Objectives: The aim of present study was to evaluate the clinical efficacy of hyperbaric oxygen therapy (HBOT) as a primary therapy combined with standard systemic corticosteroid treatment for sudden sensorineural hearing loss (SSNHL) compared to treatment without the use of HBOT (non‐HBOT) through clinical data and advanced analytical approaches.Study Design: Case–control study.Methods: Conducted across three Japanese medical centers involving 298 SSNHL patients diagnosed between 2020 and 2023. Inclusion criteria encompassed first onset and treatment, WHO grade 3 or 4 initial hearing impairment, receipt of systemic corticosteroid therapy within 14 days of symptom onset, and initiation of HBOT within the same timeframe for the case group. The primary outcome measure was the difference in hearing improvement (mean hearing level in decibels, dB) between the two groups, assessed by pure‐tone audiometry at baseline and 3 months post‐treatment, using the inverse probability of treatment weighting (IPTW) method adjusted for covariate differences.Results: The study included 67 patients in the HBOT group and 68 in the non‐HBOT group. The HBOT group exhibited significantly greater hearing improvement (IPTW‐adjusted difference: 7.6 dB, 95% CI 0.4–14.7; p = 0.038). Patients without vertigo in the HBOT group demonstrated substantial hearing improvement (11.5 dB, 95% CI 2.3–20.6; p = 0.014), whereas those with vertigo showed no significant improvement (−1.8 dB, 95% CI −11.8–8.3; p = 0.729). The HBOT group also had a significantly higher association with complete recovery (IPTW‐adjusted odds ratio: 2.57, 95% CI 1.13–5.85; p = 0.025).Conclusion: In SSHNL, HBOT combination therapy yielded slightly but significantly improved hearing outcomes compared to non‐HBOT treatment.Level of Evidence: 4.

Fluorouracil (FU) exerts its antitumor activity by inhibiting folate-mediated one-carbon metabolism. Evidence that folate may play a role in the carcinogenic process via folate-mediated one-carbon metabolism has given rise to the hypothesis that pre-diagnostic folate intake may induce heterogeneous chemosensitivity to FU-containing induction chemotherapy (IC) in head and neck cancer. To assess this hypothesis, we conducted a cohort study to investigate whether the association between prediagnostic dietary folate intake and cancer survival differed between treatment regimens with and without FU-containing IC in 504 cases of locally advanced (stage III/IV) HNSCC, using an epidemiologic database combined with clinical data. In total, 240 patients were treated with FU-containing IC followed by definitive treatment, and 264 patients were treated with definitive treatment alone. Definitive treatment is defined as (1) the surgical excision of a tumor with clear margins, with or without neck lymph node dissection; or (2) radiotherapy with or without chemotherapy. In the overall cohort of the FU-containing IC group, a higher folate intake was significantly associated with better overall survival (adjusted hazard ratios (HRs) for the highest compared to the lowest folate tertiles (HR_T3-T1) = 0.42, 95%CI, 0.25–0.76, P_trend = 0.003). Conversely, no apparent association between prediagnostic folate intake and survival was observed with definitive treatment alone (HR_T3-T1: 0.83, 95%CI, 0.49–1.42, P_trend = 0.491)). A consideration of the cumulative dose of FU-containing IC showed that the survival impact of prediagnostic folate intake differed statistically significantly by treatment regimen (Pinteraction = 0.012). In conclusion, an association between prediagnostic folate intake and HNSCC survival significantly differed by FU-containing IC. This finding indicates that in the carcinogenic process, folate status causes HNSCC to be heterogenous in terms of one-carbon metabolism.