Hearing loss is associated with cognitive decline and dementia risk. Sensorineural hearing loss suppresses hippocampal neurogenesis, resulting in cognitive decline. However, the underlying mechanism of impaired neurogenesis and the role of microglial activation and stress responses related to hearing loss in the hippocampus remains unknown. Using a conductive hearing loss (CHL) model, we investigated whether a decrease in sound level could induce impairment of hippocampal neurogenesis and examined the differences between unilateral CHL (uCHL) and bilateral CHL (bCHL). To establish the CHL mouse model, ears were unilaterally or bilaterally occluded for five weeks by auditory canal ligation. Although hearing thresholds were significantly increased following CHL, CHL mice exhibited no significant loss of spiral ganglion or hippocampal neurons. Hippocampal neurogenesis was significantly and equally decreased in both sides following uCHL. More severe decreases in hippocampal neurogenesis were observed in both sides in bCHL mice compared with that in uCHL mice. Furthermore, microglial invasion significantly increased following CHL. Serum cortisol levels, which indicate stress response, significantly increased following bCHL. Therefore, auditory deprivation could lead to increased microglial invasion and stress responses and might be a risk factor for hippocampal neurogenesis impairment.

Background: There is increasing evidence that immunotherapy with nivolumab, an anti‐programmed death 1 monoclonal antibody, is effective in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the predictive role of hematological inflammatory markers such as neutrophil‐to‐lymphocyte ratio (NLR) and the modified Glasgow prognostic score (mGPS) in patients with R/M SCCHN treated with nivolumab remains unclear.Methods: We conducted a multi‐institutional cohort study to evaluate the impact of pretreatment NLR and mGPS on overall survival (OS) and progression‐free survival (PFS) in patients with R/M SCCHN treated with nivolumab in Japan. From 2012 to 2013, 102 patients were eligible, of whom 88 were finally included in the analysis. mGPS was calculated as follows: mGPS of 0, C‐reactive protein (CRP) ≤1.0 mg/dL; 1, CRP > 1.0 mg/dL; and 2, CRP > 1.0 mg/dL and albumin < 3.5 mg/dL. Optimal cutoff point of dichotomized NLR was calculated using the area under the receiver operating characteristic curve (AUROC). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models adjusted by potential confounders.Results: Higher NLR was significantly associated with worse survival (1‐year OS: 45.3% vs 16.3%, log‐rank P‐value < .001, adjusted HR: 4.40 (95% CIs: 1.78‐10.88); one‐year PFS: 39.1% vs 9.0%, P‐value = .001, adjusted HR: 3.37 (95% CI: 1.64‐6.92)). In addition, high mGPS (=2) was significantly associated with worse survival compared to low mGPS (=0) (1‐year OS: 37.4% vs 26.1%, P‐value = .004, adjusted HR: 4.20 (95% CI:1.54‐11.49); 1‐year PFS: 41.5% vs 24.8%, P‐value = .007, adjusted HR: 2.01 (95% CI: 0.87‐4.68)). These associations were consistent with subgroup analyses stratified by potential confounders.Conclusions: Pretreatment NLR and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with nivolumab.

No real-world, long-term outcomes of immunotherapy with nivolumab for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have yet been reported. Furthermore, the prognostic impact of the best overall response (BOR) of this therapy remains unclear. We conducted a multi-institutional cohort study of the long-term efficacy and safety of this therapy and investigated prognostic factors associated with survival. Further, we evaluated the relationship between BOR and survival. Median follow-up time was 25.9 months. Median overall survival (OS) was 9.6 months, and two-year survival rate was 25.0%. Median progression-free survival (PFS) was 3.7 months, and two-year PFS rate was 19.6%. BOR was assessed as complete response (CR) in 6%, partial response (PR) in 13%, stable disease (SD) in 30%, and progressive disease (PD) in 52% of the patients. Overall response rate was 18%, and disease control rate was 48%. For immune-related adverse events (irAEs), 38 irAEs were detected in 29 patients. On multivariate analysis, the development of irAEs was significantly associated with better OS and PFS. Better BOR was significantly associated with longer OS and PFS. These findings demonstrate the long-term efficacy and safety of nivolumab therapy for R/M SCCHN in a real-world setting. The magnitude of BOR and the development of irAEs might be useful surrogate markers of survival.

OBJECTIVES: We hypothesized that patients with idiopathic sudden sensorineural hearing loss (ISSHL) would have experienced more stress prior to the onset than they typically did. This study investigated stress levels in patients before the onset of ISSHL. MATERIALS and METHODS: Forty-two patients with ISSHL were investigated. We used an original questionnaire to evaluate subjective stress levels in 1 week before onset. Serum hemoglobin A1c (HbA1c) and total cholesterol were examined to evaluate biochemical stress markers reflecting the preceding 1 to 2 months. The results on admission were compared with those at the follow-up visit. RESULTS: Significantly more patients reported greater physical exhaustion, greater mental exhaustion, or a worse physical condition on admission than at follow-up (p

This study aimed to compare the difference in maximum speech discrimination score (SDSmax) of the worse-hearing ear in asymmetric hearing loss (ASHL) patients with that in symmetric hearing loss (S...