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Insurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital cytomegalovirus (CMV) disease. The VGCV treatment is available throughout Japan, so clinicians must consider the likelihood of hearing improvement and the possibility of neutropenia before dosing. We performed a substudy of an investigator-initiated, single-arm, prospective, multicenter, clinical trial in which 24 infants with symptomatic congenital CMV disease were orally administered 16 mg/kg VGCV twice daily for 6 months as an intervention. We examined the infants' baseline characteristics associated with improved hearing impairment or a severely reduced neutrophil count. Of the 24 patients, 4 had normal hearing on assessment of their ear with the best hearing. Hearing impairment improved in 14 patients and did not respond to VGCV treatment in 6 patients at the 6-month hearing assessment. CMV DNA levels in plasma at baseline were higher in patients in whom hearing did not respond to treatment. A neutrophil count <500/mm3 occurred in 5 (21%) patients for the first 6 weeks and in 8 (33%) patients for the first 6 months. A neutrophil count at screening and the lowest neutrophil count over the 6 months showed the highest correlation (r = 0.477, p = 0.019). Infants with a low plasma viral load at screening tend to have an improvement in hearing impairment. Clinicians should be aware of neutropenia during VGCV treatment particularly in patients with a low neutrophil count during screening. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment‐refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single‐arm trial (EMPIRE‐01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE‐02) that followed on from EMPIRE‐01. Materials and Methods: The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE‐01 trial participated in EMPIRE‐02. Results: Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE‐02. The improvement in mean values of glycemic parameters observed in EMPIRE‐01 was not sustained in EMPIRE‐02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE‐02 after exclusion of this subject from analysis. Conclusions: Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option. [ABSTRACT FROM AUTHOR]

Objective: Although benign, ameloblastoma is a locally aggressive lesion in some patients and the development of additional treatments is needed. Verteporfin (VP) is a photosensitizer exhibiting considerable photocytotoxicity in various tumor cells. We aimed to investigate the effects of verteporfin photodynamic therapy (VP PDT) on ameloblastoma. Methods: Eighteen patients who underwent surgery for ameloblastoma were randomly selected. We performed an immunohistochemical assessment to investigate the expression of low‐density lipoprotein receptor (LDLR) and Yes‐associated protein (YAP), targets of VP, in human ameloblastoma tissues and cultured human ameloblastoma cell line (HAM1). The effect of VP PDT on cell proliferation and apoptosis in HAM1 was analyzed. Results: The expression of LDLR and YAP were detected in human ameloblastoma tissues and HAM1. LDLR expression was significantly higher in patients who had previously undergone surgery than in patients who were receiving it for the first time. The cytotoxic effect of the combination of low‐concentration VP administration and laser irradiation was comparable to high‐concentration VP administration with and without laser irradiation. The addition of laser irradiation to VP administration significantly accelerated apoptotic bleb formation compared with VP administration alone. Conclusion: VP PDT has the potential to become an additional treatment for large‐sized ameloblastoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) treatment includes surgery, radiotherapy, and immunotherapy with the aim of eradicating cancer cells without affecting normal tissues. HNSCC expresses epidermal growth factor receptor and cetuximab, an IgG1 monoclonal antibody targeting epidermal growth factor receptor, has been approved for the treatment of HNSCC. However, cetuximab has low reactivity. Gold nanoparticles (AuNPs) were reported to enhance the local antitumor effects of radiotherapy without damaging normal cells. This study investigated the in vitro and in vivo effects of single and combination therapy with AuNPs, cetuximab, and radiotherapy on a human HNSCC cell line. Combination treatment of AuNPs + cetuximab + radiotherapy markedly reduced HNSCC cell numbers and proliferation and enhanced apoptosis compared with single and double combination treatments. Furthermore, the in vivo combination treatment (AuNPs + cetuximab + radiotherapy) reduced the tumor volume compared with the controls. This study showed that AuNPs sensitize tumors to radiotherapy and bind to cetuximab, leading to enhanced antitumor effects. Introduction: Head and neck squamous cell carcinoma (HNSCC) treatment includes surgery, radiotherapy, and immunotherapy with the aim of eradicating cancer cells without affecting normal tissues. HNSCC expresses epidermal growth factor receptor (EGFR) and cetuximab, an IgG1 monoclonal antibody targeting epidermal growth factor receptor, has been approved for the treatment of HNSCC. However, cetuximab has low reactivity and induces serious side effects. Gold nanoparticles (AuNPs) were reported to enhance the local antitumor effects of radiotherapy without damaging normal cells. Methods and Results: This study investigated the in vitro effects of single and combination therapy with AuNPs (1.0 nM), cetuximab (30 nM), and radiotherapy (4 Gy) on a human HNSCC cell line, HSC-3. Combination treatment of AuNPs + cetuximab + radiotherapy markedly reduced HSC-3 numbers and proliferation and enhanced apoptosis compared with single and double combination treatments. Furthermore, the in vivo combination treatment (AuNPs + cetuximab + radiotherapy) of a xenograft model of HSC-3 cells transplanted into nude mice (BALB/cAJcl-nu/nu) reduced the tumor volume compared with the controls. Scanning electron microscopy demonstrated the presence of AuNPs in tumor tissues and toxicity analysis indicated that AuNPs had no toxic effect on normal tissues. Conclusions: This study showed that AuNPs alone do not have a tumor-suppressing effect, but they sensitize tumors to radiotherapy and bind to cetuximab, leading to enhanced antitumor effects. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to evaluate the postoperative efficacy and safety of using an ibuprofen gargle as a pain management strategy for patients who have undergone mandibular third molar extraction. We also ensured that the quality of treatment was not compromised throughout the study. Material and Methods: Patients were randomized in a 1:1 ratio into two groups: the ibuprofen–placebo (IP) group and the placebo–ibuprofen (PI) group. On postoperative Day (POD) 1, the IP group initiated ibuprofen administration, while the PI group started taking placebo. On POD 2, the IP group switched to using placebo, whereas the PI group switched to ibuprofen. From PODs 3–5, both groups were prescribed ibuprofen gargle. The primary endpoint was within‐subject visual analog scale (VAS) score before and 5 min after the first use of the ibuprofen or placebo gargle on PODs 1 and 2 (ΔVAS5_ibuprofen − ΔVAS5_placebo). The incidence and severity of adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0 and a subjective rating scale. Results: This study enrolled 40 patients. The within‐subject VAS5 of the IP and PI groups were 1.25 ± 12.0 and −5.26 ± 8.93 mm, respectively. The treatment effect of ibuprofen gargle was −2.01 ± 10.62 mm (p =.246). None of the patients in each group presented with serious adverse events or clinically significant complications (including dry sockets) after extraction. Transient adverse events, such as throat tingling and oral discomfort (grade 1), were observed in each group. Conclusion: Ibuprofen gargle was safe but did not provide significant pain relief when used after mandibular third molar extraction. [ABSTRACT FROM AUTHOR]

Although perineurium has an important role in maintenance of the blood–nerve barrier, understanding of perineurial cell–cell junctions is insufficient. The aim of this study was to analyze the expression of junctional cadherin 5 associated (JCAD) and epidermal growth factor receptor (EGFR) in the perineurium of the human inferior alveolar nerve (IAN) and investigate their roles in perineurial cell–cell junctions using cultured human perineurial cells (HPNCs). In human IAN, JCAD was strongly expressed in endoneurial microvessels. JCAD and EGFR were expressed at various intensities in the perineurium. In HPNCs, JCAD was clearly expressed at cell–cell junctions. EGFR inhibitor AG1478 treatment changed cell morphology and the ratio of JCAD-positive cell–cell contacts of HPNCs. Therefore, JCAD and EGFR may have a role in the regulation of perineurial cell–cell junctions. [ABSTRACT FROM AUTHOR]