients with recurrent tumors, the response rate was 11.1% (1/9). Patients with residual tumors after the initial treatment had a response rate of 47.0% (8/17). The median survival time was 490 days. Moreover, we studied the maintenance of QOL (quality of life) in 15 cases whose deaths were caused by their tumors. The maintenance duration of QOL was 162 to 1,742 days (median 330 days). The mean QOL maintenance rate, i. e., the average period of extended life with stable disease compared to the period from the eternity time of S -1 treatment until patient death, was 81.1% (36.4-98.7%). S-1 is a safe anticancer drug with fewer side-effects than other chemotherapies. S-1 did not cause any serious adverse events in the patients enrolled in this study. Therefore, S-1 appears to be useful for the treatment of patients with head and neck cancer, and it is particularly useful for improving the QOL of patients.

Synthesis and physiological activity of thiophenes and furans with 3- and 4-methoxyacetophenone derivatives.

The synthesis and physiological activity of thiophenes and furans with methoxyacetophenone derivatives were examined. 3-Methoxyacetophenone (1) and 4-methoxyacetophenone (2) were converted, respectively, to the oximes (3) and (4) by oximation with hydroxylamine hydrochloride, and to the primary amines (5) and (6) by reduction with LiAlH(4). The primary amine derivatives were further converted into the thiophene and furan compounds (5a) approximately (5h) and (6a) approximately (6h), respectively. Bioassay of these compounds (5a) approximately (5h) and (6a) approximately (6h) on the germination of lettuce(Lactuca satiba) seeds showed that compound (5b) exhibits growthpromoting activity.

Synthesis and physiological activity of ureas and amides with carvone residues.

The synthesis and herbicidal activity of ureas and amides with carvone residues were examined. (S)-(+)-(1) and (R)-(-)-Carvone(2) were converted to the respectively, primary amines(3) and (4) by oximation and reduction with LiAlH(4). Primary amine derivatives were further converted into the urea and amide compounds (3a) approximately (3e) and (4a) approximately (4e). The herbicidal activity of products (3a) approximately (3e) and (4a) approximately (4e) towards weeds found in a paddy field and field was measured in the pot. Products (3a) showed a particularly strong inhibitory effect on the growth of Amaranthus retroflexus(AR) and Setaria viridis(SV).

[Clinical phase trial of concurrent chemoradiotherapy combined TS-1 and nedaplatin].

We have treated head and neck carcinoma by concurrent chemoradiotherapy combined with 5-fluorouracil (5-FU) and cisplatin (CDDP). However,this chemoradiotherapy could not show an enormous effect in the advanced carcinoma of Stage III and IV. Therefore,we changed the contents of the chemotherapy, i.e., we replaced 5-FU, one of the agents with time dependency, to continuous administration of TS-1 for 2 weeks,also replacing CDDP, one of the agents with dose dependency, to nedaplatin (CDGP) in order to reduce kidney dysfunction. In this concurrent chemoradiotherapy, oral TS-1 was continued for 2 weeks and CDGP was administered on the 4 th day from the start of TS-1. In addition, radiotherapy was performed concurrently. In this way,we performed a phase I clinical trial of concurrent chemoradiotherapy combining TS-1 and nedaplatin (CDGP). As for the incidence of adverse events,grade 3 mucositis due to radiation was observed in two patients. As a result of the phase I clinical trial,we decided the maximum-tolerated dose (MTD) of TS-1 to be 80 mg/m2 (maximum 120 mg/body) and 100 mg/m2 for CDGP, and then determined the recommended dose(RD) of TS-1 as 80 mg/m2 (maximum 120 mg/ body) TS-1 and of CDGP as 9 0 mg/m2 CDGP.