American Society for Clinical Investigation Acta Medica Okayama 2379-3708 11 3 2025 Collagen-binding C-type natriuretic peptide enhances chondrogenesis and osteogenesis e198959 EN Kenta Hirai Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenta Sawamura Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Ryusaku Esaki Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Ryusuke Sawada Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuka Okusha Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eriko Aoyama Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Hiroki Saito Department of Orthopaedic Surgery, Kitasato University School of Medicine Kentaro Uchida Department of Orthopaedic Surgery, Kitasato University School of Medicine Takehiko Mima Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences Satoshi Kubota Department of Biochemistry and Molecular DentistryBacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Masaki Matsushita Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuyuki Hosono Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences C-type natriuretic peptide (CNP) is known to promote chondrocyte proliferation and bone formation; however, CNP’s extremely short half-life necessitates continuous intravascular administration to achieve bone-lengthening effects. Vosoritide, a CNP analog designed for resistance to neutral endopeptidase, allows for once-daily administration. Nonetheless, it distributes systemically rather than localizing to target tissues, which may result in adverse effects such as hypotension. To enhance local drug delivery and therapeutic efficacy, we developed a potentially novel synthetic protein by fusing a collagen-binding domain (CBD) to CNP, termed CBD-CNP. This fusion protein exhibited stability under heat conditions and retained the collagen-binding ability and bioactivity as CNP. CBD-CNP localized to articular cartilage in fetal murine tibiae and promoted bone elongation. Spatial transcriptomic analysis revealed that the upregulation of chondromodulin expression may contribute to its therapeutic effects. Treatment of CBD-CNP mixed with collagen powder to a fracture site of a mouse model increased bone mineral content and bone volume compared with CNP-22. Intraarticular injection of CBD-CNP to a mouse model of knee osteoarthritis suppressed subchondral bone thickening. By addressing the limitations of CNP’s rapid degeneration, CBD-CNP leverages its collagen-binding capacity to achieve targeted, sustained delivery in collagen-rich tissues, offering a promising strategy for enhancing chondrogenesis and osteogenesis. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2950-2217 3 2 2025 Erythromelalgia presenting with posterior reversible encephalopathy syndrome: A pediatric case report 100078 EN Kengo Suzuki Department of Pediatrics, Okayama University Hospital Kazuhiro Uda Department of Pediatrics, Okayama University Hospital Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kyosuke Arakawa Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Shigehara Department of Pediatrics, Okayama University Hospital Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Erythromelalgia is a rare disorder characterized by erythema, warmth, and burning pain in the extremities. We report a pediatric case of erythromelalgia in a patient who developed posterior reversible encephalopathy syndrome (PRES), without any cutaneous signs. Case presentation: A previously healthy 12-year-old girl presented to our pediatric clinic with burning extremity pain that had persisted for 6 weeks. The patient was treated with analgesics; however, the pain was refractory to these agents. Seven days after the first visit, she developed afebrile seizures and was transferred to our hospital. Her initial blood pressure was 139/105 mmHg (+2.0 SD), and brain magnetic resonance imaging revealed high intensity areas in the bilateral parietal and occipital lobes, leading to a diagnosis of PRES. Her blood pressure was difficult to control with anti-hypertensive agents. Burning pain in her extremities was relieved by cooling and worsened by warming. Although erythema was not observed in her hands or legs, erythromelalgia was suspected based on the characteristic nature of her pain. Intravenous lidocaine was administered for diagnosis, which was dramatically effective. After initiating mexiletine, the burning pain in her extremities disappeared, and hypertension improved. A final diagnosis of erythromelalgia with PRES was made. Conclusion: A history of temperature-dependent pain relief and deterioration are important indicators of disease diagnosis, even if patients indicate a lack of erythema or warmth. Physicians should be aware that persistent pain due to erythromelalgia can lead to refractory hypertension and development of PRES. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 ポストコロナの感染症 140 143 EN Kazuhiro Uda Department of Pediatric Regional Healthcare, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 3 2025 岡山大学小児医科学教室における最近の研究成果 108 117 EN Hirokazu Tsukahara Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 Changes in body mass index during early childhood on school‐age asthma prevalence classified by phenotypes and sex e70090 EN Toshihiko Yabuuchi Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masanori Ikeda Department of Pediatrics, Okayama University Medical School Naomi Matsumoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsuru Tsuge Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Few studies have explored the relationship between changes in body mass index(BMI) during early childhood and asthma prevalence divided by phenotypes and sex, and the limited results are conflicting. This study assessed the impact of BMI changes during early childhood on school-age asthma, classified by phenotypes and sex, using a nationwide longitudinal survey in Japan. Methods: From children born in 2001 (n = 47,015), we divided participants into BMI quartiles (Q1, Q2, Q3, and Q4) and the following BMI categories: Q1Q1 (i.e., Q1 at birth and Q1 at age 7), Q1Q4, Q4Q1, Q4Q4, and others. Asthma history from ages 7 to 8 was analyzed, with bronchial asthma (BA) further categorized as allergic asthma (AA) or nonallergic asthma (NA) based on the presence of other allergic diseases. Using logistic regression, we estimated the asthma odds ratio (OR) and 95% confidence intervals (CIs) for each BMI category. Results: Q1Q4 showed significantly higher risks of BA, AA, and NA. In boys, BA and NA risks were significantly higher in Q1Q4 (adjusted OR: 1.47 [95% CI: 1.17–1.85], at 1.56 [95% CI: 1.16–2.1]), with no significant difference in AA risk. In girls, no increased asthma risk was observed in Q1Q4, but AA risk was significantly higher in Q4Q4 (adjusted OR: 1.78 [95% CI: 1.21–2.6]). Conclusion: Our results demonstrated that BMI changes during early childhood impact asthma risks, particularly that the risk of NA in boys increases with BMI changes during early childhood, and the risk of AA in girls increases with consistently high BMI. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 Avoidant/restrictive food intake disorder prognosis and its relation with autism spectrum disorder in Japanese children e70040 EN Chie Tanaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mana Hanzawa Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Fujii Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshie Shigeyasu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sugihara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makiko Horiuchi Clinical Psychology Section, Department of Medical Support, Okayama University Hospital Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: There is a lack of reported clinical factors associated with the outcomes of children and adolescents with avoidant/restrictive food intake disorder (ARFID) in Japan. This study aimed to identify these clinical factors and explore the relationship between ARFID and autism spectrum disorder (ASD). Methods: This retrospective study analyzed data from 48 Japanese children and adolescents with ARFID who visited Okayama University Hospital between January 2011 and March 2022. Clinical characteristics were assessed using medical records and natural history questionnaires. The study compared patients with good and poor prognosis groups and used multiple logistic regression analysis to determine factors influencing prognosis. Results: The study included 33 patients with good prognoses and 15 with poor prognoses. Comorbid ASD was more prevalent in the poor prognosis group (60%) compared to the good prognosis group (21%). Additionally, more than half of the ARFID patients with comorbid ASD were initially undiagnosed. Multivariate analysis revealed that older age at first visit (p = 0.022) and comorbid ASD (p = 0.022) were statistically significant factors associated with poor prognosis in ARFID patients. There were no significant differences in body mass index standard deviation score and maximal weight loss between the two groups. Conclusions: The poor prognosis group had a higher prevalence of comorbid ASD diagnoses. Therefore, it is crucial to evaluate patient's developmental characteristics early in treatment and consider these characteristics throughout the course of care. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0910-8327 2025 Outcomes of ultra-high-pressure balloon angioplasty for congenital heart disease in single-center experience EN Maiko Kondo Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kurita Department of Pediatrics, Okayama University Hospital Yosuke Fukushima Department of Pediatrics, Okayama University Hospital Yusuke Shigemitsu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenta Hirai Department of Pediatrics, Okayama University Hospital Yuya Kawamoto Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayuko Hara Department of Pediatrics, Okayama University Hospital Tomoyuki Kanazawa Department of Pediatric Anesthesiology, Okayama University Hospital Tatsuo Iwasaki Department of Pediatric Anesthesiology, Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Okayama University Hospital Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Kenji Baba Department of Pediatrics, Okayama University Hospital Angioplasty using ultra-high-pressure (UHP) balloons may successfully treat stenotic lesions refractory to high-pressure dilation. The use of UHP balloons in patients with congenital heart disease is mostly for dilation of the pulmonary artery, and there have been few reports on the effectiveness and safety of balloons for other sites. We retrospectively evaluated the efficacy and safety of the ultra-high-pressure balloon angioplasty (UHP-BA) for stenotic lesions in patients with congenital heart disease between January 2020 and December 2022 at Okayama University Hospital. A total of 78 UHP-BAs were performed in 44 patients, with a median age of 6.6 years and a median weight of 17.6 kg. The balloon types used in the UHP-BAs were Yoroi® and Conquest®. UHP-BA performed 39 procedures for the pulmonary artery (PA), 24 for fenestration, 8 for SVC, 4 for shunt, and three for others. The lesion-specific acute procedural success rates for PA, Fontan fenestration, SVC, and shunt were 77%, 75%, 88%, and 75%, respectively. A complication of UHP-BA occurred in 3.8% (3/78). Two of the three patients had pulmonary hemorrhage, and the remaining patients had pulmonary artery embolization due to the migration of a thrombus. There were no fatal complications. Balloon dilation with UHP balloons was safe and effective not only for pulmonary artery stenotic lesions but also for SVC, Fontan fenestration, shunt, and other dilation sites in patients with congenital heart disease. No potential conflict of interest relevant to this article was reported.

Japanese Society for Pediatric Endocrinology Acta Medica Okayama 0918-5739 34 2 2025 Effect of calcium supplementation on bone deformity and histopathological findings of skin papules in a pediatric patient with vitamin D–dependent rickets type 2A: A case report 131 136 EN Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Tomoko Miyake Department of Dermatology, Okayama University Hospital Mina Kobashi Department of Dermatology, Okayama University Hospital Tomonori Tetsunaga Department of Dermatology, Okayama University Hospital Yuko Ago Department of Pediatrics, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Hospital Hiroyuki Miyahara Department of Pediatrics, Okayama University Hospital Yousuke Higuchi Department of Pediatrics, Okayama University Hospital Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Vitamin D–dependent rickets type 2A (VDDR2A) is an autosomal recessive disease caused by pathogenic variants of the vitamin D receptor (VDR) gene. VDDR2A rickets are usually resistant to native or active vitamin D treatment because of impaired active calcium absorption against the calcium concentration gradient, which is a ligand-dependent VDR action in the small intestine. Alopecia due to an impaired skin follicular cycle is occasionally observed in patients with VDDR2A. Among the pathogenic VDR variants, most in the DNA-binding domain and some in the ligand-binding domain, which affect the dimerization of VDR with the retinoic X receptor, are associated with alopecia. Herein, we report a case of VDDR2A caused by compound heterozygous pathogenic variants of the DNA-binding domain of VDR. Active vitamin D treatment did not ameliorate genu varum, rachitic changes in the roentgenogram, or abnormal laboratory findings. However, oral administration of calcium lactate dramatically improved these findings. The patient also experienced hair loss at two months of age and multiple papules on the skin at two yr of age, which did not improve with vitamin D or calcium supplementation. We also report the histopathological findings of skin papules in this patient. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2673-253X 7 2025 Empowering pediatric, adolescent, and young adult patients with cancer utilizing generative AI chatbots to reduce psychological burden and enhance treatment engagement: a pilot study 1543543 EN Joe Hasei Department of Medical Information and Assistive Technology Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mana Hanzawa Department of Pediatrics, Okayama University Hospital Akihito Nagano Department of Orthopedic Surgery, Gifu University Graduate School of Medicine Naoko Maeda Department of Pediatrics, NHO National Hospital Organization Nagoya Medical Center Shinichirou Yoshida Department of Orthopedic Surgery, Tohoku University Graduate School of Medicine Makoto Endo Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University Nobuhiko Yokoyama Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University Motoharu Ochi Department of Pediatrics, Okayama University Hospital Hisashi Ishida Department of Pediatrics, Okayama University Hospital Hideki Katayama Department of Palliative and Supportive Care, Okayama University Hospital Tomohiro Fujiwara Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiji Nakata Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Nakahara Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Pediatric and adolescent/young adult (AYA) cancer patients face profound psychological challenges, exacerbated by limited access to continuous mental health support. While conventional therapeutic interventions often follow structured protocols, the potential of generative artificial intelligence (AI) chatbots to provide continuous conversational support remains unexplored. This study evaluates the feasibility and impact of AI chatbots in alleviating psychological distress and enhancing treatment engagement in this vulnerable population. Methods: Two age-appropriate AI chatbots, leveraging GPT-4, were developed to provide natural, empathetic conversations without structured therapeutic protocols. Five pediatric and AYA cancer patients participated in a two-week intervention, engaging with the chatbots via a messaging platform. Pre- and post-intervention anxiety and stress levels were self-reported, and usage patterns were analyzed to assess the chatbots' effectiveness. Results: Four out of five participants reported significant reductions in anxiety and stress levels post-intervention. Participants engaged with the chatbot every 2-3 days, with sessions lasting approximately 10 min. All participants noted improved treatment motivation, with 80% disclosing personal concerns to the chatbot they had not shared with healthcare providers. The 24/7 availability particularly benefited patients experiencing nighttime anxiety. Conclusions: This pilot study demonstrates the potential of generative AI chatbots to complement traditional mental health services by addressing unmet psychological needs in pediatric and AYA cancer patients. The findings suggest these tools can serve as accessible, continuous support systems. Further large-scale studies are warranted to validate these promising results. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0031-3998 2025 Spatiotemporal expression pattern of dyslexia susceptibility 1 candidate 1 (DYX1C1) during rat cerebral cortex development EN Kazumasa Zensho Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aika Isse Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ichika Misawa Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaori Masai Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makio Oka Department of Psychosocial Medicine, National Center for Child Health and Development Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Developmental dyslexia (DD) is a common learning disorder with significant consequences for affected individuals. Although several candidate genes, including dyslexia susceptibility 1 candidate 1 (DYX1C1), have been implicated in dyslexia, their role in brain development remains unclear. We aimed to elucidate the spatiotemporal expression patterns of DYX1C1 during cerebral cortex development in rats. Methods We investigated DYX1C1 expression during cerebral cortex development using rat embryos at various gestational stages (E13.5, 15.5, 17.5 and 20.5) by immunohistochemistry (n = 7 embryos/stage), quantitative real-time PCR (n = 6), and in situ hybridization (n = 11–15). Results The DYX1C1-positive cells were predominantly located in the outermost layers of the cortical plate, particularly at E15.5. DYX1C1 mRNA expression peaked at E15.5 and subsequently declined. DYX1C1-positive cells did not co-localize with reelin-positive Cajal-Retzius cells, but co-localized with neuronal markers expressed during development, and had shorter primary cilia than DYX1C1-negative cells. Conclusions Our findings highlight the dynamic expression of DYX1C1 in the developing cerebral cortex of rats, implicating its involvement in neurodevelopmental processes. Further investigation of the functional interactions of DYX1C1, particularly its relationship with reelin and its role in cerebrocortical and hippocampal development, may provide insights into the pathophysiology of dyslexia and neurodevelopmental disorders. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1710-1492 21 1 2025 Maternal smoking during infancy increases the risk of allergic diseases in children: a nationwide longitudinal survey in Japan 4 EN Kenji Shigehara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Uda Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yukie Saito Department of Pediatrics, Okayama University Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Ikeda Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background The incidence of allergic diseases has been increasing in Japan. In particular, a serious decline in the age of onset of allergic rhinitis has been observed. Passive smoking from parental smoking has a significant impact on children’s health; however, it is difficult to restrict smoking in the home. While various studies have previously reported on the relationship between passive smoking and the development of allergic diseases in children. However, there have been no reports on passive smoking and allergic diseases on a national scale. Methods Using Japanese national longitudinal survey data (n = 38,444) for newborns born between May 10 and 24, 2010, we assessed parental smoking habits when their children were 6 months old and investigated the association with the development of allergic diseases until the age of 5.5 years. The risk ratios and 95% confidence intervals for the development of different allergic diseases were analyzed after adjusting for potential confounders using Poisson regression with a robust error variance. Results The risk ratio for developing allergic rhinitis/allergic conjunctivitis (AR/AC) in children was significantly higher in the maternal smoking groups ( ≦ 10 cigarettes/day; RR 1.15, 95% CI 1.02–1.30; ≧11 cigarettes/day; RR 1.16, 95% CI 0.93–1.44). Furthermore, associations were found between the maternal smoking group in the presence of paternal smoking and the risk of developing bronchial asthma ( ≦ 10, RR 1.33 95% CI 1.17–1.52; ≧11, RR 1.71 95% CI 1.38–2.1), food allergy ( ≦ 10, RR 1.36 95% CI 1.12–1.63; ≧11, RR 1.25 95% CI 0.84–1.86), atopic dermatitis ( ≦ 10, RR 1.42 95% CI 1.22–1.66; ≧11, RR 1.6 95% CI 1.2–2.13), and AR/AC ( ≦ 10, RR 1.21 95% CI 1.07–1.36; ≧11, RR 1.35 95% CI 1.09–1.67). Conclusions Maternal smoking during infancy increases the risk of developing AR/AC in children. Considering paternal smoking, maternal smoking further increased the risk of developing allergic diseases in children, suggesting that reducing parental smoking at home may reduce the risk of developing allergic diseases in children. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1751-0759 18 1 2024 Psychogenic fever and neurodevelopmental disorders among Japanese children 23 EN Ayumi Okada Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshie Shigeyasu Department of Pediatrics, Okayama University Hospital Chikako Fujii Department of Pediatrics, Okayama University Hospital Chie Tanaka Department of Pediatrics, Okayama University Hospital Mana Hanzawa Department of Pediatrics, Okayama University Hospital Akiko Sugihara Department of Pediatrics, Okayama University Hospital Makiko Horiuchi Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Psychosocial stress can induce various physical symptoms, including fever, which is a commonly seen symptom in pediatric practice. In cases of unexplained fever, psychogenic fever should be considered as a potential cause. Children with neurodevelopmental disorders may be more vulnerable to stress and therefore more prone to developing somatic symptoms than their peers. This study aimed to elucidate the characteristics of children with psychogenic fever and comorbidity. Methods This study included 21 patients with psychogenic fever who visited the Department of Pediatric Psychosomatic Medicine, Okayama University Hospital. Information on age, sex, disease onset, final estimated diagnosis, comorbidities, treatment course, and outcome was obtained from the patients' medical records. Results Of the 21 patients included, 7 were boys and 14 were girls, and their median age was 13.0 (range: 8.6-14.6) years. A total of 19 patients had no attendance at school, and all patients showed signs of maladjustment in school. The comorbidities included orthostatic dysregulation (n = 4) and migraine (n = 3). Neurodevelopmental disorders were observed in nine patients, eight of whom were diagnosed after the initial visit. The mean treatment duration was 37.2 months. The outcomes were complete remission (n = 9), improvement (n = 4), discontinuation (n = 1), and referral to another physician (n = 7). Conclusion Various comorbidities were observed in the patients of this study with psychogenic fever, including the coexistence of neurodevelopmental disorders, such as autistic spectrum disorder. Children with neurodevelopmental disorders are prone to psychological stress resulting from difficulties in social adjustment. It is crucial to understand the developmental characteristics and environmental adaptation of patients to facilitate accurate diagnosis and treatment. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2296-2360 12 2024 Trabecular bone scores in children with osteogenesis imperfecta respond differently to bisphosphonate treatment depending on disease severity 1500023 EN Natsuko Futagawa Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Hiroyuki Miyahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Tanaka Department of Pediatrics, Okayama Saiseikai General Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Osteogenesis imperfecta (OI) is a congenital skeletal disorder characterized by bone fragility. Bisphosphonates (BISs) have become the mainstream treatment in children with OI. However, an optimal treatment protocol has not yet been established, while BIS treatment tends to be administered to normalize bone mineral density (BMD). Bone quality is an important component of bone strength. The trabecular bone score (TBS) is a quantitative measure of the microstructure that affects bone quality. This study investigated the TBS during BIS treatment in children with OI. Materials and methods: Twenty-nine children with OI were enrolled and classified into two groups: mild (type 1) and moderate to severe (types 3 and 4). Dual-energy x-ray absorptiometry images were retrospectively analyzed for TBS calculation. The relationship between the areal BMD (aBMD), its Z-score, height-adjusted BMD (BMDHAZ) Z-score, TBS, and TBS Z-score with the treatment duration was assessed for each group. Results: In the mild group, the aBMD, its Z-score, and BMDHAZ Z-score showed a significant positive correlation with treatment duration (r = 0.68, 0.68, 0.72, respectively, p < 0.01). The TBS Z-score tended to increase with treatment duration, albeit without reaching significance. In the moderate to severe group, the TBS Z-score showed a significant positive correlation with treatment duration (r = 0.48, p < 0.01), in contrast to the aBMD Z-score, which did not increase. Finally, the BMDHAZ Z-score only showed a weak positive correlation with treatment duration (r = 0.37, p < 0.01). Conclusion: Because BIS affect the BMD and TBS differently based on the severity of OI, treatment goals may need to be stratified by disease severity. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1751-0759 18 1 2024 Assessment of the renal function of patients with anorexia nervosa 19 EN Hiroyuki Miyahara Department of Clinical Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Yoshie Shigeyasu Department of Pediatrics, Okayama University Hospital Chikako Fujii Department of Pediatrics, Okayama University Hospital Chie Tanaka Department of Pediatrics, Okayama University Hospital Hanzawa Mana Department of Pediatrics, Okayama University Hospital Akiko Sugihara Clinical Psychology Section, Department of Medical Support, Okayama University Hospital Ayumi Okada Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background A decreased glomerular filtration rate (GFR), estimated using creatinine (Cr- eGFR), is often found at the initial presentation of anorexia nervosa (AN). Its pathophysiology has been explained mainly by dehydration, and chronic hypokalemia is also thought to be a cause. However, because we have often experienced cases of AN with decreased Cr-eGFR without these conditions, we must consider different etiologies. The focus of this paper is on low free triiodothyronine (FT3) syndrome. We also discuss the utility of eGFR, estimated using cystatin-C (CysC-eGFR), for these patients. Methods The data of 39 patients diagnosed with AN between January 2005 and December 2023 was available for study. The characteristics of patients at the lowest and highest body mass index standard deviation score (BMI-SDS) were examined. Data on the parameters Cr-eGFR, CysC-eGFR, dehydration markers, potassium (K), and hormonal data and BMI-SDS were assessed during the treatment course to evaluate the correlations in these parameters. Blood hematocrit, uric acid (UA), blood urine nitrogen (BUN) level, and urine specific gravity were adopted as dehydration markers; FT3, free thyroxine, thyroid stimulating hormone, and insulin-like growth factor were adopted as hormonal data. Cr-eGFR and simultaneously evaluated dehydration markers, K, or hormonal data were extracted and correlations associated with the changes in BMI-SDS were examined. Furthermore, Cr-eGFR and simultaneously assessed CysC-eGFR were compared. Results When the BMI-SDS was at the lowest value, low-FT3 syndrome was shown. Severe hypokalemia was not found in our study. A linear relation was not found between Cr-eGFR and BMI-SDS. A statistically significant correlation was found between Cr-eGFR and FT3 (p = 0.0025). Among the dehydration markers, statistically significant correlations were found between Cr-eGFR and BUN or UA. The difference between Cr-eGFR and CysC-eGFR was prominent, and CysC-eGFR showed much higher values. Conclusions Our data indicates that low-FT3 syndrome and dehydration were related to the renal function of our patients with AN. Furthermore, our data suggest that caution is needed in the interpretation of kidney function evaluation when using CysC-eGFR in cases of AN. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 15 2024 Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients 8370 EN Mitsuru Tsuge Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Kou Hasegawa Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Yasushi Tanimoto Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Goro Kimura Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Haruto Yamada Department of Infectious Disease, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Akihiko Taniguchi Department of Allergy and Respiratory Medicine, Okayama University Hospital Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Aokage Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrine Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0172-0643 46 6 2024 Pulmonary Flow Management by Combination Therapy of Hemostatic Clipping and Balloon Angioplasty for Right Ventricular-Pulmonary Artery Shunt in Hypoplastic Left Heart Syndrome 1635 1642 EN Yusuke Shigemitsu Department of Pediatrics, Okayama University Hospital Maiko Kondo Department of Pediatrics, Okayama University Hospital Yoshihiko Kurita Department of Pediatrics, Okayama University Hospital Yosuke Fukushima Department of Pediatrics, Okayama University Hospital Yuya Kawamoto Department of Pediatrics, Okayama University Hospital Kenta Hirai Department of Pediatrics, Okayama University Hospital Mayuko Hara Department of Pediatrics, Okayama University Hospital Tomoyuki Kanazawa Department of Pediatric Anesthesiology, Okayama University Hospital Tatsuo Iwasaki Department of Pediatric Anesthesiology, Okayama University Hospital Shingo Kasahara Department of Pediatric Anesthesiology, Okayama University Hospital Koichi Kataoka Department of Cardiovascular Surgery, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Kenji Baba Department of Pediatrics, Okayama University Hospital Controlling pulmonary blood flow in patients who have undergone Norwood palliation, especially early postoperatively, is challenging due to a change in the balance of systemic and pulmonary vascular resistance. We applied a combination therapy of clipping and balloon angioplasty for right ventricle―pulmonary artery (RV-PA) shunt to control pulmonary blood flow, but the influence of the combination therapy on the PA condition is uncertain. Retrospectively analysis was conducted of all infants with hypoplastic left heart syndrome who had undergone Norwood palliation with RV-PA shunt at Okayama University Hospital from January 2008 to September 2022. A total of 50 consecutive patients underwent Norwood palliation with RV-PA shunt in this study period. Of them, 29 patients underwent RV-PA shunt flow clipping, and the remaining 21 had unclipped RV-PA shunt. Twenty-three patients underwent balloon angioplasty for RV-PA shunt with clips. After balloon angioplasty, oxygen saturation significantly increased from 69 (59–76)% to 80 (72–86)% (p < 0.001), and the narrowest portion of the clipped conduit significantly improved from 2.8 (1.8–3.4) to 3.8 (2.9–4.6) mm (p < 0.001). In cardiac catheterizations prior to Bidirectional cavo-pulmonary shunt (BCPS), there were no significant differences in pulmonary-to-systemic flow ratio (Qp/Qs), ventricular end-diastolic pressure, Nakata index, arterial saturation, mean pulmonary artery pressure and pulmonary vascular resistance index. On the other hand, in Cardiac catheterizations prior to Fontan, Nakata index was larger in the clipped group (p = 0.02). There was no statistically significant difference in the 5-year survival between the two groups (clipped group 96%, unclipped group 74%, log-rank test: p = 0.13). At least, our combination therapy of clipping and balloon angioplasty for RV-PA shunt did not negatively impact PA growth. Although there is a trend toward better but not statistically significant difference in outcomes in the clipped group compared to the non-clipped group, this treatment strategy may play an important role in improving outcomes in hypoplastic left heart syndrome. No potential conflict of interest relevant to this article was reported.

Elsevier Taiwan Acta Medica Okayama 1875-9572 65 3 2024 Postnatal longitudinal analysis of serum nitric oxide and eosinophil counts in extremely preterm infants 276 281 EN Hirokazu Watanabe Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Yosuke Washio Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Kei Tamai Department of Neonatology, Okayama Medical Center, National Hospital Organization Daisaku Morimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Tomoka Okamura Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Junko Yoshimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hidehiko Nakanishi Department of Neonatology, Maternal and Perinatal Center, Tokyo Women’s Medical University Misao Kageyama Department of Neonatology, Okayama Medical Center, National Hospital Organization Atsushi Uchiyama Department of Neonatology, Maternal and Perinatal Center, Tokyo Women’s Medical University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Satoshi Kusuda Department of Neonatology, Maternal and Perinatal Center, Tokyo Women’s Medical University Background: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities. Methods: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion. Results: Serum NOx levels (mean ± standard deviation) were 22.5 ± 14.9 μmol/L, 51.2 ± 23.7 μmol/L, 42.4 ± 15.2 μmol/L, and 33.8 ± 9.4 μmol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 ± 199/μL, 613 ± 625/μL, 466 ± 375/μL, and 292 ± 228/μL at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse. Conclusion: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1758-8103 14 2 2023 Trends in childhood obesity in Japan: A nationwide observational study from 2012 to 2021 e12636 EN Shintaro Fujiwara Department of Pediatrics, NHO Okayama Medical Center Ko Harada Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Koyama Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The persistent ascension of childhood obesity on a global scale constitutes a significant quandary. The prevalence of childhood obesity in Japan peaked in the early 2000s and has been reported to have declined since then, but recent data and its trend including the novel coronavirus disease 2019 (COVID-19) pandemic era are not available. Moreover, there is a dearth of studies examining the correlation between the trend in childhood obesity and exercise habits over the past decade. This study aims to examine the changes in the prevalence of obesity, physical fitness, and exercise habits over the past 10 years in Japanese children. We investigated the prevalence of childhood obesity in Japan, using the School Health Statistics Survey data from 2012 to 2021. The dataset has a sample size representative of children nationwide and includes variables for obesity, such as height, weight, and age. Data were classified into groups by sex and age (6–8, 9–11, and 12–14 years age). Children weighing 20% or more of the standard body weight are classified as obese. The annual percentage changes and average annual percentage changes were estimated using the joinpoint regression model. We also examined the trends in the physical fitness test score and exercise time. Average annual percentage changes of boys increased, especially in the 6- to 8-year age group (3.4%–4.6%). For girls, average annual percentage changes had increased in 6- to 8-year (2.5%–4.0%) and 9- to 11-year (0.9%–2.2%) age groups. Since the late 2010s, significantly increasing annual percentage changes were observed in 12- to 14-year age boys (6.7%–8.9%) and girls of many age groups (2.6%–8.6%). The physical fitness test score and exercise time showed decreasing trends since the late 2010s. Childhood obesity may have generally risen in Japan, in the last decade. Encouraging healthy eating and physical activity through school policies and curricula is necessary. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1552-4825 194 5 2023 Radiological characteristics of skeletal growth in neonates and infants with achondroplasia e63525 EN Daisuke Miyahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Yuko Ago Department of Pediatrics, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Miyahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yousuke Higuchi Department of Pediatrics, Okayama University Hospital Kazuki Yamada Department of Orthopedics, Okayama University Hospital Tomonori Tetsunaga Department of Orthopedics, Okayama University Hospital Tadashi Moriwake Department of Pediatrics, Iwakuni Clinical Center, National Hospital Organization Hiroyuki Tanaka Department of Pediatrics, Okayama Saiseikai General Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1710-1492 19 1 2023 Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature 103 EN Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Shigehara Department of Pediatrics, Okayama University Hospital Kazuhiro Uda Department of Pediatrics, Okayama University Hospital Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Hospital Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Hospital Yukie Saito Department of Pediatrics, Okayama University Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Masanori Ikeda Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Background Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. Case presentation A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. Conclusions Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 65 1 2023 Adverse reactions in young children receiving the coronavirus disease 2019 vaccine e15696 EN Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junya Shimizu Department of Pediatrics, National Hospital Organization, Okayama Medical Center Yuji Yokoyama Department of Pediatrics, Okayama Aiiku Clinic Hirokazu Tsukahara Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: We sought to investigate the occurrence of adverse reactions in Japanese children aged 6 months to 4 years who received the BNT162b2 coronavirus disease 2019 (COVID-19) vaccine, to examine parental considerations, and to evaluate potential risk factors associated with post-vaccination fever. Methods: This cross-sectional survey study targeted 1617 children aged 6 months to 4 years who received their primary doses of BNT162b2 from November 10, 2022, to April 30, 2023, in Okayama Prefecture. We surveyed the occurrence of local and systemic reactions within 1 week after vaccination, and described the incidence proportions of adverse reactions for 515 participants overall and by age group. The study also examined the impact of previous COVID-19 infection and co-administration of the seasonal influenza vaccine on post-vaccination fever. A survey also assessed parents' reasons for vaccinating their children and the sources of information they used. Results: Adverse reactions were infrequent (5.2%, with fever ≥37.5°C; no cases exceeded 39°C) and did not increase with vaccine doses administered. The risk of post-vaccination fever was not statistically associated with a history of COVID-19―the adjusted risk ratio (aRR) was 0.99, and the 95% confidence interval (CI) was 0.41–2.39―but was associated with co-administration of the seasonal influenza vaccine (aRR 3.24, 95% CI 1.14–9.18). Parental decisions regarding vaccination were influenced by official government guidelines and primary care physicians' opinion. Conclusion: This study provides valuable insight into the safety profile of the BNT162b2 vaccine in Japanese children aged 6 months to 4 years. Further research involving larger cohorts and appropriate control groups is needed. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 18 10 2023 A randomized controlled trial of teprenone in terms of preventing worsening of COVID-19 infection e0287501 EN Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center Yasushi Tanimoto Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center Haruto Yamada Department of Infectious Disease, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Akihiko Taniguchi Department of Allergy and Respiratory Medicine, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Aokage Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections. Methods This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or noteprenone groups in a 1:1 ratio. We stratified patients by sex, age < and >= 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate. Results One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/ 49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325). Conclusion Teprenone afforded no clinical benefit. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 24 20 2023 Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review 15450 EN Mitsuru Tsuge Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Uda Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Takahiro Eitoku Department of Pediatrics, Kawasaki Medical School Naomi Matsumoto Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children. No potential conflict of interest relevant to this article was reported.

Japanese Society for Pediatric Endocrinology Acta Medica Okayama 0918-5739 32 4 2023 Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods 221 227 EN Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Hospital Yuko Ago Department of Pediatrics, Okayama University Hospital Hiroyuki Miyahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Harada Department of Pediatrics, JCHO Osaka Hospital Mari Miyazawa Department of Pediatrics, Kochi Health Sciences Center Junko Yoshimoto Department of Pediatrics, Okayama University Hospital Kenji Baba Department of Pediatrics, Okayama University Hospital Tadashi Moriwake Department of Pediatrics, Iwakuni Clinical Center, National Hospital Organization Hiroyuki Tanaka Department of Pediatrics, Okayama Saiseikai General Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease. No potential conflict of interest relevant to this article was reported.

Japan Epidemiological Association Acta Medica Okayama 0917-5040 33 2 2023 Adverse Reactions and Attitudes Toward the BNT162b2 COVID-19 Vaccine in Children 5 to 11 Years of Age in Japan 110 111 EN Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junya Shimizu Department of Pediatrics, National Hospital Organization, Okayama Medical Center Yuji Yokoyama Department of Pediatrics, Okayama Aiiku Clinic Hirokazu Tsukahara Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 A Boy Safely Treated with Tyrosine Kinase Inhibitors for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia with Osteolysis 439 442 EN Takahiro Shiwaku Department of Pediatrics, Okayama University Hospital Hisashi Ishida Department of Pediatrics, Okayama University Hospital Yasuhisa Tatebe Department of Pharmacy, Okayama University Hospital Kosuke Tamefusa Department of Pediatrics, Okayama University Hospital Motoharu Ochi Department of Pediatrics, Okayama University Hospital Kaori Fujiwara Department of Pediatrics, Okayama University Hospital Toshihide Kubo Department of Pediatrics, National Hospital Organization Okayama Medical Center Eiji Nakata Department of Orthopaedic Surgery, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Case Report 10.18926/AMO/65757 A three-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ALL) presented with an osteolytic lesion in his right upper arm. Tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are an essential component throughout the course of treatment for Ph+ALL. However, TKIs are reported to affect the bone metabolism. In the treatment course of the current patient, the osteolytic lesion quickly improved despite the continuous use of TKIs, even during the concomitant use of corticosteroids. This suggests that TKIs can be safely given with concomitant corticosteroids to children with Ph+ALL, even when osteolytic lesions are present. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1751-0759 17 1 2023 Quality of life and physical/psychosocial factors in children and adolescents with orthostatic intolerance 23 EN Yoshie Shigeyasu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chikako Fujii Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chie Tanaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sugihara Clinical Psychology section, Department of Medical Support, Okayama University Hospital Makiko Horiuchi Clinical Psychology section, Department of Medical Support, Okayama University Hospital Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background　Orthostatic intolerance (OI), which is common in children and adolescents, negatively impacts their quality of life (QOL) due to physical symptoms that limit work, school, and daily activities. The purpose of this study is to explore the association of physical and psychosocial factors with QOL scores in children and adolescents with OI. Methods　A cross sectional observational study was conducted. The study participants included 95 Japanese pediatric patients of age 9-15 years who were diagnosed with OI from April 2010 to March 2020. The QOL scores and the QOL T-scores of children with OI assessed using the KINDL-R questionnaire at the initial visit were compared with conventional normative data. The associations of physical and psychosocial factors with the QOL T-scores were examined using multiple linear regression. Results　Pediatric patients with OI had significantly lower QOL scores than healthy children in both elementary (50.7 +/- 13.5 vs. 67.9 +/- 13.4, p < 0.001) and junior high schools (51.8 +/- 14.6 vs. 61.3 +/- 12.6, p < 0.001). This finding was observed in the physical, mental, self-esteem, friends, and school domains. Total QOL scores were significantly associated with school nonattendance (beta = - 3.2, 95% confidence interval [CI] = - 5.8 to - 0.5, p = 0.022) and poor relationship with school (beta = - 5.0, 95% CI = - 9.8 to - 0.4, p = 0.035). Conclusions　These results suggest that the assessment of QOL, including both physical and psychosocial aspects, especially school factors, needs to be implemented earlier in children and adolescents with OI. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 134 3 2022 軟骨無形成症 176 179 EN Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Hospital Hiroyuki Miyahara Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Taylor and Francis Acta Medica Okayama 1064-1955 42 1 2023 Short stature in small-for-gestational-age offspring born to mothers with hypertensive disorders of pregnancy 2187623 EN Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Takashi Mitsui Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Kazumasa Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Kei Hayata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Yosuke Washio Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Yoshimoto Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Objective: To investigate the incidence and risk factors of small-for-gestational age (SGA) short stature at 2 and 3 years of age in SGA offspring born to women with hypertensive disorders of pregnancy (HDP). Methods: We examined 226 women with HDP whose respective SGA offspring were delivered. Results: Eighty offspring (41.2%) were diagnosed with SGA short stature. The prematurity before 32 weeks of gestation was the most significant factor for catch-up growth failure. Conclusion: In SGA offspring born to women with HDP, SGA short stature incidence was high, and the risk factor was prematurity before 32 weeks of gestation. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 2296-2360 11 2023 Evaluation of the association of birth order and group childcare attendance with Kawasaki disease using data from a nationwide longitudinal survey 1127053 EN Takahiro Namba Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihito Takeuchi Department of Neonatology, National Hospital Organization Okayama Medical Center Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuru Tsuge Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Yashiro Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Kawasaki disease (KD) is a form of pediatric systemic vasculitis. Although the etiology remains unclear, infections have been identified as possible triggers. Children with a later birth order and those who attend childcare are at a higher risk of infections due to exposure to pathogens from their older siblings and other childcare attendees. However, longitudinal studies exploring these associations are limited. Thus, we aimed to elucidate the relationship between birth order, group childcare attendance, and KD, using a nationwide longitudinal survey in Japan. Methods: In total, 36,885 children born in Japan in 2010 were included. The survey used questionnaires to identify hospitalized cases of KD. We evaluated the relationship between birth order classification, group childcare attendance, and KD prevalence every year, from 6 to 66 months of age. For each outcome, odds ratios (ORs), and 95% confidence intervals (CIs) were estimated after adjusting for child factors, parental factors, and region of residence. Results: Children with higher birth orders were more likely to be hospitalized with KD at 6-18 months of age (second child OR: 1.77, 95% CI: 1.25-2.51; third child OR: 1.70, 95% CI: 1.08-2.65). This trend was stronger for children who did not attend group childcare (second child OR: 2.51, 95% CI: 1.57-4.01; third child OR: 2.41, 95% CI: 1.30-4.43). An increased risk of KD hospitalization owing to the birth order was not observed in any age group for children in the childcare group. Conclusions: Children with higher birth orders were at high risk for hospitalization due to KD at 6-18 months of age. The effect of birth order was more prominent among the children who did not attend group childcare. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 134 1 2022 RSウイルス 48 51 EN Kazuhiro Uda Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9059 11 1 2023 Longitudinal Measurement of Histidine-Rich Glycoprotein Levels in Bronchopulmonary Dysplasia: A Pilot Study 212 EN Daisaku Morimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Washio Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Tamai Division of Neonatology, Okayama Medical Center, National Hospital Organization Takeshi Sato Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Okamura Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Watanabe Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yu Fukushima Division of Neonatology, Okayama Medical Center, National Hospital Organization Junko Yoshimoto Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Misao Kageyama Division of Neonatology, Okayama Medical Center, National Hospital Organization Kenji Baba Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 mu g/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9067 9 8 2022 Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma 1253 EN Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Ikeda Okayama University School of Medicine Hirokazu Tsukahara Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2458 22 1 2022 Correlation between national surveillance and search engine query data on respiratory syncytial virus infections in Japan 1517 EN Kazuhiro Uda Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mitsuru Tsuge Department of Pediatrics Acute Diseases, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Masato Yashiro Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. Methods The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. Results A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. Conclusions Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 12 1 2022 Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways 4819 EN Hiroyuki Miyahara Department of Pediatrics, Okayama University Hospital Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Toshiaki Ohara Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teizo Yoshimura Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Under normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of beta-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS. No potential conflict of interest relevant to this article was reported.

Sage Publications Ltd Acta Medica Okayama 0300-0605 50 1 2022 Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis 03000605211070492 EN Mitsuru Tsuge Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Ikeda Department of Pediatrics, Okayama University Hospital Yoichi Kondo Department of Pediatrics, Matsuyama Red Cross Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9067 8 11 2021 Current Insights into Atopic March 1067 EN Mitsuru Tsuge Department of Pediatric Acute Diseases, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Ikeda Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as "atopic march ". Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 11 1 2021 Trajectory of body mass index and height changes from childhood to adolescence: a nationwide birth cohort in Japan 23004 EN Naomi Matsumoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihide Kubo Department of Pediatrics, National Hospital Organization, Okayama Medical Center Kazue Nakamura Department of Pediatrics, National Hospital Organization, Okayama Medical Center Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Akihito Takeuchi Department of Pediatrics, National Hospital Organization, Okayama Medical Center Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda-mu-sigma) method based on yearly height and weight information (age 1.5-15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3921 10 10 2021 Reactive Oxygen Species and Antioxidative Defense in Chronic Obstructive Pulmonary Disease 1537 EN Akihiko Taniguchi Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Mitsuru Tsuge Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Nobuaki Miyahara Department of Medical Technology, Okayama University Academic Field of Health Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences The respiratory system is continuously exposed to endogenous and exogenous oxidants. Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, leading to the destruction of lung parenchyma (emphysema) and declining pulmonary function. It is increasingly obvious that reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the progression and amplification of the inflammatory responses related to this disease. First, we described the association between cigarette smoking, the most representative exogenous oxidant, and COPD and then presented the multiple pathophysiological aspects of ROS and antioxidative defense systems in the development and progression of COPD. Second, the relationship between nitric oxide system (endothelial) dysfunction and oxidative stress has been discussed. Third, we have provided data on the use of these biomarkers in the pathogenetic mechanisms involved in COPD and its progression and presented an overview of oxidative stress biomarkers having clinical applications in respiratory medicine, including those in exhaled breath, as per recent observations. Finally, we explained the findings of recent clinical and experimental studies evaluating the efficacy of antioxidative interventions for COPD. Future breakthroughs in antioxidative therapy may provide a promising therapeutic strategy for the prevention and treatment of COPD. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1710-1492 17 2021 Anaphylaxis after jellyfish ingestion with no history of stings: a pediatric case report 99 EN Mitsuru Tsuge Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Ikeda Department of Pediatrics, Fukuyama City Hospital Osamu Mitani Department of Pediatrics, Fukuyama City Hospital Masato Yasui Department of Pediatrics, Fukuyama City Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Jellyfish stings are known to induce allergic skin reactions; however, case reports of anaphylaxis after jellyfish ingestion have been increasing, especially in Asian countries. Some cases of anaphylaxis after jellyfish ingestion have been reported in patients with a previous history of frequent jellyfish stings. Herein, we report a pediatric patient with anaphylaxis after jellyfish ingestion with no history of jellyfish stings. Case presentation A 14-year-old girl developed two episodes of anaphylaxis, and her diet diaries revealed that edible jellyfish was common to the meals in both the anaphylaxis events. A skin prick test using five types of edible jellyfish products revealed a positive reaction to some jellyfish, and anaphylaxis was observed after the ingestion of jellyfish in an oral food challenge test. She had no history of jellyfish stings or frequent swimming in the ocean. The basophil activation test showed positive results on stimulation with extracts from various types of edible jellyfish. We observed serum immunoglobulin E (IgE) reactivity to purified jellyfish collagen and jellyfish acid-soluble extracts. Moreover, immunoblotting analysis showed IgE reactivity to two bands at approximately 40 and 70 kDa using purified jellyfish collagen, which may be a causative antigen. Conclusions Edible salted jellyfish can be one of the causative foods of anaphylaxis. Clinicians should be aware of the possibility of anaphylactic reactions due to jellyfish ingestion even without a history of jellyfish stings. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9067 8 9 2021 Association between Dental Caries and Influenza Infection in Children: A Japanese Nationwide Population-Based Study 780 EN Naomi Matsumoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Kadowaki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Dental caries is the most common chronic childhood disease. Recent studies have suggested that dental caries harbor respiratory infections in adults. We investigated the association between dental caries and influenza in children. In this study, 42,812 children aged 2.5 years, 38,540 children aged 5.5 years, and 34,124 children aged 10 years were included in the analysis from the Longitudinal Survey of Newborns in the 21st Century in Japan, which targeted all children born during a certain period in 2001. We used information on dental caries treated at hospitals and clinics in the past year as exposure and influenza as outcome during the observation periods (1.5-2.5, 4.5-5.5, and 9-10 years of age). We performed a log-binomial regression analysis, adjusting for potential confounders, and stratified analysis according to previous dental caries status. The presence of dental caries increased the incidence of influenza in all three target ages compared with the absence of dental caries. The incidence of influenza increased with the presence of current dental caries, regardless of the presence of past dental caries. These associations were observed irrespective of household income. Early detection and treatment of dental caries may reduce the risk of influenza in children. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1552-4825 188A 2021 A novel pathogenic variant p.Asp797Val in IFIH1 in a Japanese boy with overlapping Singleton-Merten syndrome and Aicardi-Goutieres syndrome 249 252 EN Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Hiroyuki Tanaka Department of Pediatrics, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Hospital Hiroyuki Miyahara Department of Pediatrics, Okayama University Hospital Yousuke Higuchi Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of permanent teeth, and aortic calcification, as well as causing Aicardi-Goutières (A-G) syndrome, which shows progressive encephalopathy, spastic paraplegia, and calcification of basal ganglia. Recently, patients with overlapping syndromes presenting with features of S-M syndrome and A-G syndrome were reported. However, progression of clinical features of this condition has not been fully understood. We report a Japanese boy with a novel pathogenic IFIH1 variant who presented with clinical features of S-M syndrome and A-G syndrome. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 133 1 2021 岡山県における新型コロナウイルス感染症流行の疫学的特徴 43 48 EN Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Toshiaki Sendo Department of Pharmacy, Okayama University Hospital Nobuchika Kusano Section of Infection Control and Prevention, Okayama University Hospital Hirokazu Tsukahara Section of Infection Control and Prevention, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 3 2020 総論および岡山大学病院における新型コロナウイルス感染症への対応 152 162 EN Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Section of Infection Control and Prevention, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2324-9269 2021 Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands e1675 EN Yousuke Higuchi Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Yamashita Faculty of Human Life Sciences, Notre Dame Seishin University Hiroyuki Tanaka Department of Pediatrics, Okayama Saiseikai General Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Osteogenesis imperfecta (OI) is a rare connective-tissue disorder characterized by bone fragility. Approximately 90% of all OI cases are caused by variants in COL1A1 or COL1A2. Additionally, IFITM5 variants are responsible for the unique OI type 5. We previously analyzed COL1A1/2 variants in 22 Japanese families with OI through denaturing high-performance liquid chromatography screening, but our detection rate was low (41%). Methods To expand the genotype-phenotype correlations, we performed a genetic analysis of COL1A1/2 and IFITM5 in 96 non-consanguineous Japanese OI probands by Sanger sequencing. Results Of these individuals, 54, 41, and 1 had type 1 (mild), type 2-4 (moderate-to-severe), and type 5 phenotypes, respectively. In the mild group, COL1A1 nonsense and splice-site variants were prevalent (n = 30 and 20, respectively), but there were also COL1A1 and COL1A2 triple-helical glycine substitutions (n = 2 and 1, respectively). In the moderate-to-severe group, although COL1A1 and COL1A2 glycine substitutions were common (n = 14 and 18, respectively), other variants were also detected. The single case of type 5 had the characteristic c.-14C>T variant in IFITM5. Conclusion These results increase our previous detection rate for COL1A1/2 variants to 99% and provide insight into the genotype-phenotype correlations in OI. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Delayed Methotrexate Elimination after Administration of a Medium Dose of Methotrexate in a Patient with Genetic Variants Associated with Methotrexate Clearance 545 550 EN Yasuhisa Tatebe Department of Pharmacy, Okayama University Hospital Kiichiro Kanamitsu Department of pediatrics, Okayama University Hospital Hirotaka Kanzaki Department of Pharmacy, Okayama University Hospital Hisashi Ishida Department of pediatrics, Okayama University Hospital Kaori Fujiwara Department of pediatrics, Okayama University Hospital Kana Washio Department of pediatrics, Okayama University Hospital Yoshihisa Kitamura Department of Pharmacy, Okayama University Hospital Toshiaki Sendo Department of Pharmacy, Okayama University Hospital Akira Shimada Department of pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of pediatrics, Okayama University Hospital Case Report 10.18926/AMO/61215 Polymorphisms in methotrexate transporter pathways have been associated with methotrexate toxicities and clearance. Recent genome-wide association studies have revealed that the SLCO1B1 T521C variant is associated with methotrexate elimination. We present a case of a pediatric patient with acute lymphoblastic leukemia who suffered from persistently high plasma methotrexate concentrations and acute kidney injuries after the admin-istration of a medium dose of methotrexate. Subsequent genetic analysis showed that he was a carrier of dys-functional genetic variants associated with methotrexate clearance. This case highlights that polymorphisms of methotrexate transporter pathways can adversely affect methotrexate elimination in a clinically significant manner. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Polydactyly of the Foot Diagnosed from a Minor Nail Problem 427 429 EN Tomohiro Hiraoka Department of Pediatrics, Ochiai Hospital Haruka Senoo Department of Dermatology, Ochiai Hospital Yuka Yamazaki Department of Pediatrics, Okayama University Hospital Kosaku Suenobu Department of Plastic Surgery, Okayama Medical Center Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Case Report 10.18926/AMO/60803 Polydactyly is one of the most common foot congenital anomalies. It is often detected immediately after birth, but the diagnosis can sometimes be delayed if the symptoms are less evident. A 2-year-old girl with a complaint of recurrent bleeding from the right toenail was diagnosed with foot polydactyly. She underwent corrective surgery, and her family was satisfied with the outcome. Although the diagnosis of polydactyly may be difficult in cases with minor nail problems, further radiographic evaluation will be needed for the improvement of the patient’s quality of life. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 62 5 2020 Laboratory changes during adrenocorticotropic hormone therapy associated with renal calcified lesions 587 592 EN Hiroyuki Miyahara Department of Pediatrics, Okayama University Hospital Tomoyuki Akiyama Department of Child Neurology, Okayama University Hospital Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Mari Akiyama Department of Child Neurology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Makio Oka Department of Child Neurology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Katsuhiro Kobayashi Department of Child Neurology, Okayama University Hospital Hirokazu Tsukahara Department of Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Renal calcified lesions are known as one of the complications during adrenocorticotropic hormone (ACTH) therapy for intractable epilepsy. However, laboratory changes during the therapy or laboratory features of high‐risk cases with renal calcified lesions are yet to be clarified. Methods In this study, 43 patients with West syndrome aged ≤2 years were included. We retrospectively reviewed age and body mass index at the beginning of ACTH therapy, as well as the amount of fluid intake, daily urinary volume, and laboratory data during therapy. In addition, we studied the urinary sediment of the cases with renal calcified lesions diagnosed by computed tomography. Results After initiating ACTH treatment, urinary calcium (Ca)/creatinine ratio and urinary pH increased within 2 weeks. Urinary crystals and renal tubular epithelial cells (RTECs) in urinary sediment were frequently found in most cases. Urinary Ca levels, proteinuria or frequency of urinary crystals, and number of RTECs in the urinary sediment were significantly higher in patients with epithelial casts (ECs) or hematuria than in patients without these findings. Among the seven patients who underwent abdominal CT, ECs or hematuria were found only in those with renal calcified lesions. These findings suggested that patients with ECs or hematuria were more likely to have calcified lesions. Conclusions The risk of renal calcified lesions increased after 2 weeks of ACTH treatment. Abnormal findings in urinary sediments might be an early sign of renal calcification during ACTH therapy. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2431 20 1 2020 Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report EN Mitsuru Tsuge Department of Pediatrics, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences Machiko Miyamoto Department of Pediatrics, Matsuyama Red Cross Hospital Reiji Miyawaki Department of Pediatrics,Ehime University Graduate School of Medicine Yoichi Kondo Department of Pediatrics, Matsuyama Red Cross Hospital Hirokazu Tsukahara Department of Pediatrics, Matsuyama Red Cross Hospital Background Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13). Case presentation An 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13. Conclusions It is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay. No potential conflict of interest relevant to this article was reported.

Hindawi Acta Medica Okayama 0278-0240 2018 Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion 2380179 EN Yosuke Fujii Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Yashiro Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mutsuko Yamada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomonobu Kikkawa Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuyuki Nosaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukie Saito Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Tsukahara Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Masanori Ikeda Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuneo Morishima Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Procalcitonin (PCT) is used as a biomarker in severe infections. Here, we retrospectively investigated levels of serum PCT, C-reactive protein (CRP), and inflammatory cytokines (IL-6, TNF-alpha, and IFN-gamma) in the second phase of patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Nine AESD pediatric patients (4 men, 5 women; AESD group) admitted to Okayama University Hospital from 2010 to 2016 were compared with 10 control patients with febrile seizures (FS) (3 men, 7 women; FS group). Mean PCT concentrations (ng/mL) in the AESD and FS groups were significantly different, at 9.8 +/- 6.7 and 0.8 +/- 0.9, respectively (p = 0 0006). CRP (mg/dL) were 0.79 +/- 0.89 and 1.4 +/- 1.0 (p = 0 94), respectively; IL-6 (pg/mL) were 449.7 +/- 705.0 and 118.3 +/- 145.4 (p = 0 20), respectively; TNF-alpha (pg/mL) were 18.6 +/- 12.5 and 16.6 +/- 6.0 (p = 0 67), respectively; and IFN-gamma (pg/mL) were 79.6 +/- 158.5 and 41.9 +/- 63.7 (p = 0 56), respectively. Ratios of PCT to CRP were 27.5 +/- 34.2 and 3.2 +/- 6.8 (p < 0 0001), respectively. The sensitivity and specificity in the diagnosis of AESD using a cutoff of PCT/CRP ratio of 1.0 were 79% and 100%, respectively. These results suggest that PCT and the PCT/CRP ratio are useful in auxiliary diagnosis of the second stage of AESD, and in AESD, PCT is likely to increase through a different mechanism. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 2052-0492 7 2019 Long-stay pediatric patients in Japanese intensive care units: their significant presence and a newly developed, simple predictive score 38 EN Emily Knaup Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobuyuki Nosaka Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Human Ecology, Graduate School of Environmental and Life Science, Okayama University Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Naitou Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University the JaRPAC Study Group BACKGROUND: The length of stay (LOS) in intensive care units (ICUs) has been used as a good indicator not only for resource consumption but also for health outcomes of patients. However, data regarding pediatric LOS in Japanese ICUs are limited. The primary aim of this study was to characterize the Japanese pediatric ICU patients based on their LOS. Second, we aimed to develop a simple scoring system to predict long-stay pediatric ICU patients on admission. METHODS: We performed a retrospective cohort study using consecutive pediatric data (aged < 16 years) registered in the Japanese Registry of Pediatric Acute Care (JaRPAC) from October 2013 to September 2016, which consisted of descriptive and diagnostic information. The factors for long-stay patients (LSPs; LOS > 14 days) were identified using multiple regression analysis, and subsequently, a simple predictive scoring system was developed based on the results. The validity of the score was prospectively tested using data from the JaRPAC registration from October 2016 to September 2017. RESULTS: Overall, 4107 patients were included. Although LSPs were few (8.0% [n = 330]), they consumed 38.0% of ICU bed days (9750 for LSPs versus 25,659 overall). Mortality was seven times higher in LSPs than in short-stay patients (9.1% versus 1.3%). An 11-variable simple predictive scoring system was constructed, including Pediatric Index of Mortality 2 ≥ 1 (2 points), liver dysfunction (non-post operation) (2 points), post-cardiopulmonary resuscitation (1 point), circulatory disorder (1 point), post-operative management of liver transplantation (1 point), encephalitis/encephalopathy (1 point), myocarditis/cardiomyopathy (1 point), congenital heart disease (non-post operation) (1 point), lung tissue disease (1 point), Pediatric Cerebral Performance Category scores ≥ 2 (1 point), and age < 2 years (1 point). A score of ≥ 3 points yielded an area under the receiver operating characteristic curve (AUC) of 0.79, sensitivity of 87.0%, and specificity of 59.4% in the original dataset. Reproducibility was confirmed with the internal validation dataset (AUC 0.80, sensitivity 92.6%, and specificity 60.2%). CONCLUSIONS: Pediatric LSPs possess a significant presence in Japanese ICUs with high rates of bed utilization and mortality. The newly developed predictive scoring system may identify pediatric LSPs on admission. No potential conflict of interest relevant to this article was reported.

Japanese Society for Pediatric Endocrinology Acta Medica Okayama 0918-5739 28 4 2019 Novel AVPR2 variant in a male infant with nephrogenic diabetes insipidus who showed delayed head control 155 158 EN Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Hiromi Ihoriya Advanced Critical Care and Emergency Center, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Hospital Yousuke Higuchi Department of Pediatrics, Okayama University Hospital, Okayama, Japan Hiroki Tsuchiya Department of Child Neurology, Okayama University Hospital Takashi Shibata Department of Child Neurology, Okayama University Hospital Yumiko Hayashi Department of Child Neurology, Okayama University Hospital Katsuhiro Kobayashi Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 2 2017 Intracranial Pressure Monitoring for Pediatric Acute Encephalopathy 179 180 EN Nobuyuki Nosaka Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Kohei Tsukahara Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Emily Knaup Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Toshihiko Yabuuchi Department of Pediatrics, Okayama University Hospital Tomonobu Kikkawa Department of Pediatrics, Okayama University Hospital Yosuke Fujii Department of Pediatrics, Okayama University Hospital Masato Yashiro Department of Pediatrics, Okayama University Hospital Takao Yasuhara Department of Neurological Surgery, Okayama University Hospital Ayumi Okada Department of Pediatrics, Okayama University Hospital Toyomu Ugawa Advanced Emergency and Critical Care Center of Okayama University Hospital Atsunori Nakao Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Hospital Isao Date Department of Neurological Surgery, Okayama University Hospital Short Communication 10.18926/AMO/54987 Newly published clinical practice guidelines recommend intracranial pressure (ICP) monitoring in critical care for the management of pediatric acute encephalopathy (pAE), but the utility of ICP monitoring for pAE has been poorly studied. We recently performed direct ICP monitoring for two patients. We observed that although the direct ICP monitoring had clinical benefits with less body weight gain and no vasopressor use in both cases, this monitoring technique is still invasive. Future studies should determine the utility of non-invasive ICP monitoring systems in pAE to further improve the quality of intensive-care management. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 1 2017 Effects of Therapeutic Hypothermia for Neuroprotection from the Viewpoint of Redox Regulation 1 9 EN Nobuyuki Nosaka Department of Pediatrics, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Okada Department of Pediatrics, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/54819 Redox regulation has recently been recognized as an important factor in acute illnesses as well as in chronic diseases. It has also become a target for neuroprotection in acute intensive care. Despite its well-known therapeutic effects, therapeutic hypothermia has recently been re-evaluated for its potential use in emergency and critical care medicine. Hypothermia is an undesirable physiological condition that can increase oxidative stress and decrease anti-oxidative potency. However, many studies have shown that under ischemia/reperfusion conditions, therapeutic hypothermia actually suppresses enhanced oxidative stress and maintains or increases anti-oxidative potency. This review provides an overview and outlook for the future of therapeutic hypothermia for neuroprotection from the perspective of redox regulation in patients with post-cardiac arrest syndrome and traumatic brain injury. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 6 2016 Urinary Cross-linked N-terminal Telopeptide of Type I Collagen Levels of Infants with Osteogenesis Imperfecta and Healthy Infants 435 439 EN Miho Yamashita Department of Pediatrics, Okayama University Hospital Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Yousuke Higuchi Department of Pediatrics, Okayama University Hospital Takayuki Miyai Department of Pediatrics, Okayama University Hospital Ayumi Okada Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Tanaka Department of Pediatrics, Okayama Saiseikai General Hospital Hirokazu Tsukahara Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/54805 The urinary cross-linked N-terminal telopeptide of type I collagen (uNTx) levels in infantile osteogenesis imperfecta (OI) have not been well studied. Here we investigated the levels of uNTx in infants with OI and healthy infants. We collected spot urine samples from 30 infants with OI (male/female, 14/16; Sillence classification, I/II/III/IV: 15/3/6/6; age, 5.2±4.4 months) and 120 healthy infants (male/female, 75/45; age, 5.1±4.1 months) for the measurement of uNTx levels. The uNTx levels of the OI infants were significantly lower than those of the healthy infants (mean±SD, 1,363.7±530.1 vs. 2,622.2±1,202.6 nmol BCE/mmol Cr; p＜0.001). The uNTx levels of the infants with type I OI were significantly lower than those of the age-matched healthy infants, although an overlap was observed between the 2 groups. Among the 1-month-old infants, the uNTx levels of the infants with types I, III or IV OI were significantly lower than those of the healthy infants, without overlap (1,622.5±235.8 vs. 3,781.0±1,027.1 nmol BCE/mmol Cr; p＜0.001). These results indicate that uNTx levels are significantly lower in infants with OI than in healthy infants, and they suggest that uNTx might be useful as a reference for diagnosing OI. No potential conflict of interest relevant to this article was reported.

Sage Acta Medica Okayama 0300-0605 43 5 2015 Evaluation of Rapid Immunochromatographic Tests for Norovirus in Neonatal and Infant Faecal Specimens 648 652 EN Department of Paediatrics, Fukuyama Medical Centre Ikuko Nojima Department of Paediatrics, Fukuyama Medical Centre Tooru Araki Department of Paediatrics, Fukuyama Medical Centre Mizue Takasugi Department of Paediatrics, Fukuyama Medical Centre Tomoko Sakane Department of Paediatrics, Fukuyama Medical Centre Aya Kodera Department of Paediatrics, Fukuyama Medical Centre Masanori Ikeda Department of Paediatrics, Fukuyama Medical Centre Hirokazu Tsukahara Department of Paediatrics, Okayama University Hospital Objectives: To compare the diagnostic performance of two norovirus rapid immunochromatographic kits (QuickNavi(®)-Norovirus [QN] and QuickNavi®-Norovirus 2 [QN2]; Denka Seiken, Niigata, Japan) for neonatal and infant faecal specimens. Methods: Monthly faecal samples were collected from infants from birth to 12 months of age, and tested for norovirus using QN and QN2. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used as the gold standard for norovirus detection. The diagnostic performance of the kits was calculated. Results: A total of 343 specimens from 81 infants were analysed. In all samples, the specificity of QN and QN2 was 80% (275/343) and 99% (339/343), respectively. In infants aged <1 month, the specificity of QN was 33% (23/70), increasing to 93% at 4 months of age. Specificity of QN2 was ≥94% in infants between 0 and 12 months of age. Conclusions: QN2 offers improved performance and is more useful than QN for the diagnosis of norovirus infection in the neonatal and infant period. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 4 2016 Validity of Mothers’ Reports of Children’s Weight in Japan 255 259 EN Nobuyuki Nosaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeo Fujiwara Department of Social Medicine, National Research Institute for Child Health and Development Emily Knaup Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Ayumi Okada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/54500 Estimation methods for pediatric weight have not been evaluated for Japanese children. This study aimed to assess the accuracy of mothersʼ reports of their childrenʼs weight in Japan. We also evaluated potential alternatives to the estimation of weight, including the Broselow tape (BT), Advanced Pediatric Life Support (APLS), and Parkʼs formulae. We prospectively collected cross-sectional data on a convenience sample of 237 children aged less than 10 years who presented to a general pediatric outpatient clinic with their mothers. Each weight estimation method was evaluated using Bland-Altman plots and by calculating the proportion within 10 and 20 of the measured weight. Mothersʼ reports of weight were the most accurate method, with 94.9 within 10 of the measured weight, the lowest mean difference (0.27kg), and the shortest 95 limit of agreement (－1.4 to 1.9kg). The BT was the most reliable alternative, followed by APLS and Parkʼs formulae. Mothersʼ reports of their children ʼs weight are more accurate than other weight estimation methods. When no report of a childʼs weight by the mother is available, BT is the best alternative. When an aged-based formula is the only option, the APLS formula is preferred. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 3 2015 血管内皮機能を対象にした基礎および臨床医学研究 187 195 EN Hirokazu Tsukahara No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 5 2015 Inhibitory Effects of Edaravone, a Free Radical Scavenger, on Cytokine-induced Hyperpermeability of Human Pulmonary Microvascular Endothelial Cells:A Comparison with Dexamethasone and Nitric Oxide Synthase Inhibitor 279 290 EN Yukie Saito Yousuke Fujii Masato Yashiro Mitsuru Tsuge Nobuyuki Nosaka Nobuko Yamashita Mutsuko Yamada Hirokazu Tsukahara Tsuneo Morishima Original Article 10.18926/AMO/53674 Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Fluorescein-labeled dextran was added. Then the trans-human PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α＋IL-1β markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 2 2013 マウスインフルエンザ肺炎におけるレドックス制御蛋白チオレドキシン（TRX-1）の治療的効果 109 112 EN Masato Yashiro Hirokazu Tsukahara Akihiro Matsukawa Mutsuko Yamada Yosuke Fujii Yoshiharu Nagaoka Mitsuru Tsuge Nobuko Yamashita Toshihiro Ito Masao Yamada Hiroshi Masutani Junji Yodoi Tsuneo Morishima No potential conflict of interest relevant to this article was reported.