吉川 哲史

OBJECTIVE: To evaluate the long-term hearing outcomes of infants with symptomatic congenital cytomegalovirus (CMV) disease who received 16 mg/kg of oral valganciclovir (VGCV) twice daily for six months. STUDY DESIGN: We have currently performed a long-term extension study of an investigator-initiated, single-arm, prospective, multicenter clinical trial, in which 24 infants were treated with VGCV. Hearing outcomes up to three years after treatment initiation were described and the longitudinal changes in the proportion of "Improved hearing" were analyzed using logistic regression. The factors associated with these outcomes were explored. Adverse events that occurred after the completion of the administration period were assessed. RESULTS: At 3 years, among 48 ears from 24 infants, the number of "improved hearing," which was 19 (40.0 %) ears at 6 months, increased to 27 (56.3 %) ears (p = 0.032). When including "maintaining normal hearing" or "maintaining normal hearing or the same degree of hearing impairment", the corresponding numbers were observed in 35 (72.9 %) and 45 (93.7 %) ears at 3 years, which were 25 (52.5 %) and 45 (93.7 %) ears at 6 months, respectively. Infants with milder hearing impairment at baseline showed high likelihood of hearing improvement (p for trend = 0.018 by the regression analysis). No adverse events were observed after completion of the administration period. CONCLUSION: Oral administration of VGCV demonstrated efficacy in improving hearing in infants with symptomatic congenital CMV disease at 3 years of age. These results suggest that the treatment response may be particularly favorable in patients with a lower initial degree of hearing impairment.

OBJECTIVES: In developing countries, acute gastroenteritis (AGE) is a leading cause of death in children younger than 5 years. In Myanmar, no comprehensive study has been done to investigate the microorganisms responsible for AGE among hospitalized children. Multiplex polymerase chain reaction (PCR) was used to identify the microorganisms responsible for AGE in children hospitalized in Myanmar before the introduction of the rotavirus vaccine. METHODS: This prospective study enrolled children younger than 12 years with AGE who were hospitalized at the Yankin Children's Hospital in Yangon, Myanmar, between September 2019 and February 2020. Multiplex PCR (FilmArrayTM GI panel, BioFire Diagnostics, Salt Lake City, USA) and genotyping with Sanger sequencing of rotavirus were performed. Clinical data, including disease severity, were collected from the medical records. RESULTS: We collected stool samples from 92 patients. Multiple microorganisms (median 3; interquartile range 2-4) were detected in 81 patients (88%). Rotavirus and norovirus were detected in 77 (84%) and 33 patients (36%), respectively. The most frequent bacterial pathogen detected was Enteroaggregative E. coli (n = 62/92, 67%). The most common rotavirus genotypes were G1P [8] (19/73; 26%) and G2P [4] (19/73; 26%). CONCLUSIONS: Rotavirus is the predominant pathogen associated with AGE in hospitalized children in Myanmar. The introduction of a rotavirus vaccine will reduce the morbidity and mortality of children with rotavirus-associated AGE in Myanmar.

UBA1 is an E1 ubiquitin-activating enzyme that initiates the ubiquitylation of target proteins and is thus a key component of the ubiquitin signaling pathway. Three disorders are associated with pathogenic variants of the UBA1 gene: vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, lung cancer in never smokers (LCINS), and X-linked spinal muscular atrophy (XL-SMA, SMAX2). We here report a case of infantile respiratory distress syndrome followed by continuing neuromuscular symptoms. We identified a de novo hemizygous mutation, c.1660 C > T (p.Pro554Ser), in exon 15 of the UBA1 gene in this baby. This missense mutation was located with the AAD (active adenylation domain) of the protein, a known hotspot of SMAX2 mutations. This case lends support to the genotype-phenotype correlation regarding the UBA1 mutation and its related diseases.