Basophils Predict Mite Sensitization in Patients with Kawasaki Disease.

Background: Patients with Kawasaki disease (KD) are at a significantly increased risk of allergic diseases. Immunoglobulin E (IgE) is an immunoglobulin that mediates allergic sensitization to various allergens and is related to various allergic diseases. However, few studies have analyzed specific IgE on allergy biomarkers after KD is diagnosed. Objective: This study aimed to investigate the pattern of specific IgE levels against food and inhalant allergens. Methods: This retrospective study was conducted in Taiwan to identify patients admitted with KD. A subset of 453 admitted KD children younger than or equal to five years of age with intravenous immunoglobulin (IVIG) was followed up at our clinic with available specific IgE data. Results: The most common allergens were Dermatophagoides farina or pteronyssinus, house-dust, and cockroach mix. Positive specific IgE for Dermatophagoides farina or pteronyssinus was less common in children diagnosed with KD who were two years old or younger (p = 0.028). KD patients with higher basophils before IVIG (p = 0.010 and 0.018 for two different mites) and higher C-reactive protein (CRP, p = 0.030 and 0.028) after IVIG were at higher risk of mite sensitization. Integrated mite sensitization demonstrated higher basophils before IVIG, age at KD diagnosis, and the male sex to be clinically meaningful after logistic regression models. Conclusions: This study is the first to suggest that specific IgE in KD patients may be correlated with age at KD diagnosis, as well as basophils. Further longitudinal prospective studies are warranted to clarify the unique profile of specific IgE in KD patients.

Impact of Protein Binding Capacity and Daily Dosage of a Drug on Total Serum Bilirubin Levels in Susceptible Infants.

Hyperbilirubinemia is a common pathological condition in neonates. Free bilirubin can penetrate the blood-brain barrier (BBB), which can lead to bilirubin neurotoxicity. In the context of predicting the risk of bilirubin neurotoxicity, although the specificity and sensitivity of free bilirubin levels are higher than those of total serum bilirubin (TSB), free bilirubin is not widely monitored in clinical practice. The threshold TSB levels at which phototherapy must be administered have been established previously. However, TSB levels are not well correlated with neurodevelopmental outcomes. Currently, TSB levels are commonly used to guide phototherapy for neonatal hyperbilirubinemia. Some clinical drugs can displace bilirubin from its albumin-binding sites, and consequently upregulate plasma bilirubin. Daily dosages play a vital role in regulating bilirubin levels. A drug with both a high protein binding capacity and high daily dosage significantly increases bilirubin levels in infants. Premature or very low birth weight (VLBW) infants are vulnerable to the upregulation of bilirubin levels as they exhibit the lowest reserve albumin levels and consequently the highest bilirubin toxicity index. Because bilirubin is involved in maintaining the balance between pro-oxidant and antioxidant agents, the downregulation of bilirubin levels is not always desirable. This review provides insights into the impact of protein binding capacity and daily dosage of drugs on the bilirubin levels in susceptible infants.

Perinatal Characteristics and the Sensitization to Cow Milk, Egg Whites and Wheat in Children up to 3 Years of Age.

Food sensitization in early life identifies children at risk of developing allergic diseases. We investigated the sensitization to cow milk (CM), egg whites, and wheat. Newborns and infants under 3 years of age with available specific immunoglobulin E (sIgE) data were identified. A retrospective survey was conducted using data from the Chang Gung Research Database. Perinatal characteristics, such as singleton or multiples in a single pregnancy, parity, meconium staining, maternal age, spontaneous delivery or cesarean section, meconium passage, weeks of gestation, birth length, body weight, head and chest circumferences, and season, were obtained. The data on sIgE were collected, and a logistic regression model was used to determine the odds of sensitization. Positive sIgE for CM and egg whites was more likely to occur in boys than in girls. Early-life egg white and wheat sensitization was associated with increased birth body length and weight. A multivariate analysis indicated an association between egg white sIgE positivity and logarithmic total IgE. Higher total IgE levels and younger age were associated with egg white sensitization, and elevated weight and length at birth were linked to food sensitization, particularly to egg whites and wheat.

Multimedia Mixed Reality Interactive Shared Decision-Making Game in Children with Moderate to Severe Atopic Dermatitis, a Pilot Study.

(1) Objective: Atopic dermatitis (AD) is a recurring skin disease that affects children's daily activities and sleep quality. Due to the limitations of children's understanding and ability to express themselves, shared decision making (SDM) is often made by guardians, which thus affects the acceptance and effectiveness of children's treatments. Previous studies have demonstrated that involving both children and parents in decision making may help improve treatment outcomes; thus, we designed a multimedia mixed reality (MR) interactive game of SDM for children with moderate to severe AD. (2) Methods: Research participants included 6-18-year-old patients with moderate to severe AD. This research consisted of the following steps: designing SDM; character setting and visual design; performing games; system modification and optimization; screen editing and dubbing; and user testing and questionnaires by the System Usability Scale (SUS). (3) Results: We completed the SDM design for children with moderate to severe AD. Four different treatments were biologics, oral immune-modulating drugs, phototherapy, and wet wrap. An animated PowerPoint slide showed the AD apple rolling around before treatments and the AD apple sleeping soundly after treatments. Instructions with video teaching for the four different treatments were played, and then, the MR was turned on so that the patients could help the AD apple in the metaverse to undergo these four treatments. A total of 12 moderate to severe AD patients and six control patients used the game, all aged between six and eighteen years old, with an average SUS score of 81.0 and a standard error of 2.1 points. Adjective ratings yielded a rating between good and excellent. The game showed acceptable usability. We found no statistically significant differences in SUS scores between patients with and without moderate to severe AD or between boys and girls nor significant associations between SUS and age or severity. The analysis identified that the two items with the lowest SUS scores were "I think that I would need the support of a technical person to be able to use this product" and "I needed to learn a lot of things before I could get going with this product". Both of these comments show the limitations of this game. (4) Conclusions: Overall, this study provides the first MR SDM game that has passed the SUS and can be used as an aid in clinical SDM.

Comparison of glucocorticoids and painkiller prescribed days between rheumatoid arthritis patients receiving early and late treatment with a biological agent via a population-based cohort study.

Comparison between early biologics treatment and late biologics treatment of rheumatoid arthritis (RA) patients in decreasing prescription days of glucocorticoids and painkillers by using the Taiwan National Health Insurance Research database from January 1, 1997 to December 31, 2013. We defined early use of biologics as biologics prescribed within 2.24 years after the RA diagnosis, and the late use of biologics was defined as those prescribed after 2.24 years of the RA diagnosis. These definitions are based on previous studies defining early arthritis as arthritis within 2 years of diagnosis, while we needed another 3 months for application biologics here in Taiwan, which equals a total of 2.24 years. Among the 821 patients, 410 patients (50%) were classified in the Early group, and the other 411 patients (50%) were classified in the Late group. The use of any of these 3 types of medication, including steroids, disease modifying antirhuematic drugs, and nonsteroid anti-inflammatory drug (NSAID) was changed significantly after biologics treatment. Comparing between before and after biologics treatment, oral medication was significantly tapered (all P < .0001). The results show that men are 1.81 times more likely than women to taper oral glucocorticoids and NSAIDs. Younger age (<45) patients are 1.91 times more likely to taper steroids and NSAIDs than those aged over 65 years old. Both gender and age were found to be independent factors that could decrease days of prescription of both steroids and NSAIDs in early use of biologics agents. This study indicates that younger patients only need short-term (2.53 ±â€…1.92 years, P = .03) and early treatment with biologics (within 2.24 years of diagnosis of RA), just in order to taper steroids and NSAIDs to less than 50% compared to the steroids and NSAIDs doses before biologics treatment.

The Clinical Implication of Serogroup Distribution and Drug Resistance of Non-Typhoidal Salmonella in Children: A Single Center Study in Southern Taiwan during 2004-2019.

Background: A regional antibiotic susceptibility database of certain pathogens is crucial for first-line physicians in terms of providing clinical judgement and appropriate selection of antimicrobial agents. The aim of this study is to update the epidemiological data of Salmonella serogroups and drug resistance in pediatric patients. Methods: This is a single-center retrospective study enrolling patients aged from 0 to 18 years who were hospitalized with cultured proven non-typhoidal Salmonella (NTS) infection from 2004 to 2019. The isolates were collected and the demographic data, serogroups of Salmonella and antimicrobial susceptibilities were further analyzed. Results: A total of 1583 isolates of NTS were collected. Serogroup C2 was prone to cause invasive non-typhoidal salmonellosis (iNTS), especially bacteremia. Patients aged < 2 years were associated with serogroups B and C2 infection, while those aged ≥ 2 years were associated with serogroups D and E infection. The prevalence of serogroup B declined with simultaneous increase in prevalence of serogroups D and E. Serogroups B and E were associated with ceftriaxone resistance, while Serogroup D was less drug-resistant than the others. The prevalence of ceftriaxone-resistant Salmonella had not increased, although more ciprofloxacin-resistant isolates were found in iNTS infection. Conclusions: Age < 2 years is a risk factor of iNTS for children, and the distribution of serogroup changes should be closely monitored. Ceftriaxone is still the drug of choice for treating pediatric iNTS infection, and although no increase was observed in the prevalence of ceftriaxone-resistant strains in this study, continuing surveillance of such cases is warranted.

Increased Total Serum Bilirubin Level Post-Ibuprofen Use Is Inversely Correlated with Neonates' Body Weight.

Backgrounds: Drugs with the ability to displace bilirubin from albumin-binding sites subsequently leading to an increased bilirubin level may cause hyperbilirubinemia in neonates. Ibuprofen is commonly used to treat patent ductus arteriosus (PDA) in neonates, yet the use of ibuprofen has drawn mixed conclusions. We performed a retrospective study to determine how ibuprofen use influences the total serum bilirubin (TSB) level in neonates of differing birth weight (BW). Materials and methods: Neonates (including premature infants) born at Chang Gung Memorial Hospital, Taiwan during January 2004 to July 2020 were entered into this study. We recorded the phototherapy duration, including the initial day and end day, and determined the average influence of one-day phototherapy on TSB level. The highest monitored TSB level post-ibuprofen use minus the one measured prior to ibuprofen use was considered the TSB change following ibuprofen administration in this study, and the above-mentioned influence of daily phototherapy on the TSB level was used to correlate the results. Neonates with any of the following conditions were excluded: those who received ceftriaxone, those with intraventricular hemorrhage, and those infected with TORCH. Results: The average daily influence of phototherapy on the TSB level of neonates was −0.20 (−0.57~0.05) mg/dL, −0.28 (−0.84~0.13) mg/dL, −0.75 (−1.77~0.10) mg/dL, and −1.60 (−2.70~−0.50) mg/dL in neonates with BWs of <1 kg, 1−1.49 kg, 1.5−2.49 kg, and ≥2.5 kg, respectively, indicating that neonates with a BW ≥ 1.5 kg experienced a greater reduction in TSB level following phototherapy as compared with those with a BW < 1.5 kg. The average TSB increase following ibuprofen use in neonates was 3.38 ± 2.77 mg/dL, 2.04 ± 2.53 mg/dL, and 1.34 ± 2.24 mg/dL in neonates with BWs of <1 kg, 1−1.49 kg, and ≥1.5 kg, respectively, i.e., an elevated TSB change with a decreased neonate BW was noted post-ibuprofen use (p = 0.026, one-way analysis of variance (ANOVA)). Conclusions: As ibuprofen use is correlated with an apparent increase in TSB level in neonates with a lower BW, especially in those with a BW < 1 kg, iv acetaminophen can be an appropriate alternative to ibuprofen for ELBW neonates for the treatment of PDA if they are experiencing severe unconjugated hyperbilirubinemia.

Allergen Tests of Fruit Sensitization Involving Children with Allergic Diseases.

Fruit is a kind of plant food which is rich in nutrients and immune-regulating ingredients. A meta-analysis has demonstrated that fruits have a protective effects against asthma. On the other hand, clinical syndromes of allergic reactions to fruits manifest as an oral allergy syndrome. We aimed to investigate the patterns and associated factors of fruit allergen-specific IgE (sIgE) sensitization among patients with suspected clinical symptoms. Data were extracted from the Chang Gung Research Database. Fruit sensitization in Taiwan was evaluated using the presence of IgE antibodies against specific fruits. The overall prevalence of positive sIgE responses to fruit allergens in Taiwan, in order of decreasing importance, was pineapple, kiwi, banana, and papaya. Children aged 0-18 had a higher positive rate of allergic responses to pineapple, kiwi, banana, and papaya than adults over the age of 18. Positive specific IgE for kiwi, banana, or papaya was more frequent in younger than in older children and children with a higher total IgE of both logarithmic (log) and arithmetic values. The analysis of log IgE for pineapple positive vs. negative children determined an optimal cutoff value, log IgE 2.2, with both sensitivity (0.9) and specificity (0.5). Dermatitis was significantly more prevalent in children with positive IgE for pineapple, kiwi, banana, and papaya than negative specific IgE. The highest positive rate of sIgE against fruits was pineapple among children. Even in older children, the positive rate of pineapple allergens was high. IgE discriminates with and without sIgE for pineapple, with an optimal cutoff of 158.5 U/mL.

Multiple intravenous antibiotics usage is associated with intravenous immunoglobulin resistance in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a form of systemic vasculitis that primarily affects children under the age of 5 years old. Antibiotics are often prescribed for KD patients even before a diagnosis is made due to their prolonged fever and elevated inflammatory markers. Therefore, the purpose of this study was to investigate the impact of antibiotics usage on the disease outcome of KD. METHODS: We carried out a retrospective chart review of children between 2005 and 2017 for initial immunoglobulin (IVIG) treatment of KD. KD children with initial IVIG treatment more than 10 days after the onset of symptoms were excluded. RESULTS: In total, 280 children were eligible for this study, among which 209 had been treated with antibiotic(s) and 71 had not been. The IVIG resistance rates were 5.6% (4/71), 8.9% (10/112), and 21.6% (21/97) in non-users, single-drug users, and multiple-drug users, respectively (r = 0.205, p = 0.003). The IVIG resistance rate of the multiple antibiotics drug users in KD patients was significantly higher than the other two groups. Furthermore, the likelihood of IVIG resistance was found to increase with elevated C-reactive protein (CRP) values (1.010/unit, p < 0.001) but not with total white blood cell (WBC) count (p = 0.466). CONCLUSION: The probability of IVIG resistance increases with elevated CRP values and the use of multiple IV antibiotics, thus indicating that physicians should be prudent in administering multiple IV antibiotics when treating assumed infections in KD children.

Higher Hospitalization Rate for Lower Airway Infection in Transfusion-Naïve Thalassemia Children.

Few studies have addressed the risk of infection in transfusion-naïve thalassemia patients. We aimed to investigate whether transfusion-naïve thalassemia population has higher hospitalization rates for lower airway infection-related diseases than non-thalassemia population in children. A nationwide population-based retrospective cohort study was conducted using detailed medical records of the Taiwan National Health Insurance Research Database. Transfusion-naïve thalassemia patients were compared with a matched cohort at a ratio of 1:4. Data of the selected patients were adjusted for age, sex, and related comorbidities. We recorded the frequency of admissions or outpatient clinic visits for patients with a diagnosis of pneumonia or acute bronchitis/bronchiolitis. Based on our results, the hospitalization rates and incidence rate ratios of bronchitis/bronchiolitis and pneumonia for transfusion-naïve thalassemia children were all higher than those for non-thalassemia controls. Therefore, we conclude that transfusion-naïve thalassemia children are more likely to experience lower airway infections and have a higher probability of hospitalization for these conditions.

Correlation of symptomatic enterovirus infection and later risk of allergic diseases via a population-based cohort study.

Infants who are exposed to the rhinovirus or respiratory syncytial virus are at a higher risk of subsequently developing wheezing or asthma. This study aims to determine whether preschoolers with a history of symptomatic enterovirus infection are at an increased risk of developing allergic diseases or not.We used data from the Taiwan National Health Insurance Research Database from 1999 to 2006 for this nationwide population-based cohort study. The subsequent risks for allergic diseases, which included asthma (International Classification of Diseases [ICD]-9: 493.X), allergic rhinitis (AR; ICD-9 CM code 477.X), and atopic dermatitis (AD; ICD-9-CM code 691.X), were compared between herpangina (ICD-9: 074.0) and hand, foot, and mouth disease (HFMD; ICD-9: 074.3) throughout the follow-up period using the Cox proportional hazards model.In this database, 12,016 neonates were born between January 1999 and December 1999. Among them, we further evaluated 8337 subjects; 3267 children infected with either herpangina or HFMD served as the study cohort, and the other 5070 children made up the comparison cohort. Children in the herpangina group had a higher risk of developing AR and AD, with adjusted hazard ratios of 1.15 (1.02-1.30, 95% CI) and 1.38 (1.17-1.63. 95% CI), respectively, while children suffered from HFMD had decreased risks of asthma, with an adjusted hazard ratio of 0.76 (0.63-0.93, 95% CI).Children who previously suffered from herpangina experienced an increased risk of subsequently developing AD and AR. Meanwhile, children who had suffered from HFMD experienced a decrease in the subsequent occurrence of asthma compared to the general population.

Effect of curcumin supplementation on physiological fatigue and physical performance in mice.

Curcumin (CCM) is a well-known phytocompound and food component found in the spice turmeric and has multifunctional bioactivities. However, few studies have examined its effects on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of CCM supplementation on fatigue and ergogenic function following physical challenge in mice. Male ICR mice were divided into four groups to receive vehicle or CCM (180 µg/mL) by oral gavage at 0, 12.3, 24.6, or 61.5 mL/kg/day for four weeks. Exercise performance and anti-fatigue function were evaluated after physical challenge by forelimb grip strength, exhaustive swimming time, and levels of physical fatigue-associated biomarkers serum lactate, ammonia, blood urea nitrogen (BUN), and glucose and tissue damage markers such as aspartate transaminase (AST), alanine transaminase (ALT), and creatine kinase (CK). CCM supplementation dose-dependently increased grip strength and endurance performance and significantly decreased lactate, ammonia, BUN, AST, ALT, and CK levels after physical challenge. Muscular glycogen content, an important energy source for exercise, was significantly increased. CCM supplementation had few subchronic toxic effects. CCM supplementation may have a wide spectrum of bioactivities for promoting health, improving exercise performance and preventing fatigue.