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Introduction: Scarring and pain are postoperative complications in patients after head and neck cancer treatment; however, there is no effective treatment. These complications are affected by local blood flow disorders, and it is well known that the transcutaneous application of carbon dioxide (CO2) improves local blood flow. Previously, we have shown that the transcutaneous application of carbon dioxide causes absorption of CO2 and increase the oxygen (O2) pressure in the treated tissue; it is expected that the application of CO2 may reduce scarring and pain caused by cancer treatment. We newly introduced the CO2 paste as a new CO2 application method, which does not need to use CO2 gas directly. In this study, we aimed to apply of CO2 paste to healthy people and to investigate its usefulness, safety and feasibility by analysing the increase in blood flow and frequency of adverse events. Methods: We applied carbon dioxide paste to skin over the sternocleidomastoid and gastrocnemius muscles of eight healthy volunteers. The changes in blood flow before and after the CO2 paste application using dynamic MRI, and changes in the vital signs were evaluated. Results: In the neck area and middle layer of the lower leg, the signal intensity (SI) significantly increased 60 seconds after application. In the surface layer of the lower leg, the SI was significantly increased 60 and 300 seconds after paste application. Although mild heat was noted after the paste application, no obvious adverse events occurred. Conclusion: We demonstrated the increase in SI by dynamic MRI at the site of the carbon dioxide paste application, which indicates the paste application is effective in improving the blood flow.

Background: Congenital cytomegalovirus (CMV) disease, a common mother-to-child infection, can lead to neurological sequelae. Some clinical trials have shown that oral valganciclovir (VGCV) can improve hearing and neurodevelopmental impairment in infants with congenital CMV disease. However, VGCV has neither been approved in Japan nor other countries as a treatment for this disease by the government health insurance. Methods: This study is a non-randomized, prospective, open-label, multicenter, single-arm clinical trial and will include subjects meeting the following criteria: confirmation of positive CMV-DNA amplification in urine by an in vitro diagnostic test within 21 days of age; congenital CMV disease with one or more central nervous system disorders-microcephaly, hydrocephalus or ventricular enlargement, periventricular calcification, cortical hypoplasia or white matter injury, retinal choroiditis, and abnormal auditory brainstem response (ABR); and infants within 2 months of age with a gestational age >= 32 weeks at birth and weighing >= 1800 g at the time of registration. Subjects will be orally administered 16 mg/kg VGCV twice daily for 6 months. The target number of cases for enrollment between February 3, 2020 and July 31, 2021 is 25. Primary endpoint is the change in whole blood CMV loads before and after 6 months of treatment. The important secondary endpoint is the change in ABR (both best and total ear hearing assessments) before and after 6 months of treatment. The safety endpoints are adverse events and drug side effects. Discussion: To the best of our knowledge, this multicenter, open-label, single-arm study will be the first well-designed clinical trial to evaluate the efficacy of oral VGCV in infants with congenital CMV diseases. The findings will reveal the efficacy and safety of oral VGCV treatments and enable the approval of oral VGCV as a treatment for infants with congenital CMV disease by the government health insurance of Japan.