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Background: The health-related quality of life (HRQL) of people with food allergies should be evaluated to provide high-quality medical care. Currently, there is no available easy-to-use and reliable instrument for assessing HRQL clinically in Japan., Methods: The Food Allergy Quality of Life Questionnaire 10 (FAQLQ10) in English was translated into Japanese, and this was referred to as the Japanese version of the Food Allergy Quality of Life Questionnaire 10 (FAQLQ10-J). Participants aged up to 18 years, who had food allergy, and their parents were instructed to complete the FAQLQ10-J and the Food Allergy Independent Measure, a self-report instrument. For comparison, participants without food allergies were also included in the survey., Results: The FAQLQ10-J, which included forms for individuals aged 8-12 years, teenagers, and caregivers was developed. The responders completed each form within approximately 3 min. An analysis of responses showed that each form had a good internal consistency, test-retest reliability, construct validity, and discriminant validity. Moreover, based on an examination of the relationship between demographic data and FAQLQ10-J scores, items such as possession of an adrenaline auto-injector, participant age, and number of eliminated foods might influence HRQL., Conclusions: We developed the FAQLQ10-J, which is a simple, reliable, and effective tool for assessing HRQL among Japanese individuals with food allergy. Its use may provide a more detailed understanding of HRQL among individuals with food allergy in clinical settings and may facilitate the development of more individual-oriented treatments., Competing Interests: The authors report no competing interests., (© 2024 The Authors.)

Background: Alarmins resulting from cell death or oxidative stress are involved in the development of Kawasaki disease (KD) vasculitis. In a previous study, we demonstrated the potential role of interleukin (IL)-33 as an alarmin in the development of KD vasculitis. Although edematous dissociation (necrotic change) of the tunica media is thought to be a major source of IL-33 in KD vasculitis, it has not yet been elucidated., Methods and Results: We investigated the impact of IL-33 released from necrotic human coronary artery smooth muscle cells (HCASMCs) on human coronary artery endothelial cells (HCAECs) using a coculture assay. Subsequently, we evaluated the anti-inflammatory effects of anti-IL-33 and anti-suppression of tumorigenicity 2 (ST2) antibodies compared with conventional therapies of KD, such as high-dose IgG or anti-tumor necrosis factor (TNF)-α antibody. Primary necrosis of HCASMCs induced significant release of IL-33. In cocultures of necrotic HCASMCs with HCAECs, the necrotic HCASMCs significantly induced the production of various proinflammatory cytokines in the HCAECs. Anti-IL-33 and anti-ST2 antibodies exhibited unique inhibitory effects on the production of platelet-derived growth factor-BB or IL-12(p70) in HCAECs., Conclusions: There is potential involvement of edematous dissociation of the tunica media in the development of KD vasculitis. Furthermore, the distinctive anti-inflammatory effects of the anti-IL-33/ST2 axis drugs suggest novel therapeutic options for patients with refractory KD.

Kawasaki disease (KD) is an acute, self-limiting, febrile systemic vasculitis of unknown cause associated with the development of coronary artery lesions (CALs) during childhood. Damage-associated molecular patterns (DAMPs) from cell death and oxidative stress have been shown to be involved in the development of KD vasculitis. Interleukin (IL)-33 is released from damaged endothelial cells and acts as a DAMP. We studied whether IL-33 and its receptor (ST2) might be involved in KD pathogenesis. Serum levels of soluble ST2 (sST2) in KD patients were measured before their first therapy. Furthermore, we investigated the impact of IL-33 on human coronary artery endothelial cells (HCAECs). Serum levels of sST2 were significantly higher in KD patients with CALs than in those with normal coronary arteries. In vitro, IL-33 upregulated the expression of ST2L and increased production of sST2, IL-6, IL-8, and monocyte chemoattractant protein-1 in HCAECs in a time- and concentration-dependent manner. Moreover, IL-33 induced significantly greater production of IL-6 and IL-8 in HCAECs compared to the condition stimulated with isoconcentration of tumor necrosis factor-α. The results of the present study suggest that the IL-33/ST2 axis might be involved in the development of KD vasculitis. The IL-33/ST2 axis may be a therapeutic target for the treatment of KD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pandemic influenza virus A(H1N1)pdm09 infection occurred in healthy children and young adults, but asthmatic patients presented more rapid progression of respiratory distress and plastic bronchitis. To investigate the pathogenesis of worsening respiratory symptoms after A(H1N1)pdm09 infection, we focused on matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1). MMP-9 and TIMP-1 levels in bronchoalveolar lavage fluid and serum from mice with and without asthma were evaluated after A(H1N1)pdm09 or seasonal A(H1N1) infection. MMP-9 levels were more elevated in Asthma/A(H1N1)pdm09-infected mice than in non-Asthma/A(H1N1)pdm09-infected mice on both 3 and 7 days post-infection. Immunohistochemical findings in this pneumonia model showed that MMP-9 and TIMP-1 positive cells were observed in blood vessels and bronchus of lung tissue in severe pathological findings of pneumonia with asthma. Microscopically, shedding cells and secretions were conspicuous in the trachea on days 3 and 7 post-infection, in the A(H1N1)pdm09-infected mice with asthma. Our results suggest that MMP-9 and TIMP-1 expressions are related to severe pneumonia in the A(H1N1)pdm09 infection with asthma, leading to cause epithelial cell shedding., (© 2022 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: Kawasaki disease (KD) is an acute and febrile systemic vasculitis that occurs during childhood. Infliximab (IFX) is a chimeric monoclonal antibody that binds to tumor necrosis factor-α. Although IFX therapy is a useful option for refractory KD, vaccine-associated infections may develop after therapy. In Japan, IFX therapy is recommended after a duration of at least 3 months after live vaccinations or at least 6 months after Bacillus Calmette-Guérin (BCG) in children with KD. However, the appropriate duration between live vaccinations and IFX therapy is unclear., Methods: We investigated children who developed KD within 3 months after live vaccinations or within 6 months after BCG. Clinical characteristics, side effects of therapies and efficacy of live vaccinations were retrospectively investigated., Results: Forty-eight patients developed KD within 3 months of live vaccinations or within 6 months after BCG. Eight patients underwent IFX therapy. There were no apparent vaccine-associated infections. The patients who underwent IFX acquired protective IgG antibody titers in the 5 of 6 live vaccines., Conclusions: Safe and appropriate duration between live vaccinations and IFX therapy for KD patients could be shorter in the future, although more studies are warranted to establish the safe duration., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The association between pollen food allergy syndrome (PFAS) and allergic march remains unclear. In this prospective cohort study of the general population in Tokyo (T-Child Study), we found that sensitization to Cry j 1 and Fel d 1 at ages 5 and 9 years was associated with an increased risk of PFAS at 13 years old (at 5 years, Cry j 1: adjusted odds ratio aOR, 2.74; 95% confidence interval CI, 1.53-4.91; Fel d 1: aOR, 2.61; 95% CI, 1.31-5.19; at 9 years, Cry j 1: adjusted odds ratio aOR, 4.28; 95% confidence interval CI, 1.98-9.25; Fel d 1: aOR, 2.40; 95% CI, 1.33-4.32). In particular, sensitization to Bet v 1 at ages 5 and 9 years was associated with a strong risk of PFAS at the age of 13 years (at 5 years: aOR, 10.6; 95% CI, 2.64-42.5; at 9 years: aOR, 9.1; 95% CI, 4.71-17.6). PFAS risk by age 13 years was increased by any allergic symptom at 5 or 9 years, a combination of wheezing, eczema, and rhinitis, and Bet v 1 sensitization. Our findings suggest that PFAS may be associated with allergic march.

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobin E-mediated food hypersensitivity disorder. However, little is known about the clinical features of FPIES in patients with Down syndrome (DS). Medical records of children with DS diagnosed at our hospital between 2000 and 2019 were retrospectively reviewed. Among the 43 children with DS, five (11.6%) were diagnosed with FPIES; all cases were severe. In the FPIES group, the median age at onset and tolerance was 84 days and 37.5 months, respectively. Causative foods were cow's milk formula and wheat. The surgical history of colostomy was significantly higher in the FPIES group than in the non-FPIES group. A colostomy was performed in two children in the FPIES group, both of whom had the most severe symptoms of FPIES, including severe dehydration and metabolic acidosis. The surgical history of colostomy and postoperative nutrition of formula milk feeding may have led to the onset of FPIES. Therefore, an amino acid-based formula should be considered for children who undergo gastrointestinal surgeries, especially colostomy in neonates or early infants. When an acute gastrointestinal disease is suspected in children with DS, FPIES should be considered. This may prevent unnecessary tests and invasive treatments.

Competing Interests: The authors declare no conflict of interest.

Background: Severe asthma exacerbation is an important comorbidity of the 2009 HIN1 pandemic (A(H1N1)pdm09) in asthmatic patients. However, the mechanisms underlying severe asthma exacerbation remain unknown. In this study, airway hyperresponsiveness (AHR) was measured in pediatric asthma patients infected with A(H1N1)pdm09. We also evaluated AHR in asthmatic mice with A(H1N1)pdm09 infection and those with seasonal influenza for comparison., Methods: AHRs in asthmatic children were defined as the provocative acetylcholine concentration causing a 20% reduction in forced expiratory volume in 1 s (PC 20 ). To investigate the pathophysiology using animal models, BALB/c mice aged 6-8 weeks were sensitized and challenged with ovalbumin. Either mouse-adapted A(H1N1)pdm09, seasonal H1N1 virus (1 × 10 5 pfu/20 μl), or mock treatment as a control was administered intranasally. At 3, 7, and 10 days after infection, each group of mice was evaluated for AHR by methacholine challenge using an animal ventilator, flexiVent. Lung samples were resected and observed using light microscopy to assess the degree of airway inflammation., Results: AHRs in the children with bronchial asthma were temporarily increased, and alleviated by 3 months after discharge. AHR was significantly enhanced in A(H1N1)pdm09-infected asthmatic mice compared to that in seasonal H1N1-infected mice (p < .001), peaking at 7 days postinfection and then becoming similar to control levels by 10 days postinfection. Histopathological examination of lung tissues showed more intense infiltration of inflammatory cells and severe tissue destruction in A(H1N1)pdm09-infected mice at 7 days postinfection than at 10 days postinfection., Conclusion: Our results suggest that enhanced AHR could contribute to severe exacerbation in human asthmatic patients with A(H1N1)pdm09 infection., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Early-onset sarcoidosis (EOS) and Blau syndrome (BS) are systemic inflammatory granulomatous diseases without visible pulmonary involvement, and are distinguishable from their sporadic and familial forms. The diseases are characterized by a triad of skin rashes, symmetrical polyarthritis, and recurrent uveitis. The most common morbidity is ocular involvement, which is usually refractory to conventional treatment. A gain-of-function mutation in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene has been demonstrated in this disease; however, little is known about the relationship between the activation of NOD2 and the pathophysiology of EOS/BS. Here we describe EOS/BS with a novel mutation in the NOD2 gene, as well as detection of Propionibacterium acnes (P. acnes) in the granulomatous inflammation., Case Presentation: An 8-year-old Japanese girl presented with refractory bilateral granulomatous panuveitis. Although no joint involvement was evident, she exhibited skin lesions on her legs; a skin biopsy revealed granulomatous dermatitis, and P. acnes was detected within the sarcoid granulomas by immunohistochemistry with P. acnes-specific monoclonal (PAB) antibody. Genetic analyses revealed that the patient had a NOD2 heterozygous D512V mutation that was novel and not present in either of her parents. The mutant NOD2 showed a similar activation pattern to EOS/BS, thus confirming her diagnosis. After starting oral prednisolone treatment, she experienced an anterior vitreous opacity relapse despite gradual prednisolone tapering; oral methotrexate was subsequently administered, and the patient responded positively., Conclusions: We presented a case of EOS/BS with a novel D512V mutation in the NOD2 gene. In refractory granulomatous panuveitis cases without any joint involvement, EOS/BS should be considered as a differential diagnosis; genetic analyses would lead to a definite diagnosis. Moreover, this is the first report of P. acnes demonstrated in granulomas of EOS/BS. Since intracellular P. acnes activates nuclear factor-kappa B in a NOD2-dependent manner, we hypothesized that the mechanism of granuloma formation in EOS/BS may be the result of NOD2 activity in the presence of the ligand muramyl dipeptide, which is a component of P. acnes. These results indicate that recognition of P. acnes through mutant NOD2 is the etiology in this patient with EOS/BS.

Acute pericarditis is inflammation of the pericardium with or without pericardial effusion. In the pediatric population, most patients with acute pericarditis are diagnosed with idiopathic pericarditis. Herein, we present two children with idiopathic pericarditis who underwent immunological assessment of pericardial effusion for the first time. Both patients showed equally high levels of interleukin-6 in the pericardial effusion. However, they had different treatment responses, in accordance with the pericardial effusion and serum interleukin-10 concentrations. Our present cases suggest that interleukin-10 may be associated with the response to anti-inflammatory therapy in idiopathic acute pericarditis.

Diazoxide, a drug used to treat hyperinsulinemic hypoglycemia (HH), is associated with pulmonary hypertension (PH), as reported by the US Food and Drug Administration. However, no report has detailed the association between diazoxide dose and PH development. We report a case of an infant with HH, subsequently complicated by diazoxide-induced PH. When diazoxide was introduced, PH did not appear initially, but it developed during increased dosing. We monitored PH via regular echocardiography examinations. PH gradually improved with tapering of the diazoxide dose and disappeared after drug discontinuation. Our case suggests a diazoxide dose threshold might induce PH. Therefore, close echocardiography examinations should accompany diazoxide treatment.

Background: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and impaired consciousness. The efficacy of hypothermia/normothermia therapy in patients with AESD has rarely been reported on., Methods: We enrolled 15 patients with AESD admitted to Yamaguchi University Hospital and Yamaguchi-ken Saiseikai Shimonoseki General Hospital between 2005 and 2019 and retrospectively evaluated the long-term efficacy of hypothermia therapy compared to that of non-hypothermia therapy. We compared the long-term sequelae of patients with AESD treated with or without hypothermia therapy. We used the Pediatric Cerebral Performance Category (PCPC) scale and intelligence tests including the Wechsler Intelligence Scale for Children, Tanaka-Binet Intelligence Scale, and Enjoji Infantile Developmental Scale to evaluate neurological sequelae and mental disability. The preventive effect of hypothermia therapy was assessed based on the development of post-encephalopathic epilepsy (PEE)., Results: There was no significant between-group difference in the PCPC score (p = 0.53). The subjects with severe mental disability in the hypothermia therapy group were 0 (0%), while those in the non-hypothermia group were 2 (29%); however, the difference was not significant. Notably, there were no patients with onset of PEE in the hypothermia therapy group, while there were 4 (57.1%) in the non-hypothermia group (p = 0.03)., Conclusions: Our study suggests that hypothermia therapy may be effective in the long-term sequelae of AESD in terms of preventing the development of PEE. We propose that hypothermia therapy could contribute to improve the quality of life in these patients by preventing the subsequent onset of PEE., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: Intravenous immunoglobulin (IVIG) therapy is a useful first-line treatment for Kawasaki disease (KD); however, 10-20% of patients fail to respond and require additional IVIG. Soluble CD163 (sCD163) is considered a biomarker for macrophage activation. There are no reports measuring serum sCD163 in KD patients. This study aimed to explore its possible utility in the clinical management of patients with KD. Methods: Eighty-seven patients with well-defined KD were retrospectively enrolled together with 19 healthy individuals with comparable ages. KD patients were classified into three groups, Group A (initial IVIG responders), Group B (additional IVIG responders), and Group C (additional IVIG non-responders). Serum sCD163 together with complete blood counts, C-reactive protein, d-dimer, albumin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured before the initial IVIG treatment in all cases, and afterward in a fraction of cases. Results: Serum sCD163 in KD patients before initial IVIG was generally much higher than the control group. The median (interquartile range) of sCD163 was as follows: Control 446 (385-521) ng/mL; Group A, 699 (478-1,072); Group B, 1,349 (1,116-1,390); and Group C, 665 (544-1,094). In general, sCD163 showed close positive correlation with ALT and AST, but none with other markers. Among the KD groups, Group B showed the highest sCD163: Group B vs. A: p = 0.0003; B vs. C: p = 0.035). Serum sCD163 was significantly increased after IVIG in Group A, while no change occurred in others. Conclusion: The serum sCD163 levels could be a useful biomarker in the clinical management of KD, especially for predicting responsiveness to IVIG., (Copyright © 2020 Azuma, Suzuki, Okada, Matsuguma, Wakiguchi, Ohnishi, Furuta, Miyake, Yasudo, Ichihara, Ohga and Hasegawa.)

Background: The precise mechanism of hyponatremia in Kawasaki disease (KD) remains elusive because assessment of volume status based on serial changes in body weight is lacking in previous reports., Methods: Seventeen patients who were diagnosed with KD and hyponatremia (serum sodium levels <135 mmol/L) were analyzed. Volume status was assessed based on serial changes in body weight. Plasma arginine vasopressin (ADH), urine electrolytes, and serum cytokine levels were measured on diagnosis of hyponatremia. An increase in body weight by >3% was defined as hypervolemia and a decrease in body weight by >3% was defined as hypovolemia., Results: The volume status was hypervolemic in three patients (18%), euvolemic in 14 (82%), and hypovolemic in none (0%). Five (29%) patients were diagnosed with "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH) and no patients were diagnosed with hypotonic dehydration. The contribution of decreased total exchangeable cations (salt loss) to hyponatremia (5.9% [interquartile range, 4.3%, 6.7%]) was significantly larger than that of increased total body water (-0.7% [-1.8%, 3.1%]) (P = 0.004). Serum interleukin-6 levels were elevated in all of the nine patients who were evaluated. Among the 12 (71%) patients who did not meet the criteria of SIADH and hypotonic dehydration, plasma ADH levels were inappropriately high in ten patients. These patients were also characterized by euvolemic or hypervolemic hyponatremia and salt loss, which might be compatible with a diagnosis of SIADH., Conclusions: Our study shows that hyponatremia in KD is euvolemic or hypervolemic and is associated with nonosmotic secretion of ADH and salt loss in the majority of patients., (© 2019 Japan Pediatric Society.)

Delayed physical growth is a common complication of pediatric obstructive sleep apnea syndrome (OSAS). Adenotonsillectomy (AT) is the first-line treatment for pediatric OSAS. Only a few studies have performed time-course BMI evaluation in pediatric OSAS patients post-operatively. Thus, we aimed to evaluate the time-course changes in pediatric OSAS patients after AT. Thirty-three children with OSAS who underwent AT were included and divided into two groups on the basis of their BMI z-scores (delayed physical growth group, n = 15; non-delayed physical growth group, n = 18). Clinical records of height and weight were collected before AT and at 6, 12, 24, and 36 months after AT. Changes in the mean BMI z-scores of the two groups were assessed up to 36 months. The mean BMI z-score was significantly increased in the delayed physical growth group at 6 months after AT. In contrast, the increase in mean BMI z-score was not observed in the non-delayed physical growth group. Growth improvement was noted in pediatric OSAS patients with delayed physical growth after AT. Our results suggest that AT is a promising therapy for improving the physical growth of pediatric OSAS patients with such problems., (Copyright © 2020 Fukuda, Yasudo, Ohta, Narumi, Abe, Tarumoto, Yamashita, Ichihara, Ohga and Hasegawa.)

Objective: To evaluate the diagnostic utility of wall hypertrophy of the duodenal bulb with a hyperechoic lumen, designated as the "HH sign," using ultrasound sonography (US) in pediatric duodenal ulcer (DU) patients. Study design: We performed a US for five pediatric subjects diagnosed with DU by upper gastroscopy to determine the presence of the potentially diagnostic HH sign. The sonographic images were analyzed before and after DU treatment. Computed tomography was performed in three cases and fecal occult blood test (FOBT) in all five cases. Results: Upper gastroscopy confirmed DU in all patients. While the HH sign was observed using US in four cases, with the DU located in the anterior bulb, the FOBT was positive in only one case. In these four cases, the HH sign diminished in response to treatment, as visualized by US. This was observed for both the initial as well as recurrent episodes. A mass-like region was observed in only one case, with the ulcer located in the proximity of the inferior duodenal wall. Conclusion: The HH sign is useful for the follow-up of DU, and US may be a suitable modality for the follow-up. We believe that this diagnostic marker can aid in following up a greater number of DU cases., (Copyright © 2020 Sakata, Yasudo, Uchida, Saito, Azuma and Hasegawa.)

Background: Respiratory viral and mycoplasma infections are associated with childhood asthma exacerbations. Here, we explored epidemiologic profile of causative pathogens and possible factors for exacerbation in a single center over a three-year period., Methods: Hospitalized asthmatic children with attack aged 6 months-17 years were recruited between 2012 and 2015 (n = 216). Nasopharyngeal mucosa cell samples were collected from the participants and examined by reverse transcription-polymerase chain reaction to detect rhinovirus (RV), respiratory syncytial virus (RSV), enterovirus (EV), parainfluenza virus (PIV), Mycoplasma pneumoniae, and others. Clinical features, laboratory data, asthma exacerbation intensity, and asthma severity were compared among participants. Epidemiologic profile of causative pathogens and possible factors for exacerbation were explored., Results: Viruses and/or Mycoplasma pneumoniae were detected in 75% of the participants. Rhinovirus (48%) was the most commonly detected virus in the participants with single infection, followed by RSV (6%). The median age at admission in the RV group was significantly higher than that in the RSV group. Insufficient asthma control and allergen sensitization were significantly related to RV-associated asthma exacerbation. There was no seasonality of pathogen types associated with asthma exacerbation although a sporadic prevalence of EV-D68 was observehinovirud. Rhinovirus were repeatedly detected in multiple admission cases., Conclusion: Our three-year analysis revealed that patients with RV infection were significantly prone to repeated RV infection in the subsequent exacerbation and good asthma control could prevent RV-associated asthma development and exacerbation. Multiple-year monitoring allowed us to comprehend the profile of virus- and/or mycoplasma-induced asthma exacerbation., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Kawasaki disease (KD) is acute and self-limited vasculitis caused by unknown origin, and the critical complication in KD patients is coronary artery lesions (CALs). The endothelial glycocalyx is a network of membranes luminally covering the endothelium. This study aimed to evaluate the clinical utility of serum glycocalyx components as biomarkers of predicting the onset CALs in KD., Methods: Seventy subjects with complete type KD, 18 subjects as febrile control (FC), and 15 subjects as afebrile controls (AC) were enrolled. Medical, demographic, echocardiography, and laboratory data from the medical records were retrospectively analyzed. Serum syndecan-1 and hyaluronan levels prior to intravenous immunoglobulin (IVIG) therapy were measured at the acute phase, immediately after IVIG, the subacute phase, and the time of discharge at the convalescent phase., Results: Serum syndecan-1 and hyaluronan levels were higher in the KD group than in the AC and FC groups at all three phases. Further, these levels were compared between KD patients with and without the development of CALs. Serum syndecan-1 and hyaluronan levels at the acute phase were significantly elevated in KD patients with the CALs than in those without CALs. Serum hyaluronan, not syndecan-1, was determined as the most contributory parameter to predict CALs by a multiple logistic analysis., Conclusions: Circulating syndecan-1 and hyaluronan can be useful biomarkers to predict the development of CALs in KD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Objectives: Upper urinary tract infection is the most common serious bacterial infection in childhood. Patients with upper urinary tract infection have a risk for renal scarring with subsequent complications including hypertension, proteinuria, and progressive renal failure. However, the predictive biomarkers of renal scarring in children with upper urinary tract infection are still unknown. In this study, we evaluated whether soluble ST2 levels can be biomarkers of subsequent renal scarring in patients with upper urinary tract infection., Design, Setting, Participants, and Measurements: We retrospectively studied pediatric patients with upper urinary tract infection at a tertiary center. Twenty-eight children had an upper urinary tract infection with (n = 14) and without (n = 14) renal scarring and underwent 99mtechnetium dimercaptosuccinic acid imaging. In addition, 13 control subjects were enrolled. The clinical data and serum cytokine levels, including soluble ST2 levels, were compared between those with and without renal scars., Results: Serum soluble ST2 levels were significantly higher in the scar group than in the non-scar group, whereas there was no difference in the levels of serum interferon-γ, interleukin-6, interleukin-10, soluble tumor necrosis factor receptor 1, and transforming growth factor-β between the scar and non-scar groups. The area under the curve for differentiating between the non-scar and scar groups on the basis of measurements of serum soluble ST2 was 0.79, with a sensitivity and specificity of 92.9% and 64.3%, respectively., Conclusion: These results suggest that serum soluble ST2 levels on admission could be a useful biomarker of subsequent renal scarring in pediatric patients with upper urinary tract infection., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS.

Smith-Lemli-Opitz syndrome is an autosomal recessive disease caused by mutations in 7-dehydrocholesterol reductase ( DHCR7 ), which is rarely observed in Japan. We report a Japanese case with 46,XY disorder of sex development and Y-shaped 2-3 toe syndactyly. DHCR7 gene analysis revealed compound heterozygous mutations including the novel mutation H442R. Early diagnosis led to starting cholesterol treatment at an early age., Competing Interests: The authors declare no conflict of interest.

Background: Egg allergy is one of the most common food allergies in young children. While oral immunotherapy (OIT) is not routinely recommended in current guidelines, it has been considered as a potential alternative treatment strategy. Studies on OIT for food allergy have been explored, but no controlled trials have been reported in Japan., Methods: The first oral food challenge (OFC) was performed before treatment to ensure diagnosis and evaluate the threshold dose for egg using the double-blind, placebo-controlled food challenge. Participants were randomly assigned by computerized algorithm to receive OIT using egg (OIT group) or no egg (egg elimination [EE] group). A second OFC was performed in both groups approximately 6 months after therapy. Blood samples were collected and egg white-specific immunoglobulin (Ig)E and IgG4 were measured before and after the treatment period., Results: Eight of the 14 patients (57%) in the OIT group had no allergic reaction to 4 g dry egg powder whereas none of the 16 patients in the EE group did. All 14 patients in the OIT group had increased threshold for egg powder in the second OFC compared with baseline. There was no significant change in egg white-specific IgE level during therapy. After therapy, egg white-specific IgG4 increased significantly in the OIT group, but not in the EE group., Conclusion: OIT is effective in increasing the threshold for allergens and inducing desensitization in Japanese egg allergy patients, similarly to North American and European patients., (© 2016 Japan Pediatric Society.)

We report the case of a 9-year-old girl who presented with mixed-type fulminant autoimmune hemolytic anemia (AIHA) at the onset of systemic lupus erythematosus (SLE). On admission, laboratory investigations indicated very severe anemia (Hb, 2.7 g/dL) with reticulocytosis and positive direct/indirect Coombs tests. In addition, agglutinative reaction was clinically observed. Based on further examinations, the patient was diagnosed with AIHA complicated with SLE, and mixed-type AIHA was clinically identified. With oral prednisolone and methylprednisolone pulse therapy, the patient entered remission., (© 2016 Japan Pediatric Society.)

Pediatric cutaneous mastocytosis is a rare disease caused by mast cell hyperplasia. We report the case of an infant diagnosed as cutaneous mastocytosis and seasonal allergies. The wheals, flushing, and pruritus of the mastocytosis were unresponsive to combination therapy with an antihistamine, a mast cell stabilizer (sodium cromoglycate), and a leukotriene antagonist. Addition of suplatast tosilate as a treatment for the seasonal allergy also dramatically improved his cutaneous symptoms and signs. Further trials of suplatast tosilate in selected cases of cutaneous mastocytosis are warranted., (© 2015 Wiley Periodicals, Inc.)

Objective: When fractured, zygomas rotate and dislocate. The present study quantitatively elucidates the pattern of the rotation., Methods: 50 patients with tri-pod-type zygoma fractures were involved in this study. After defining a 3-dimensional coordinate system--consisting of the M-L axis (the axis directed from the medial to lateral side of the skull), I-S axis (directed from the inferior to superior side), and P-A axis (directed from the posterior to anterior side), the degree with which the fractured zygomas rotated around each of these axes was measured using 3-dimensional graphic software. Thereafter, the tendency of the rotation was compared between the three rotational axes., Results: Rotation around the I-S axis was the most frequent with a 96% incidence, followed by a substantial margin by rotation around the M-L axis with a 26% incidence; rotation around the P-A axis was rare, with an incidence of 10%. Furthermore, the degree of P-A axis rotation was minor compared to I-S and M-L axis rotations., Conclusion: The main factor of zygoma dislocation in zygoma fracture is rotation around the I-S axis. This finding is helpful for effective performance to reposition fractured zygomas., (Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Mast cells are major effectors in high-affinity IgE receptor (FcɛRI)-dependent allergic reactions. Here we show that phospholipase C (PLC)-β3 is crucial for FcɛRI-mediated mast cell activation. Plcb3(-/-) mice showed blunted FcɛRI-dependent late-phase, but not acute, anaphylactic responses and airway inflammation. Accordingly, FcɛRI stimulation of Plcb3(-/-) mast cells exhibited reduced cytokine production but normal degranulation. Reduced cytokine production in Plcb3(-/-) cells could be accounted for by increased activity of the negative regulatory Src family kinase Lyn and reduced activities of the positive regulatory protein kinases MAPKs. Mechanistically, PLC-β3 constitutively interacts with FcɛRI, Lyn, and SHP-1 (protein phosphatase). SHP-1 probably recognizes its substrates Lyn and MAPKs via the recently described kinase tyrosine-based inhibitory motif, KTIM. Consistent with PLC-β3- and SHP-1-mediated repression of Lyn activity by dephosphorylation at Tyr396, FcɛRI-mediated phenotypes were similar in Plcb3(-/-) and SHP-1 mutant mast cells. Thus, we have defined a PLC-β3- and SHP-1-mediated signaling pathway for FcɛRI-mediated cytokine production., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies including myeloproliferative neoplasm (MPN). Our recent study found that phospholipase C (PLC)-β3 is a novel tumor suppressor involved in MPN, lymphoma and other tumors. Stat5 activity is negatively regulated by the SH2 domain-containing protein phosphatase SHP-1 in a PLC-β3-dependent manner. PLC-β3 can form the multimolecular SPS complex together with SHP-1 and Stat5. The close physical proximity of SHP-1 and Stat5 brought about by interacting with the C-terminal segment of PLC-β3 (PLC-β3-CT) accelerates SHP-1-mediated dephosphorylation of Stat5. Here we identify the minimal sequences within PLC-β3-CT required for its tumor suppressor function. Two of the three Stat5-binding noncontiguous regions, one of which also binds SHP-1, substantially inhibited in vitro proliferation of Ba/F3 cells. Surprisingly, an 11-residue Stat5-binding peptide (residues 988-998) suppressed Stat5 activity in Ba/F3 cells and in vivo proliferation and myeloid differentiation of hematopoietic stem/progenitor cells. Therefore, this study further defines PLC-β3-CT as the Stat5- and SHP-1-binding domain by identifying minimal functional sequences of PLC-β3 for its tumor suppressor function and implies their potential utility in the control of hematopoietic malignancies.

Given its catalytic activity to generate diacylglycerol and inositol 1,4,5-trisphosphate, phospholipase C (PLC) is implicated in promoting cell growth. However, we found that PLC-beta3-deficient mice develop myeloproliferative disease, lymphoma, and other tumors. The mutant mice have increased numbers of hematopoietic stem cells with increased proliferative, survival, and myeloid-differentiative abilities. These properties are dependent on Stat5 and can be antagonized by the protein phosphatase SHP-1. Stat5-dependent cooperative transformation by active c-Myc and PLC-beta3 deficiency was suggested in mouse lymphomas in PLC-beta3(-/-) and in Emicro-myc;PLC-beta3(+/-) mice and human Burkitt's lymphoma cells. The same mechanism for malignant transformation seems to be operative in other human lymphoid and myeloid malignancies. Thus, PLC-beta3 is likely a tumor suppressor.