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Objectives: To investigate the clinical characteristics and management of plexiform neurofibromas (PNs) in Japanese children with neurofibromatosis 1 (NF1) in the beginning of a new era of treatment with mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor selumetinib., Study Design: Primary and secondary surveys were conducted targeting 1612 departments of pediatrics and dermatology in hospitals with ≥300 beds and children's hospitals, which followed up pediatric patients with NF1-associated PN between April 1, 2022, and April 30, 2024, in Japan., Results: The response rates in the primary and secondary surveys were 40.4 % and 33.8 %, respectively, and 49 patients were followed up in 23 departments. Their ages at the time ranged from 3.3 to 18.8 years and the onset of PN was most frequently recognized during the first year of life. PN was most often observed superficially in the face (39 %), neck (27 %), and head (24 %), followed by the buttocks (20 %), back (18 %), and thighs (18 %). In addition, PNs could be identified radiologically in the spinal/paraspinal regions (18 %) and pelvis (16 %), where they were rarely visible on the corresponding body surfaces. Major morbidities were cosmetic disfigurement (78 %), pain (53 %), and dysfunction (61 %). Selumetinib use was frequent (69 %) and significantly associated with pain (chi-square test, p = 0.014) and dysfunction (p = 0.014)., Conclusions: This retrospective nationwide study revealed early onset, diverse tumor locations, and varying morbidities in children with NF1-PN, underscoring the need for early evaluation and optimal treatment. A prospective multicenter registry system is warranted to attain better management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HN received honoraria for lectures and manuscript writing from Alexion, AstraZeneca Rare Diseases. YY received honoraria for lectures and travel reimbursement from Alexion, AstraZeneca Rare Disease. AA received honoraria for lectures from Alexion, AstraZeneca Rare Disease. MM received honoraria for lectures and travel reimbursement from Alexion, AstraZeneca Rare Disease. The company was not involved in any of the study design, collection, analysis, interpretation of data, writing of the report, and decision to submit the paper for publication. The other authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Niemann-Pick disease type C (NPC) is a lysosomal lipid storage disorder characterized by progressive neurodegeneration and hepatic dysfunction. A cyclic heptasaccharide, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), is currently under clinical investigation for NPC, but its adverse events remain problematic. We previously identified that a cyclic octasaccharide, 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD), also ameliorated NPC manifestations with higher biocompatibility than HP-β-CD. However, preclinical studies describing the associations between the biodistribution and pharmacodynamics of these compounds, which are essential for clinical application, are still lacking. Here, we investigated these properties of HP-γ-CD by measuring its organ biodistribution and therapeutic effect after systemic and central administration. The effect of HP-γ-CD on disturbed cholesterol homeostasis appeared within several hours after exposure and persisted for several days in NPC model cells and mice. Tissue distribution indicated that only a small fraction of subcutaneously administered HP-γ-CD rapidly distributed to peripheral organs and contributed to disease amelioration. We found that a subcutaneous dose of HP-γ-CD negligibly ameliorated neurological characteristics because it has limited penetration of the blood-brain barrier; however, an intracerebroventricular microdose unexpectedly attenuated hepatic dysfunction without the detection of HP-γ-CD in the liver. These results demonstrate that central administration of HP-γ-CD can indirectly attenuate peripheral manifestations of NPC., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: Niemann-Pick type C (NPC) is a rare lysosomal storage disease characterized by hepatosplenomegaly and progressive neurological deterioration due to abnormal intracellular cholesterol transport. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPBCD) is an effective treatment for NPC; however, few reports have shown its long-term efficacy and safety. To demonstrate long-term efficacy and safety of intrathecal HPBCD (IT-HPBCD) treatment for NPC, we herein reports five patients with NPC treated using IT-HPBCD for 4-11 years., Cases and Results: Patients' ages at the onset ranged from 1.5 to 20 years. Notably, all patients showed rapid disease progression despite treatment with miglustat before IT-HPBCD treatment. Similarly, some patients showed transient improvement; however, all patients' conditions stabilized after long-term IT-HPBCD therapy. Mild-to-moderate hearing loss was observed in three patients. Furthermore, long-term treatment with IT-HPBCD may suppress neurological deterioration in patients with NPC; however, patients still experience some disease progression., Conclusions: Long-term treatment with IT-HPBCD may suppress neurological deterioration in patients with NPC; however, the treatment outcome is dependent on the neurological status at the time of diagnosis, and disease progression is not completely inhibited. Awareness of the disease and newborn screening is needed for earlier disease detection. In addition, further optimization of the treatment protocol and additional treatments are needed to improve patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Guanfacine, used as a medication for attention-deficit/hyperactivity disorder (ADHD), leads to a high incidence of somnolence, in contrast to methylphenidate, which leads to a high incidence of insomnia. The impact of somnolence on continuing guanfacine treatment is unclear. Therefore, we investigated the reasons for discontinuing guanfacine and analyzed the factors associated with discontinuation caused by somnolence. We surveyed 96 patients under guanfacine from July 2017 to December 2021 at the Saga University Hospital. Patients who discontinued guanfacine by the end date of our study were divided into a median early and late group. We compared the reasons for discontinuation in both groups. Of all patients, 47 continued and 49 discontinued guanfacine. A higher percentage of patients discontinued guanfacine caused by somnolence for ≤70 d than for >70 d of treatment (44.0 vs. 8.3%; p = 0.008). When stratified by the concomitant use of other ADHD drugs, somnolence resulted in a higher discontinuation rate for ≤70 d than for >70 d of treatment without concomitant use (55.0 vs. 7.1%; p = 0.009). Nonetheless, concomitant use resulted in no difference. In conclusion, somnolence affects the early discontinuation of guanfacine as an ADHD drug. The combination of methylphenidate or atomoxetine may decrease withdrawal caused by somnolence.

Rationale: Juvenile polyps (JPs) are the most common polyp type and can be observed in 1% of all preschoolers. The peak incidence is observed at ages 3 to 5 years, constituting 90% of all polyps in children. Elevated levels of fecal calprotectin (FC) are often seen in children with JPs., Patient Concerns: A 15-month-old girl was referred to our hospital for blood on the stool surface persisting for 3 months. She was healthy, with no abdominal pain, diarrhea, anorexia, or weight loss and no complaints other than hematochezia. Her physical examination, vital signs and laboratory date were unremarkable., Diagnosis: JPs., Intervention: Total colonoscopy for her found 2 JPs in the sigmoid colon, which were subsequently resected endoscopically., Outcomes: At the age of 5 years, this patient again had bloody stools. Her FC measurement at that time was 1020 mg/kg, which normalized to 42 mg/kg 3 months after her second resection., Lessons: Single or multiple solitary JPs require follow-up that fully considers the possibility of recurrence. Establishing a method for early confirmation of JP recurrence based on bloody stools, fecal occult blood testing, and FC measurement is necessary., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Niemann-Pick disease type C (NPC) is a fatal neurodegenerative disorder caused by abnormal intracellular cholesterol trafficking. Cyclodextrins (CDs), the most promising therapeutic candidates for NPC, but with concerns about ototoxicity, are cyclic oligosaccharides with dual functions of unesterified cholesterol (UC) shuttle and sink that catalytically enhance the bidirectional flux and net efflux of UC, respectively, between the cell membrane and the extracellular acceptors. However, the properties of CDs that regulate these functions and how they could be used to improve treatments for NPC are unclear., Methods: We estimated CD-UC complexation for nine CD derivatives derived from native α-, β-, and γ-CD with different cavity sizes, using solubility and molecular docking analyses. The stoichiometry and complexation ability of the resulting complexes were investigated in relation to the therapeutic effectiveness and toxicity of each CD derivative in NPC experimental models., Findings: We found that shuttle and sink activities of CDs are dependent on cavity size-dependent stoichiometry and substituent-associated stability of CD-UC complexation. The ability of CD derivatives to form 1:1 and 2:1 complexes with UC were correlated with their ability to normalize intracellular cholesterol trafficking serving as shuttle and with their cytotoxicity associated with cellular UC efflux acting as sink, respectively, in NPC model cells. Notably, the ability of CD derivatives to form an inclusion complex with UC was responsible for not only efficacy but ototoxicity, while a representative derivative without this ability negligibly affected auditory function, underscoring its preventability., Conclusions: Our findings highlight the importance of strategies for optimizing the molecular structure of CDs to overcome this functional dilemma in the treatment of NPC., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Vonoprazan (VPZ)-based regimen for Helicobacter pylori (H. pylori) is safe and more efficacious than the proton pump inhibitor-based regimen mainly in adults. This study aimed to evaluate the efficacy and safety of a VPZ-based regimen for H. pylori eradication therapy in adolescents., Methods: An H. pylori screening and treatment longitudinal project for third-year junior high school students in Saga Prefecture began in 2016. Students who tested positive for both urine and stool tests received a VPZ-based regimen. On the checklist, students were asked for diarrhea, fever, abdominal pain, nausea, vomiting, urticaria, dysgeusia, or bloody stool occurrence during the therapy., Results: The longitudinal project for H. pylori screening and treatment among third-grade students in Saga Prefecture targeted 41,115 students from 2017 to 2021 and 836 as positive. Of the 645 students, 542 (84.0% in per protocol [PP] analysis and 73.6% in intention-to-treat [ITT] analysis) were successful in primary eradication therapy. The secondary eradication therapy was successful in 79 (96.3% in PP analysis and 76.7% in ITT analysis) of 82 students. In the primary eradication therapy, abdominal pain occurred in 164 (27.9%), diarrhea in 217 (36.9%), nausea or vomiting in 7 (1.2%), and urticaria in 13 (2.2%) students. In the secondary eradication therapy, abdominal pain occurred in 12 (19.4%) and diarrhea in 17 (27.4%) students. The eradication therapy of 5 students was interrupted due to adverse events only by primary eradication therapy., Conclusions: VPZ-based regimen for H. pylori was efficacious and safe for adolescents, as in adults, for both primary and secondary eradication therapies., (© 2022. Japanese Society of Gastroenterology.)

Cyclodextrin (CD), a cyclic oligosaccharide, is a pharmaceutical additive that improves the solubility of hydrophobic compounds. Recent research has focused on the potential active pharmaceutical abilities of CD. Lysosomal storage diseases are inherited metabolic diseases characterized by lysosomal dysfunction and abnormal lipid storage. Niemann-Pick disease type C (NPC) is caused by mutations in cholesterol transporter genes (NPC1, NPC2) and is characterized by cholesterol accumulation in lysosomes. A biocompatible cholesterol solubilizer 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was recently used in NPC patients for compassionate use and in clinical trials. HP-β-CD is an attractive drug candidate for NPC; however, its adverse effects, such as ototoxicity, should be solved. In this review, we discuss the current use of HP-β-CD in basic and clinical research and discuss alternative CD derivatives that may outperform HP-β-CD, which should be considered for clinical use. The potential of CD therapy for the treatment of other lysosomal storage diseases is also discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Niemann-Pick disease type C (NPC) is a fatal disorder with abnormal intracellular cholesterol trafficking resulting in neurodegeneration and hepatosplenomegaly. A cyclic heptasaccharide with different degrees of substitution of 2-hydroxypropyl groups, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), acts as a strong cholesterol solubilizer and is under investigation for treating this disease in clinical trials, but its physicochemical properties and ototoxicity remain a concern. Here, we evaluated the potential of mono-6-O-α-maltosyl-γ-CD (G2-γ-CD), a single-maltose-branched cyclic octasaccharide with a larger cavity than HP-β-CD, for treating NPC. We identified that G2-γ-CD ameliorated NPC manifestations in model mice and showed lower ototoxicity in mice than HP-β-CD. To investigate the molecular mechanisms of action behind the differential ototoxicity of these CDs, we performed cholesterol solubility analysis, proton nuclear magnetic resonance spectroscopy, and molecular modeling, and estimated that the cholesterol inclusion mode of G2-γ-CD maintained solely the 1:1 inclusion complex, whereas that of HP-β-CD shifted to the highly-soluble 2:1 complex at higher concentrations. We predicted the associations of these differential complexations of CDs with cholesterol with the profile of disease attenuation and of the auditory cell toxicity using specific cell models. We proposed that G2-γ-CD can serve as a fine-tuned cholesterol solubilizer for treating NPC, being highly biocompatible and physicochemically suitable for clinical application., Competing Interests: Conflict of Interest Statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Niemann-Pick disease Type C (NPC) is a lysosomal storage disorder caused by mutation of the NPC1/NPC2 genes, which ultimately results in the accumulation of unesterified cholesterol (UEC) in lysosomes, thereby inducing symptoms such as progressive neurodegeneration and hepatosplenomegaly. This study determines the effects of 6-O-α-maltosyl-β cyclodextrin (Mal-βCD) on lipid levels and synthesis in Npc1-deficient (Npc1-KO cells) and vehicle CHO cells. Compared to vehicle cells, Npc1-KO cells exhibited high level of UEC, and low levels of esterified cholesterols (ECs) and long-chain fatty acids (LCFAs). The difference in lipid levels between Npc1-KO and CHO cells was largely ameliorated by Mal-βCD administration. Moreover, the effects of Mal-βCD were reproduced in the lysosomes prepared from Npc1-KO cells. Stable isotope tracer analysis with extracellular addition of D4-deuterated palmitic acid (D4-PA) to Npc1-KO cells increased the synthesis of D4-deuterated LCFAs (D4-LCFAs) and D4-deuterated ECs (D4-ECs) in a Mal-βCD-dependent manner. Simultaneous addition of D6-deuterated UEC (D6-UEC) and D4-PA promoted the Mal-βCD-dependent synthesis of D6-/D4-ECs, consisting of D6-UEC and D4-PA, D4-deuterated stearic acid, or D4-deuterated myristic acid, in Npc1-KO cells. These results suggest that Mal-βCD helps to maintain normal lipid metabolism by restoring balance among UEC, ECs, and LCFAs through acting on behalf of NPC1 in Npc1-KO cells and may therefore be useful in designing effective therapies for NPC., Competing Interests: Conflicts of interest The authors declare no conflicts of interest. The funding sponsors had no role in the design of the study; collection, analyses, or interpretation of data; writing of the manuscript; or decision to publish the results. Mal-βCD was a gift from Ensuiko Sugar Refining Co. Ltd. This company played no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: This study evaluated the feasibility of a matching-pair test using eye-tracking technology to assess nusinersen effectiveness in patients with advanced spinal muscular atrophy (SMA) type I., Methods: This prospective, observational study enrolled patients with 5q-SMA type I who had lost gross motor function. Three different levels of matching-pair tests were conducted using the eye-gaze system (My Tobii; TobiiDynavox Inc.) at baseline, and after 9 and 24 weeks of nusinersen treatment. The primary endpoint was the change from baseline in matching-pair test scores and response times (i.e., the time to answer matching-pair test) at 24 weeks from baseline. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Pediatric Quality of Life inventory for patients with Neuromuscular Disease (PedsQL-NM) and Numerical Rating Scale (NRS) scores were also assessed as secondary endpoints. Analysis of ocular fixation was performed as an additional analysis. This study was registered at https://www.umin.ac.jp/ctr/ (UMIN000033935)., Results: Seven patients (one male, six female) aged 5-21 years (median 11 years) were enrolled; all patients were bedridden and six patients were ventilated. All seven patients were able to conduct level 1 matching-pair tests at each assessment; five patients were also able to conduct levels 2 and 3. Two patients (those with the highest CHOP-INTEND scores) were able to complete all tests correctly within 60 s. There was a non-significant trend toward improvement in CHOP-INTEND, PedsQL-NM, and NRS scores over the 6-month period. There were no significant differences in the number of actions, errors, correct answers, or response times between baseline and Week 9 or 24 at any level. However, the result of an additional analysis suggests that detection of eye movement would be useful to evaluate for advanced SMA., Conclusions: Eye-tracking systems are possibly feasible for the assessment of treatment efficacy in patients with advanced SMA type I., Competing Interests: This study received funding from Biogen Japan Ltd (Tokyo, Japan). The funder had the following involvement with the study: design, analysis and interpretation, writing and the decision to submit this article for publication. All named authors have contributed significantly to the intellectual content of the manuscript, and have critically reviewed all drafts and approved the final version for submission. Author KY has received speaker honoraria from Biogen Japan, Novartis Japan, and Chugai Pharmaceutical for activities unrelated to the present work. Author OK has received honoraria from Biogen Japan and UCB Japan for activities unrelated to the present work. Authors SM and TF have attended a Biogen Japan advisory board unrelated to the present work. Author YYu has received honoraria from Shionogi, Novartis, Takeda, Daiichi Sankyo, Novel Pharma and Janssen for activities unrelated to the present work. Author MC is an employee of Biogen Japan Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yae, Yuge, Maeda, Ichinose, Matsuo, Kobayashi, Okanari, Baba, Yonee, Maruyama, Shibata, Fujii, Chinen and Yamashita.)

Background and Aim: Smart Gene™ was developed based on the concept of point-of-care genetic testing. We evaluated the detection performance of a reagent for Helicobacter pylori (H. pylori) clarithromycin (CAM)-resistant mutation assessment and determined the association between the results of Smart Gene™ and those of eradication therapy for H. pylori., Methods: In 2020, the present study was conducted on participants of the H. pylori test and treat project in Saga Prefecture. The submitted stool samples were measured for H. pylori gene and CAM-resistant mutation by Smart Gene™, and the results were compared with real-time polymerase chain reaction (PCR) and sequencing analysis. Finally, the results of the eradication therapy were examined for each result of Smart Gene™., Results: Stool samples were obtained from 139 patients who were tested positive by stool antigen test and were analyzed. The H. pylori detection rate was 95.7% by Smart Gene™, 92.8% by real-time PCR (P < 0.01), and 89.2% by sequencing analysis (P = 0.06). The overall concordance rate for CAM-resistant mutation between Smart Gene™ and sequencing analysis was 96.7%. Moreover, 35 of 48 students with CAM-resistant mutation and 33 of the 35 students with a mutation without CAM resistance succeeded in CAM-containing triple therapy, and the success rate was significantly higher for the mutation without CAM resistance (P = 0.012)., Conclusions: The detection performance of Smart Gene™ was comparable with that of real-time PCR and sequencing analysis. It is expected that the success rate of eradication would be further improved by using the reagent., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objectives: To investigate whether the immunoglobulin G (IgG4) subclass is associated with recurrent wheezing and/or asthma in infants., Subjects and Methods: From April 2015 to March 2016, 77 infants under 3 years old who attended our hospital were enrolled in four groups (Group 1, controls; Group 2, infants with recurrent wheezing and multiple hospitalizations despite starting inhaled corticosteroids [ICS]; Group 3, infants with recurrent wheezing and without hospitalization after starting ICS; Group 4, allergic infants without wheezing). The relationship between IgG subclasses, especially IgG4, and recurrent wheezing resistant to ICS and requiring multiple hospitalizations in infants was examined., Results: The serum IgG, IgM, IgA, IgG1, IgG2, and IgG3 levels did not differ significantly among the four groups. The IgG4 level in Group 2 infants (3.1 ± 0.2 mg/dl) was significantly lower than in Groups 1, 3, and 4 (9.9 ± 8.0, 8.4 ± 6.1, and 23.4 ± 18.0 mg/dl). Of the 16 infants in Group 2, 10 could be followed to age 6 years. Nine of them had no recurrent wheezing at 6 years without medication. In addition, their IgG4 levels at age 6 years (16.1 ± 7.1 mg/dl) were significantly increased from those in infancy (3.0 ± 0.1 mg/dl)., Conclusion: A transient low IgG4 level in infancy might cause recurrent wheezing and/or asthmatic symptoms in infants, and it may be one of the types of early transient wheezing., (© 2022 Wiley Periodicals LLC.)

Background: BLEIA ™ "EIKEN" Helicobacter pylori antigen (B[EIA]) is based on the bioluminescent enzyme immunoassay (BLEIA) method that was newly developed with high sensitivity in detecting Helicobacter pylori ( H. pylori ) antigen in feces., Methods: In the project for H. pylori screening and treatment in Saga Prefecture in 2019, 141 students received the stool H. pylori antigen test as a secondary test. For 141 students, a comparative test was conducted between B (EIA) and extracorporeal diagnostic agents that were marketed in Japan as of 2019. The detection performance of H. pylori ATCC43504 standard strain and H. pylori antigen in commercial human fecal specimens were conducted., Results: The comparison of B (EIA) with Quick Chaser TM H. pylori (Q [IC]) revealed positive and negative concordance ratios of B (EIA) to Q (IC) of 100.0% (110/110) and 71.0% (22/31), respectively. A comparative test was conducted between B (EIA) and extracorporeal diagnostic agents that were marketed in Japan as of 2019, and B (EIA) was most sensitive on "detecting H. pylori antigen of ATCC43504 standard strain" and "detecting H. pylori antigen in commercial human fecal specimens," compared with other kits. Nine dissociated specimens that were negative for Q (IC) and positive for B (EIA) were confirmed. The measured value of B (EIA) in the dissociation samples were 1.3-87.4 cutoff index in the range that can be evaluated as negative by other fecal H. pylori antigen test kits, all the dissociation samples were H. pylori antigen-positive cases, and finally the cause of result divergence was presumed as false negative due to insufficient sensitivity of Q (IC)., Conclusion: B (EIA) that is based on the BLEIA method, which applies firefly luciferase luminescence, is more sensitive than stool antigen test kits that are currently marketed in Japan and is very useful in diagnosing H. pylori infection, especially in situations where noninvasive tests are preferred, such as in children., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Toshihiko Kakiuchi et al.)

Rationale: Hepatitis-associated aplastic anemia (HAAA) is a rare illness that results in bone marrow failure following hepatitis development. The etiological agent remains unknown in most HAAA cases. However, clinical features of the disease and immunotherapy response indicate that immune-mediated factors play a central role in the pathogenesis of HAAA. Activation of cytotoxic T cells and increase in CD8 cells could exert cytotoxic effects on the myelopoietic cells in the bone marrow., Patient Concerns: A 15-month-old boy was brought to our hospital with complaints of generalized petechiae and purpura observed a week prior to hospitalization. His liver was palpated 3 cm below the costal margin, platelet count was 0 × 104/μL, and alanine aminotransferase level was 1346 IU/L. A blood test indicated cytomegalovirus infection, and 3 bone marrow examinations revealed progressive HAAA. As the disease progressed to the 3rd, 6th, and 9th week after onset, CD4+ T cells were markedly decreased, CD8+ T cells were markedly increased, and the CD4/CD8 ratio was significantly decreased. The number of B cells and natural killer cells decreased with time, eventually reaching 0.0%., Diagnosis: HAAA., Interventions: Rabbit antithymocyte globulin and eltrombopag olamine (a thrombopoietin receptor agonist) were administered., Outcomes: The patient's platelet count returned to normal, and bone marrow transplantation was avoided. The peripheral blood lymphocytes (PBLs) improved as the patient's general condition recovered., Lessons: This case demonstrates that HAAA induced by cytomegalovirus infection features decreasing CD4+ and increasing CD8+ PBLs as the bone marrow hypoplasia progresses. The PBLs return to their normal levels with the recovery from the disease. Our case findings thus support the involvement of immunological abnormality in HAAA., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Menkes disease (MD) is an X-linked recessive disorder caused by mutations in ATP7A . Patients with MD exhibit severe neurological and connective tissue disorders due to copper deficiency and typically die before 3 years of age. Early treatment with copper injections during the neonatal period, before the occurrence of neurological symptoms, can alleviate neurological disturbances to some degree. We investigated whether early symptoms can help in the early diagnosis of MD. Abnormal hair growth, prolonged jaundice, and feeding difficulties were observed during the neonatal period in 20 of 69, 16 of 67, and 3 of 18 patients, respectively. Only three patients visited a physician during the neonatal period; MD diagnosis was not made at that point. The mean age at diagnosis was 8.7 months. Seven patients, who were diagnosed in the prenatal stage or soon after birth, as they had a family history of MD, received early treatment. No diagnosis was made based on early symptoms, highlighting the difficulty in diagnosing MD based on symptoms observed during the neonatal period. Patients who received early treatment lived longer than their elderly relatives with MD. Three patients could walk and did not have seizures. Therefore, effective newborn screening for MD should be prioritized., Competing Interests: The study protocol was approved by the Institutional Review Board of Teikyo University School of Medicine (TEIRIN No. 12-014, No. 08-114, No. 10-053).The authors declare no conflict of interest. The funding body had no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication., (© 2022 The Authors.)

Objective: To clarify the incidence and risk factors of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in pediatric patients with febrile status epilepticus (FSE)., Methods: We retrospectively surveyed patients with FSE (≥20 min and ≥40 min) who were younger than 6 years by mailing a questionnaire to 1123 hospitals in Japan. The survey period was 2 years. We then collected clinical data on patients with prolonged febrile seizures (PFS) ≥40 min and those with AESD, and compared clinical data between the PFS and AESD groups., Results: The response rate for the primary survey was 42.3%, and 28.0% of hospitals which had applicable cases responded in the secondary survey. The incidence of AESD was 4.3% in patients with FSE ≥20 min and 7.1% in those with FSE ≥40 min. In the second survey, a total of 548 patients had FSE ≥40 min (AESD group, n = 93; PFS group, n = 455). Univariate analysis revealed significant between-group differences in pH, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, NH 3 , procalcitonin (PCT), uric acid, blood urea nitrogen, creatinine (Cr), and lactate. Multivariate analysis using stratified values showed that high PCT was an only risk factor for AESD. A prediction score of ≥3 was indicative of AESD, as determined using the following indexes: HCO3 - < 20 mmol/L (1 point), Cl <100 mEq/L (1 point), Cr ≥0.35 mg/dL (1 point), glucose ≥200 mg/dL (1 point), and PCT ≥1.7 pg/mL (2 points). The scoring system had sensitivity of 84.2% and specificity of 81.0%., Conclusion: Incidence data and prediction scores for AESD will be useful for future intervention trials for AESD., Competing Interests: Conflict of Interest Disclosures Study funding: This work was supported by scholarship grants for M. Matsuo from Otsuka Pharmaceutical Co., Ltd. and Shionogi & Co., Ltd. The other authors declare no competing interests., (Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma of the face, small stature, sparse scalp hair, juvenile cataract, radial aplasia, and predisposition to cancers. Due to the rarity of RTS, the situation of patients with RTS in Japan has not been elucidated., Methods: In 2010 and 2020, following the results of a primary questionnaire survey, a secondary questionnaire survey on RTS was conducted nationwide to investigate the number of RTS cases and their associated skin lesions, bone lesions, other clinical features, and quality of life in Japan., Results: In 2010 and 2020, 10 and eight patients with RTS were recruited, respectively. Skin lesions such as poikiloderma, erythema, pigmentation, and abnormal scalp hair were observed in almost all cases. Bone lesions were observed in four cases in the 2010 and 2020 surveys, respectively. Two cases had mutations in the RECQL4 gene in the 2020 survey., Conclusions: Two nationwide surveys have shown the actual situation of patients with RTS in Japan. Cutaneous and bone manifestations are important for the diagnosis of RTS. However, many patients have no RECQL4 mutations. The novel causative gene of RTS should be further elucidated., (© 2022 Japan Pediatric Society.)

Background: In children, relationships between developmental disorders such as attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder and allergic diseases remain controversial, because these diseases show age- and sex-related differences. A proper understanding of the relationships between developmental disorders and allergic diseases should improve medical care for both diseases. We confirmed the prevalence of allergic diseases in elementary school-age children with developmental disorders by grade and sex., Methods: The subjects were 446 lower grade and 312 upper grade elementary school-age children who had visited our hospital. The prevalence of allergic diseases among subjects with and without developmental disorders by grade and sex was examined using the diagnostic names on medical records., Results: The prevalence of allergic diseases was significantly higher in lower grade boys and girls with developmental disorders than in those without developmental disorders (boys: OR 3.22, 95%; CI 1.49-6.95; girls: OR: 3.87, 95% CI: 1.27-11.82). The prevalence of allergic diseases was significantly higher in higher grade boys with developmental disorders than in those without developmental disorders (OR: 3.46, 95% CI: 1.59-7.53). Multiple logistic regression analysis in lower grades revealed that ADHD correlated with bronchial asthma (adjusted OR: 3.72, 95% CI: 1.42-9.69) and that autism spectrum disorder correlated with atopic dermatitis (adjusted OR: 4.26, 95% CI: 1.36-13.36). Analyses of children in the upper grades showed that ADHD correlated with atopic dermatitis (adjusted OR: 5.06, 95% CI: 1.28-20.05)., Conclusions: Elementary school-age children with developmental disorders were more likely to have allergic diseases. The types of allergic diseases related to developmental disorders differed by grade and sex., (© 2022 Japan Pediatric Society.)

Background: Developmental disorders and high Helicobacter pylori ( H. pylori ) infection rates have been reported. This study aimed to examine the prevalence of H. pylori in a special needs school where all students had developmental disorders in Japan. Methods: In 2017, third-grade junior high school and second- and third-grade high school students attending a special needs school with developmental disorders were enrolled. Participants of Saga Prefecture's H. pylori test and treat project, which comprised third-grade junior high school students not from special needs school, were assigned to the control group. Results: In the control group, H. pylori positive results were 3.18% (228/7,164) students. Similarly, in developmental disorder group, H. pylori positive results were 6.80% (13/191) students. For the developmental disorder and control groups, this present examination sensitivity was 7.03% (13/185), specificity was 96.76% (6,815/7,043), positive predictive value was 5.39% (13/241), negative predictive value was 97.54% (6,815/6,987), Likelihood ratio of a positive result 2.17 and Odds ratio was 2.26 (95% confidence interval: 1.27-4.03, p = 0.005). Conclusion: The prevalence of H. pylori infection was significantly higher in adolescents with developmental disorders than in typically developing adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kakiuchi, Takamori and Matsuo.)

Objective: The relationship between Helicobacter pylori and the intestinal microbiota has not yet been clearly demonstrated in children and adolescents. The present study aimed at evaluating how H. pylori infection could affect the intestinal microbiota in adolescents using genetic analysis., Design: Cross-sectional study., Setting and Participants: We included subjects from a longitudinal project involving H. pylori screening and treatment of junior high school third-grade students (aged 14 or 15 years) in Saga Prefecture. The study included a control group (n=79) and an H. pylori group (n=80) tested negative and positive for the anti- H. pylori antibody in the urine and H. pylori antigen in stool specimens, respectively., Interventions: The intestinal microbiota was evaluated in stool specimens using 16S rRNA gene/DNA/amplicon sequencing with next-generation sequencing., Primary and Secondary Outcome Measures: We assessed alpha and beta diversity, just as well as relative abundances within the bacterial composition at the genus level in both groups., Results: As shown by the alpha diversity of the 16S rRNA gene/DNA/amplicon sequence data, the control group exhibited lower microbial species richness with lower alpha diversity compared with the H. pylori group (p<0.001). The beta diversity of the intestinal microbiota profile also differed between the two groups (p<0.01). The relative abundance of the Prevotella genus was higher in the H. pylori group (p<0.01) concomitant with a gain in body mass index (BMI) in the H. pylori group (p<0.01) compared with the control group., Conclusion: H. pylori infection significantly affected the intestinal microbiota in Japanese adolescents. In addition, the prevalence of the Prevotella genus is concomitantly increased along with the BMI in H. pylori -infected students., Trial Registration Number: UMIN000028721., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with disrupted intracellular cholesterol trafficking. A cyclic heptasaccharide, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), is a cholesterol solubilizer that is being developed to treat NPC, but its ototoxicity and pulmonary toxicity remain important issues. We have characterized 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD), a cyclic octasaccharide with a larger cavity than HP-β-CD, as a candidate drug to treat NPC. However, the molecular target of HP-γ-CD with respect to NPC and its potential for clinical application are still unclear., Experimental Approach: We investigated the mode of interaction between HP-γ-CD and cholesterol by phase-solubility analysis, proton NMR spectroscopy and molecular dynamics simulations. We then evaluated the therapeutic effects of HP-γ-CD compared with HP-β-CD using cellular and murine NPC models. Mouse auditory and pulmonary function tests were also conducted., Key Results: HP-γ-CD solely formed a 1:1 inclusion complex with cholesterol with an affinity similar to that of HP-β-CD. In vitro, HP-γ-CD and HP-β-CD amelioration of NPC-related manifestations was almost equivalent at lower concentrations. However, at higher concentrations, the cholesterol inclusion mode of HP-β-CD shifted to the highly soluble 2:1 complex whereas that of HP-γ-CD maintained solely the 1:1 complex. The constant lower cholesterol solubilizing ability of HP-γ-CD conferred it with significantly reduced toxicity compared with HP-β-CD, but equal efficacy in treating a mouse model of NPC., Conclusions and Implications: HP-γ-CD can serve as a fine-tuned cholesterol solubilizer for the treatment of NPC with a wider safety margin than HP-β-CD in terms of ototoxicity and pulmonary toxicity., (© 2021 The British Pharmacological Society.)

The recent increase in macrolide-resistant Mycoplasma pneumoniae in Asia has become a continuing problem. A point-of-care testing method that can quickly detect M. pneumoniae and macrolide-resistant mutations (MR mutations) is critical for proper antimicrobial use. Smart Gene (Mizuho Medy Co., Ltd., Tosu City, Saga, Japan) is a compact and inexpensive fully automatic gene analyzer that combines amplification with PCR and the quenching probe method to specify the gene and MR mutations simultaneously. We performed a clinical evaluation of this device and its reagents on pediatric patients with suspected M. pneumoniae respiratory infections and evaluated the impact of the assay on antimicrobial selection. Using real-time PCR as a comparison control, the sensitivity of Smart Gene was 97.8% (44/45), its specificity was 93.3% (98/105), and its overall concordance rate was 94.7% (142/150). The overall concordance rate of Smart Gene diagnosis of MR mutations in comparison with sequence analysis was 100% (48/48). The ratio of MR mutations was significantly higher at high-level medical institutions than at a primary medical clinic ( P  = 0.023), and changes in antibiotic therapy to drugs other than macrolides were significantly more common in patients with MR mutations ( P  = 0.00024). Smart Gene demonstrated excellent utility in the diagnosis of M. pneumoniae and the selection of appropriate antimicrobials for MR mutations at primary medical institutions, which play a central role in community-acquired pneumonia care. The use of this device may reduce referrals to high-level medical institutions for respiratory infections, thereby reducing the medical and economic burdens on patients.

Background: The screening and treatment of Helicobacter pylori infection for all junior high students in Saga Prefecture, Japan, were started in 2016. The present study aims to evaluate the influence of adverse reactions on the success of the eradication therapy., Methods: From 2017 to 2019, 25,006 third-grade junior high school students were tested for urinary anti-H. pylori antibodies. Positive cases were confirmed by H. pylori stool antigen tests. Of the 531 students who were found to be H. pylori-positive, 390 (358 in first-line and 32 in second-line therapy) underwent eradication therapy, and 274 (242 in first-line and 32 in second-line) students actually completed a self-reported form to rate stool consistency (based on the Bristol Stool Scale), the maximum number of bowel movements, and abdominal symptoms during the 7 days of treatment., Results: Among the 274 students, the total of primary and secondary eradication success rates was 87% (95% confidential interval: 82.9-90.1) in intention-to-treat analysis. On days 4, 5, and 6, stool consistency was looser in the primary eradication failure group than in the success group (p < .05). Looser stool consistencies were observed in male students with abdominal pain compared to those who did not experience pain (p < .05). Abdominal pain and diarrhea were detected in 28.5% and 42.7% of the subjects, respectively. The overall incidence of other adverse events was low (n = 8/274, 2.9%), and only two students discontinued treatment because of adverse events., Conclusions: Softening of the stool was related to the eradication failure in the junior high school students, especially in males with abdominal pain. Adverse effects did not induce discontinuation of the eradication treatment., (© 2020 John Wiley & Sons Ltd.)

Corticosteroids and biologics are used to treat moderate-to-severe active pediatric ulcerative colitis (UC); however, it is often difficult to continue administration because of systemic side reactions. Vedolizumab is considered to have few adverse effects due to its mechanism of action and it is expected to be used in children, but the long-term administration of vedolizumab to Japanese pediatric patients with UC has not been reported. We report a case of pediatric moderate active UC with anti-tumor necrosis factor-failure that was successfully treated with vedolizumab in Japan.

Atypical eye gaze is an established clinical sign in the diagnosis of autism spectrum disorder (ASD). We propose a computerized diagnostic algorithm for ASD, applicable to children and adolescents aged between 5 and 17 years using Gazefinder, a system where a set of devices to capture eye gaze patterns and stimulus movie clips are equipped in a personal computer with a monitor. We enrolled 222 individuals aged 5-17 years at seven research facilities in Japan. Among them, we extracted 39 individuals with ASD without any comorbid neurodevelopmental abnormalities (ASD group), 102 typically developing individuals (TD group), and an independent sample of 24 individuals (the second control group). All participants underwent psychoneurological and diagnostic assessments, including the Autism Diagnostic Observation Schedule, second edition, and an examination with Gazefinder (2 min). To enhance the predictive validity, a best-fit diagnostic algorithm of computationally selected attributes originally extracted from Gazefinder was proposed. The inputs were classified automatically into either ASD or TD groups, based on the attribute values. We cross-validated the algorithm using the leave-one-out method in the ASD and TD groups and tested the predictability in the second control group. The best-fit algorithm showed an area under curve (AUC) of 0.84, and the sensitivity, specificity, and accuracy were 74, 80, and 78%, respectively. The AUC for the cross-validation was 0.74 and that for validation in the second control group was 0.91. We confirmed that the diagnostic performance of the best-fit algorithm is comparable to the diagnostic assessment tools for ASD., Competing Interests: SH and MN are employed by JVCKENWOOD Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tsuchiya, Hakoshima, Hara, Ninomiya, Saito, Fujioka, Kosaka, Hirano, Matsuo, Kikuchi, Maegaki, Harada, Nishimura and Katayama.)

Moyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries. Although RNF213 was identified as a susceptibility gene for MMD, the exact pathogenesis remains unknown. Immunohistochemical analysis of autopsy specimens from a patient with MMD revealed marked accumulation of hyaluronan and chondroitin sulfate (CS) in the thickened intima of occlusive lesions of MMD. Hyaluronan synthase 2 was strongly expressed in endothelial progenitor cells in the thickened intima. Furthermore, MMD lesions showed minimal staining for CS and hyaluronan in the endothelium, in contrast to control endothelium showing positive staining for both. Glycosaminoglycans of endothelial cells derived from MMD and control induced pluripotent stem cells demonstrated a decreased amount of CS, especially sulfated CS, in MMD. A computational fluid dynamics model showed highest wall shear stress values in the terminal portion of the internal carotid artery, which is the predisposing region in MMD. Because the peri-endothelial extracellular matrix plays an important role in protection, cell adhesion and migration, an altered peri-endothelial matrix in MMD may contribute to endothelial vulnerability to wall shear stress. Invading endothelial progenitor cells repairing endothelial injury would produce excessive hyaluronan and CS in the intima, and cause vascular stenosis.

Niemann-Pick disease type C (NPC) is a recessive hereditary disease caused by mutation of the NPC1 or NPC2 gene. It is characterized by abnormality of cellular cholesterol trafficking with severe neuronal and hepatic injury. In this study, we investigated the potential of glycoprotein nonmetastatic melanoma protein B (GPNMB) to act as a biomarker reflecting the therapeutic effect of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in an NPC mouse model. We measured serum, brain, and liver expression levels of GPNMB, and evaluated their therapeutic effects on NPC manifestations in the brain and liver after the intracerebroventricular administration of HP-β-CD in Npc1 gene-deficient ( Npc1 -/- ) mice. Intracerebroventricular HP-β-CD inhibited cerebellar Purkinje cell damage in Npc1 -/- mice and significantly reduced serum and cerebellar GPNMB levels. Interestingly, we also observed that the intracerebral administration significantly reduced hepatic GPNMB expression and elevated serum ALT in Npc1 -/- mice. Repeated doses of intracerebroventricular HP-β-CD (30 mg/kg, started at 4 weeks of age and repeated every 2 weeks) drastically extended the lifespan of Npc1 -/- mice compared with saline treatment. In summary, our results suggest that GPNMB level in serum is a potential biomarker for evaluating the attenuation of NPC pathophysiology by intracerebroventricular HP-β-CD treatment.

Background: The resistance rate of Helicobacter pylori to clarithromycin (CAM) is high among infected children in Japan. Therefore, a new method for detecting CAM-resistant H. pylori using a minimally invasive technique is strongly desired. We aimed to investigate the clinical usefulness of our newly developed nested polymerase chain reaction-quenching probe (Nested PCR-QP) method using stool specimens., Methods: We first evaluated our method using a residual solution of the H. pylori stool antigen test for adolescents. Then, we evaluated our method using culture testing for adults., Results: Among 57 middle school students with H. pylori, the Nested PCR-QP test results of 53 (90.3%) were able to be analyzed. A total of 28 students had CAM resistance mutations. We found a genetic mutation in 28 students and no mutation in 23 students, and these results were consistent with those of PCR-direct sequencing. In the 23 adults who were diagnosed with H. pylori infection using the rapid urease test and culture testing, we were able to use Nested PCR-QP for analyzing 21 adults who tested positive in the stool H. pylori antigen test. The results obtained for all 21 adults were consistent with those obtained via the drug susceptibility test., Conclusions: Our novel method could be useful for non-invasively detecting CAM resistance mutations in H. pylori. This may help select a drug to reduce eradication failure rates against H. pylori. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (no. UMIN000030632, https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000034977 ) on 29 December 2017.

Competing Interests: Competing interests: None declared.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by telangiectasias in multiple organs. We experienced an infant with cerebral hemorrhaging and suspected HHT based on his family history of HHT. Computed tomography angiography confirmed a cerebral arteriovenous fistula. The onset of cerebral arteriovenous fistulas associated with HHT is relatively early, and the incidence of bleeding is relatively common. When HHT is suspected based on a family history, early imaging screening is recommended to improve the neurological prognosis, even in asymptomatic cases. (Received April 7, 2020; Accepted May 7, 2020; Published August 1, 2020).

Background: Probiotics are beneficial to patients with Helicobacter pylori infections by modulating the gut microbiota. Biofermin-R (BFR) is a multiple antibiotic-resistant lactic acid bacteria preparation of Enterococcus faecium 129 BIO 3B-R and is effective in normalizing the gut microbiota when used in combination with antibiotics. This study aimed to determine the effect of BFR in combination with vonoprazan (VPZ)-based therapy on gut microbiota., Methods: Patients with positive urinary anti-H pylori antibody test (primary test) and fecal H pylori antigen test (secondary test) were examined. Patients in group 1 (BFR - ) received VPZ (20 mg twice daily), amoxicillin (750 mg twice daily), and clarithromycin (400 mg twice daily) for 7 days. Patients in group 2 (BFR + ) received BFR (3 tablets/day) for 7 days, in addition to the aforementioned treatments. Following treatment, the relative abundance, α-diversity, and β-diversity of gut microbiota were assessed., Results: Supplementation with BFR prevented the decrease in a-diversity after eradication therapy (Day 7). β-diversity was similar between groups. The incidence rate of diarrhea was non-significantly higher in the BFR - than in the BFR + group (73.1% vs 56.5%; P = .361). Stool consistency was comparable in the BFR + group on Days 7 and 1 (3.86 ± 0.95 vs 3.86 ± 1.46; P = .415)., Conclusion: Biofermin-R combined with VPZ-based therapy resulted in higher microbial α-strain diversity and suppressed stool softening during H pylori eradication therapy., (© 2020 John Wiley & Sons Ltd.)

A 13-year-old boy presented to the hospital with a 3-month history of repeated vomiting and abdominal pain. Results of esophagogastroduodenoscopy revealed a diagnosis of eosinophilic gastroenteritis (EGE). We initiated a short-term six-food elimination diet (SFED) and reintroduction therapy over five days. On the third day of SFED, the patient's abdominal symptoms completely disappeared. However, he experienced unbearable abdominal pain six hours after the reintroduction of milk and peanuts. His symptoms remain completely controlled at present after eliminating milk and peanut products. The SFED and reintroduction therapy for EGE may be effective even for short-term treatments over a five-day period.

Background: Elucidating developmental changes in the symptoms of autism spectrum disorder (ASD) is important to support individuals with ASD. However, no report has clarified the developmental changes in attention to social information for a broad age range. The aim of this study was to investigate the developmental changes in attention to social information from early childhood to adolescence in individuals with ASD and typically developed (TD) children., Methods: We recruited children with ASD (n = 83) and TD participants (n = 307) between 2 and 18 years of age. Using the all-in-one-eye-tracking system, Gazefinder, we measured the percentage fixation time allocated to areas of interest (AoIs) depicted in movies (the eyes and mouth in movies of a human face with/without mouth motion, upright and inverted biological motion in movies showing these stimuli simultaneously, people and geometry in preference paradigm movies showing these stimuli simultaneously, and objects with/without finger-pointing in a movie showing a woman pointing toward an object). We conducted a three-way analysis of variance, 2 (diagnosis: ASD and TD) by 2 (sex: male and female) by 3 (age group: 0-5, 6-11, and 12-18 years) and locally weighted the scatterplot smoothing (LOESS) regression curve on each AoI., Results: In the face stimuli, the percentage fixation time to the eye region for the TD group increased with age, whereas the one for the ASD group did not. In the ASD group, the LOESS curves of the gaze ratios at the eye region increased up to approximately 10 years of age and thereafter tended to decrease. For the percentage fixation time to the people region in the preference paradigm, the ASD group gazed more briefly at people than did the TD group., Limitations: It is possible that due to the cross-sectional design, the degree of severity and of social interest might have differed according to the subjects' age., Conclusions: There may be qualitative differences in abnormal eye contact in ASD between individuals in early childhood and those older than 10 years.

Rationale: Although percutaneous endoscopic gastrojejunostomy (PEG-J) tubes are believed to reduce the side effect of aspiration, cautious catheter management is required. Intussusception is a serious complication of these tubes., Patient Concerns: A 7-year-old boy bedridden with hypoxic encephalopathy owing to drowning at the age of 1 year was admitted our hospital with urinary retention for 1 month. At the age of 4 years, a PEG-J tube was inserted. Concomitant with hyperaldosteronemia, an intestinal intussusception from the duodenum to the jejunum was observed via computed tomography (CT). The patient's condition worsened dramatically; gastrointestinal perforation was suspected, and laparotomy was performed., Diagnosis: Jejuno-jejunal intussusception., Interventions: Open surgery was performed to release the intussusception. By assessing the reduced intestinal tract, the intussusception starting from a 50 cm portion from the Treitz ligament had been extended to 100 cm from the Treitz ligament. The oral side jejunum was dilated. No evidence of intestinal perforation or strangulated ileus was observed, and the intussusception was manually remediable., Outcomes: Preoperative CT examination showed intussusception from the duodenum to the jejunum. Laparotomy showed intussusception on the anal side of the Treitz ligament. With regard to the CT findings associated with the progression of intussusception to the duodenal site, as a result of the telescope phenomenon extending to the duodenum due to the relaxation of the Treitz ligament through repeated intussusception, it was considered that CT examination revealed intussusception extending from the jejunum to the duodenum of oral side. After 3 postoperative weeks, the patient was finally able to return home., Lessons: If the ileus is observed during the insertion of a PEG-J, clinicians should consider the possibility of intussusception even in the duodenum.

Rationale: Helicobacter pylori infection causes atrophic gastritis in childhood, but atrophic gastritis due to H pylori infection is extremely rare in infancy. The relationship between H pylori infection and chronic diarrhea without protein leakage remains controversial., Patient Concerns: An 8-month-old male infant presented to our hospital with severe watery diarrhea, erythema, and failure to thrive from approximately 1 month after birth. Blood, stool, esophagogastroduodenoscopy, total colonoscopy, and H pylori urease analysis results were positive, thereby suggesting atrophic gastritis., Diagnoses: Atrophic gastritis and chronic diarrhea due to H pylori infection., Interventions: We performed H pylori eradication therapy using triple therapy with vonoprazan (6 mg/kg), amoxicillin (300 mg/d), and clarithromycin (120 mg/kg) for 7 days., Outcomes: From approximately 1 week after the H pylori eradication therapy, the frequency of defecation had decreased, stool shape had improved, and body weight had gradually increased., Lessons: H pylori infection can cause atrophic gastritis and chronic diarrhea even in infancy. Early eradication therapy for H pylori infection may be useful for prevention of gastric cancer and improvement in growth disorders.

Background: Selection of test-negative controls takes less time and costs less than traditional control selection for evaluating vaccine effectiveness (VE). Here, rotavirus VE was evaluated using hospital controls and compared with test-negative controls to determine whether using the latter can substitute for the former., Methods: We recorded gastroenteritis in children from 2 months to 2 years of age at six medical facilities in Saga City between January 4th and May 31st, 2014. Stools from all identified acute gastroenteritis patients were tested for rotavirus using immunochromatography. Rotavirus gastroenteritis (RVGE) cases had test-positive stool, whereas test-negative controls had gastroenteritis but no rotavirus infection; hospital controls were outpatients visiting the same facility for indications other than gastroenteritis. Vaccination status was verified by inspecting maternal and child health records, and demographic data were obtained from a questionnaire completed by the patients' guardians or from the medical records. Unconditional logistic regression analysis was used to adjust for possible confounding factors., Results: Sixty-four RVGE cases, 260 test-negative controls, and 589 hospital controls were enrolled. The characteristics of the two control groups, including RV vaccination history, were similar. The RVGE cases were more likely to have used daycare services than children from either of the two control groups. The VE against RVGE estimated using hospital controls was 86.6% (95% confidence interval [CI], 55.9-96.0%), very similar to the VE using test-negative controls (84.9% [95% CI, 49.6-95.5%])., Conclusions: The estimated VE using test-negative controls and hospital controls is similar. Therefore, test-negative controls are considered appropriate for establishing VE.