Role of NF-κB Signaling Pathway in "Reflux Esophagitis-esophageal Cancer" and Traditional Chinese Medicine Intervention：A Review / 中国实验方剂学杂志

Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise， and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa， causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue， which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B （NF-κB） signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation， autophagy， apoptosis， and inflammatory response of esophageal epithelial cells and tumor cells， accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently， there is no specific treatment for reflux esophagitis and esophageal cancer， and large side effects often appear. Therefore， finding a promising and safe drug remains a top priority. In recent years， traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway， and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， but there is a lack of comprehensive and systematic elaboration. Therefore， this paper summarized the relevant studies in recent years， analyzed the relationship among NF-κB signaling pathway， reflux esophagitis， esophageal cancer， and transformation from inflammation to cancer， and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.

Is it Always Laryngopharyngeal Reflux? How Voice Disorders Can Manifest as LPR

Introduction: Laryngopharyngeal reflux (LPR) manifests with a constellation of common throat symptoms and inconclusive signs on laryngoscopic exam. It is a diagnosis, often made clinically, that can lead to prescriptions of proton pump inhibitors that are unnecessary and potentially harmful. Glottic insufficiency (GI) and the accompanying hyperfunctional laryngeal behaviors can also present with similar, common throat complaints that may or may not include a qualitative change to the voice. Methods: This is a reflection article. It is written to summarize, explain, and support with evidence the opinion of the author on the topic of how symptoms of voice disorders can easily be mistaken for symptoms of LPR. The offered reflection is based on his experience, research and the available literature. Reflection: This article intends to explore the similarities between GI and LPR, how to ultimately differentiate them and how to approach treatment with a broader differential diagnosis. Conclusion: LPR and GI can present with identical, vague throat, and voice symptoms. Empiric medication trials, behavioral interventions and objective laryngovideostroboscopy, impedance-based reflux, and esophageal motility testing may all be needed, sometimes in a trial and error fashion, to correctly diagnose and treat a patient's symptoms.

Introducción: El reflujo laríngeo-faríngeo (LPR, por sus siglas en inglés) se manifiesta con una serie de síntomas comunes en la garganta y signos no concluyentes en el examen larinoscópico. Es un diagnóstico que a menudo se realiza clínicamente y que puede llevar a la prescripción de inhibidores de la bomba de protones que son innecesarios y potencialmente perjudiciales. La insuficiencia glótica (IG) y los comportamientos laríngeos hiperfuncionales que la acompañan también pueden presentar síntomas de garganta comunes similares, que pueden o no incluir un cambio cualitativo en la voz. Métodos: Este es un artículo de reflexión. Está escrito para resumir, explicar y respaldar con evidencia la opinión del autor sobre cómo los síntomas de los trastornos de la voz pueden confundirse fácilmente con los síntomas del LPR. La reflexión ofrecida se basa en su experiencia, investigación y la literatura disponible. Reflexión: Este artículo tiene la intención de explorar las similitudes entre la IG y el LPR, cómo diferenciarlos finalmente y cómo abordar el tratamiento con un diagnóstico diferencial más amplio. Conclusión: El LPR y la IG pueden presentar síntomas idénticos y vagos en la garganta y la voz. Puede ser necesario realizar ensayos de medicación empírica, intervenciones conductuales y pruebas objetivas de laringovideostroboscopia, reflujo basado en impedancia y motilidad esofágica, a veces de manera experimental, para diagnosticar y tratar correctamente los síntomas de un paciente.

Dynamic and static ultrasound features predictive of vesicoureteral reflux and renal damage in children and adolescents with neurogenic bladder

ABSTRACT Purpose: This study aimed to analyze the diagnostic accuracy of dynamic and static ultrasound (DSUS) in detecting vesicoureteral reflux (VUR) and renal scarring in a cohort of children with neurogenic bladder (NB). Materials and Methods: A retrospective, longitudinal, observational study was conducted using the Reporting Diagnostic Accuracy Studies guideline. The DSUS (index test) data were compared with voiding cystourethrography (VCUG) and renal scintigraphy 99mTc-dimercaptosuccinic (reference tests). Overall performance for predicting VUR and renal scarring was assessed using renal pelvic diameter (RPD)/distal ureteral diameter and renal parenchymal thinning on DSUS, respectively. Results: A total of 107 patients (66 girls, median age 9.6 years) participated. Seventeen patients (15.9%) presented VUR, eight bilateral. For overall reflux grade, the AUC was 0.624 for RPD and 0.630 for distal ureteral diameter. The diagnostic performance for detecting high-grade VUR was slightly better for DSUS parameters. The AUC was 0.666 for RPD and 0.691 for distal ureteral diameter. The cut-offs of 5 mm for RPD and 6.5 mm for distal ureteral diameter presented the best diagnostic odds ratio (DOR) to identify high-grade VUR. The increase of RPD during detrusor contractions showed an accuracy of 89.2%. The thinness of renal parenchyma presented an accuracy of 88% for renal scarring. Conclusion: DSUS predicts VUR and renal scarring in children with NB with fair to good accuracy, and all measurements exhibited a high negative predictive value (NPV). The increase in RPD during voiding or detrusor contractions proved to be the most accurate parameter for indicating the presence of VUR in this study.

Esophagogastric Junction Contractile Integral (EGJ-CI) in Various Phenotypes of Gastroesophageal Reflux Disease (GERD)

Introduction: Two parameters of high-resolution esophageal manometry are used to observe the function of the esophagogastric junction (EGJ): the anatomical morphology of the EGJ and contractile vigor, which is evaluated with the esophagogastric junction contractile integral (EGJ-CI). To date, how these parameters behave in different gastroesophageal reflux disease (GERD) phenotypes has not been evaluated. Materials and methods: An analytical observational study evaluated patients with GERD confirmed by pH-impedance testing and endoscopy undergoing high-resolution esophageal manometry. The anatomical morphology of the EGJ and EGJ-CI was assessed and compared between reflux phenotypes: acid, non-acid, erosive, and non-erosive. Results: 72 patients were included (63% women, mean age: 54.9 years), 81.9% with acid reflux and 25% with erosive esophagitis. In the latter, a decrease in EGJ-CI (median: 15.1 vs. 23, p = 0.04) and a more significant proportion of patients with type IIIa and IIIb EGJ (83.3% vs 37.1%, p < 0.01) were found. No significant differences existed in the manometric parameters of patients with and without acid and non-acid reflux. Conclusion: In our population, EGJ-CI significantly decreased in patients with erosive GERD, suggesting that it could be used to predict this condition in patients with GERD. This finding is also related to a higher proportion of type III EGJ and lower pressure at end-inspiration of the lower esophageal sphincter in this reflux type.

Introducción: Para observar la función de la unión esofagogástrica (UEG) se utilizan dos parámetros de la manometría esofágica de alta resolución: la morfología anatómica de la UEG y el vigor contráctil, el cual se evalúa con la integral de contractilidad distal de la unión esofagogástrica (IC-UEG). Hasta el momento, no se ha evaluado cómo se comportan estos parámetros en los diferentes fenotipos de enfermedad por reflujo gastroesofágico (ERGE). Metodología: Estudio observacional analítico en el que se evaluaron pacientes con ERGE confirmado por pH-impedanciometría y endoscopia, llevados a manometría esofágica de alta resolución. Se evaluó la morfología anatómica de la UEG y la IC-UEG, y se comparó entre los diferentes fenotipos de reflujo: ácido, no ácido, erosivo y no erosivo. Resultados: Se incluyó a 72 pacientes (63% mujeres, edad media: 54,9 años), 81,9% con reflujo ácido y 25% con esofagitis erosiva. En este último grupo se encontró una disminución de la IC-UEG (mediana: 15,1 frente a 23, p = 0,04) y una mayor proporción de pacientes con UEG tipo IIIa y IIIb (83,3% frente a 37,1%, p < 0,01). No se encontraron diferencias significativas en los parámetros manométricos de los pacientes con y sin reflujo ácido y no ácido. Conclusión: En nuestra población, la IC-UEG estuvo significativamente disminuida en los pacientes con ERGE erosivo, lo que sugiere que podría ser utilizada como un predictor de esta condición en pacientes con ERGE. Este hallazgo también se relaciona con mayor proporción de UGE tipo III y menor presión al final de la inspiración del esfínter esofágico inferior en este tipo de reflujo.

Colecistectomía como factor de riesgo para reflujo duodenogástrico

El reflujo biliar o reflujo duodenogástrico (RDG) es el flujo retrógrado del contenido duodenal (principalmente bilis) hacia el estómago, capaz de producir daño químico a la mucosa y desencadenar mutaciones hacia el desarrollo de metaplasia intestinal, displasia e incluso, cáncer gástrico. El objetivo de este estudio fue estimar la prevalencia del reflujo biliar primario en pacientes colecistectomizados e identificar si la colecistectomía es un factor de riesgo para el RDG. Se realizó un estudio observacional transversal analítico, en el que fueron incluidos todos los pacientes que se realizaron endoscopía digestiva alta entre febrero y junio del 2023, en un centro endoscópico privado en la ciudad de Lima, Perú. De acuerdo al reporte endoscópico, los pacientes fueron divididos en dos grupos: con RDG y sin RDG. Se analizaron estadísticamente las características demográficas, el antecedente de colecistectomía y los hallazgos endoscópicos. Fueron incluidos 408 pacientes. La edad media de la población fue 48,18 ± 16,82años; el 61,52% fueron mujeres. La prevalencia de RDG fue de 25,74% en la población y de 52,11% en pacientes colecistectomizados. La prevalencia de RDG en pacientes colecistectomizados fue 2,58 veces en comparación a los pacientes sin colecistectomía (p< 0,001). La edad ≥50 años también se comportó como factor de riesgo para RDG (p=0,025). No hubo diferencias significativas respecto a diabetes, infección por Helicobacter pylori ni consumo de tabaco. En conclusión, el antecedente de colecistectomía y la edad demostraron ser factores de riesgo para el desarrollo de RDG primario.

Bile reflux or duodenogastric reflux (DGR), refers to the retrograde flow of duodenal contents (mainly bile) into the stomach; capable of producing chemical damage to the mucosa, and triggering mutations towards the development of intestinal metaplasia, dysplasia and even gastric cancer. Objective: This study aimed to estimate the prevalence of primary bile reflux in cholecystectomized patients and to identify whether cholecystectomy is a risk factor for development of DGR. An analytical cross-sectional and observational study was conducted, in which all patients who underwent upper digestive endoscopy from February to June 2023 in a private endoscopic center in Lima, Peru, were included. According to the endoscopic report, patients were divided into two groups as those with DGR and those without DGR. Demographic characteristics, history of cholecystectomy, and endoscopic findings were statistically analyzed. 408 patients were included. The mean age of the population was 48.18 ± 16.82 years; 61.52% were female. The prevalence of DGR was 25.74% in the population, while in cholecystectomized patients it was 52.11%. The prevalence of DRG in patients with a history of cholecystectomy was 2.58 times compared to patients without cholecystectomy (p<0.001). Age ≥50 years also behaved as a risk factor for RDG (p=0.025). No significant difference in diabetes, Helicobacter pylori infection or smoking were found. In conclusion, a history of cholecystectomy as well as age were found to be risk factors for development of primary DGR.

Dolor torácico severo tras retención de cápsula inalámbrica de pH

La cápsula inalámbrica para medir el reflujo gastroesofágico o tambien conocida como cápsula de pHmetría, es una técnica utilizada en la monitorización ambulatoria del reflujo. Esta cápsula es introducida mediante una guía al esofágo y se coloca mediante un sistema de succión y anclaje a la mucosa esofágica. De alli, se comunica con un dispositivo externo mediante señales de radio para registrar la actividad del ácido gástrico en el esófago durante un período determinado de tiempo. A diferencia de la técnica convencional, que implica la inserción de un tubo a través de la nariz hasta el esófago, la cápsula inalámbrica puede ser una alternativa más cómoda y tolerable para los pacientes, lo que podría mejorar la adherencia al procedimiento. Sin embargo, algunos pacientes pueden presentar dolor torácico tras la colocación de la cápsula de pHmetría. Presentamos el caso de una mujer con cuadro clínico de reflujo gastroesofágico, con colocación capsula de pHmetría inalámbrica, lo cual generó dolor torácico severo que precisó la retirada de la cápsula vía endoscópica.

The wireless capsule to measure gastroesophageal reflux, also known as pH monitoring capsule, is a technique used in ambulatory reflux monitoring. This capsule is introduced through a guide into the esophagus and is placed using a suction system and anchored to the esophageal mucosa. From there, it communicates with an external device using radio signals to record the activity of gastric acid in the esophagus over a specified period of time. Unlike the conventional technique, which involves inserting a tube through the nose into the esophagus, the wireless capsule may be a more comfortable and tolerable alternative for patients, potentially improving adherence to the procedure. In some cases, patients may present chest pain after placement of the pH monitoring capsule, however there is little evidence about the etiology and management. We present the case of a woman with a clinical picture of gastroesophageal reflux, with pH monitoring capsule placement, which resulted in severe chest pain that required endoscopic capsule removal.

Detalles técnicos para prevenir la Enfermedad por Reflujo Gastroesofágico durante la Gastrectomía en manga

La gastrectomía en manga es el procedimiento bariátrico más frecuentemente efectuado en la actualidad. La complicación alejada más frecuente es el aumento de la tasa de enfermedad por reflujo gastro-esofágico. Se han descrito las razones anatómicas y fisiopatológicas de su origen. En este artículo se describen los puntos claves de la técnica quirúrgica de la manga gástrica para su prevención como también otros procedimientos que han sugerido tanto para su prevención como tratamiento.

Sleeve gastrectomy is the most frequently performed bariatric procedure today. The most common distant complication is the increased rate of gastroesophageal reflux disease. The anatomical and pathophysiological reasons for its origin have been described. This article describes the key points of the gastric sleeve surgical technique for its prevention as well as other procedures that have been suggested both for its prevention and treatment.

Abscesos renales: experiencia en un hospital pediátrico de referencia

Introducción: El absceso renal es infrecuente en pediatría, con clínica y laboratorio inespecíficos. Ante su sospecha, es necesario realizar imágenes para establecer diagnóstico. Objetivo: Describir las características clínico-epidemiológicas, microbiológicas, diagnósticas y terapéuticas de abscesos renales en pediatría. Pacientes y Métodos: Estudio retrospectivo, descriptivo, de pacientes internados con absceso renal, en seguimiento por Infectología del Hospital de Niños Ricardo Gutiérrez, durante 9 años. Resultados: 15 pacientes (67% varones), mediana de edad 9 años (rango [r] 0,7-17). Cuatro pacientes con comorbilidades. El síntoma más frecuente fue fiebre seguido por dolor lumbar. El recuento medio de leucocitos en sangre fue de 15.700/mm3 (r: 7.100-45.000) y la PCR de 193 mg/L (r: 1-362). Cuatro pacientes presentaron urocultivo positivo: dos Escherichia coli, uno Klebsiella pneumoniae y E. coli y otro Candida albicans y K. pneumoniae. Ningún paciente presentó bacteriemia. El diagnóstico se confirmó por ecografía. Se realizó drenaje en siete pacientes, con aislamiento de Staphylococcus aureus en dos y Pseudomonas aeruginosa en uno. El tratamiento incluyó terapia combinada en 67%. Mediana de antibioterapia intravenosa fue 16 días (r: 7-49), total de 28 (r: 14-91). Un paciente requirió terapia intensiva y dos, nefrectomía. Conclusión: Los abscesos renales son infrecuentes, con gran morbimortalidad. Sospechar en paciente con infección del tracto urinario (ITU) de evolución tórpida que persiste febril. En nuestro estudio, la alta sensibilidad de la ecografía renal permitió su diagnóstico precoz.

Background: Renal abscesses are infrequent in pediatrics, with nonspecific clinical and laboratory findings. When suspected, imaging is essential to establish the diagnosis. Aim: To describe the clinical-epidemiological, microbiological, diagnostic and therapeutic characteristics of renal abscesses in pediatrics. Methods: Retrospective and descriptive study of hospitalized patients with renal abscess, followed by Infectious Diseases Department of Ricardo Gutiérrez Children's Hospital during 9 years. Statistical analysis: Epi Info 7.2.2.6. Results: 15 patients (67% male), median age 9 years (range [r] 0.7-17) were included. Four patients had underlying disease. The most frequent symptom was fever, with a median duration of 10 days (r:1-36), followed by lumbar pain. The median white blood cell count was 15,700/mm3 (r: 7,100-45,000) and CRP 193mg/L (r: 1-362). Four patients presented positive urine culture: 2 Escherichia coli, 1 Klebsiella pneumoniae and E. coli and 1 Candida albicans and K. pneumoniae. No patient had bacteremia. The diagnosis of abscess was confirmed by ultrasound. Surgical drainage was performed in 7 patients, with isolation of Staphylococcus aureus in 2 and Pseudomonas aeruginosa in 1. Empirical treatment included 3rd generation cephalosporin, combined in 67% of cases. The median of intravenous antibiotic therapy was 16 days (r: 7-49) with a total of 28 days (r:14-91). One patient required transfer to intensive care unit and 2 nephrectomy. Conclusion: Renal abscesses are infrecuent in pediatrics, but they present significant morbidity and mortality. It should be suspected in patients with urinary tract infection (UTI)with torpid evolution that persists with fever without antibiotic response. In our study, the high sensitivity of renal ultrasound allowed early diagnosis.

Frequency of functional esophageal disorders in patients with refractory reflux symptoms in Lima, Peru

Gastroesophageal reflux disease (GERD) is a clinical condition in which gastric reflux causes symptoms or damage to the esophageal mucosa. It is managed with proton pump inhibitors, however, up to 45% of patients with suspected GERD are refractory to treatment. It is necessary to establish a true GERD diagnosis by means of a digestive endoscopy, which does not show lesions in approximately 70% of patients. In this scenario, it is necessary to perform an esophageal pH-impedance measurement, a procedure that allows to determine whether exposure to gastric acid is pathological. Of this group, patients with pathological acid exposure are diagnosed as true non-erosive reflux disease (NERD). If, in addition to not presenting esophageal lesions, they have a physiological exposure to gastric acid, they suffer from esophageal hypersensitivity or functional heartburn, which are functional disorders. These require a different approach from that of GERD or NERD, as the symptoms are not due to pathological exposure to gastric acid. The aim was to calculate the frequency of esophageal hypersensitivity and functional heartburn in patients with suspected NERD. This was a cross-sectional study. Data was collected by reviewing pH-impedance and manometry reports, 166 patients were selected. The frequency for functional disorders was 86.15%, being 46.9% for functional heartburn and 39.2% for esophageal hypersensitivity. The frequency of functional disorders was higher than that reported in previous studies. In conclusion, age, psychological conditions, dietary, cultural, ethnic or lifestyle factors inherent to our environment might play important roles in the development of functional disorders.

La enfermedad por reflujo gastroesofágico (ERGE) es una condición clínica en la que el reflujo gástrico provoca síntomas o daños en la mucosa esofágica. Se maneja con inhibidores de la bomba de protones; sin embargo, hasta el 45% de los pacientes con sospecha de ERGE son refractarios al tratamiento. Por lo cual, es necesario establecer un verdadero diagnóstico de ERGE mediante una endoscopia digestiva, que no muestra lesiones en aproximadamente el 70% de los pacientes. En este escenario, es necesario realizar una medición de pH-impedancia esofágica, procedimiento que permite determinar si la exposición al ácido gástrico es patológica. De este grupo, los pacientes con exposición patológica al ácido son diagnosticados como verdadera enfermedad por reflujo no erosiva (ERNE). Si además de no presentar lesiones esofágicas, tienen una exposición fisiológica al ácido gástrico, padecen hipersensibilidad esofágica o pirosis funcional, que son trastornos funcionales. Estos requieren un enfoque diferente al ERGE o ERNE, ya que los síntomas no se deben a una exposición patológica al ácido gástrico. El objetivo fue calcular la frecuencia de hipersensibilidad esofágica y pirosis funcional en pacientes con sospecha de ERNE. Este fue un estudio transversal. Los datos se recopilaron mediante la revisión de informes de pH-impedancia y manometría, se seleccionaron 166 pacientes. La frecuencia de trastornos funcionales fue de 86,15%, siendo 46,9% de pirosis funcional y 39,2% de hipersensibilidad esofágica. La frecuencia de trastornos funcionales fue superior a la reportada en estudios previos. En conclusión, la edad, las condiciones psicológicas, los factores dietéticos, culturales, étnicos o de estilo de vida inherentes a nuestro entorno podrían jugar un papel importante en el desarrollo de trastornos funcionales.

Combined multi-channel intraluminal impedance measurement and pHmetry in the detection of gastroesophageal reflux disease in children with cystic fibrosis

Abstract Objective To assess the prevalence of GERD exclusively by means of multichannel intraluminal impedanciometry associated with pH monitoring (MIIpH) and compare it with respiratory symptoms in children with CF. To compare MIIpH with pHmetry alone to perform GERD diagnosis. Methods An analytical cross-sectional study was conducted with children diagnosed with CF who underwent MIIpH. Clinical and laboratory markers, including respiratory and digestive symptoms, were used for comparative analyses. High-resolution chest computed tomography was performed on patients with symptoms of chronic lung disease. Severity was classified according to the Bhalla score. Results A total of 29 children < 10 yo (18 girls) were evaluated; 19 of whom with physiological GER and 10 with GERD. Of the children with GERD, seven had predominantly acid GER, two acid+non-acid GER, and one non-acid GER. Three patients had GERD diagnosed only by MIIpH. Bhalla scores ranged from seven to 17.75 with no significant relationship with GERD. The number of pulmonary exacerbations was associated with a decrease in esophageal clearance regardless of the position in pHmetry and MIIpH. Conclusions The prevalence of GERD was 34% in children with CF. There was no association between respiratory disease severity and GER types. MIIpH detected 30% more patients with GERD than pHmetry.

Diagnostic utility of salivary pepsin in laryngopharyngeal reflux: a systematic review and meta-analysis

Abstract Objective: Salivary pepsin has emerged as a biomarker for Laryngopharyngeal Reflux (LPR), which, however, has been questioned for its efficacy due to a lack of supporting medical data. Therefore, this study analyzed the diagnostic value of salivary pepsin for LPR and assessed a better cutoff value. Methods: Studies were searched in PubMed, Embase, and Cochrane Library from their receptions to October 1, 2021. Then, RevMan 5.3 and Stata 14.0 were utilized to summarize the diagnostic indexes for further meta-analysis. Data were separately extracted by two reviewers according to the trial data extraction form of the Cochrane Handbook. The risk of bias in Randomized Control Trials (RCTs) was evaluated with the Cochrane Risk of Bias Tool. Results: A total of 16 studies matched the criteria and were subjected to meta-analysis. The results revealed a pooled sensitivity of 61% (95% CI 50%-71%), a pooled specificity of 67% (95% CI 48%-81%), a positive likelihood ratio of 2 (95% CI 1.2-2.8), a negative likelihood ratio of 0.58 (95% CI 0.47-0.72), and the area under the receiver operating characteristic curve of 0.67 (95% CI 0.63-0.71). Subgroup analyses indicated that the cutoff value of pepsin at 50 ng/mL had a higher degree of diagnostic accuracy than that of pepsin at 16 ng/mL in cohort studies. Conclusion: The review demonstrated low diagnostic performance of salivary pepsin for LPR and that the cutoff value of 50 ng/mL pepsin had superior diagnostic accuracy. Nevertheless, the diagnostic value may vary dependent on the utilized diagnostic criteria. Therefore, additional research is needed on the improved way of identifying salivary pepsin in the diagnosis of LPR, and also longer-term and more rigorous RCTs are warranted to further assess the effectiveness of salivary pepsin.

The link between airway reflux and non-acid reflux in children: a review

Abstract Objective: Airway reflux, a member of extra-esophageal reflux, has been linked to countless respiratory pathologies amongst children. The advent of novel instrumentation has enabled the discovery of non-acid reflux which was postulated as the main culprit of airway reflux. The objective of this review is to outline the association between non-acid reflux and airway reflux in children. Methods: A comprehensive review of recent literature on non-acid reflux and airway reflux in children was conducted. Studies ranged from January 2010 till November 2021 were searched over a period of a month: December 2021. Results: A total of eleven studies were identified. All studies included in this review revealed a strong link between non-acid reflux and airway reflux in children. 6 of the included studies are prospective studies, 3 retrospective studies, 1 cross-section study, and type of study was not mentioned in 1 study. The most common reported respiratory manifestation of non-acid reflux in children was chronic cough (7 studies). Predominant non-acid reflux was noted in 4 studies. The total number of children in each study ranges from 21 to 150 patients. MII-pH study was carried out in all studies included as a diagnostic tool for reflux investigation. Conclusion: Non-acid reflux is the culprit behind airway reflux as well as other myriads of extra-esophageal manifestations in children. Multicentre international studies with a standardized protocol could improve scientific knowledge in managing non-acid reflux in airway reflux amongst children.

Translation and cultural adaptation of the Short Version of the Reflux Symptom Score: Reflux Symptom Score-12 into Brazilian Portuguese

Abstract Objective: To describe the process of translation into Brazilian Portuguese and cross-cultural adaptation of the French Reflux Symptom Score-12 questionnaire used for the diagnosis of laryngopharyngeal reflux. Methods: This was across-cultural translation and adaptation study of a health instrument, with a cross-sectional design. It was carried out in eight stages: translation from French into Brazilian Portuguese, cultural adaptation by a panel of experts, application of the first version (pilot test 1), adaptation by a panel of experts, application of the second version (pilot test 2), back translation, reviewing by a committee in conjunction with the author of the original instrument and, application of the final version. The Brazilian Portuguese versions of the questionnaire were applied to individuals with symptoms and signs of laryngopharyngeal reflux who underwent pHmetry and esophageal manometry at the study site. Results: In pilot test 1, the first version of the RSS-12 in Brazilian Portuguese was applied to 30 patients. The patients had no difficulty to understand any of the 12 symptom items, but 15 patients (50%) had difficulty interpreting the symptom frequency score. After adapting the format of the frequency score, a version 2 of the RSS-12 in Brazilian Portuguese was applied to another 23 patients, who completed the questionnaire in full without any difficulty. Along with the review committee, the author of the original RSS-12 considered the version 2 to be adequate and did not propose any changes, so it was approved as the final version of the Brazilian Portuguese RSS-12. Conclusion: The Brazilian Portuguese version of the instrument, called Reflux Symptom Score-12 PT-BR, shows good understanding and linguistic, conceptual and content equivalence, in relation to the original Reflux Symptom Score-12.

A cross-sectional study to evaluate the prevalence and risk factors of gastro-esophageal reflux disease among the undergraduate medical students of a tertiary-care Indian setting

Introduction: Gastro-esophageal reflux disease (GERD) is a condition characterized by the reflux of stomach contents into the esophagus, causing unpleasant symptoms and/or consequences like heartburn and acid regurgitation. GERD in the student stages can hurt their quality of life, college attendance, everyday activities, and overall well- being of the individual. Materials and Methods: This is a cross-sectional study that was conducted among medical students of a tertiary care setting from August 2021 to October 2021 for a three-month duration. A convenient sample of 458 participants from all the years of MBBS was included in this study. Results: A total of 458 medical students were made part of this study of which most of them (58.9%) were females and 41.1% were males. The average age among the study participants was 22 ± 2.3 years (range of 18–27 years). The average BMI of the individuals was 23.48 (range 14.58–32.41), with the majority (54.8%) of them having a normal BMI. Discussion: In our study, we found that the prevalence of GERD in the medical students of a rural Indian tertiary care setting was 24.2%, and was observed that irregular meal timings and consuming coffee and soft drinks are the crucial risk factors for developing GERD in the medical students in comparison to the general population. Conclusion: Medical students should be trained on proper eating habits, maintaining ideal body weight, good sleep hygiene, and avoiding drinking alcohol and smoking to lessen the burden of GERD.

Vascular pressurisation and super-reflux techniques applied in free anterolateral thigh flap / 中华显微外科杂志

Objective:To investigate the clinical effect of vascular pressurisation and super reflux on free anterolateral thigh flap (ALTF).Methods:From January 2017 to September 2021, the Department of Hand and Foot Microsurgery, the Second Affiliated Hospital of Hainan Medical College had treated 31 cases of soft tissue defects of the limbs. The patients were 23 males and 8 females, aged 4-76 years old at 40 years old in average. All the patients received transfer of free ALTFs carrying 2 groups of blood vessels of the descending and oblique branches of lateral circumflex femoral artery (LCFA). The vascular pressurisation and super-reflux techniques were applied in wound repair. Soft tissue defect area 7 cm × 5 cm-22 cm × 10 cm. The sizes of flaps were 8 cm×6 cm-23 cm×11 cm. All the donor sites were sutured directly. Fifteen patients had inner flap pressurisation (or super-reflux) and the rest of 16 patients had external flap pressurisation (or super-reflux). After surgery, scheduled follow-ups were conducted through outpatient clinic, telephone and WeChat reviews or home visits to evaluate the efficacy of wound repair.Results:All the 31 flaps survived, except 2 flaps that had mild infection after surgery. The wounds of donor and recipient sites healed completely. The time of follow-up was 3-55 months. The skin of flaps achieved good texture, colour, lustre and appearance. TPD of the flaps ranged 7-12 mm.Conclusion:Vascular pressurisation and super reflux technique are stable and reliable in the clinical application of free ALTF to repair soft tissue defects of limbs.

Consensus on endoscopic anterior fundoplication with MUSE for gastroesophageal reflux disease / 中华消化杂志

Endoscopic anterior fundoplication with the MUSE is an endoscopic therapy that combines ultrasound and endoscopic anti-reflux technology for moderate to severe gastroesophageal reflux disease. Training and learning procedures are required to obtain qualifications for this endoscopic therapy before clinical operations. At present, there is limited high-quality evidence-based medical evidence on MUSE treatment, and lack of expert consensus or guidance for training and the standard of MUSE therapy procedure. This consensus is based on the published literature, and formulated by experts with MUSE clinical experience in China, to provide guidance for the training and clinical standard operation of this technique.

Study on the correlation between dietary inflammatory index and reflux esophagitis / 中华消化杂志

Objective:To evaluate the correlation between inflammatory diet and reflux esophagitis (RE) with the dietary inflammatory index (DII), and to provide scientific evidence for the prevention and treatment of RE at the level of dietary guidance.Methods:From December 2021 to September 2022, 145 RE patients (RE group) who visited the First Affiliated Hospital of Xinjiang Medical University were recruited. During the same period, 145 subjects who underwent check-ups at the First Affiliated Hospital of Xinjiang Medical University were selected as the healthy control group, and age and gender were matched according to the ratio of 1 to 1. The baseline data of the 2 groups, including body mass index, the history of smoking and drinking, poor dietary habits, and physical activity intensity were collected. Dietary intake of the patients was assessed by a semi-quantitative food frequency questionnaire, and the overall DII was calculated to evaluate the potential anti-inflammatory or pro-inflammatory effects of diet. According to the tertiles of the DII of the healthy control group (33.3% and 66.7% as the cut-off), dietary inflammatory potential was divided into low (<-0.06), moderate (-0.06 to 1.11) and high pro-inflammatory potential diet (>1.11). Logistic regression model was performed to analyze the correlation between DII and RE risk. Linear trend test was used to compare the overall change trend of RE risk OR value along with the increase of DII. Independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The body mass index of RE group was higher than that of healthy control group( (24.11±2.57) kg/m 2 vs. (23.38 ±2.60) kg/m 2), and the difference was statistically significant ( t=-2.41, P=0.017). The proportions of smoking, drinking, over-eating, and eating within 3 h before bedtime of RE group was higher than those of the healthy control group (42.8%, 62/145 vs. 31.0%, 45/145; 31.0%, 45/145 vs. 16.6%, 24/145; 33.1%, 48/145 vs. 17.9%, 26/145; 52.4%, 76/145 vs. 13.1%, 19/145), and the differences were statistically significant ( χ2=4.28, 8.39, 8.78 and 50.86, P=0.039, 0.004, 0.003 and<0.001). While the proportions of night snacking and moderate to severe physical activity of RE group were lower than those of the healthy control group (14.5%, 21/145 vs. 24.1%, 35/145; 22.8%, 33/145 vs.37.2%, 54/145), and the differences were statistically significant ( χ2=4.34 and 7.24, P=0.037 and 0.007). The DII of RE group was higher than that of the healthy control group (1.05 (0.03, 1.62) vs. 0.34(-0.61, 1.35)), and the difference was statistically significant ( Z=8 661.50, P=0.010). Compared with the low pro-inflammatory potential diet, high pro-inflammatory potential diet had a 1.30-fold increased the risk of RE ( OR=2.30, 95% confidence interval (95% CI) 1.29 to 4.09, P=0.005). After adjusting for total energy intake, age, gender, ethnicity, body mass index, education level, and physical activity intensity, the high pro-inflammatory potential diet was still positively correlated with the risk of RE ( OR=2.58, 95% CI 1.16 to 5.76, P=0.020). In the continuous DII, the risk of RE increased by 36% for each 1 increase in DII ( OR=1.36, 95% CI 1.11 to 1.68, P=0.003). After adjusting for major confounding factors, the continuous DII was still positively correlated with the risk of RE ( OR=1.41, 95% CI 1.08 to 1.85, P=0.012; OR=1.42, 95% CI 1.05 to 1.93, P=0.023). The results of trend test showed that the higher the DII, the greater the risk of RE ( P=0.039). Conclusions:Pro-inflammatory diet is correlated with the increased risk of RE, and there is a certain dose-response relationship. Reasonable reduction of the intake of pro-inflammatory food may be beneficial to reduce the risk of RE.

Analysis of biliary microbiota in experimental pigs before and after enteral extended biliary stents implantation / 中华消化内镜杂志

Objective:To compare the changes of biliary microbiota after enteral extended biliary stents (EEBS) implantation with that of conventional plastic stents in animal experiment, and to preliminarily investigate its possible mechanism in preventing stents occlusion.Methods:A total of 12 healthy Bama minipigs were randomly assigned to the conventional plastic stent group ( n=6) and the EEBS group ( n=6) using simple random method. The bile samples of all pigs were collected before stents implantation and 4 weeks after stents placement. The biliary microbiota composition and diversity before and after different stents implantation were analyzed by 16S rRNA gene sequencing and compared. Results:No complications including acute cholangitis, perforation, bleeding, or death occurred in 12 pigs. Eight days after stents implantation, stents were out of bile duct in all pigs under endoscopy, while the bile samples were collected again for analysis. The main composition of biliary microbiota at the phylum level were Proteobacteria, Firmicutes and Bacteroidota. Alpha-diversities revealed the Shannon ( P=0.004) and Simpson index ( P=0.008) significantly decreased in the conventional stent group after stents placement, and Bata diversity analysis also showed a significant difference in microbial composition (Anosim: R=0.514 8, P=0.011). There was no significant difference in Observed species index ( P=0.095), Chao1 index ( P=0.136), Shannon index ( P=0.353), Simpson index ( P=0.227) or Bata diversity (Anosim: R=0.059 3, P=0.187) in the EEBS group before and after stents placement. LEfSe algorithm indicated Bacteroides_ fragilis and Proteobacteria- Gammaproteobacteria- Enterobacterales- Enterobacteriaceae- scherichia_ Shigella- Escherichia_ coli significantly increased in the conventional stent group, and Desulfobacterota- Desulfovibrionia- Desulfovibrionales- Desulfovibrionaceae- Bilophila significantly increased in the EEBS group after stents placement. Conclusion:The biliary microbiota change slightly after EEBS implantation in the short-term, and EEBS may prevent duodenobiliary reflux by prolonging the reflux path.

Characteristics of reflux and manifestation under probe-based confocal laser endoscopy in patients with endoscopic negative heartburn / 中华消化内镜杂志

Objective:To study reflux characteristics of patients with endoscopic negative heartburn and their manifestation under probe-based confocal laser endoscopy (pCLE) based on the Rome Ⅳ standard.Methods:Thirty-six endoscopic negative outpatients with typical heartburn at the Department of Gastroenterology of the Second Affiliated Hospital of Baotou Medical College from September 2020 to March 2021 were included, and underwent 24-hour multichannel intraluminal impedance-pH monitor and pCLE. According to Rome Ⅳ diagnostic process, patients were divided into non-erosive reflux disease (NERD) group ( n=16), reflux hypersensitivity (RH) group ( n=8) and functional heartburn (FH) group ( n=12). The Gerd-Q scale score, 24-hour pH monitoring results and microstructure changes under pCLE were compared among the three groups. Results:There was no significant difference in the total score, positive symptom score, negative symptom score or positive influence score of Gerd-Q scale among the three groups ( P>0.05). DeMeester score [28.45 (20.08, 34.53)] and acid reflux times (24.88±9.05) in the NERD group were significantly higher than those in the RH group [7.30 (3.90, 11.38), P<0.001; 13.63±5.76, P=0.003] and FH group [6.90 (4.80, 9.73), P<0.001; 7.42±8.32, P<0.001]. But there was no significant difference between the RH group and the FH group ( P>0.05). The diameter of intra-papillary capillary loop (IPCL) (18.68±2.12 μm) and dilation of intercellular space (3.95±0.97 μm) in the NERD group were significantly higher than those in the RH group (13.91±1.99 μm, P<0.001; 2.97±0.55 μm, P=0.006) and FH group (13.83±2.00 μm, P<0.001; 2.31±0.54 μm, P<0.001), but there was no significant difference between the RH group and the FH group ( P>0.05). The number of IPCL in the NERD group, RH group and FH group were 2.0 (1.00, 2.75), 2.0 (1.00, 2.75) and 1.5 (1.00, 2.00), respectively with no significant difference ( P=0.697). Conclusion:Gerd-Q scale is not suitable for differential diagnosis of patients with endoscopic negative heartburn. Compared with functional esophageal diseases (RH and FH), acid reflux and mucosal microstructure changes are of more important pathogenic significance in NERD.

Feasibility of modified endoscopic anti-reflux mucosectomy for refractory gastroesophageal reflux disease with moderate hiatus hernia / 中华消化内镜杂志

Objective:To evaluate the efficiency and safety of modified endoscopic anti-reflux mucosectomy (ARMS) for refractory gastroesophageal reflux disease (rGERD) with moderate hiatus hernia.Methods:A total of 30 patients with rGERD with moderate hiatus hernia (3-5 cm) diagnosed at the Department of Gastroenterology of Northern Jiangsu People's Hospital from June 2017 to June 2020 were randomly divided into 2/3 circumferential mucosal resection group ( n=15) and 3/4 circumferential mucosal resection group ( n=15) using random number table method, and received modified ARMS of the corresponding mucosal resection range. The GERD symptoms, esophagitis under endoscopy, 24 h pH results, and lower esophageal sphincter (LES) resting pressure were compared before and after the procedure. The therapeutic effect and complications of the two groups were analyzed. Results:In 2/3 resection group, the GERD questionnaire scores (9.53±0.36 VS 11.93±0.57, t=6.874, P<0.001), acid exposure time (19.81%±1.72% VS 31.45%±2.78%, t=8.020, P<0.001) and the DeMeester score based on 24 h esophageal pH monitoring (40.98±4.55 VS 55.33±5.65, t=6.408, P<0.001) at 6 months after the treatment showed a significant reduction compared with those before. In 3/4 resection group, the GERD questionnaire scores (9.0±0.57 VS 12.47±0.68, t=8.650, P<0.001), acid exposure time (20.07%±2.19% VS 29.96%±3.00%, t=7.444, P<0.001) and the DeMeester score (33.67±3.47 VS 51.17±6.03, t=4.973, P<0.001) at 6 months after the treatment were lower than those before. There was no significant difference in the GERD questionnaire scores ( t=0.790, P=0.436), acid exposure time ( t=0.093, P=0.926) or the DeMeester score ( t=1.278, P=0.212) between the two groups at 6 months after treatment. In the two groups, there was no significant difference in the ratio of esophagitis grade C and D (10/15 VS 5/15, χ2=3.894, P=0.063; 8/15 VS 4/15, χ2=2.778, P=0.125) or LES resting pressure [3.29 (2.66,8.29) mmHg VS 3.98 (3.67,9.43) mmHg, P=0.334;5.78 (1.9,8.46) mmHg VS 5.88 (3.28,8.99) mmHg, P=0.125] before and after the treatment. No postoperative delayed bleeding or perforation was observed. The incidence of postoperative esophageal stenosis of 2/3 resection group was lower than that of the other group (1/15 VS 6/15, χ2=4.658, P=0.021). Conclusion:Modified ARMS is effective for controlling reflux symptoms and esophageal acid exposure in rGRED patients with moderate hiatus hernia (3-5 cm), but cannot significantly increase the postoperative resting pressure of LES. Compared with 3/4 circumferential mucosal resection, 2/3 circumferential mucosal resection can reduce the incidence of postoperative esophageal stenosis.