Impact of Remnant Nodules on Immediate and Long-term Outcomes of Voice Therapy for Vocal Fold Nodules.

OBJECTIVES: In this study, we aimed to assess whether remnant vocal fold nodules (VFN) influence immediate and long-term voice outcomes after voice therapy. STUDY DESIGN: This is a retrospective cohort study evaluating immediate and long-term voice outcomes. METHODS: Twenty-five adult patients with VFN who completed voice therapy were included in this study. Patients were classified into remnant (n = 18) and nonremnant (n = 7) groups according to the presence of remnant nodules immediately after completion of voice therapy. Acoustic and perceptual parameters, as well as voice handicap index (VHI), were compared between groups immediately (immediate outcome) and more than 3 months (long-term outcome) after completion of voice therapy. RESULTS: Immediately after voice therapy, there were no significant differences between groups in grade-roughness-breathiness-asthenia-strain (GRBAS) score, jitter, shimmer, noise-to-harmonics ratio, voice range profile, or s/z ratio. Postvoice therapy VHI scores did not significantly differ between the two groups (9.29 ± 8.94 in the nonremnant group vs. 12.78 ± 9.01 in the remnant group, P = 0.392). The overall GRBAS grade of all patients was maintained at 0 or 1 during long-term follow-up. There was no significant difference between the long-term VHI scores of the remnant group (10.00 ± 8.58) and the nonremnant group (5.67 ± 8.71) (P = 0.306). CONCLUSIONS: Immediately after voice therapy, perceptual scores, acoustic parameters, and VHI scores all significantly improved regardless of presence of remnant nodules. Favorable outcomes of voice therapy were maintained during long-term follow-up regardless of presence of remnant nodules after voice therapy.

The Use of Inhaled N-Acetylcysteine for Laryngopharyngeal Reflux Disease: A Randomized Controlled Trial.

OBJECTIVES: Proton pump inhibitors (PPIs) are the mainstay of the medical treatment for laryngopharyngeal reflux disease (LPRD). However, extraesophageal symptoms of LPRD, such as globus, are often refractory to PPI treatment. Many kinds of adjunctive medications have been attempted to address those refractory cases. We aimed to study whether inhaled N-acetylcysteine (NAC), a mucolytic agent, has additive effects for the treatment of LPRD when used in conjunction with PPIs. METHODS: Patients with reflux symptom index (RSI) greater than 13 and reflux finding scores (RFS) greater than 7 were prospectively enrolled and were randomly assigned to control or study group. Patients were treated with oral rabeprazole in the control group and with oral rabeprazole and inhaled NAC in the study group. Patients were followed once a month for 2 months with questionnaires and stroboscopic examination. At every follow-up, RSI and RFS were checked. The extent of improvements of RSI and RFS were evaluated and compared between two groups. RESULTS: With treatment, the mean RSI changed from 21.0 to 7.6 (P < 0.001) in control group and from 19.7 to 4.5 (P < 0.001) in study group. The mean RFS also changed from 12.9 to 7.1 (P < 0.001) in control group and from 13.5 to 6.9 (P < 0.001) in study group. For both RSI and RFS, the extents of improvement were not significantly different between two groups. In patients whose RSI improved less than nine at the first follow-up (poor early responders), RSI became significantly lower in the study group (4.6 ± 2.0) than in the control group (9.5 ± 4.6) at second follow-up (P = 0.019). In good early responders, however, RSI was not significantly different between the two groups in the second follow-up. CONCLUSIONS: In this study, there were no significant differences in the overall outcome between patients treated with inhaled NAC and PPI and those with PPI alone. Interestingly, some additional therapeutic effect of NAC appeared late for the patients with poor early response. Further studies are required to investigate the underlying mechanism for this.

Temporomandibular Joint Herniation: Review of the Literature.

OBJECTIVE: To define clear clinical characteristics and management strategies of herniation of temporomandibular joint (TMJ) into the external auditory canal (EAC). DATA SOURCE: MEDLINE, PubMed, and EMBASE databases. STUDY SELECTION: A search was conducted using the keywords "temporomandibular joint" and "herniation" with all of their synonyms. Literature selection criteria included articles published in English, and articles dating back no further than 1970. RESULTS: Forty articles regarding 51 cases were eligible for critical appraisal. According to the previously published papers, TMJ herniation has following characteristics; symptoms are nonspecific, but a distinguishable feature is a protruding mass into the EAC that can be seen to appear and disappear as the mouth opens and closes. High-resolution computed tomography scans are sensitive to the bony defect and are helpful in diagnosing TMJ herniation. In the surgical treatment of TMJ herniation, wall reconstruction rather than simple mass excision could be a safe and long-lasting strategy. CONCLUSIONS: Herniation of TMJ into the EAC is a rare condition, but can be encountered in the clinic at any time. This literature review could be helpful in the diagnosis and treatment of TMJ herniation into the EAC.

Phosphorylation of eIF2α suppresses cisplatin-induced p53 activation and apoptosis by attenuating oxidative stress via ATF4-mediated HO-1 expression in human renal proximal tubular cells.

Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of human cancers. However, the nephrotoxicity of cisplatin limits its use as a therapeutic agent. It has been suggested that oxidative stress and p53 activation play important roles in cisplatin-induced nephrotoxicity. It has been demonstrated that the eukaryotic translation initiation factor 2α (eIF2α) may protect HK-2 human renal proximal tubular cells against cisplatin-induced apoptosis through inhibition of reactive oxygen species (ROS)­mediated p53 activation. The aim of the present study was to investigate the effects of siRNA­mediated knockdown of the PKR-like endoplasmic reticulum kinase (PERK) gene, which induces the phosphorylation of eIF2α, or Sal003, a selective inhibitor of eIF2α dephosphorylation, on cisplatin­induced apoptosis in HK-2 cells. Cisplatin induced eIF2α phosphorylation as well as p53 activation. In particular, inhibition of p53 by pifithrin­α, and upregulation of eIF2α phosphorylation by Sal003, reduced cisplatin-induced apoptosis. Of note, Sal003­mediated upregulation of eIF2α phosphorylation suppressed cisplatin­induced p53 activation. Furthermore, reduction of eIF2α phosphorylation by PERK knockdown enhanced cisplatin-induced p53 activation and apoptosis. In addition, the ROS scavenger N-acetyl-L-cysteine inhibited eIF2α phosphorylation as well as p53 activation in HK-2 cells treated with cisplatin, suggesting that oxidative stress induced by cisplatin may lead to apoptosis through p53 activation; furthermore, this stress may confer resistance to apoptosis via eIF2α phosphorylation, which was further supported by the finding that cisplatin­induced ROS generation was attenuated by Sal003, whereas it was enhanced by PERK knockdown. Furthermore, cisplatin induced the expression of activating transcription factor 4 (ATF4) and heme oxygenase-1 (HO-1) that were enhanced by Sal003 and reduced by PERK knockdown. Taken together, these results suggest that phosphorylation of eIF2α suppresses cisplatin­induced p53 activation and apoptosis by attenuating oxidative stress via ATF4-mediated HO-1 expression in HK-2 cells, as ATF4 expression is usually dependent on the phosphorylation of eIF2α and may also transcriptionally induce the expression of HO-1 in response to oxidative stress. Therefore, regulation of eIF2α phosphorylation may play an important role in alleviating cisplatin-induced nephrotoxicity.