Effect of Hearing Rehabilitation Therapy Program in Hearing Aid Users: A Prospective Randomized Controlled Study

ObjectivesDespite sufficient hearing gains, many patients with hearing loss have difficulty using hearing aids due to poor word recognition ability. This study was performed to introduce our hearing rehabilitation therapy (HRT) program for hearing aid users and to evaluate its effect on hearing improvement.MethodsIn this prospective randomized case-control study, 37 participants with moderate or moderate-severe sensorineural hearing loss who had used bilateral hearing aids for more than 3 months with sufficient functional hearing gain were enrolled in this study. Nineteen participants were randomly assigned to the control group (CG) and 18 patients were assigned to participate in our HRT program once a week for 8 consecutive weeks (hearing rehabilitation therapy group [HRTG]). Their hearing results and questionnaire scores for hearing handicap and hearing aid outcomes were prospectively collected and compared between the two groups.ResultsAfter completing 8 weeks of the HRT program, the HRTG showed a significantly greater improvement in scores for consonant-only and consonant-vowel sound perception than the CG (P<0.05). In addition, the HRTG showed a significant improvement in hearing ability as measured by two questionnaires (P<0.05), while no differences were observed in the CG. However, word and sentence recognition test results did not show significant differences between the two groups.ConclusionEven after short-term HRT, patients had subjectively better hearing outcomes and improved phoneme perception ability; this provides scientific evidence regarding a possible positive role for HRT programs in hearing aid users. Further validation in a larger population through a long-term follow-up study is needed.     

Induction of apoptotic cell death in human bladder cancer cells by ethanol extract of Zanthoxylum schinifolium leaf,through ROS-dependent inactivation of the PI3K/Akt signaling pathway

BACKGROUND/OBJECTIVESZanthoxylum schinifolium is traditionally used as a spice for cooking in East Asian countries. This study was undertaken to evaluate the anti-proliferative potential of ethanol extracts of Z. schinifolium leaves (EEZS) against human bladder cancer T24 cells.MATERIALS/METHODSSubsequent to measuring the cytotoxicity of EEZS, the anti-cancer activity was measured by assessing apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). In addition, we determined the underlying mechanism of EEZS-induced apoptosis through various assays, including Western blot analysis.RESULTSEEZS treatment concentration-dependently inhibited T24 cell survival, which is associated with apoptosis induction. Exposure to EEZS induced the expression of Fas and Fas-ligand, activated caspases, and subsequently resulted to cleavage of poly (ADP-ribose) polymerase. EEZS also enhanced the expression of cytochrome c in the cytoplasm by suppressing MMP, following increase in the ratio of Bax:Bcl-2 expression and truncation of Bid. However, EEZS-mediated growth inhibition and apoptosis were significantly diminished by a pan-caspase inhibitor. Moreover, EEZS inhibited activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and the apoptosis-inducing potential of EEZS was promoted in the presence of PI3K/Akt inhibitor. In addition, EEZS enhanced the production of ROS, whereas N-acetyl cysteine (NAC), a ROS scavenger, markedly suppressed growth inhibition and inactivation of the PI3K/Akt signaling pathway induced by EEZS. Furthermore, NAC significantly attenuated the EEZS-induced apoptosis and reduction of cell viability.CONCLUSIONSTaken together, our results indicate that exposure to EEZS exhibits anti-cancer activity in T24 bladder cancer cells through ROS-dependent induction of apoptosis and inactivation of the PI3K/Akt signaling pathway.     

SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.     

Brief Report: Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A_2A receptor (A_2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A_2AR inhibition by the Food and Drug Administration–approved A_2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin’s antitumor activity. Collectively, our study identifies A_2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.     

Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multi-institutional analysis (KROG 19-04)

Objective:The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC.Methods:A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV).Results:In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05).Conclusions:CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).     

Association between the Dietary Inflammatory Index and Gastric Disease Risk: Findings from a Korean Population-Based Cohort Study

Evidence suggests that diets with high pro-inflammatory potential may play a substantial role in the origin of gastric inflammation. This study aimed to examine the association between the energy-adjusted dietary inflammatory index (E-DII^TM) and gastric diseases at baseline and after a mean follow-up of 7.4 years in a Korean population. A total of 144,196 participants from the Korean Genome and Epidemiology Study_Health Examination (KoGES_HEXA) cohort were included. E-DII scores were computed using a validated semi-quantitative food frequency questionnaire. Multivariate logistic regression and Cox proportional hazards regression were used to assess the association between the E-DII and gastric disease risk. In the prospective analysis, the risk of developing gastric disease was significantly increased among individuals in the highest quartile of E-DII compared to those in the lowest quartile (HR_quartile4vs1 = 1.22; 95% CI = 1.08–1.38). Prospective analysis also showed an increased risk in the incidence of gastritis (HR_quartile4vs1 = 1.19; 95% CI = 1.04–1.37), gastric ulcers (HR_quartile4vs1 = 1.47; 95% CI = 1.16–1.85), and gastric and duodenal ulcers (HR_quartile4vs1 = 1.46; 95% CI = 1.17–1.81) in the highest E-DII quartile compared to the lowest quartile. In the cross-sectional analysis, the E-DII score was not associated with the risk of gastric disease. Our results suggest that a pro-inflammatory diet, indicated by high E-DII scores, is prospectively associated with an increased risk of gastric diseases. These results highlight the significance of an anti-inflammatory diet in lowering the risk of gastric disease risk in the general population.     

A Case Report of MPO-ANCA-Associated Vasculitis Following Heterologous mRNA1273 COVID-19 Booster Vaccination

Despite that clinical trials have been examining the safety profile of coronavirus disease 2019 (COVID-19) vaccines, there are concerns about long-term side effects as the number of vaccinations increases. Herein, we report a case of new-onset renal-limited anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis after booster vaccination with the mRNA 1273 (Moderna) vaccine. A 72-year-old woman with no specific past history, and who had a normal renal function, developed ANCA-associated vasculitis following heterologous booster with mRNA1273 (Moderna) vaccine. After a kidney biopsy, she was diagnosed with ANCA-associated pauci-immune crescentic glomerulonephritis. Her renal function and constitutional symptoms have been improved with treatment with plasmapheresis, intravenous cyclophosphamide and steroid pulse therapy (intravenous 500 mg of methylprednisolone sodium succinate for 3 days) followed by a reduced steroid regimen.     

Comparison of the effects of inhalational and total intravenous anesthesia on quality of recovery in patients undergoing endoscopic transsphenoidal pituitary surgery: a randomized controlled trial

Background: Endoscopic transsphenoidal pituitary surgery has shown promising results. However, fast and high-quality recovery after this procedure remains a challenge for neuroanesthesiologists. This study aimed to compare the quality of recovery after transsphenoidal pituitary surgery between patients who received inhalational anesthesia with sevoflurane and patients who received propofol-based total intravenous anesthesia (TIVA).Methods: Eighty-two patients undergoing transsphenoidal pituitary surgery were randomized to receive either sevoflurane inhalation with manual infusion of remifentanil (sevoflurane group) or effect-site target-controlled infusion of propofol and remifentanil (TIVA group). The primary outcome was the 40-item Quality of Recovery (QoR-40) score on postoperative day 1. The QoR-40 questionnaire was completed by patients the day before surgery and on postoperative days 1 and 2. Emergence agitation and recovery characteristics were also assessed.Results: There were no significant differences between the groups in the global QoR-40 scores on both postoperative days 1 and 2 (difference -8.7, 95% CI -18.0 to 0.7, and P = 0.204; -3.6, 95% CI -13.0 to 5.8, and P > 0.999, respectively). The time to verbal response and time to extubation were significantly shorter in the sevoflurane group than in the TIVA group (P < 0.001 and P < 0.001, respectively). However, the incidence of emergence agitation was lower in the TIVA group than in the sevoflurane group (P < 0.001).Conclusions: Both inhalational anesthesia with sevoflurane and propofol-based TIVA were appropriate anesthetic techniques for patients undergoing endoscopic transsphenoidal pituitary surgery in terms of the quality of recovery up to 2 days postoperatively. Rapid emergence was observed in the sevoflurane group, while smooth emergence was observed in the TIVA group.