Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

Familial Temperature-Sensitive Auditory Neuropathy: Distinctive Clinical Courses Caused by Variants of the OTOF Gene.

Objective: To investigate the clinical course and genetic etiology of familial temperature-sensitive auditory neuropathy (TSAN), which is a very rare subtype of auditory neuropathy (AN) that involves an elevation of hearing thresholds due to an increase in the core body temperature, and to evaluate the genotype-phenotype correlations in a family with TSAN. Methods: Six members of a non-consanguineous Chinese family, including four siblings complaining of communication difficulties when febrile, were enrolled in this study. The clinical and audiological profiles of the four siblings were fully evaluated during both febrile and afebrile episodes, and the genetic etiology of hearing loss (HL) was explored using next-generation sequencing (NGS) technology. Their parents, who had no complaints of fluctuating HL due to body temperature variation, were enrolled for the genetics portion only. Results: Audiological tests during the patients' febrile episodes met the classical diagnostic criteria for AN, including mild HL, poor speech discrimination, preserved cochlear microphonics (CMs), and absent auditory brainstem responses (ABRs). Importantly, unlike the pattern observed in previously reported cases of TSAN, the ABRs and electrocochleography (ECochG) signals of our patients improved to normal during afebrile periods. Genetic analysis identified a compound heterozygous variant of the OTOF gene (which encodes the otoferlin protein), including one previously reported pathogenic variant, c.5098G > C (p.Glu1700Gln), and one novel variant, c.4882C > A (p.Pro1628Thr). Neither of the identified variants affected the C2 domains related to the main function of otoferlin. Both variants faithfully cosegregated with TSAN within the pedigree, suggesting that OTOF is the causative gene of the autosomal recessive trait segregation in this family. Conclusion: The presence of CMs with absent (or markedly abnormal) ABRs is a reliable criterion for diagnosing AN. The severity of the phenotype caused by dysfunctional neurotransmitter release in TSAN may reflect variants that alter the C2 domains of otoferlin. The observations from this study enrich the current understanding of the phenotype and genotype of TSAN and may lay a foundation for further research on its pathogenesis.

Association between Laryngeal Pepsin Levels and the Presence of Vocal Fold Polyps.

Objective To determine whether pepsin, the main component of refluxed gastric contents, is significantly associated with vocal fold polyps and to evaluate the diagnostic value of pepsin in vocal fold polyps' tissues. Study Design Cross-sectional study. Setting Nanfang Hospital of Southern Medical University. Subjects and Methods The study included 32 patients with vocal fold polyps and 16 healthy controls between 2011 and 2012. Reflux symptom index and reflux finding score assessments, 24-hour combined multichannel intraluminal impedance and pH monitoring, and biopsy of the vocal fold polyp tissues or posterior laryngeal mucosa (healthy controls) for immunohistochemical pepsin staining were performed. Results The expression of pepsin was significantly higher in patients with vocal fold polyps than in controls (28/32, 75% vs 5/16, 31.25%; P < .001). The pepsin levels were significantly positively correlated with upright position pharyngeal acid reflux and esophageal reflux parameters adjusted by age. Based on pepsin staining data, the sensitivity and negative predictive values of 24-hour pH monitoring, the reflux symptom index, and the reflux finding score were 70% to 84.62%, whereas their specificity and positive predictive values were relatively low (20%-31.58%). Conclusion Pepsin reflux may be a risk factor for vocal fold polyps formation. In addition, pepsin immunohistochemical analysis of polyp biopsy samples appears to be a more sensitive and effective test for diagnosing laryngopharyngeal reflux than the reflux symptom index, the reflux finding score, and 24-hour pH monitoring in a clinical setting.

Comparison of chirp versus click and tone pip stimulation for cervical vestibular evoked myogenic potentials.

The current study explored differences among cervical vestibular evoked myogenic potentials (cVEMP) that were evoked by CE-chirp and click and tone pip in healthy controls, and tried to explain the differences of cVEMP between the three of them. Thirty normal volunteers were used as subjects for CE-chirp and click and tone-pip (Blackman pip) stimuli. The latency of P1, N1, peak-to-peak P1-N1 amplitude, and cVEMP interaural difference were obtained and analyzed. The response rates of cVEMP were 93 % for click and 100 % for both Blackman pip and CE-chirp, respectively. The P1 and N1 latencies of cVEMP evoked by CE-chirp were the shortest, followed by click, with Blackman pip the longest (F = 6,686.852, P < 0.001). All indices of cVEMP evoked by the three stimuli showed no significant difference between the left and right ears or between genders. cVEMP responses were significantly different between the three stimuli. Compared with the currently used stimulus, CE-chirp can evoke cVEMP with shorter latencies and demonstrates increased speed and reliability.

[Influence of the quantified surface electromyography of sternocleidomastoid on cervical vestibular evoked myogenic potential].

OBJECTIVE: This study investigated the correlations between electromyography (EMG) of sternocleidomastoid (SCM) and cervical vestibular evoked myogenic potentials (cVEMP), and intended to quantify the influence of EMG of SCM on cVEMP by recording the EMG of SCM and cVEMP in different head positions. METHODS: Thirty healthy subjects (60 ears), without the history of ear illnesses, were enrolled in this study. In addition, the recruited subjects also showed favorable differentiation of cVEMP waves induced by Blackman pip cVEMP, and EMG were recorded in different head positions(with sagittal at 90°, 60°,45° and 30°angle), as well as to analyze and quantify the influence of EMG on cVEMP. RESULTS: In the case of the different EMG levels: P1 latency, (12.50 ± 2.39)ms; N1 latency, (19.79 ± 3.16)ms, and the latencies shown no statistical difference (P > 0.05). The amplitude was affected by EMG level, there was significant difference between the amplitudes(F = 55.47, P < 0.01). The different head positions on subjects their EMG level or area of EMG effects were statistically significant (P < 0.01). The study found a linear dependence of the amplitude from the EMG levels(r(2) = 0.591, Adjusted-r(2) = 9.590). CONCLUSIONS: The cVEMP amplitude increases as a function of EMG target level, and the latency remains constant. The quantized data will increase the amplitude in clinical diagnosis application of sensitivity, and it will improve the diagnosis of the vestibular system diseases and some related diseases.

Correlation of pepsin-measured laryngopharyngeal reflux disease with symptoms and signs.

OBJECTIVE: Pepsin detection in throat sputum has been posited as a reliable biological marker of laryngopharyngeal reflux disease (LPRD). This study was designed to further correlate pepsin concentration with symptoms and signs of LPRD. STUDY DESIGN: Cross-sectional study. SETTING: Nanfang Hospital of Southern Medical University. SUBJECTS AND METHODS: Fifty-six laryngitis patients were divided into a reflux laryngitis group and a chronic laryngitis group based on the reflux symptom index (RSI), reflux finding score (RFS), and proton pump inhibitor treatment for two weeks. Oral and hypopharyngeal secretions from the study patients and from 15 healthy subjects were collected. Thirty-six obstructive sleep apnea (OSA) patients were divided into a mild-moderate group and a severe group by the apnea-hypopnea index (AHI). Bedtime and first-morning oral secretions were collected. Enzyme-linked immunosorbent assay was used to measure the pepsin concentration. RESULTS: In laryngitis patients, the total score of RSI and RFS (P < 0.05), and the symptoms, including clearing throat often, coughing, and sensing a lump in the throat (P < 0.006), were more severe in the pepsin-positive group. No significant differences were found between the oral and hypopharyngeal secretions. In OSA, pepsin levels in the first-morning oral secretions were correlated with AHI, mean SaO(2), and mini SaO(2) (P < 0.01). However, RSIs were not significantly correlated with these indicators. CONCLUSION: Higher levels of pepsin in sputum were associated with higher RSI and RFS in cases of laryngitis. There was no relationship between pepsin levels and RSI in cases of OSA. There were no differences of pepsin concentration in sputum collection methods or in collection timing.

[Association of CXCR4 and SDF-1alpha with organ-specific metastasis of nasopharyngeal carcinoma].

OBJECTIVE: To explore the role of CXCR4/SDF-1alpha axis in organ-specific metastasis of nasopharyngeal carcinoma (NPC) by assessment of CXCR4 expression in NPC cells and SDF-1alpha expression in distant target organs of NPC. METHODS: Thirty patients with NPC and fifteen normal subjects were recruited in this study. The expressions of CXCR4 in NPC and normal cases were identified by RT-PCR and immunohistochemistry (IHC), then the relationship between CXCR4 expression and clinicopathological factors was analyzed. IHC was also used to analyze the SDF-1alpha protein expression in normal cervical lymph nodes (including normal superior and inferior deep cervical lymph nodes), bone marrow, lung, liver, kidney and colon tissues of NPC patients (5 cases/each group). RESULTS: The relative expression level of CXCR4 mRNA in NPC (0.71 +/- 0.22) was significantly higher than that of normal nasopharynx tissues (0.14 +/- 0.07, F = 27.94, P < 0.05). The relative expression level of CXCR4 protein in NPC (1.58 +/- 0.59) was significantly higher than that of normal nasopharynx tissues (0.51 +/- 0.22, F = 17.75, P < 0.05). The high expression levels of CXCR4 mRNA and protein in NPC were closely related to clinical stage, cervical lymph node metastasis and cancer cell differentiation (P < 0.05). SDF-1alpha protein was strongly expressed in normal superior deep cervical lymph nodes, bone marrow, lung and liver (2.35 +/- 0.67), but absent or very poor expression in inferior deep cervical lymph nodes, kidney and colon tissues (0.68 +/- 0.23), and the differences between them were statistically significant (t = 10.13, P < 0.01). CONCLUSION: CXCR4 is closely correlated to metastasis of nasopharyngeal carcinoma. CXCR4/SDF-1alpha axis may play an important role in organ-specific metastasis of NPC.

[Pepsin immunoassay in the sputum for detection of laryngopharyngeal reflux].

OBJECTIVE: To study whether the presence of gastric pepsin in the sputum might be used as a reliable criteria of laryngopharyngeal reflux. METHODS: Fifty-six patients with the symptoms of laryngopharyngitis and fifteen healthy people were recruited. Fifty-six patients were divided into laryngopharyngeal reflux group and chronic laryngitis group by the reflux symptom index (RSI), by the reflux finding score (RFS) and by their treating experiment taking omeprazole 20 mg bid for 2 weeks. Sputum in all three groups was obtained in the morning. Pepsin in the sputum was measured by enzyme-linked immunoadsorbent assay. RESULTS: The positive rate of pepsin in sputum among LPR group, chronic laryngopharyngitis group and normal group were 93.8% (30/32), 75.0% (18/24), 20.0% (3/15) respectively, and the median concentration of pepsin were 5.3 [1.3; 53.4] ng/ml, 0.8 [0.1; 17.2] ng/ml, 0.0[0.0;0.0] ng/ml (H = 23.29, P = 0.000). Compared with co-diagnosis as gold standard, the sensitivity of RSI, RFS treating experiment and the pepsin immunoassay was 59.4%, 84.4%, 81.3% and 93.8%, and the specificity of those was 87.2%, 61.5%, 95.8% and 46.2% respectively. CONCLUSIONS: Detection of pepsin in sputum by immunoassay might provide a high sensitive, noninvasive method for laryngopharyngeal reflux.