The Time-Point Distribution Characteristics of Laryngopharyngeal Reflux in Elderly Patients.

OBJECTIVE: To identify the characteristics of the time-point distribution of the occurrence of hypopharyngeal-proximal reflux episodes (HREs) in elderly and younger patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Retrospective cohort study. SETTING: Analysis of data from patients with LPR-related symptoms and 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH (24-hour HEMII-pH) monitoring from February 2017 to September 2022 at Sixth Medical Center of PLA General Hospital. METHODS: Patients were divided into 2 age groups: the elderly group (>60 years) and the younger group (≤60 years). The time series of HREs and meals within 24 hours were analyzed based on HEMII-pH. RESULTS: A total of 305 patients were included (126 elderly patients). In younger patients, except for nonacid-gas HREs, the incidence of the remaining types of HREs tended to increase within 2 hours after meals, especially after dinner. The incidence of all types of HREs pre- and postmeal was not significantly different in the elderly group (χ2 = 0.080, P = .777). The incidence of nighttime HREs in elderly patients was statistically higher than in younger patients (6.23% vs 3.96%, P = .030), particularly acid-/nonacid-liquid HREs. CONCLUSION: HREs tend to increase within 2 hours after meals in younger LPR patients, except for nonacid-gas HREs. In elderly LPR patients, the incidence of all types of HREs pre- and postmeal were not significantly different, and nighttime fluid HREs was more prone to occur than in younger patients.

A Study of the Diagnostic Value of the Sign and Symptom Questionnaires for Laryngopharyngeal Reflux Disease.

OBJECTIVE: To investigate the diagnostic value of symptom questionnaires, sign questionnaires, and the combination of 2 questionnaires for laryngopharyngeal reflux disease (LPRD). STUDY DESIGN: Prospective, single-centered. SETTING: Seventy-seven patients who were hospitalized in the Department of Otolaryngology-Head and Neck Surgery from October 2022 to April 2023 were included. METHODS: Included patients completed the RSS, RSI, RSA, and RFS questionnaires and underwent 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH). The RSS, RSI, RSA, RFS, RSS+RSA, RSS+RFS, RSI+RSA, RSI+RFS, and RSI+RFS diagnostic value were compared using Cohen's k test and receiver operating characteristic analysis. RESULTS: Based on the 24 hours HEMII-pH results, 52 patients had LPRD, and 25 patients did not have LPRD. The Kappa values of RSS, RSI, RSA, RFS, RSS+RSA,2 RSS+RFS, RSI+RSA, and RSI+RFS with the 24 hours HEMII-pH monitoring results were 0.565, 0.442, 0.318, 0.431, 0.517, 0.631, 0.451, and 0.461, respectively. The RSS+RFS questionnaire had the highest AUC of 0.836 (95% confidence interval [CI] 0.762-0.909) and the RSA questionnaire had the lowest AUC (AUC = 0.665, 95% CI 0.560-0.790). The sensitivity of RSS was the highest (98%), the specificities of RSS+RFS and RSI+RFS were the highest (96%), and the specificity of RSS was the lowest (52%). RSS+RFS had a sensitivity of 75%, second only to RSS and RFS (76%). CONCLUSION: Among the 8 methods, the RSS combined with the RFS had the highest concordance with 24 hours HEMII-pH monitoring results and AUC values when screening for LPRD.

Can pepsin immunohistochemical staining of laryngeal lesions accurately diagnose non-acid laryngeal reflux?

BACKGROUND: Non-acid reflux is the most common form of laryngopharyngeal reflux (LPR). However, the damage caused by non-acid reflux to the laryngeal mucosa is weaker than that caused by acid reflux. AIMS: To evaluate whether pepsin immunohistochemical (IHC) staining of laryngeal lesions can accurately diagnose acidic and non-acidic LPR. MATERIALS AND METHODS: Hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring was performed, and the patients were divided into acid reflux and non-acid reflux groups. Pathological sections of laryngeal lesions were examined using pepsin IHC staining, which was positive when pepsin was detected in the cytoplasm. RESULTS: The study included 136 patients, with 58 in the acid reflux group, 43 in the non-acid reflux group, and 35 in the without reflux group. There were no significant differences in the positive rate of pepsin IHC staining between the non-acid and acid reflux groups (p = .421). The sensitivity of pepsin IHC staining for the diagnosis of acid and non-acid reflux was 94.8% and 90.7%, respectively. CONCLUSIONS: The sensitivity of pepsin IHC staining for laryngeal lesions in the diagnosis of non-acidic LPR is satisfactory. SIGNIFICANCE: Pepsin IHC staining is suitable for LPR screening of patients with laryngeal lesions as it is economical, non-invasive, and highly sensitive.

Two-timescale recurrent neural networks for distributed minimax optimization.

In this paper, we present two-timescale neurodynamic optimization approaches to distributed minimax optimization. We propose four multilayer recurrent neural networks for solving four different types of generally nonlinear convex-concave minimax problems subject to linear equality and nonlinear inequality constraints. We derive sufficient conditions to guarantee the stability and optimality of the neural networks. We demonstrate the viability and efficiency of the proposed neural networks in two specific paradigms for Nash-equilibrium seeking in a zero-sum game and distributed constrained nonlinear optimization.

Optimal Timing of the Salivary Pepsin Test for the Diagnosis of Laryngopharyngeal Reflux.

OBJECTIVE: To investigate the optimal time point for diagnosing laryngopharyngeal reflux (LPR) through combining 24-h hypopharyngeal-esophageal multichannel intraluminal impedance-pH (24-h HEMII-pH) monitoring and the multi-time point salivary pepsin test (MTPSPT). STUDY DESIGN: Prospective uncontrolled trial. METHOD: Patients with and without LPR symptoms were included as the test group and the control group, respectively. The patients in the test group underwent 24-h HEMII-pH and MTPSPT. The results of 24-h HEMII-pH were used as a diagnostic criterion for LPR, and the diagnostic value of salivary pepsin tests performed at different time points was compared by receiver operating characteristic (ROC) analysis. RESULTS: A total of 153 patients were included. Based on 24-h HEMII-pH, the positive rate of LPR in the test group of patients was 84.00%. In the control group, only one person (3.57%) had a positive salivary pepsin test result. The area under the curve (AUC) of the MTPSPT was 0.827. In addition, we separately calculated the AUC of the combined salivary pepsin test at different time points, and found good diagnostic value (AUC = 0.799) when the test was combined with the waking, 1 and 2 h after breakfast and lunch, and 1 h after dinner tests. However, when the number of tests were further increased, the diagnostic value did not improve significantly. CONCLUSION: Salivary pepsin testing combined with waking, 1 h and 2 h after breakfast and lunch, and 1 h after dinner has almost the same diagnostic value as MTPSPT, and testing at these time points can be an effective method for diagnosing LPR. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1706-1711, 2023.

Comparison of Reflux Symptom Score versus Reflux Symptom Index in screening laryngopharyngeal reflux.

OBJECTIVES: To compare the screening value of the Reflux Symptom Score (RSS) and the Reflux Symptom Index (RSI) for laryngopharyngeal reflux (LPR). METHODS: All included patients attending the Department of Otolaryngology at the Sixth Medical Center of the PLA General Hospital from February 2022 to August 2022, completed the RSS and the RSI and underwent 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH (24 h HEMII-pH) monitoring. The results of 24 h HEMII-pH were used as a diagnostic criterion for LPR, consistency between two questionnaires (RSS, RSI) and 24 h HEMII-pH was compared by the weighted Cohen's kappa statistic and the screening value of RSS and RSI for LPR was compared by receiver operating characteristics analysis. RESULTS: A total of 77 patients, 58 males, and 19 females, were included. The Kappa values of between RSS, RSI, and 24 h HEMII-pH were 0.663 (p < 0.001) and 0.213 (p < 0.05), respectively. The sensitivity of RSS and RSI were 92.8% and 48.2%, respectively, the specificity was 71.4% and 80.9%. The negative predictive value and positive predictive value of RSI were 36.9%, 87.1%, and that of RSS were 78.9%, 89.6%. The area under curve of the RSS (0.783; 95% CI = 0.53, 0.75) is significantly higher than RSI (0.633; 95% CI = 0.72, 0.90). CONCLUSION: The RSS has a higher consistency and better screening value for LPR compared to RSI. In addition, the RSS includes more reflux symptoms, which may reduce the number of missed diagnoses in patients with LPR to some extent. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2104-2109, 2023.

Characteristics of Laryngopharyngeal Reflux in Patients of Different Genders and Ages.

OBJECTIVES: To investigate the differences in laryngopharyngeal reflux (LPR) characteristics between gender and age groups based on the Reflux Symptom Index (RSI), Reflux Finding Score (RFS) scale and 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH (HEMII-pH) monitoring. METHODS: The enrolled were patients with LPR symptoms completed the 24h-HEMII-pH monitoring and divided into two gender groups (male and female) and elderly group (>60 years), middle-aged group (41-60 years) and young group (18-40 years). The total RSI and RFS scores of individuals were counted. Various potential differences as well as incidence of each type of LPR events between gender and age groups were analyzed. RESULTS: A total of 420 patients were included, with 333 (79.3%) diagnosed with LPR confirmed by 24h-HEMII-pH monitoring. Females (n=49) had a statistically higher LPR positivity (91.0% vs. 76.6%, P < 0.01) than males (n=342). Female patients with LPR had significantly higher RSI scores (14.08 ± 6.72 vs. 11.08 ± 4.82, P < 0.001) than male patients. The positive rate of LPR were 82.6%, 80.7% and 63.3% in the elderly, middle-aged and young groups. The Elderly group had significantly lower RSI scores (10.20 ± 4.06 vs. 12.80 ± 6.58, 12.24 ± 5.57, P < 0.001) but higher RFS scores (9.37 ± 3.25 vs. 8.16 ± 3.34, 8.57 ± 2.58, P < 0.05) than the other two groups. The number of acid hypopharyngeal-proximal reflux episodes (HREs) and distal esophageal acid reflux were significantly higher in elderly than in young patients. Except for non-acid gas HREs, the positive rates of other types of HREs were increasing from young to middle-aged to the elderly group (P < 0.05). CONCLUSIONS: Female patients with suspected LPR symptoms had a higher positive rate of LPR and RSI score than males. The prevalence of LPR and the number of acid reflux were progressively increasing with age, but the perception of reflux symptoms may diminish.

Laryngopharyngeal Reflux Disease and Gastroesophageal Reflux Disease Can Mutually Influence.

OBJECTIVE: To investigate the mutually relationship between gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux disease (LPRD). METHODS: All included patients completed simultaneous 24-hour hypopharyngeal intraluminal multichannel impedance pH monitoring (24h-MII-pH), Reflux Symptom Index (RSI), and Reflux Finding Score (RFS). The LPRD diagnosis was based on the occurrence of ≥1 acid or non-acid hypopharyngeal proximal reflux episode(HRE), GERD was defined as a length of time >4.0% of the 24-hour recording spent below pH 4.0 or a DeMeester score >14.72. Patients with both positive LPRD and GERD were classified as LPRD & GERD group, patients with positive LPRD and negative GERD were classified as ILPRD group, patients with negative LPRD and positive GERD were classified as IGERD group, and patients with both negative LPRD and GERD were classified as N group. The differences in clinical characteristics of reflux between the groups were statistically analyzed. RESULTS: A total of 437 patients were included, including 248 (56.75%) in the ILPRD group, 98 (22.43%) in the LPRD & GERD group, 23 (5.26%) in the IGERD group, and 68 (15.56%) in the N group. There was no significant difference between the types of gastroesophageal reflux in patients with GERD. The number of weak acid/acid/gas/liquid HREs was significantly more in LPRD & GERD patients than in ILPRD patients (P < 0.01), and the number of distal acid reflux events and Longest distal acid clearance time were significantly higher in LPRD & GERD patients than in IGERD patients (P > 0.01). CONCLUSION: GERD and LPRD are not the same disease but can mutually influence. Combined GERD increased all types of laryngopharyngeal reflux events in patients with LPRD, whereas combined LPRD only increased acidic distal reflux events and acid clearance time in patients with GERD.

The Profiles of Laryngopharyngeal Reflux in Patients With Different Vocal Fold Lesions.

OBJECTIVES: To investigate the profiles of laryngopharyngeal reflux (LPR) and the relationship between hypopharyngeal-proximal reflux episodes (HREs) and the positive rate of salivary pepsin testing in patients with vocal fold lesions (VFLs). METHODS: The enrolled patients were divided into vocal fold cancer group (VFCG), vocal fold leukoplakia group (VFLG), benign vocal fold lesion group (BVFLG) and control group (CG). Patients benefited from multichannel intraluminal impedance-pH monitoring (MII-pH) and multi-time point salivary pepsin testing (MTPSPT). The LPR profiles of patients with VFLs were studied by analyzing the MII-pH findings. The relationship between HREs and positive rate of MTPSPT was investigated through the nonparametric test. RESULTS: 177 patients were included. According to 24 h MII-pH, the occurrence of HREs tended to increase after meals. 55.75%, 63.98%, 66.82% and 55.77% of the HREs in the VFCG, VFLG, BVFLG and CG occurred within 3 h after meals, respectively. The overall positive rate of MTPSPT was higher in the VFCG than the remaining groups. In the VFCG, there was a significant correlation between overall positive results of MTPSPT and HREs occurring within 3 h after meals. CONCLUSION: In the Chinese population, the occurrence of HREs tend to more frequently after meals in patients with VFLs, and most HREs occur within 3 h after meals. By analyzing the 24h MII-pH findings, we can develop a more individualized anti-reflux therapeutic strategy for LPR patients.

Does hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring for the diagnosis of laryngopharyngeal reflux have to be 24 h?

PURPOSE: To investigate the diagnostic value of combined multi-timepoint salivary pepsin testing (MTPSPT) and hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) for laryngopharyngeal reflux (LPR) and whether an appropriate reduction in the duration of HEMII-pH would affect the accuracy of diagnosis of LPR. METHODS: Recruited patients were studied with both MTPSPT and HEMII-pH. The diagnosis of LPR was based on the occurrence of > 1 reflux event and/or positive results on any of the MTPSPT. The diagnostic value of combined diagnosis was studied through combining a breakdown of the 24-h HEMII-pH finding and the results of the MTPSPT. The diagnostic value was expressed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Based on 24-h HEMII-pH and MTPSPT, the positive rate of LPR was 83.33% and 74.69%, respectively. According to the combined diagnosis, the positive rate of LPR was 90.74%. The sensitivity and specificity of the combined diagnosis both were 89.51% and 100%, when the HEMII-pH intervals were 7 a.m.-6 p.m. and 7 a.m.-7 p.m., respectively. However, when the monitoring time was extended to 8 p.m. and bedtime, the sensitivity, specificity, PPV and NPV of the combined diagnosis both were 100%. CONCLUSIONS: The combination of MTPSPT and HEMII-pH increased the sensitivity and accuracy of diagnosis of LPR. For patients with positive MTPSPT results, the duration of HEMII-pH can be appropriately shortened to reduce patient sufferings.

Erratum: Withdrawal notice to Eruption of plaques, hemorrhagic bullae and vesicles: [JAAD Case Reports 21 (2022) 80-82].

[This corrects the article DOI: 10.1016/j.jdcr.2021.04.040.].

Whole exome sequencing is an alternative method in the diagnosis of mitochondrial DNA diseases.

BACKGROUND: Mitochondrial disease (MD) is genetically a heterogeneous group of disorders with impairment in respiratory chain complexes or pathways associated with the mitochondrial function. Nowadays, it is still a challenge for the genetic screening of MD due to heteroplasmy of mitochondrial genome and the complex model of inheritance. This study was designed to investigate the feasibility of whole exome sequencing (WES)-based testing as an alternative option for the diagnosis of MD. METHODS: A Chinese Han cohort of 48 patients with suspect MD features was tested using nanoWES, which was a self-designed WES technique that covered the complete mtDNA genome and 21,019 nuclear genes. Fourteen patients were identified with a single genetic variant and three with single deletion in mtDNA. RESULTS: The heteroplasmy levels of variants in mitochondrial genome range from 11% to 100%. NanoWES failed to identify multiple deletions in mtDNA compared with long range PCR and massively parallel sequencing (LR-PCR/MPS). However, our testing showed obvious advantages in identifying variations in nuclear DNA. Based on nanoWES, we identified two patients with nuclear DNA variation. One of them showed Xp22.33-q28 duplication, which indicated a possibility of Klinefelter syndrome. CONCLUSION: NanoWES yielded a diagnostic rate of 35.4% for MD. With the rapid advances of next generation sequencing technique and decrease in cost, we recommend the usage of nanoWES as a first-line method in clinical diagnosis.

Vocal cord lesions classification based on deep convolutional neural network and transfer learning.

PURPOSE: Laryngoscopy, the most common diagnostic method for vocal cord lesions (VCLs), is based mainly on the visual subjective inspection of otolaryngologists. This study aimed to establish a highly objective computer-aided VCLs diagnosis system based on deep convolutional neural network (DCNN) and transfer learning. METHODS: To classify VCLs, our method combined the DCNN backbone with transfer learning on a system specifically finetuned for a laryngoscopy image dataset. Laryngoscopy image database was collected to train the proposed system. The diagnostic performance was compared with other DCNN-based models. Analysis of F1 score and receiver operating characteristic curves were conducted to evaluate the performance of the system. RESULTS: Beyond the existing VCLs diagnosis method, the proposed system achieved an overall accuracy of 80.23%, an F1 score of 0.7836, and an area under the curve (AUC) of 0.9557 for four fine-grained classes of VCLs, namely, normal, polyp, keratinization, and carcinoma. It also demonstrated robust classification capacity for detecting urgent (keratinization, carcinoma) and non-urgent (normal, polyp), with an overall accuracy of 0.939, a sensitivity of 0.887, a specificity of 0.993, and an AUC of 0.9828. The proposed method also outperformed clinicians in the classification of normal, polyps, and carcinoma at an extremely low time cost. CONCLUSION: The VCLs diagnosis system succeeded in using DCNN to distinguish the most common VCLs and normal cases, holding a practical potential for improving the overall diagnostic efficacy in VCLs examinations. The proposed VCLs diagnosis system could be appropriately integrated into the conventional workflow of VCLs laryngoscopy as a highly objective auxiliary method.

Two-Timescale Multilayer Recurrent Neural Networks for Nonlinear Programming.

This article presents a neurodynamic approach to nonlinear programming. Motivated by the idea of sequential quadratic programming, a class of two-timescale multilayer recurrent neural networks is presented with neuronal dynamics in their output layer operating at a bigger timescale than in their hidden layers. In the two-timescale multilayer recurrent neural networks, the transient states in the hidden layer(s) undergo faster dynamics than those in the output layer. Sufficient conditions are derived on the convergence of the two-timescale multilayer recurrent neural networks to local optima of nonlinear programming problems. Simulation results of collaborative neurodynamic optimization based on the two-timescale neurodynamic approach on global optimization problems with nonconvex objective functions or constraints are discussed to substantiate the efficacy of the two-timescale neurodynamic approach.

Are Multiple Tests Necessary for Salivary Pepsin Detection in the Diagnosis of Laryngopharyngeal Reflux?

OBJECTIVES: To evaluate the necessity of multiple salivary pepsin tests within a day when diagnosing laryngopharyngeal reflux. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary hospitals. METHODS: A total of 138 patients with signs and/or symptoms associated with laryngopharyngeal reflux were included. Salivary pepsin was detected on the day of 24-hour pH monitoring, and the results of salivary pepsin detected once in the morning and multiple times in 1 day were compared with the results of pH monitoring. RESULTS: Among the 138 patients, pH monitoring results were positive in 112. Salivary pepsin was positive in 47 cases in the morning, which was not consistent with the results of pH monitoring (kappa value = 0.117). With the pH monitoring results as the standard, the salivary pepsin detected once in the morning had a sensitivity of 38.4% (43/112) and a specificity of 84.6% (22/26) for the diagnosis of laryngopharyngeal reflux. When salivary pepsin was detected multiple times per day, 102 patients tested positive. The consistency with pH monitoring was moderate (kappa value = 0.587). The sensitivity was 86.6% (97/112), and the specificity was 80.8% (21/26). Of the 97 patients with positive results from pH monitoring and salivary pepsin detected multiple times a day, 54 had negative findings for a single detection in the morning, indicating that 55.7% (54/97) of the true positive cases were missed. CONCLUSION: Although a single detection of salivary pepsin in the morning is more economical, the sensitivity is too low, and it is necessary to detect it multiple times a day.