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.

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.

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.

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.

Analysis on the pharyngeal microbiota in patients with laryngopharyngeal reflux disease

Abstract Objective(s): In this study, the laryngopharynx microbiome alterations were characterized after proton pump inhibitor treatment in patients with Laryngopharyngeal Reflux Disease (LPRD) and healthy people. The potential outcome-predictive biomarker was explored. Methods: Patients with LPRD and healthy controls were enrolled. The composition of their laryngopharynx microbiota was analyzed both by traditional plate count of the main bacterial groups and PCR amplification followed by denaturing gradient gel electrophoresis. Shannon-Wiener index and evenness index based on Dice index were used to assess the bacterial diversity. Droplet digital PCR was used to determine the total bacterial RNA and relative abundance of Klebsiella oxytoca. Receiver operating characteristic curve was plotted to explore the potential of Klebsiella oxytoca as an outcome-predictive biomarker. Results: A total of 29 LPRD cases and 28 healthy subjects were enrolled. The composition of the laryngopharynx microbiota was almost similar, except Klebsiella oxytoca. The cluster analysis showed that the similarity between healthy and treatment-effective groups, as well as pretreatment and treatment-invalid groups, was close. Statistical analysis showed that there were differences in the diversity index and richness among the healthy, treatment-effective, pretreatment and treatment-invalid groups. The abundance of Klebsiella oxytoca in the treatment-effective LPRD group was lower than that of the treatment-invalid LPRD group. The abundance of Klebsiella oxytoca can distinguish treatment-effective and -invalid groups (AUC = 0.859) with a sensitivity of 77.78% and specificity of 90.91%. Conclusion: There were differences in the diversity of cecal contents microbial community between treatment-invalid and treatment-effective LPRD groups. Klebsiella oxytoca has potential to distinguish treatment outcomes. Level of evidence: How common is the problem? Level 1. Is this diagnostic or monitoring test accurate? (Diagnosis) Level 4. What will happen if we do not add a therapy? (Prognosis) Level 5. Does this intervention help? (Treatment Benefits) Level 4. What are the COMMON harms? (Treatment Harms) Level 4. What are the RARE harms? (Treatment Harms) Level 4. Is this (early detection) test worthwhile?(Screening) Level 4.

Laparoscopic antireflux surgery: were old questions answered? partial or total fundoplication? / Cirurgia laparoscópica antirrefluxo: perguntas antigas foram respondidas? fundoplicatura parcial ou total?

ABSTRACT Laparoscopic total fundoplication is currently considered the gold standard for the surgical treatment of gastroesophageal reflux disease. Short-term outcomes after laparoscopic total fundoplication are excellent, with fast recovery and minimal perioperative morbidity. The symptom relief and reflux control are achieved in about 80 to 90% of patients 10 years after surgery. However, a small but clinically relevant incidence of postoperative dysphagia and gas-related symptoms is reported. Debate still exists about the best antireflux operation; during the last three decades, the surgical outcome of laparoscopic partial fundoplication (anterior or posterior) were compared to those achieved after a laparoscopic total fundoplication. The laparoscopic partial fundoplication, either anterior (180°) or posterior, should be performed only in patients with gastroesophageal reflux disease secondary to scleroderma and impaired esophageal motility, since the laparoscopic total fundoplication would impair esophageal emptying and cause dysphagia.

RESUMO A fundoplicatura total laparoscópica é considerada, atualmente, o padrão ouro para o tratamento cirúrgico da doença do refluxo gastroesofágico. Os resultados de curto prazo após a fundoplicatura total laparoscópica são excelentes, com recuperação rápida e morbidade perioperatória mínima. O alívio dos sintomas e o controle do refluxo são alcançados em cerca de 80 a 90% dos pacientes, 10 anos após a cirurgia. No entanto, é relatada uma incidência pequena, mas clinicamente relevante, de disfagia pós-operatória e sintomas relacionados a gases. Ainda existe debate sobre a melhor operação antirrefluxo e, nas últimas três décadas, os resultados cirúrgicos da fundoplicatura parcial laparoscópica (anterior ou posterior) foram comparados aos obtidos após uma fundoplicatura total laparoscópica. A fundoplicatura parcial laparoscópica, seja anterior (180°) ou posterior, deve ser realizada apenas em pacientes com doença do refluxo gastroesofágico secundária a esclerodermia e motilidade esofágica ineficiente, pois uma fundoplicatura total laparoscópica prejudicaria o esvaziamento esofágico e causaria disfagia.

GASTRIC PLICATION ASSOCIATED WITH FUNDOPLICATION IN INDIVIDUALS WITH CLASS I OBESITY AND GASTROESOPHAGEAL REFLUX DISEASE: WEIGHT LOSS OUTCOMES, REFLUX-RELATED SYMPTOMS, ENDOSCOPIC AND pH MONITORING FINDINGS / PLICATURA GÁSTRICA ASSOCIADA A FUNDOPLICATURA EM INDIVÍDUOS COM OBESIDADE GRAU I E DOENÇA DO REFLUXO GASTROESOFÁGICO: ANÁLISE DE PERDA DE PESO, SINTOMAS DE REFLUXO, ACHADOS ENDOSCÓPICOS E DE pHMETRIA

ABSTRACT BACKGROUND: The association of gastric plication with fundoplication is a reliable option for the treatment of individuals with obesity associated with gastroesophageal reflux disease. AIMS: To describe weight loss, endoscopic, and gastroesophageal reflux disease-related outcomes of gastric plication with fundoplication in individuals with mild obesity. METHODS: A retrospective cohort study was carried out, enrolling individuals who underwent gastric plication with fundoplication at a tertiary private hospital from 2015-2019. Data regarding perioperative and weight loss outcomes, endoscopic and 24-hour pH monitoring findings, and gastroesophageal reflux disease-related symptoms were analyzed. RESULTS: Of 98 individuals, 90.2% were female. The median age was 40.4 years (IQR 32.1-47.8). The median body mass index decreased from 32 kg/m2 (IQR 30,5-34) to 29.5 kg/m2 (IQR 26.7-33.9) at 1-2 years (p<0.05); and to 27.4 kg/m2 (IQR 24.1-30.6) at 2-4 years (p=0.059). The median percentage of total weight loss at 1-2 years was 7.8% (IQR −4.1-14.7) and at 2-4 years, it was 16.4% (IQR 4.3-24.1). Both esophageal and extra-esophageal symptoms showed a significant reduction (p<0.05). A significant decrease in the occurrence of esophagitis was observed (p<0.01). The median DeMeester score decreased from 30 (IQR 15.1-48.4) to 1.9 (IQR 0.93-5.4) (p<0.0001). CONCLUSIONS: The gastric plication with fundoplication proved to be an effective and safe technique, leading to a significant and sustained weight loss in addition to endoscopic and clinical improvement of gastroesophageal reflux disease.

RESUMO RACIONAL: A associação de plicatura gástrica com fundoplicatura é uma opção atrativa para o tratamento de indivíduos com obesidade associada à doença do refluxo gastroesofágico. OBJETIVOS: Descrever a evolução ponderal, clínica, endoscópica e de pHmetria após a gástrica com fundoplicatura em indivíduos com obesidade grau I e doença do refluxo gastroesofágico. MÉTODOS: Um estudo de coorte histórica foi realizado, incluindo indivíduos que realizaram gástrica com fundoplicatura em um hospital privado terciário de 2015 a 2019. Os dados sobre os resultados perioperatórios e de perda de peso, achados endoscópicos e de pHmetria de 24 horas e sintomas relacionados à doença do refluxo gastroesofágico foram analisados. RESULTADOS: Dos 98 indivíduos, 90,2% eram do sexo feminino. A idade mediana foi de 40,4 (IQR 32,1-47,8) anos. A mediana do índice de massa corporal diminuiu de 32 (IQR 30,5-34) kg/m2 para 29,5 (IQR 26,7-33,9) kg/m2 em 1-2 anos (p<0,05); de 2 a 4 anos, foi de 27,4 (IQR 24,1-30,6) kg/m2 (p=0,059). A mediana da porcentagem da perda total de peso em 1-2 anos foi de 7,8% (IQR −4,1-14,7) e em 2-4 anos, foi de 16,4% (IQR 4,3-24,1). Tanto os sintomas esofágicos quanto os extras esofágicos apresentaram redução significativa (p<0,05). Observou-se diminuição significativa na ocorrência de esofagite (p<0,01). A pontuação mediana do escore de DeMeester diminuiu de 30 (IQR 15,1-48,4) para 1,9 (IQR 0,93-5,4) (p<0,0001). CONCLUSÕES: A associação entre plicatura gástrica e fundoplicatura laparoscópica mostrou-se uma técnica eficaz e segura, levando a perda de peso significativa, bem como melhora endoscópica e clínica da doença do refluxo gastroesofágico.

Magnetic sphincter augmentation device for gastroesophageal reflux disease: effective, but postoperative dysphagia and risk of erosion should not be underestimated. a systematic review and meta-analysis / Dispositivo magnético no esfincter para doença do refluxo gastroesofágico: eficaz, mas a disfagia pós-operatória e o risco de erosão não devem ser subestimados. uma revisão sistemática e meta-análise

ABSTRACT BACKGROUND: Magnetic ring (MSA) implantation in the esophagus is an alternative surgical procedure to fundoplication for the treatment of gastroesophageal reflux disease. AIMS: The aim of this study was to analyse the effectiveness and safety of magnetic sphincter augmentation (MSA) in patients with gastroesophageal reflux disease (GERD). METHODS: A systematic literature review of articles on MSA was performed using the Medical Literature Analysis and Retrieval System Online (Medline) database between 2008 and 2021, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effect model was used to generate a pooled proportion with 95% confidence interval (CI) across all studies. RESULTS: A total of 22 studies comprising 4,663 patients with MSA were analysed. Mean follow-up was 27.3 (7-108) months. The weighted pooled proportion of symptom improvement and patient satisfaction were 93% (95%CI 83-98%) and 85% (95%CI 78-90%), respectively. The mean DeMeester score (pre-MSA: 34.6 vs. post-MSA: 8.9, p=0.03) and GERD-HRQL score (pre-MSA: 25.8 vs. post-MSA: 4.4, p<0.0001) improved significantly after MSA. The proportion of patients taking proton pump inhibitor (PPIs) decreased from 92.8 to 12.4% (p<0.0001). The weighted pooled proportions of dysphagia, endoscopic dilatation and gas-related symptoms were 18, 13, and 3%, respectively. Esophageal erosion occurred in 1% of patients, but its risk significantly increased for every year of MSA use (odds ratio — OR 1.40, 95%CI 1.11-1.77, p=0.004). Device removal was needed in 4% of patients. CONCLUSIONS: Although MSA is a very effective treatment modality for GERD, postoperative dysphagia is common and the risk of esophageal erosion increases over time. Further studies are needed to determine the long-term safety of MSA placement in patients with GERD.

RESUMO RACIONAL: A implantação de anel magnético (AM) no esôfago é um procedimento cirúrgico alternativo à fundoplicatulra, para o tratamento da doença do refluxo gastroesofágico. OBJETIVOS: O objetivo deste estudo foi analisar a eficácia e segurança do anel magnético em pacientes com doença do refluxo gastroesofágico (DRGE). MÉTODOS: Uma revisão sistemática da literatura de artigos sobre AM foi realizada usando o banco de dados Medline entre 2008 e 2021, seguindo as diretrizes PRISMA. Um modelo de efeito aleatório foi usado para gerar uma proporção agrupada com intervalo de confiança (IC) de 95% em todos os estudos. RESULTADOS: Um total de 22 estudos compreendendo 4.663 pacientes submetidos à colocação do AM foram analisados. O seguimento médio foi de 27,3 (7-108) meses. A proporção ponderada de melhora dos sintomas e satisfação do paciente foi de 93% (IC95% 83-98%) e 85% (IC95% 78-90%), respectivamente. A pontuação média de DeMeester (pré-AM: 34,6 versus pós-AM: 8,9, p=0,03) e pontuação GERD-HRQL (pré-AM: 25,8 versus pós-AM: 4,4, p<0,0001) melhoraram significativamente após a colocação do anel. A proporção de pacientes em uso de inbidor de bomba de prótons (IBP) diminuiu de 92,8% para 12,4% (p<0,0001). A erosão esofágica ocorreu em 1% dos pacientes, o risco aumentou significativamente para cada ano de uso do AM (OR 1,40; IC95% 1,11-1,77, p=0,004). A remoção do dispositivo foi necessária em 4% dos pacientes. CONCLUSÕES: O AM é uma modalidade de tratamento eficaz para a DRGE. A disfagia pós-operatória é comum, e o risco de erosão esofágica aumenta com o tempo.

Using RSI and RFS scores to differentiate between reflux-related and other causes of chronic laryngitis

Abstract Objective: To establish if the Reflux Symptom Index (RFI) and the Reflux Finding Score (RFC) can help establish the differential diagnosis in patients with distinct causes of chronic laryngopharyngitis. Methods: A group of 102 adult patients with chronic laryngopharyngitis (Group A - 37 patients with allergic rhinitis; Group B - 22 patients with Obstructive Sleep Apnea (OSA); Group C -43 patients with Laryngopharyngeal Reflux (LPR)) were prospectively studied. Chronic laryngitis was diagnosed based on suggestive symptoms and videolaryngoscopic signs (RSI ≥ 13 and RFS ≥7). Allergies were confirmed by a positive serum RAST, OSA was diagnosed with a positive polysomnography, and LPR with a positive impedance-PH study. Discriminant function analysis was used to determine if the combination of RSI and RFS scores could differentiate between groups. Results: Patients with respiratory allergies and those with LPR showed similar and significantly higher RSI scores when compared to that of patients with OSA (p < 0.001); Patients with OSA and those with LPR showed similar and significantly higher RFS scores when compared to that of patients with Respiratory Allergies (OSA vs. Allergies p < 0.001; LPR vs. Allergies p < 0.002). The combination of both scores held a higher probability of diagnosing OSA (72.73%) and Allergies (64.86%) than diagnosing LPR (51.16%). Conclusions: RSI and RFS are not specific for reflux laryngitis and are more likely to induce a false diagnosis if not used with diligence.

Seguimiento de dilatación del tracto urinario neonatal diagnosticada en la evaluación de infección del tracto urinario

Objetivo: Mostrar las características y seguimiento de la dilatación del tracto urinario en recién nacidos con infección del tracto urinario. Métodos: Estudio observacional, descriptivo, realizado desde 1992 hasta 2019, en neonatos ingresados con infección del tracto urinario. A todos se les realizó ultrasonido renal y uretrocistografía miccional. Se analizaron las características clínicas y de radioimagen de presentación en el seguimiento de la dilatación del tracto urinario. Resultados: Se estudiaron 403 pacientes. La mediana de seguimiento fue de 13 meses. El ultrasonido renal resultó positivo para dilatación del tracto urinario en 148 (36,7 %). Predominaron los grados de dilatación ligera (5-10 mm.) sobre grados moderados y severos. En 38 casos (9,4 %) la dilatación del tracto urinario se asoció a reflujo vésico-ureteral. La condición más común fue la dilatación transitoria con una mediana de desaparición de la dilatación 5 meses. Hubo asociación estadística significativa de la desaparición de la dilatación del tracto urinario con el grado de esta y entre aquellos casos calificados de transitoria con los otros portadores de alguna anomalía del tracto urinario que también tuvieron desaparición de la dilatación en algún momento de su evolución. Conclusiones: Cerca de una tercera parte de los neonatos con infección del tracto urinario tuvieron dilatación del tracto urinario en ultrasonido renal, con predominio de grado ligero, como probable expresión de una anomalía del tracto urinario subyacente. Con frecuencia ocurre resolución de la dilatación del tracto urinario en aquellos casos no asociados con anomalía del tracto urinario, habitualmente dentro del primer año de vida.

OBjective: To show the characteristics and follow-up of urinary tract dilatation in neonates with urinary tract infection. Methods: Observational, descriptive study performed from 1992 to 2019, in neonates admitted with urinary tract infection. All underwent renal ultrasound and voiding urethrocystography. The clinical and radioimaging features of presentation were analyzed in the follow-up of urinary tract dilatation, Results: 403 patients were studied. The median follow-up was 13 months. Renal ultrasound was positive for urinary tract dilatation in 148 (36.7%). Mild degrees of dilatation (5-10 mm) predominated over moderate and severe degrees. In 38 cases (9.4%) urinary tract dilatation was associated with vesico-ureteral reflux. The most common condition was transient dilatation with a median disappearance of dilatation 5 months. There was significant statistical association of the disappearance of urinary tract dilatation with the degree of dilatation and between those cases qualified as transient with the other carriers of some urinary tract anomaly who also had disappearance of dilatation at some point in their evolution. Conclusions: About one third of neonates with urinary tract infection had dilatation of the urinary tract on renal ultrasound, predominantly of mild degree, probably expression of an underlying anomaly. Resolution of dilatation frequently occurs in those cases not associated with urinary tract anomaly, usually within the first year of life.