Buckwheat Allergy in Asia.

PURPOSE OF REVIEW: Buckwheat (BW) allergy is a significant issue in Asia. This review delves into three types of BW allergy: immediate food allergy; food-dependent, exercise-induced anaphylaxis (FDEIA) as a subset of immediate food allergy; and food protein-induced enterocolitis syndrome (FPIES); by comparing data from Asian and non-Asian countries. RECENT FINDINGS: Most studies on BW have been published in Japan and Korea, and only a few studies on the topic have been done outside Asia. To date, seven components of common BW (Fagopyrum esculentum) and four components of Tartary BW (Fagopyrum tartaricum) have been implicated in BW allergy. Although BW-sIgE has limited utility for evaluating immediate BW allergy, Fag e 3-specific IgE, one of the components of common BW, and the skin prick test are diagnostically useful. The present review aims to shed light on the current state of knowledge, highlight research gaps, and suggest future directions in the management and understanding of BW allergy.

Assessing effects of mechanical stimulation of fluid shear stress on inducing matrix Metalloproteinase-9 in cultured corneal epithelial cells.

Blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells. Therefore, we evaluated whether fluid shear stress affects matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human corneal epithelial cells (HCECs). No other study has shown the influence of fluid shear stress on HCECs regarding mRNA expression and the protein levels of MMPs. Cultured HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) for 12 and 24 h with the parallel-plate type of flow chamber. Gene expression of MMPs and TIMPs was measured by real-time polymerase reaction. Concentrations of MMP-1 and MMP-9 in cell lysates were determined using bead-based amplified luminescent proximity homogenous assay-linked immunosorbent assay. The expression of MMP-9 and MMP-1 in HCECs exposed to low and high flow for 12 and 24 h, respectively, increased significantly compared with those under static conditions. The expression of MMP-9 in the cells exposed to high flow for 24 h increased significantly compared with those under static and low flow conditions. Levels of MMP-9 in cell lysates exposed to fluid flow for 24 h were elevated significantly with increasing shear stress. Fluid shear stress exerted on HCECs affected MMPs, which was associated with inflammation and pathogenesis. Mechanical stress induced by blinking might influence expression of MMPs on the ocular surface. Further studies are warranted to establish the molecular mechanism of shear stress-induced alternations of MMPs.

Surgical Treatment of Ossified Cephalhematoma in Young Child.

Cephalhematoma is a subperiosteal collection of blood. The lesion generally spontaneously resolves, but if cephalhematoma persists beyond this period, it typically begins to ossify and may require surgical treatment for correction. The incidence of ossified cephalhematoma is rare, and its pathogenesis is unclear. There have been reports of surgical treatment of ossified cephalhematoma in newborns and infants, but few reports in 5-year-old children. We experienced the surgical treatment of an ossified cephalhematoma in a 5-year-old boy. We performed periosteal reattachment with onlay bone autograft. Follow-up examination at 2 years revealed a good cosmetic result and a computed tomography scan showed excellent reconstitution of the contour of the skull.

Effects of Glucocorticoids on Hospitalized Children With Anaphylaxis.

BACKGROUND: The benefits of glucocorticoid treatment and recent trends of adjunctive treatments during episodes of anaphylaxis remain unclear. OBJECTIVES: The aims of this study were to investigate the recent practice patterns and compare the effects of glucocorticoid for children hospitalized with anaphylaxis. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we compared the length of hospital stay, risk of 10-day readmission, and total hospitalization cost between the steroid and nonsteroid groups. We also evaluated recent trends of adjunctive treatments for anaphylaxis. RESULTS: From 2010 to 2014, the proportions of H1-receptor antagonist use increased from 65.1% to 71.8% (Ptrend = 0.02). The proportions of H2-receptor antagonist use showed an upward trend, ranging from 12.8% to 16.7% (Ptrend = 0.01). No significant change in glucocorticoid use was observed (from 86.7% to 82.6%; Ptrend = 0.08). Stabilized inverse probability-weighting analyses showed that the total length of hospital stay was 0.39 days longer in the steroid group than in the nonsteroid group (95% confidence interval, 0.29-0.49 days). Total hospitalization cost was greater in the steroid group than in the nonsteroid group (difference, ¥3896; 95% confidence interval, ¥2464-¥5562). No significant difference in risk of 10-day readmission was observed between the groups. Instrumental variable analyses showed similar results to stabilized inverse probability-weighting analyses. CONCLUSIONS: We observed increasing trends of H1- and H2-receptor antagonist use. Length of hospital stay and total hospitalization cost were greater in the steroid group than in the nonsteroid group, whereas readmission risks were similar between the 2 groups.

Nationwide survey of the prevalence of wheeze, rhino-conjunctivitis, and eczema among Japanese children in 2015.

BACKGROUND: Global surveys and cohort studies have been conducted to evaluate the prevalence of allergic disease in childhood, but only a few nationwide surveys have been conducted in Japan. We aimed to report the prevalence of childhood allergic disease in Japan and determine the prevalence distribution by sex and prefecture. METHODS: In 2015, we conducted a school-based questionnaire survey using the Japanese version of the International Study of Asthma and Allergies in Childhood questionnaire among two age groups: primary school students (PS, 6-8 years old) and middle school students (MS, 13-15 years old). The schools were randomly selected from each prefecture. RESULTS: Valid responses were obtained from 42,582 PS and 36,638 MS. Among PS and MS, the prevalence of wheeze was 10.2% and 8.2%, that of allergic rhino-conjunctivitis was 18.7% and 26.7%, and that of eczema was 14.6% and 9.7%, respectively. In terms of sex, the prevalence of wheeze and rhino-conjunctivitis was higher in male PS while that of rhino-conjunctivitis and eczema was higher in female MS. In terms of prefecture, there was a two-fold difference in the prevalence of wheeze and eczema and a four-fold difference in the prevalence of rhino-conjunctivitis, with each disease showing different distribution patterns. CONCLUSIONS: We demonstrated the prevalence of allergic disease among PS and MS in 2015. The prevalence tended to be higher in male PS and female MS. Each disease exhibited different prevalence ranges and distributions. Identifying the factors behind these differences is a topic for future research.

The prevalence of oral symptoms caused by Rosaceae fruits and soybean consumption in children; a Japanese population-based survey.

BACKGROUND: Pollen food Syndrome (PFS) to Rosaceae fruits and soybean, related to Bet v 1 homologue sensitization has been reported increasingly throughout Japan, possibly due to the wide distribution of alder. METHODS: In 2015, we conducted a school-based questionnaire survey among two age groups; students in primary school (Years 1-2) and secondary school (Years 8-9) from each of the 47 prefectures of Japan. We analyzed the prevalence, demographic and clinical characteristics of children with oral symptoms to Rosaceae fruits/soybean; defined as oral symptoms occurring shortly after ingesting apple, peach, cherry or soybean. Additionally, we assessed the correlation between the prevalence and external data on alder sensitization rates by prefecture. RESULTS: Responses from 41,264 primary and 35,302 secondary school students were analyzed. The prevalence of oral symptoms to Rosaceae fruits/soybean was 0.99%, 95%CI: 0.89-1.09% and 2.75%, 95%CI: 2.59-2.93% among each age group, respectively. Children with oral symptoms were more likely to have parental and personal history of allergic disease compared to those without symptoms. Oral symptoms were experienced more often in children with severe spring allergic rhinitis or have both allergic rhinitis and wheeze. There was a strong correlation between the prevalence of oral symptoms and alder sensitization rates by prefecture among both age groups (r = 0.63, p < 0.001 and r = 0.76, p < 0.001, respectively). CONCLUSIONS: Oral symptoms to Rosaceae fruits/soybean, which is suggestive of PFS was reported by 1-3% Japanese school children. It was associated with the geographic alder sensitization rate, supporting the underlying sensitization to Bet v 1.

Pattern of care in adjuvant therapy for resected Stage I non-small cell lung cancer: real-world data from Japan.

BACKGROUND: Adjuvant tegafur/uracil (UFT) chemotherapy is recommended for patients with completely resected Stage I non-small cell lung cancer (NSCLC) in Japan. A Phase III trial, the Japan Clinical Oncology Group (JCOG) 0707, comparing the survival benefit of UFT and S-1 (tegafur/gimeracil/oteracil) for this population is being conducted. However, the selection of patients in the randomized clinical trial (RCT) may not represent the real-world population. The present study aimed to investigate the pattern of care for patients receiving adjuvant chemotherapy for completely resected NSCLC. METHODS: Patients with completely resected pathological Stage I (T1 > 2 cm and T2 in 6th TNM edition) NSCLC eligible for the JCOG0707 trial but excluded from it during the enrollment period (2008-13) were eligible for this study. Physicians from institutions that participated in the JCOG0707 retrospectively assessed the medical records of each patient. RESULTS: This study enrolled 5006 patients, 85% of those initially considered for participation in the JCOG0707 trial (5006 of 5923 patients). Among them, 2389 were ineligible for the trial and 2617 had not been enrolled despite being eligible. The most frequent reason for non-enrollment despite eligibility was the decline in patients' participation, and the major reasons for trial ineligibility were concomitant malignancy and comorbidities. Of all the patients enrolled in our study, 1659 received adjuvant chemotherapy, mainly UFT. CONCLUSIONS: Our study indicates that only 15% of the real-world patients with completely resected NSCLC were enrolled into the adjuvant chemotherapy RCT, and among those not participating in the trial, one-third received adjuvant chemotherapy.

An independent relation of atopic dermatitis to exercise-induced wheezing in asthmatic children.

BACKGROUND: Atopic dermatitis (AD) and exercise-induced asthma (EIA) are common in asthmatic children, and exercise is the most common trigger other than infection for acute onset asthma attack in children. We examined whether AD is related to exercise-induced wheezing (EIW), some proxy for EIA. METHODS: Japanese version of the International Study of Asthma and Allergies in Childhood questionnaires were used. For 12,405 asthmatic school children, AD was defined as itchy rash coming and going for at least 6 months at any time in the last 12 months with affecting places of flexural parts of body, and severity of AD was rated according to frequency of being kept awake at night with the itch as follows: never in the past 12 months, less than one night per week and one or more nights per week. RESULTS: Adjusted for frequency of asthma attack, odds ratios (OR) of children with current AD as compared to those without AD for having EIW were 1.32 (95% confidence interval = 1.15-1.52), 1.35 (1.14-1.68) and 1.10 (0.92-1.31) for primary school, junior high school and high school children, respectively. EIW was more likely observed in accordance with increasing severity of AD in the primary school children with ORs of 1.12, 1.59 and 1.54 (p for trend < 0.01), and in the junior high school ones with ORs of 1.18, 1.31, 2.03 (<0.01), respectively. CONCLUSIONS: AD may be possibly related to EIW. Further studies investigating effect of AD treatment on EIW may be required.

Stressors of School-age Children With Allergic Diseases: A Qualitative Study.

PURPOSE: Most studies of stress in children with chronic diseases have been geared toward parents and caregivers have not considered allergic diseases together. This study aimed to identify the stressors associated with allergic diseases in Japanese school-age children. DESIGN AND METHODS: Stressors associated with allergic diseases of 11 school-age children (seven boys and four girls; age range: 9-12 years) were investigated using semi-structured interviews. RESULTS: In the qualitative thematic analysis of stressors about allergic diseases, two themes: allergic disease-specific stressors and common stressors in chronic diseases, and 12 categories were identified. A thematic map was applied to four domains of stressor: physiological factors, psychological factors, social factors, and environmental factors. CONCLUSIONS: The results showed that school-age children with allergic diseases have a variety of stressors. Future studies should aim to develop an allergic disease-specific stress management program with school-age children. PRACTICE IMPLICATIONS: In children with allergic diseases, not only is stress management in daily life important, but also stress management for disease-specific matters to control the symptoms and maintain mental health. Stress management should be supported for school-age children with allergic diseases.

Childhood asthma control in Japan: A nationwide, cross-sectional, web-based survey.

BACKGROUND: Recent surveys have shown that many patients with asthma experience uncontrolled symptoms and decreased quality of life due to their disease. However, few large population-based studies have evaluated asthma control in Japanese children. OBJECTIVE: To show the reality of asthma control and the pattern of asthma controller medication use among Japanese children. METHODS: In 2012, a web-based survey was conducted to identify children aged 6 to 11 years with asthma in Japan. Among children with current asthma, we collected information regarding their asthma controller medication use and evaluated the control level of asthma using the Childhood Asthma Control Test (C-ACT). In this study, a C-ACT score of 19 or less, 20 to 22 and over 22 were classified as uncontrolled asthma, well-controlled asthma, and optimally controlled asthma, respectively. RESULTS: Among the 3,033 children with current asthma, 442 (14.6%), 635 (20.9%), and 1,956 (64.5%) children had uncontrolled, well-controlled, and optimally controlled disease, respectively. In the past 1 month, 1,387 (45.7%) reported receiving at least 1 asthma controller medication with 638 (21.0%) reported receiving inhaled corticosteroid. Among the children with uncontrolled asthma, 67 (15.2%) were not receiving any asthma controller mediations. Among children receiving asthma controller medication, 27.0%, 31.4% and 41.5% had uncontrolled, well-controlled, and optimally controlled asthma, respectively. CONCLUSIONS: Although more than half of children with current asthma had optimally controlled disease, some children without any controller medications and more than a quarter of the children receiving asthma controller medications had uncontrolled disease.

[THE COURSE OF ASTHMA SYMPTOMS IN JAPANESE CHILDREN; THE FIRST REPORT FROM A MULTICENTER PROSPECTIVE COHORT STUDY].

BACKGROUND: The use of asthma control guidelines and anti-inflammatory drugs have significantly decreased the number of severe asthma cases including death from asthma. However, there are few prospective cohort studies among pediatric asthma patients in Japan describing the course of asthma symptoms with the treatment taken into consideration. METHOD: We recruited a total of 851 children diagnosed with asthma through 90 hospitals and clinics in 2004 to 2006. Questionnaires were posted annually to collect data on their asthma symptoms, treatment and environmental exposures. We analyzed the disease course in the first 5 years among the children who were registered at age 4 or younger. RESULTS: The disease course of a total of 641 children, aged 2.8+/-1.1 (mean+/-SD) at registration were analyzed. The proportion of children who had intermittent symptoms increased from 37.6% at registration to 86.5% at 5 years, and the proportion of children with intermittent severity increased from 7.0% to 38.9%, showing a significant decrease in the overall severity. The proportion of children using ß2 stimulants decreased from 87.8% at registration to 53.5% at 5 years, while the use of inhaled cortico-steroids were 41.6% at registration and 38.1% at 5 years. CONCLUSION: Most of the children with pre-school onset asthma had their symptoms controlled, and had decreased severity over 5 years.

Impact of pediatric obesity on acute asthma exacerbation in Japan.

BACKGROUND: Asthma and obesity are common health problems in children. This study investigated the impact of obesity on children hospitalized with acute asthma exacerbation. METHODS: We obtained the hospital discharge records of inpatients aged 3-8 years with a diagnosis of asthma using a national inpatient database in Japan. The patients were classified into underweight, normal weight, overweight, and obese groups using weight for height and body mass index for age provided by the World Health Organization. We compared 30-day re-admission, need for intensive care, mean total hospitalization costs, and length of hospital stay between the 4 groups using multivariable regression models. RESULTS: Overall, 38 679 patients were identified, including 3177 underweight, 28 904 normal weight, 3334 overweight, and 3264 obese patients. The obese group showed significantly higher 30-day re-admission (adjusted odds ratio, 1.26; 95% confidence interval, 1.03-1.54) and longer length of stay (adjusted difference, 0.12 days; 95% confidence interval, 0.10-0.20 days) than the normal weight group. The threshold was a 91st percentile of weight for length or body mass index for the relationship with 30-day re-admission. No significant difference was observed between the 4 groups regarding the need for intensive care and total hospitalization costs. CONCLUSION: These findings demonstrated that obesity was a risk factor for repeated admissions caused by asthma in children, indicating the importance for the prevention of pediatric obesity.

Accessory left gastric artery aneurysms in granulomatosis with polyangiitis: a case report and literature review.

Aneurysm formation is a potential complication of granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis. It is a very rare complication, but immediate diagnosis and therapy should be performed because an aneurysm can be life-threatening if it ruptures. An accessory left gastric artery (ALGA) is also a rare variant gastric artery that may obtain its blood supply from the left hepatic artery and left gastric artery. We herein describe a 57-year-old Japanese man who was diagnosed with GPA complicated by aneurysm rupture in an ALGA. Emergency surgery was performed after failure of arterial coil embolization to interrupt blood flow in the ALGA. The patient underwent partial resection of the lesser omentum, which contained all aneurysms. During partial resection of the lesser omentum, both the left gastric artery and ALGA were ligated because they were thought to be feeders of the aneurysms. Postoperative recovery was uneventful; no bleeding or recurrence of the aneurysms occurred. Immediate diagnosis and therapy should be performed for patients with GPA with symptoms of vascular ischemia or aortitis. Endovascular intervention is the first-choice therapy especially for hemodynamically stable patients with ruptured aneurysms or aneurysms located on variant arteries, which may have multiple blood supplies. In the present case, although endovascular treatment failed, the approach described herein was helpful during open surgery.

[A Case of Slowly Progressive Brain Metastasis with Minor Bleeding after Removal of and Chemotherapy for Non-Small Cell Lung Cancer].

Of all brain metastases, the most common primary lesion is derived from the lung. These types of metastases enlarge aggressively with unfavorable prognoses. We report the case of a 75-year-old male patient who had a history of pulmonary resection for Stage IA non-small cell lung cancer(NSCLC), and received chemotherapy. One year after NSCLC surgery, he experienced a cardiogenic cerebral infarction, and anticoagulant therapy was initiated. Mass lesions with hemorrhage were detected bilaterally in the frontal lobes through magnetic resonance imaging three years after the NSCLC surgery. The lesions slowly enlarged during follow-up. However, there were no clinical symptoms. There was no finding indicating a local recurrence or metastasis through positron emission tomography(PET). Two and a half years after the detection of the lesion, left hemiplegia was observed. Massive hemorrhage from the right frontal lobe lesion was observed on computed tomography(CT). Craniotomy and evacuation of the hematoma were performed. The histopathological findings showed adenocarcinoma and the diagnosis was brain metastasis of the lung cancer. This case reveals brain metastasis of lung cancer that progressed without extracranial metastases for three years. The brain tumor enlarged, accompanied by hemorrhage, extremely slowly without any symptoms. It was difficult to differentiate between metastasis and cavernous hemangioma, considering the extremely slow progress and image analyses. Of the reported prognostic factors associated with postoperative brain metastasis from surgically resected NSCLC, three factors were applicable to this case:adenocarcinoma, a small number of brain metastases, and the absence of extracranial metastases at the diagnosis of brain metastasis. We should consider the possibility of a metastatic brain tumor secondary to lung cancer even long after thoracic surgery.

Tumor volume determines the feasibility of cell-free DNA sequencing for mutation detection in non-small cell lung cancer.

Next-generation sequencing (NGS) and digital PCR technologies allow analysis of the mutational profile of circulating cell-free DNA (cfDNA) in individuals with advanced lung cancer. We have now evaluated the feasibility of cfDNA sequencing for mutation detection in patients with non-small cell lung cancer at earlier stages. A total of 150 matched tumor and serum samples were collected from non-small cell lung cancer patients at stages IA-IIIA. Amplicon sequencing with DNA extracted from tumor tissue detected frequent mutations in EGFR (37% of patients), TP53 (39%), and KRAS (10%), consistent with previous findings. In contrast, NGS of cfDNA identified only EGFR, TP53, and PIK3CA mutations in three, five, and one patient, respectively, even though adequate amounts of cfDNA were extracted (median of 4936 copies/mL serum). Next-generation sequencing showed a high accuracy (98.8%) compared with droplet digital PCR for cfDNA mutation detection, suggesting that the low frequency of mutations in cfDNA was not due to a low assay sensitivity. Whereas the yield of cfDNA did not differ among tumor stages, the cfDNA mutations were detected in seven patients at stages IIA-IIIA and at T2b or T3. Tumor volume was significantly higher in the cfDNA mutation-positive patients than in the negative patients at stages T2b-T4 (159.1 ± 58.0 vs. 52.5 ± 9.9 cm3 , P = 0.014). Our results thus suggest that tumor volume is a determinant of the feasibility of mutation detection with cfDNA as the analyte.

Environmental factors associated with childhood eczema: Findings from a national web-based survey.

BACKGROUND: Genetic and environmental factors are known to be related to the development of childhood eczema. Our aim was to assess the environmental factors associated with the prevalence of eczema among children using a web-based survey. METHODS: In June 2012, we conducted a nation-wide web-based survey to identify the prevalence and characteristics of allergic diseases among Japanese children. The prevalence of allergic diseases including eczema was assessed using the International Study of Asthma and Allergies in Childhood core questionnaire. The associations between eczema prevalence and environmental factors, as well as those between background characteristics and comorbid allergic diseases among 6-12 year old children were assessed. RESULTS: A total of 28,348 children were included in the analysis. The prevalence of current eczema was 13.0%. Current eczema was significantly associated with a higher prevalence of wheeze, rhinitis, and food allergy. In multiple logistic regression models, birth during autumn (aOR: 1.18 95%CI: 1.06-1.31) or winter (aOR: 1.21 95%CI: 1.08-1.34), duration of exclusive breastfeeding for at least 6 months (aOR: 1.14 95%CI: 1.06-1.23), and ownership of a pet from infancy (aOR: 2.61 95%CI: 1.68-4.07) were also associated with a higher prevalence of eczema. The prevalence was lower in those with a high annual household income (aOR: 0.90 95%CI: 0.81-0.99) and 2 or more siblings (aOR: 0.86 95%CI: 0.76-0.97). CONCLUSIONS: Duration of breastfeeding, season of birth, pet ownership, household income, and the number of siblings were associated with the prevalence of childhood eczema in a nationwide web survey.