Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C/D Esophagitis: A Systematic Review and Network Meta-analysis.

INTRODUCTION: Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making. METHODS: A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score. RESULTS: Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety. DISCUSSION: Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.

Development and Validation of Serum Markers as Noninvasive Diagnostic Methods for Achalasia.

INTRODUCTION: Currently, the diagnosis of achalasia mainly relies on invasive or radioactive examinations. This study aimed to develop a noninvasive diagnostic method for achalasia based on specific serum markers. METHODS: Serum levels of profilin-1, galectin-10, immunoglobulin heavy variable 3-9, vasodilator-stimulated phosphoprotein, and transgelin-2 were measured in patients with achalasia and controls by enzyme-linked immunosorbent assay. The diagnostic values and thresholds were determined by the receiver operating characteristic curve analysis. Then, patients with dysphagia were prospectively enrolled to validate the ability of these molecules for achalasia diagnosing. RESULTS: A total of 142 patients with achalasia and 50 nonachalasia controls (healthy volunteers and patients with reflux esophagitis) were retrospectively included. The serum levels of profilin-1, galectin-10, and transgelin-2 in patients with achalasia were significantly higher than those in healthy volunteers and patients with reflux esophagitis ( P all < 0.001). Profilin-1, galectin-10, and transgelin-2 were of good performance in diagnosing achalasia, with optimal thresholds of 2,171.2, 33.9, and 1,630.6 pg/mL, respectively. Second, 40 patients with dysphagia were prospectively enrolled to the validation of achalasia. For profilin-1, the positive predictive value, negative predictive value, sensitivity, and specificity were 100.0%, 64.5%, 45.0%, and 100.0%, respectively. The figures for transgelin-2 were 65.5%, 90.9%, 95.0%, and 50.0%. When both increased, the positive predictive value reached to 100.0%. When both indexes were normal, the negative predictive value was 100.0%. DISCUSSION: Profilin-1 and transgelin-2 were promising biomarkers for achalasia diagnosis and performed better in combination. Further multicenter studies are necessary to verify their application as preliminary screening tools for achalasia.

Current complementary and alternative therapy forgastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a widely prevalent gastrointestinal disorder, affecting ∼13.3% of the global population. There are shortages and limitations of current GERD treatment modalities, and complementary and alternative therapy (CAT) is a promising option to fill in the gap. Dietary and lifestyle modifications might play an important and complementary role in alleviating GERD symptoms. Traditional Chinese medicine and brain-gut behavior therapy, particularly transcutaneous electrical acustimulation and diaphragmatic breathing therapy were shown to be useful adjuncts or alternatives in treating GERD. CAT may help to relieve GERD symptoms, minimize medication dosage, and slow the demand for surgery. The aim of this review was to summarize the existing evidence of some common CATs in treating symptomatic GERD, including dietary modification, lifestyle change, traditional Chinese medicine, and brain-gut behavior therapy.

Numerical Study on Local Entropy Production Mechanism of a Contra-Rotating Fan.

Contra-rotating fans (CRFs) have garnered significant attention due to their higher power-to-weight ratio compared to traditional fans; however, limited focus has been given to the localization and development of local aerodynamic losses. Furthermore, there is a need for further research on the impact of load distribution along the radius on local entropy production. Therefore, this study aims to investigate a contra-rotating fan as the research subject. An optimal design for load distribution along the radius is achieved by constructing a surrogate model in combination with a genetic algorithm. The effectiveness of this design has been verified through experimentation using a specific test device. In this study, a local entropy production rate (EPR) model adapted to the shear stress transport-detached eddy simulation (SST-DES) technique is constructed to evaluate the loss distribution of the contra-rotating fan. This paper primarily focuses on comparing and analyzing the blade profile and overall performance of the CRFs before and after optimization. The EPR contribution of each interval along the radius is compared to the corresponding blade channel to identify the approximate range of high-EPR regions. Furthermore, an investigation is conducted to examine the distribution of EPR along the streamwise direction in these high-EPR regions. After that, by comparing the development of the flow structure near a stall before and after optimization, combined with the analysis of the EPR contours, the EPR mechanism of this CRF is revealed.

Achalasia: The Current Clinical Dilemma and Possible Pathogenesis.

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients' quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

Effect of the Radial Velocity Distribution on the Loss Generation of a Contra-Rotating Fan in a Ventilation System.

Quantification of the loss generation of ducted contra-rotating fan (CRF) blades is difficult to achieve, since there are no guide vanes between rotors. A blade design program was established to investigate the relationship between radial velocity distribution and incurred loss. Numerical and experimental techniques were used to confirm the optimal configuration's overall performance. The relationship between loss and velocity distribution under the impact of spanwise load distribution was confirmed by the entropy contour from various perspectives. The appropriate radial velocity distribution can improve the operating efficiency of a CRF by reducing the entropy around the annulus under design and near-stall conditions. This regularity could provide some strategies in the design of contra-rotating blades.

Characterization of cardiac involvement in patients with LMNA splice-site mutation-related dilated cardiomyopathy and sudden cardiac death.

Introduction: LMNA splicing mutations occur in 9.1% of cases with cardiac involvement cases, but the phenotype and severity of disease they cause have not yet been systematically studied. The aim of this study was to understand the clinical and pathogenic characteristics of the LMNA splice-site mutation phenotype in patients with LMNA-related dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Methods and Results: First, we reported a novel family with LMNA-related DCM and SCD, and the clinical characteristics of all current patients with LMNA splicing mutations were further summarized through the ClinVar database. Seventeen families with a total of 134 individuals, containing a total of 15 LMNA splicing mutation sites, were enrolled. A total of 42 subjects (31.3%) had SCD. Compared without with the non-DCM group (n = 56), the patients within the DCM group (n = 78) presented a lower incidence of atrioventricular block (AVB) (p = 0.015) and a higher incidence rates of non-sustained ventricular tachycardia (p = 0.004),) and implantable cardioverter defibrillator (ICD) implantation (p = 0.005). Kaplan‒Meier survival analysis showed that the patients with pacemaker (PM) implantation had a significantly reduced the occurrence of SCD compared to patientswith those without PM implantation (log-rank p < 0.001), while there was no significant difference in ICD implantation between the two groups (log-rank p = 0.73). Second, we identified the family that we reported with a mutation in an LMNA c.513+1 G>A mutation in the reported family, and pathogenic prediction analysis showed that the mutation site was extremely harmful. Next, we conducted gene expression levels and cardiac pathological biopsy studies on the proband of this family. We found that the expression of normal LMNA mRNA from the proband was significantly downregulated in peripheral blood mononuclear cells than incompared with healthy individuals. Finally, we comprehensively summarized the pathological characteristics of LMNA-related DCM, including hypertrophy, atrophy, fibrosis, white blood cell infiltration, intercalated disc remodeling, and downregulation of desmin and connexin 43 (Cx43) expression. Discussion: Above all, Cardiaccardiac involvement in patients with LMNA splice-site mutation presented with a high rate of SCD. Implanting a pacemaker significantly reduced the SCD rate in non-DCM patients with AVB. The pathogenic characterization was not only haveinvolved suppressed the expression of the healthy LMNA allele, but was also associated with abnormal expression and distribution of desmin and Cx43.

Fast measurement of the thickness and group refractive index distribution of solid plates by line-field dispersive interferometry.

Real-time measurement of the thickness and group refractive index is crucial for semiconductor devices. In this paper, we proposed a fast synchronous method for measuring the thickness and group refractive index distribution of solid plates based on line-field dispersive interferometry. The proposed method measured the line-field distribution in an illuminated region through a single step. A low-cost spectrometer calibration method using an eight-channel dense wavelength division multiplexer was developed for verification. The line-field distribution of a three-step silicon wafer was successfully measured within 3.3 ms. The combined uncertainties for the geometrical thickness and group refractive index were <50 nm and 4 × 10-4, respectively.

Real-time dynamic absolute ranging with frequency scanning interferometry using a robust Monte-Carlo-based particle filter.

A particle-filter-based data processing for a frequency-scanning interferometry system for dynamic long absolute ranging is presented in this paper. Because the particle filter is not restricted by linearity or noise Gaussianity requirements, the proposed system achieves high robustness and accuracy levels when tracking dynamic objects at long standoff distances. We experimentally demonstrate that the proposed system exhibits a standard deviation below 6 µm for a quasi-static target, and superior tracking performance for a vibrating target with vibration amplitude exceeding 10 µm and frequencies of 1-5 Hz at a 15 m standoff distance.

Dynamic cascade-model-based frequency-scanning interferometry for real-time and rapid absolute optical ranging.

A new frequency-scanning interferometry (FSI) scheme using in-phase and quadrature (IQ) detection for real-time and rapid absolute optical ranging is presented. Dynamic measurement with FSI modulates interference signal frequency by both target movement and time-varying optical-frequency scanning rate; hence, a dynamic model is proposed to decouple dynamic absolute distance from the instantaneous frequency of interference signals. The unscented Kalman filter and particle filter algorithms are implemented for the nonlinear first-layer and non-Gaussian second-layer models, respectively. The proposed FSI scheme eliminates nonlinear optical-frequency scanning effects in dynamic measurements and realizes real-time measurement only current observed data are used. Experimental results verify high tracking performance for a vibrating target with approximately 10 µm amplitude and 50-500 Hz frequency.

Extraction of interference phase in frequency-scanning interferometry based on empirical mode decomposition and Hilbert transform.

Nonlinear optical frequency scanning is inevitable in frequency scanning interferometry with tunable lasers and seriously reduces the accuracy of interference signal phase extraction. To address this, we propose a phase-extraction algorithm based on empirical mode decomposition and Hilbert transformation. The method can effectively eliminate the influence of the optical frequency scanning nonlinearity. The validity and stability of the method have been verified through simulations and experiments. Moreover, the single-cycle relative error of the phase between adjacent peaks and the standard deviation of the measurement system improved to 0.6% and 0.7 µm, respectively, with a 5 MHz sampling rate.

Frequency-scanning interferometry using a time-varying Kalman filter for dynamic tracking measurements.

Frequency scanning interferometry (FSI) with a single external cavity diode laser (ECDL) and time-invariant Kalman filtering is an effective technique for measuring the distance of a dynamic target. However, due to the hysteresis of the piezoelectric ceramic transducer (PZT) actuator in the ECDL, the optical frequency sweeps of the ECDL exhibit different behaviors, depending on whether the frequency is increasing or decreasing. Consequently, the model parameters of Kalman filter appear time varying in each iteration, which produces state estimation errors with time-invariant filtering. To address this, in this paper, a time-varying Kalman filter is proposed to model the instantaneous movement of a target relative to the different optical frequency tuning durations of the ECDL. The combination of the FSI method with the time-varying Kalman filter was theoretically analyzed, and the simulation and experimental results show the proposed method greatly improves the performance of dynamic FSI measurements.