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.

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.

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.

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.

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.

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.

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.

The occurrence and progress of immune inflammatory response involved in gastroesophageal reflux disease / 中国医师进修杂志

Objective:To investigate the role of immune and inflammatory responses in the pathogenesis of gastroesophageal reflux disease (GERD).Methods:Fifteen patients with GERD who underwent biopsy and histopathology during painless gastroscopy in the digestive endoscopy center of the General Hospital of the PLA from December 2018 to September 2019 were analyzed retrospectively. They were divided into three groups: 6 cases of non erosive reflux disease (NERD), 8 cases of reflux esophagitis (RE) and 1 case of RE with high-grade intraepithelial neoplasia (RE-HIN). HE staining was used to analyze the inflammatory reaction of each group. The expression of cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, myeloperoxidase (MPO), IL-4, nuclear factor kappa-B(NF-κB), IL-8, reactive oxygen species (ROS-1) were monitored by immunohistochemistry. Chi square test was used to analyze the positive rate of immune and inflammatory indexes in each group.Results:The three groups showed mild and moderate inflammatory cell infiltration, mostly lymphocyte infiltration, and basal cell hyperplasia in 3 cases. There was no significant difference between inflammatory cell infiltration, basal hyperplasia and inflammatory grade in NERD and RE( P>0.05). Immune and inflammatory factors COX-2(positive rate:NERD 4/6, RE4/8, RE-HIN 1/1), iNOS(positive rate:NERD 4/6, RE 3/8, RE-HIN 0), IL-1β(positive rate:NERD 6/6, RE 7/8, RE-HIN 1/1), MPO(positive rate:NERD 4/6, RE 7/8, RE-HIN 1/1), IL-4(positive rate:NERD 3/6, RE 4/8, RE-HIN 0), IL-8(positive rate:NERD 2/6, RE 6/8, RE-HIN 1/1), ROS-1(positive rate:NERD 3/6, RE 1/8, RE-HIN 0) and signal pathway NF- κ B (positive rate:NERD 4/6, RE 8/8, RE-HIN 1/1) were positive in three groups. The expressions of IL-1β, MPO and NF-κB were statistically significant among the three groups ( P<0.05). Conclusions:There is an inflammatory cascade mediated by immune inflammatory factors and mediators in GERD patients, and NF-κB signaling pathway is involved. It provides a basis for finding targets to block immune and inflammatory responses in the later stage to treat GERD.

The safety and short-term efficacy of laparoscopic proximal gastrectomy for proximal gastric cancer and adenocarcinoma of esophagogastric junction: a multicenter study / 中华消化外科杂志

Objective:To investigate the safety and short-term efficacy of laparoscopic pro-ximal gastrectomy (LPG) for proximal gastric cancer and adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinicopathological data of 385 patients with proximal gastric cancer and adenocarcinoma of esophagogastric junction who underwent LPG in the 15 medical centers, including the First Affiliated Hospital of Xiamen University et al, from January 2014 to March 2022 were collected. There were 304 males and 81 females, aged (63±9)years. Of the 385 patients, 335 cases undergoing LPG were divided into the laparoscopic group and 50 cases undergoing open proximal gastrectomy were divided into the open group. Observation indicators: (1) intraoperative and postoperative situations; (2) follow-up; (3) stratified analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Intraoperative and postoperative situations. The operation time, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, cases with postoperative pathological staging as stage 0?Ⅰ and stage Ⅱ?Ⅲ, duration of postoperative hospital stay, cases with postoperative early complications were (212±96)minutes, 270, 65, 177, 107, 10(range, 8?14)days, 40 in patients of the laparoscopic group, with 51 cases missing the data of postoperative pathological staging. The above indicators were (174±90)minutes, 39, 11, 22, 28, 10(range, 8?18)days, 10 in patients of the open group. There were significant differences in the opera-tion time and postoperative pathological staging between the two groups ( t=2.62, χ2=5.93, P<0.05), and there was no significant difference in the reconstruction of digestive tract, duration of post-operative hospital stay, postoperative early complications between the two groups ( χ2=0.19, Z=0.40, χ2=2.50, P>0.05). (2) Follow-up. Of the 385 patients,202 cases were followed up during the post-operative 12 months, including 187 cases in the laparoscopic group and 15 cases in the open group. Cases with reflux esophagitis, cases with esophageal anastomotic stenosis were 48, 11 in patients of the laparoscopic group, versus 5, 2 in patients of the open group, showing no significant difference in the above indicators between the two groups ( P>0.05). The body mass index (BMI), hemoglobin (Hb), albumin (Alb) at postoperative 6 months and 12 months were (21±3)kg/m 2, (130±15)g/L, (40±4)g/L and (21±3)kg/m 2, (132±14)g/L, (41±4)g/L in patients of the laparoscopic group, versus (21±3)kg/m 2, (121±19)g/L, (37±5)g/L and (21±3)kg/m 2, (125±21)g/L, (43±6)g/L in patients of the open group. There were significant differences in postoperative Hb between the two groups ( Fgroup=5.88, Ftime=5.49, Finteraction=19.95, P<0.05) and there were significant differences in time effect of postopera-tive BMI and Alb between the two groups ( Ftime=9.53, 49.88, P<0.05). (3) Stratified analysis. ① Incidence of postoperative of reflux esophagitis and esophageal anastomotic stenosis in patients with different reconstruction of digestive tract. Of the 202 patients, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis were 168 and 34, respectively. The incidence rates of postoperative of reflux esophagitis were 26.79%(45/168)and 23.53%(8/34)in cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, showing no significant difference between them ( χ2=0.16, P>0.05). Cases undergoing esophageal anastomotic stenosis were 13 in patients with reconstruction of diges-tive tract as esophagogastric anastomosis. ② The BMI, Hb, Alb in patients with different reconstruc-tion of digestive tract. The BMI, Hb, Alb were (24±3)kg/m 2, (135±20)g/L, (41±5)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis before the operation, versus (23±3)kg/m 2, (130±19)g/L, (40±4)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis before the operation, showing no significant difference between them ( t=1.44, 1.77, 1.33, P>0.05). The BMI, Hb, Alb at postoperative 6 months and 12 months were (21±3)kg/m 2, (128±16)g/L, (39±4)g/L and (21±3)kg/m 2, (131±16)g/L, (41±4)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis, versus (20±4)kg/m 2, (133±13)g/L, (43±3)g/L and (21±3)kg/m 2, (135±12)g/L, (44±3)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis. There were significant differences in the group effect and time effect of postoperative Alb between patients with different reconstruction of diges-tive tract ( Fgroup=15.82, Ftime=5.43, P<0.05), and there was also a significant difference in the time effect of postoperative BMI between them ( Ftime=4.22 , P<0.05). Conclusion:LPG can be used to the treatment of proximal gastric cancer and adenocarcinoma of esophagogastric junction, with a good safety and short-term efficacy.

Current status and prospect of proximal gastrectomy modified muscle flap anastomosis / 中华消化外科杂志

In recent years, the incidence of proximal gastric cancer and early gastric cancer as well as the proportion of proximal gastrectomy has been increased year by year. However, severe reflux esophagitis will occur after proximal gastrectomy, which will affect the quality of life of patients after operation. Therefore, the research on anti-reflux surgery has become a focus in the field across the world in recent years. Due to closing to the normal cardiac physiological structure, double muscle flap anastomosis has a good anti-reflux effect in proximal gastrectomy, which has been widely verified in clinical application. However, due to the disadvantages of traditional double muscle flap anastomosis, such as complex operation, long learning curve and high rate of anastomotic stenosis, researchers at home and abroad have continuously tried various modified muscle flap anastomosis. Among which, the modified double muscle flap anastomosis based on using the double barbed sutures has showed encouraging effects. At mean time, laparoscopic double muscle flap anastomosis through the left diaphragm muscle in the left thoracic cavity also further expands the application of double muscle flap anastomosis. The authors consult relevant research and focus on the discussion of current status and prospect of different modified muscle flap anastomosis in proximal gastrec-tomy, in order to promote the popularization and application of muscle flap anastomosis.

Effects of primary duodenogastric reflux on Helicobacter pylori infection and drug resistance in children in Wuxi area / 中国小儿急救医学

Objective:To investigate the effect of primary duodenal bile reflux(DGR)on Helicobacter pylori(HP)infection and drug resistance in children in Wuxi area, and to provide the basis for the selection of anti-HP drugs in children with subsequent DGR.Methods:The clinical data of children who had received upper gastrointestinal endoscopy and HP examination because of abdominal pain, nausea, vomiting, gastrointestinal bleeding, dyspepsia and other upper gastrointestinal symptoms were collected from January 2020 to February 2022 in the Gastroenterology Department of Wuxi Children′s Hospital.According to the results of endoscopy, children were divided into DGR group (217 cases) and control group without DGR (1 252 cases), and their age, gender, HP infection rate and abdominal pain were analyzed.Results:A total of 1 469 children were included in this study, with a median age of 11(9, 14) years, 808(55.0%) males and 661(45.0%) females.HP infection was detected in 322(21.9%) cases.The median age of DGR group was higher than that in control group[13(11, 15) years vs. 11(8, 14) years, P<0.001], and the incidence of DGR was increased in the elder group( χ2=45.963, P<0.001). There was no significant difference between DGR group and control group in sex and whether abdominal pain was the first symptom ( P>0.05). There were 47(22.0%) cases positive for HP in DGR group and 275(22.0%)cases in control group, with no significant difference( P>0.05). A total of 256 cases were isolated and cultured positive of HP.And in vitro susceptibility tests of strains, there was no significant difference between DGR group and control group in the single and combined resistance rates of HP to metronidazole, clarithromycin, levofloxacin, amoxicillin, furazolidone and tetracycline hydrochloride( P>0.05). Conclusion:Elder children are more likely to have primary DGR.The occurrence of primary DGR has no significant effect on HP infection and drug resistance.

Effects of abdominal breathing exercises at different periods on the gastrointestinal symptoms in patients with gastroesophageal reflux disease / 中国实用护理杂志

Objective:To explore the effect of abdominal breathing exercises at different periods on the gastrointestinal symptoms, quality of life and proton pump inhibitor dependency in patients with gastroesophageal reflux disease (GERD). To provide reference for patients to choose the best time for abdominal breathing exercises.Methods:This was a prospective study. From March 2020 to December 2021, totally 108 GERD patients were collected in digestive outpatient clinic of Yibin Hospital of Chinese Medicine Hospital by convenient sampling method, they were randomly divided into pre meal group, 1 h postprandial group and 2 h postprandial group with 36 cases in each group. All patients in the three groups were given abdominal breathing training for 8 weeks on the basis of conventional acid suppression drug treatment and nursing. The training time of pre meal group, 1 h postprandial group and 2 h postprandial group was at 30 min before meal, 1 h after meal, 2 h after meal, respectively. Before and after 8 weeks of intervention, the difference of gastrointestinal symptoms and quality of life were assessed by Reflux Disease Ouestionnaire (RDQ) and the MOS 36 Item Short Form Health Survey (SF-36). Patients followed up for 12 weeks after drug withdrawal, the medication of proton pump inhibitor (PPI) between three groups were compared.Results:There was no significant difference in RDQ score and SF-36 score among the three groups before intervention ( P>0.05). After intervention, the symptom scores were (7.89 ± 1.86) in the 1 h postprandial group, lower than in the pre meal group (10.38 ± 1.81) and in the 2 h postprandial group (9.64 ± 1.65), the difference was statistically significant ( t = 5.83, 4.06, both P<0.01). The scores of each demensions in SF-36 were higher in the 1 h postprandial group compared to the pre meal group and the 2 h postprandial group, the differences were statistically significant ( t values were 2.04-3.70, all P<0.05). After followed up for 12 weeks, the PPI discontinuation rate was 71.43% in the 1 h postprandial group, higher than in the pre meal group 44.12% and in the 2 h postprandial group 45.45%, the differences were statistically significant ( χ2 = 5.28, 4.73, both P<0.05). Conclusions:Abdominal breathing exercises at 1 hour after meal can effectively alleviate gastrointestinal symptoms, promote quality of life and decrease the proton pump inhibitor dependency of GERD patients.

Research progress of TCM non-drug therapy in gastroesophageal reflux disease / 国际中医中药杂志

Traditional Chinese Medicine (TCM) non-drug therapy for gastroesophageal reflux mainly includes appropriate TCM techniques, such as conventional acupuncture, moxibustion, fire needle, etc. Emotional therapy, such as regulating emotion, transforming the patient's spirit and change the state of qi, the five-element music therapy, etc; exercise therapy, such as Baduanjin and Zhanzhuang, can be used alone, or in combination, or in combination with oral administration of Chinese materia medica. By reducing the probability of esophageal sphincter relaxation, inhibiting gastric acid secretion, improving esophageal motility disorder, reducing visceral hypersensitivity, immune regulation and other effects, it can alleviate the symptoms of acid reflux, heartburn and pharyngeal discomfort, and help to improve the patients' anxiety, depression and other negative emotions. It has the characteristics of simplicity and fewer adverse reactions, at the same time, according to the patient's condition and compliance to choose the appropriate therapy. The mechanism of TCM non-drug therapy in the treatment of this disease needs to be further explored, so as to better guide clinical popularization and application.