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We investigated the association of proton pump inhibitor (PPI) use with the risk of stroke and ischemic heart disease (IHD). The Korean National Health Insurance Service-Health Screening cohort from 2002 to 2003, the participants of which were followed up until 2019, was used. In study I, 45,905 participants who were diagnosed with stroke were matched with 91,810 control I participants. The history of PPI medication was examined. In study II, 40,928 participants who were diagnosed with IHD were matched with 81,856 control II participants. In both study I and study II, the previous history of PPI medication was examined. A propensity score overlap-weighted multivariable logistic regression analysis was conducted to estimate the overlap-weighted odds ratios (ORs) of PPI use for stroke (study I) and IHD (study II). Current PPI use was linked with higher odds for stroke in study I. The odds for stroke were higher in groups with a longer duration of PPI use (OR = 0.96 [95% CI = 0.92–1.00] < 1.55 [1.50–1.61] < 1.62 [1.57–1.68] for < 30 days, 30 to 180 days, and ≥180 days of PPI use). Previous PPI use was linked with higher odds for IHD in study II. The odds for stroke were higher in groups with a longer duration of PPI use (OR = 1.13 [95% CI = 1.08–1.18] < 2.12 [2.04–2.21] < 2.60 [2.51–2.69] for <30 days, 30 to 180 days, and ≥180 days of PPI use). Current PPI medication is associated with a high risk of stroke and IHD. A longer duration of PPI medication was related to a higher risk of stroke and IHD. However, a prior history of PPI medication was not linked with a high risk of stroke or IHD. [ABSTRACT FROM AUTHOR]

Concomitant medications may alter the effect of biological therapy in inflammatory bowel disease. The aim was to investigate the effect of proton pump inhibitors on remission rates in patients with inflammatory bowel disease treated with the gut-selective vedolizumab. Patients from the Hungarian nationwide, multicenter vedolizumab cohort were selected for post hoc analysis. Primary outcomes were the assessment of clinical response and endoscopic and clinical remission at weeks 14 and 54. Secondary outcomes were the evaluation of the combined effect of concomitant steroid therapy and other factors, such as smoking, on remission. A total of 108 patients were identified with proton pump inhibitor data from 240 patients in the original cohort. Patients on steroids without proton pump inhibitors were more likely to have a clinical response at week 14 than patients on concomitant PPI (95% vs. 67%, p = 0.005). Non-smokers with IBD treated with VDZ were more likely to develop a clinical response at week 14 than smokers, particularly those not receiving PPI compared with patients on co-administered PPI therapy (81% vs. 53%, p = 0.041, and 92% vs. 74%, p = 0.029, respectively). We found that the use of PPIs in patients treated with VDZ may impair the achievement of response in certain subgroups. Unnecessary PPI prescriptions should be avoided. [ABSTRACT FROM AUTHOR]

Background: Intermediate-stage hepatocellular carcinoma (BCLC B HCC) occurs in a heterogeneous group of patients and can be addressed with a wide spectrum of treatments. Consequently, survival significantly varies among patients. In recent years, several subclassification systems have been proposed to stratify patients' prognosis. We analyzed and compared these systems (Bolondi, Yamakado, Kinki, Wang, Lee, and Kim criteria) in patients undergoing systemic therapy. Methods: We considered 171 patients with BCLC B HCC treated with sorafenib as first-line systemic therapy in six Italian centers from 2010 to 2021 and retrospectively applied the criteria of six different subclassification systems. Results: Except for the Yamakado criteria, all the subclassification systems showed a statistically significant correlation to overall survival (OS). In the postestimation analysis, the Bolondi criteria (OS of subgroups 22.5, 11.9, and 6.6 mo, respectively; C-index 0.586; AIC 1338; BIC 1344) and the Wang criteria (OS of subgroups 20.6, 11.9, and 7.0, respectively; C-index 0.607; AIC 1337; BIC 1344) presented the best accuracy. Further analyses of these two subclassification systems implemented with the prognostic factor of alpha-fetoprotein (AFP) > 400 ng/mL have shown an increase in accuracy for both systems (C-index 0.599 and 0.624, respectively). Conclusions: Intermediate-stage subclassification systems maintain their predictive value also in the setting of systemic therapy. The Bolondi and Wang criteria showed the highest accuracy. AFP > 400 ng/mL enhances the performance of these systems. [ABSTRACT FROM AUTHOR]

Background: The European Society of Gastroenterology and Endoscopy recommends a primarily flexible endoscopic approach for the treatment of Zenker's diverticulum. Due to the rarity of the disorder, evidence for its effectiveness and safety comes mainly from small, retrospective, single-center studies., Methods: In this retrospective, observational, multicenter cohort study, data from six German tertiary referral centers were analyzed. The primary outcome parameters were technical and clinical success; among the secondary outcomes, the rates of adverse events (AE) and re-admission with symptomatic recurrence and mortality were the most relevant., Results: Between 2003 and 2024, 384 treatments were performed in 327 patients (61.8% male, mean age 74.70 (± 10.60)). Incision methods/techniques were 250 needle knives, 44 ESD knives, 64 stag beetle knives, 24 staplers, one APC-probe, and one Z-POEM. The Zenker's diverticulum overtube was used in 65.1%, prophylactic clipping in 30.2%, and antibiotic therapy in 25.3% of treatments. The rates of technical and clinical success were 99.2% and 97.4%, and the rates of AE and re-admission with symptomatic recurrence were 11.2% and 16.7%, respectively. Mortality was 0.3%. Comparative subgroup analyses of 312 diverticula without prior treatment versus 72 symptomatic recurrences and incision methods/techniques showed no significant differences in outcome parameters. The use of additional devices and prophylactic measures (clipping, antibiotic therapy) were not independent predictors of technical/clinical success or AE in uni-/multivariable regression analysis., Conclusions: Flexible endoscopic Zenker's diverticulotomy is a safe and effective minimally invasive treatment. Recurrences can be treated by flexible endoscopy with comparable results. None of the cutting methods, ancillary devices, or prophylactic measures showed superiority in effectiveness or safety., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: There is currently no reference standard test for the detection of the extra-esophageal manifestations of gastroesophageal reflux disease (GERD). The current suite of diagnostic tests principally assesses reflux events in the esophagus. A new scintigraphic technique has been developed and validated against reference standards. It allows direct visualization of refluxate in the laryngopharynx and lungs., Methods: Fifty patients were assessed by scintigraphy before and after fundoplication at a single nuclear medicine facility. Standardized reflux symptom indices (RSIs) were obtained from each patient before and after surgery. Patients were scanned after oral 99 m technetium Fyton administration with early dynamic images and delayed SPECT/CT images of the head, neck, and lungs. ANOVA, Spearman correlation, and the Student's t-test were utilized for analysis., Results: The study population (35F, 15 M) had a mean age of 63.9 years. Mean BMI was 26.8 with 67% being overweight or obese. All patients had significant reflux. SPECT/CT showed LPR events in 45/50 and pulmonary micro-aspiration (PMA) in 45/50 preoperatively and in 36/50 and 20/50 postoperatively, respectively. The RSI, cough, and throat clearing indices showed a significant fall postoperatively (p < 0.001). Frequency of scintigraphic reflux events was reduced from a mean of 4.5 in 30 min to 2.9 (t = 9.1, p = 0.004)., Conclusion: The novel scintigraphic test detects esophageal and extra-esophageal reflux events and permits direct visualization of refluxate in the head and neck structures and lungs. It correlates well with symptoms of reflux in the esophagus and extra-esophageal structures and the response to therapy., Level of Evidence: Although prospective, the study did not randomize patients and in effect each patient became their own control following an intervention (fundoplication). Thus, the study is Level 3 evidence Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: This study aimed to investigate the knowledge, attitudes and practices (KAP) of patients with chronic pharyngitis in Suzhou, China toward laryngopharyngeal reflux (LPR). Methods: This cross-sectional study was conducted in patients with chronic pharyngitis in Suzhou, China at the otolaryngology outpatient clinic of the First Affiliated Hospital of Soochow University between November, 2022, and May, 2023. Data was collected through a self-designed online questionnaire encompassing the sociodemographic characteristics and three dimensions of KAP. The questionnaire was administered using SoJump, and data were exported from this platform. Subsequently, statistical analysis, including Structural Equation Modeling, was performed using SPSS 22 software to evaluate the KAP scores. Results: A total of 487 valid questionnaires were collected, with 275 (56.35%) female patients. The mean score of KAP were 4.76 ± 2.93 (possible range: 0–11), 33.10 ± 4.46 (possible range: 8–40), 31.29 ± 6.04 (possible range: 8–40), respectively. Pearson's correlation analysis showed significant positive correlations between knowledge and attitude dimensions (r = 0.413, P < 0.001), knowledge and practice dimensions (r = 0.355, P < 0.001), and attitude and practice dimensions (r = 0.481, P < 0.001). Structural equation modeling revealed that education exhibited positive effect on knowledge (β = 0.476, P < 0.001) and attitude (β = 0.600, P < 0.001), and having family history of chronic pharyngitis showed positive effect on knowledge (β = 0.580, P = 0.047), experienced with reflux symptoms showed positive effect on knowledge (β = 0.838, P = 0.001) and attitude (β = 0.631, P = 0.085). Moreover, knowledge showed positive effect on attitude (β = 0.555, P < 0.001) and practice (β = 0.351, P < 0.001). Attitude, in turn, showed positive effect on practice (β = 0.511, P < 0.001). Conclusion: Patients with chronic pharyngitis had inadequate knowledge, positive attitudes and suboptimal practices toward LPR. Education, family history of chronic pharyngitis, experienced with reflux symptoms might have effect on their KAP. [ABSTRACT FROM AUTHOR]

Endoscopic retrograde cholangiopancreatography (ERCP) is considered the preferred method for managing biliary obstructions. However, the prevalence of surgically modified anatomies often poses challenges, making the standard side-viewing duodenoscope unable to reach the papilla in most cases. The increasing instances of surgically altered anatomies (SAAs) result from higher rates of bariatric procedures and surgical interventions for pancreatic malignancies. Conventional ERCP with a side-viewing endoscope remains effective when there is continuity between the stomach and duodenum. Nonetheless, percutaneous transhepatic biliary drainage (PTBD) or surgery has historically been used as an alternative for biliary drainage in malignant or benign conditions. The evolving landscape has seen various endoscopic approaches tailored to anatomical variations. Innovative methodologies such as cap-assisted forward-viewing endoscopy and enteroscopy have enabled the performance of ERCP. Despite their utilization, procedural complexities, prolonged durations, and accessibility challenges have emerged. As a result, there is a growing interest in novel enteroscopy and endoscopic ultrasound (EUS) techniques to ensure the overall success of endoscopic biliary drainage. Notably, EUS has revolutionized this domain, particularly through several techniques detailed in the review. The rendezvous approach has been pivotal in this field. The antegrade approach, involving biliary tree puncturing, allows for the validation and treatment of strictures in an antegrade fashion. The EUS-transmural approach involves connecting a tract of the biliary system with the GI tract lumen. Moreover, the EUS-directed transgastric ERCP (EDGE) procedure, combining EUS and ERCP, presents a promising solution after gastric bypass. These advancements hold promise for expanding the horizons of comprehensive and successful biliary drainage interventions, laying the groundwork for further advancements in endoscopic procedures. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) motility disorders comprise a wide range of different diseases affecting the structural or functional integrity of the GI neuromusculature. Their clinical presentation and burden of disease depends on the predominant location and extent of gut involvement as well as the component of the gut neuromusculature affected. A comprehensive literature review was conducted using the PubMed and Medline databases to identify articles related to GI motility and functional disorders, published between 2016 and 2023. In this article, we highlight the current knowledge of molecular and genetic mechanisms underlying GI dysmotility, including disorders of gut–brain interaction, which involve both GI motor and sensory disturbance. Although the pathophysiology and molecular mechanisms underlying many such disorders remain unclear, recent advances in the assessment of intestinal tissue samples, genetic testing with the application of 'omics' technologies and the use of animal models will provide better insights into disease pathogenesis as well as opportunities to improve therapy. [ABSTRACT FROM AUTHOR]

Achalasia is a rare esophageal motility disorder characterized by abnormal esophageal peristalsis and the inability of the lower esophageal sphincter to relax, resulting in poor esophageal emptying. This can be relieved by endoscopic and surgical treatments; each comes with certain advantages and disadvantages. This review aims to guide the clinician in clinical decision making on the different treatment options for achalasia regarding the efficacy, safety, and important predictors. Botulinum toxin injection is only recommended for a selective group of achalasia patients because of the short term effect. Pneumatic dilation improves achalasia symptoms, but this effect diminishes over time and requiring repeated dilations to maintain clinical effect. Heller myotomy combined with fundoplication and peroral endoscopic myotomy are highly effective on the long term but are more invasive than dilations. Gastro-esophageal reflux complaints are more often encountered after peroral endoscopic myotomy. Patient factors such as age, comorbidities, and type of achalasia must be taken into account when choosing a treatment. The preference of the patient is also of great importance and therefore shared decision making has to play a fundamental role in deciding about treatment. [ABSTRACT FROM AUTHOR]

Proton pump inhibitor (PPI) treatment is responsible for substantial gastrin elevation secondary to reduced intragastric acidity. Due to the increasing global prevalence of PPI users, concerns have been raised about the clinical significance of continuous gastrin elevation and its potential long-term side effects. Hypergastrinemia secondary to PPIs has trophic effects on gastric mucosa, leading to enterochromaffin-like cell hyperplasia and gastric (fundic) polyp formation, and it is believed to provoke acid rebound following PPI withdrawal that induces PPI overutilization. Previous studies have found higher gastrin release following PPI therapy in females compared with males, and sex differences have also been demonstrated in pharmacokinetic parameters and dose requirements for acid reflux. It is conceivable that females might be at increased risk of PPI overuse, because they often receive higher milligram-per-kilogram doses. The prevalence of PPI use is more common among females, and the female sex is a risk factor for adverse drug reactions. This non-systematic review outlines the current knowledge of the impact of biological sex on the response to PPIs. The aim is to highlight the female sex as a potential risk factor that could be a step toward precision medicine and should be considered in future research on the response to PPI treatment. [ABSTRACT FROM AUTHOR]

Once considered a rare disease, eosinophilic oesophagitis (EoE) is becoming increasingly prevalent, yet many healthcare professionals (HCPs) remain unfamiliar with the underlying pathophysiology and optimal management approaches. For this study, we developed a faculty-led, online, continuing medical education activity on EoE. The effectiveness of this activity was evaluated according to Moore's framework, with changes in knowledge and competence (Moore's Levels 3 and 4) assessed for a cohort of gastroenterologists, dietitians, allergists and immunologists (N = 300), using questionnaires completed before and after participation. Changes in HCP confidence in treating EoE were also reported and remaining educational gaps were identified. The activity was viewed by a global audience of 5,330 participants within 6 months, and significant improvements in knowledge and competence were reported following participation in the activity across all specialities, regions and experience (mean [standard deviation] score pre- versus post-activity: 4.32 [1.38] versus 5.46 [0.82]; p < 0.001). Confidence in treating EoE also increased from pre- to post-activity, with the proportion of participants reporting that they felt moderately or extremely confident increasing from 53% to 82%. Several educational unmet needs were identified, which can be used to inform the design of future educational activities in EoE [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an immune-mediated disease that manifests with dysphagia and is characterized by the predominantly eosinophilic infiltration of the esophageal mucosa. Several instruments have been developed to assess the symptoms of EoE: the Daily Symptom Questionnaire (DSQ), EoE Activity Index (EEsAI), Pediatric EoE Symptom Severity (PEESSv2), etc. The use of the EREFS is a gold standard for endoscopic diagnosis. The EoE histologic scoring system (EoEHSS) was elaborated for the assessment of histological features in EoE. However, the remission criteria are not clearly defined and vary greatly in different studies. Gastroenterologists establish the severity of EoE mainly based on endoscopic findings. At the same time, EoE requires a multidisciplinary approach. The recently developed Index of Severity of Eosinophilic Esophagitis (I-SEE) that is built on symptoms, endoscopic findings, and histological features is promising. [ABSTRACT FROM AUTHOR]

The relationship between food and the pathophysiological mechanisms of gastroesophageal reflux disease (GERD) is unclear. There are few data on the impact of dietary habits on GERD symptoms and on the incidence of GERD in subjects undergoing plant-based diets. In this study, we investigated the association between diet and GERD, using data collected through an online survey of the Italian general population. In total, 1077 subjects participated in the study. GERD was defined according to the Montreal Consensus. For all subjects age, gender, body mass index (BMI), marital status, education, occupation, alcohol consumption, and smoking habits were recorded. All participants also completed the SF-36 questionnaire on Quality of Life. A total of 402 subjects (37.3%) were vegans and 675 (62.7%) non-vegans. The prevalence of GERD in the total population was 9%. Subjects with GERD-related symptoms recorded a worse quality of life according to SF-36 analysis (p < 0.05 for all dimensions). In multivariate analysis, after adjusting for confounders, participants undergoing a vegan diet had a significantly lower risk of GERD (OR = 0.47, 95% CI 0.28–0.81, p = 0.006). These findings should be taken into account to inform the lifestyle management of GERD. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancers are characterized by high incidence and mortality. However, there are well-established methods of screening. The endoscopy exam provides the macroscopical image and enables harvesting the tissue samples for further histopathological diagnosis. The efficiency of endoscopies relies not only on proper patient preparation, but also on the skills of the personnel conducting the exam. In recent years, a number of reports concerning the application of artificial intelligence (AI) in medicine have arisen. Numerous studies aimed to assess the utility of deep learning/ neural network systems supporting endoscopies. In this review, we summarized the most recent reports and randomized clinical trials regarding the application of AI in screening and surveillance of gastrointestinal cancers among patients suffering from esophageal, gastric, and colorectal cancer, along with the advantages, limitations, and controversies of those novel solutions. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease of unknown etiology. Researchers have recently drawn attention to the possible role of viruses in the development of IBS and provided evidence in this regard. In this study, it was decided to investigate the possible role of rotavirus infection in the onset of IBS. Methods: Stool and serum samples were collected from 40 patients with IBS and 40 healthy individuals. To evaluate the previous exposure to rotavirus we checked the presence and concentration of anti-rotavirus IgG by ELISA. ELISA test was performed on the serum samples. A real-time polymerase chain reaction (PCR) test was also used to measure the viral load in the stool. Finally, the data were analyzed by SPSS version 22 software. Results: No significant relationship was found between anti-rotavirus IgG presence and its level in the serum of case and healthy individuals (P value>0.05). Moreover, there was no significant difference between the viral genome load in the stool samples of the two groups (P value>0.05). Conclusion: According to the results, it seems unlikely that a link exists between rotavirus infection and the onset of IBS, but the possible role of other gastrointestinal viruses, including coronavirus, remains. [ABSTRACT FROM AUTHOR]

Simple Summary: There has been an exponential rise in the availability of artificial intelligence systems in endoscopy in recent years. As a result, maintaining an informed understanding of the utility and efficacy of existing systems has become increasingly complex. This review aims to summarise the expanse of research in this area to guide proceduralists in making informed decisions regarding the use of artificial intelligence in colonoscopy. It focuses primarily on the application of artificial intelligence for the detection and characterisation of colorectal polyps in order to improve the efficacy of colorectal cancer screening and prevention. Colorectal cancer remains a leading cause of cancer-related morbidity and mortality worldwide, despite the widespread uptake of population surveillance strategies. This is in part due to the persistent development of 'interval colorectal cancers', where patients develop colorectal cancer despite appropriate surveillance intervals, implying pre-malignant polyps were not resected at a prior colonoscopy. Multiple techniques have been developed to improve the sensitivity and accuracy of lesion detection and characterisation in an effort to improve the efficacy of colorectal cancer screening, thereby reducing the incidence of interval colorectal cancers. This article presents a comprehensive review of the transformative role of artificial intelligence (AI), which has recently emerged as one such solution for improving the quality of screening and surveillance colonoscopy. Firstly, AI-driven algorithms demonstrate remarkable potential in addressing the challenge of overlooked polyps, particularly polyp subtypes infamous for escaping human detection because of their inconspicuous appearance. Secondly, AI empowers gastroenterologists without exhaustive training in advanced mucosal imaging to characterise polyps with accuracy similar to that of expert interventionalists, reducing the dependence on pathologic evaluation and guiding appropriate resection techniques or referrals for more complex resections. AI in colonoscopy holds the potential to advance the detection and characterisation of polyps, addressing current limitations and improving patient outcomes. The integration of AI technologies into routine colonoscopy represents a promising step towards more effective colorectal cancer screening and prevention. [ABSTRACT FROM AUTHOR]

Introduction: Advanced endoscopic therapy techniques have been developed and have created alternative treatment options to surgical therapy for several gastrointestinal diseases. This work will focus on new endoscopic tools for special indications of advanced endoscopic resections (ER), especially endoscopic submucosal dissection (ESD), which were developed in our institution. This paper aims to analyze these specialized instruments and identify their status. Methods: Initially, the technical process of ESD was analyzed, and the following limitations of the different endoscopic steps and the necessary manipulations were determined: the problem of traction–countertraction, the grasping force needed to pull on tissue, the instrument tip maneuverability, the limited angulation/triangulation, and the mobility of the scope and instruments. Five instruments developed by our team were used: the Endo-dissector, additional working channel system, external independent next-to-the-scope grasper, 3D overtube working station, and over-the-scope grasper. The instruments were used and applied according to their special functions in dry lab, experimental in vivo, and clinical conditions by the members of our team. Results: The Endo-dissector has a two-fold function: (1) grasping submucosal tissue with enough precision and strength to pull it off the surrounding mucosa and muscle, avoiding damage during energy application and (2) effectively dividing tissue using monopolar energy. The AWC system quickly fulfills the lack of a second working channel as needed to complete the endoscopic task on demand. The EINTS grasper can deliver a serious grasping force, which may be necessary for a traction–countertraction situation during endoscopic resection for lifting a larger specimen. The 3D overtube multifunctional platform provides surgical-like work with bimanual-operated instruments at the tip of the scope, which allows for a coordinated approach during lesion treatment. The OTSG is a grasping tool with very special features for cleaning cavities with debris. Conclusions: The research and development of instruments with special features can solve unmet needs in advanced endoscopic procedures. The latter may help to increase indications for the endoscopic resections of gut lesions in the future. [ABSTRACT FROM AUTHOR]

Our review delves into the realm of peroral endoscopic myotomies (POEMs) in the upper gastrointestinal tract (UGT). In recent years, POEMs have brought about a revolution in the treatment of UGT motility disorders. Esophageal POEM, the first to be introduced, has now been validated as the primary treatment for achalasia. Subsequently developed, G-POEM displays promising results in addressing refractory gastroparesis. Over time, multiple endoscopic myotomy techniques have emerged for the treatment of Zenker's diverticulum, including Z-POEM, POES, and hybrid approaches. Despite the well-established efficacy outcomes, new challenges arise in the realm of POEMs in the UGT. For esophageal POEM, the future scenario lies in customizing the myotomy extent to the minimum necessary, while for G-POEM, it involves identifying patients who can optimally benefit from the treatment. For ZD, it is crucial to validate an algorithm that considers various myotomy options according to the diverticulum's size and in relation to individual patients. These challenges align with the concept of precision endoscopy, personalizing the technique for each subject. Within our text, we comprehensively examine each myotomy technique, analyzing indications, outcomes, and adverse events. Additionally, we explore the emerging challenges posed by myotomies within the context of the evolving field of precision endoscopy. [ABSTRACT FROM AUTHOR]

Background: Pneumatic dilation (PD) is an effective first line treatment option for many patients with achalasia. PD use may be limited in adults with achalasia who are older than 65 because of concern for adverse events (AE), and less efficacious therapies are often utilized. We explored the periprocedural safety profile of PD in older adults. Methods: An international real world cross-sectional study of patients undergoing PD between 2006–2020 in two tertiary centers. Thirty-day AEs were compared between older adults (65 and older) with achalasia and younger patients. Results: A total of 252 patients underwent 319 PDs. In 319 PDs, 18 (5.7%) complications occurred: 6 (1.9%) perforations and 12 (3.8%) emergency department referrals with benign (non-perforation) chest pain, of which 9 (2.8%) were hospitalized. No bleeding or death occurred within 30 days. Perforation rates were similar in both age groups and across achalasia subtypes. Advanced age was protective of benign chest pain complications in univariate analysis, and the limited number of AEs precluded multivariable analysis. Conclusions: The safety of PD in older adults is at least comparable to that of younger patients and should be offered as an option for definitive therapy for older patients with achalasia. Our results may affect informed consent discussions. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by eosinophilic infiltration of the esophagus. It arises from a complex interplay of genetic predisposition (susceptibility loci), environmental triggers (allergens and dietary antigens), and a dysregulated immune response, mainly mediated by type 2 T helper cell (Th2)-released cytokines, such as interleukin (IL)-4, IL-5, and IL-13. These cytokines control eosinophil recruitment and activation as well as tissue remodeling, contributing to the characteristic features of EoE. The pathogenesis of EoE includes epithelial barrier dysfunction, mast cell activation, eosinophil degranulation, and fibrosis. Epithelial barrier dysfunction allows allergen penetration and promotes immune cell infiltration, thereby perpetuating the inflammatory response. Mast cells release proinflammatory mediators and promote eosinophil recruitment and the release of cytotoxic proteins and cytokines, causing tissue damage and remodeling. Prolonged inflammation can lead to fibrosis, resulting in long-term complications such as strictures and dysmotility. Current treatment options for EoE are limited and mainly focus on dietary changes, proton-pump inhibitors, and topical corticosteroids. Novel therapies targeting key inflammatory pathways, such as monoclonal antibodies against IL-4, IL-5, and IL-13, are emerging in clinical trials. A deeper understanding of the complex pathogenetic mechanisms behind EoE will contribute to the development of more effective and personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: To achieve early detection and curative treatment options, surveillance imaging for hepatocellular carcinoma (HCC) must remain of quality and without substantial limitations in liver visualization. However, the prevalence of limited liver visualization during HCC surveillance imaging has not been systematically assessed. Utilizing a systematic review and meta-analytic approach, we aimed to determine the prevalence of limited liver visualization during HCC surveillance imaging. Methods: MEDLINE and Embase electronic databases were searched to identify published data on liver visualization limitations of HCC surveillance imaging. An analysis of proportions was pooled using a generalized linear mixed model with Clopper-Pearson intervals. Risk factors were analysed using a generalized mixed model with a logit link and inverse variance weightage. Results: Of 683 records, 10 studies (7,131 patients) met inclusion criteria. Seven studies provided data on liver visualization limitations on ultrasound (US) surveillance exams: prevalence of limited liver visualization was 48.9% (95% CI: 23.5–74.9%) in the overall analysis and 59.2% (95% CI: 24.2–86.9%) in a sensitivity analysis for cirrhotic patients. Meta-regression determined that non-alcoholic fatty liver disease was associated with limited liver visualization on US. Four studies provided data for liver visualization limitations in abbreviated magnetic resonance imaging (aMRI), with inadequate visualization ranging from 5.8% to 19.0%. One study provided data for complete MRI and none for computed tomography. Conclusion: A substantial proportion of US exams performed for HCC surveillance provide limited liver visualization, especially in cirrhosis, which may hinder detection of small observations. Alternative surveillance strategies including aMRI may be appropriate for patients with limited US visualization. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the peculiarities of trait anxiety and heart rate variability parameters as well as their relationship depending on the catechol O-methyltransferase (COMT) gene Val158Met polymorphism in children with irritable bowel syndrome. Materials and methods. A total of 26 children aged 6-12 years with a verified diagnosis of irritable bowel syndrome according to the Rome IV criteria were examined. Beforehand, all the patients underwent molecular genetic testing for the COMT Val158met single nucleotide polymorphism by using the polymerase chain reaction-restriction fragment length polymorphism method. Heart rate variability was analyzed via cardiointervalography (Neurosoft) based on short five-minute resting-state ECG recordings. The CMAS (Children's Manifest Anxiety Scale) test was used to measure trait anxiety levels. The Pearson's test was used to assess correlations between heart rate variability parameters and anxiety levels. Data were processed using Microsoft Excel 2016 and analyzed with GraphPad (Prism 5.0). Results. Depending on the functional COMT Val158met polymorphism, all the patients were allocated to 3 groups: 8 children with 472 GA (Val/Met) COMT genotype; 10 children with 472 AA (Met/Met) genotype; 8 children with 472 GG (Val/Val) genotype. Time and frequency domain parameters of heart rate variability were significantly different in each group. The highest level of anxiety and the largest percentage of LF component (mainly sympathetic activity) in the structure of heart rate variability was noted among Met/Met carriers. Val/Val carriers had a significantly lower anxiety level and an autonomic imbalance with a higher percentage of HF component (parasympathetic activity). Positive correlations between trait anxiety and heart rate variability parameters were found only in Val/Val and Val/Met groups. Conclusions. Our study has revealed the influence of the COMT Val158met polymorphism on the level of trait anxiety and heart rate variability parameters. It is important for a better understanding of the gut-brain axis dysregulation and impaired stress resilience in children with irritable bowel syndrome. Also, these data could be used to improve current schemes for the treatment of irritable bowel syndrome, supplementing them with activation therapy, psychotherapy, psychopharmacotherapy. [ABSTRACT FROM AUTHOR]

Background/Aims: Conflicting results have been reported regarding the interaction between proton pump inhibitors (PPIs) and clopidogrel. We investigated whether concomitant PPI use influenced the risk of recurrence in patients with stroke and myocardial infarction (MI). Methods: This study used two databases for two different designs, the Korean National Health Insurance Service (NHIS) database for a self-controlled case series design, and the national sample cohort of the NHIS data base converted to the Observational Medical Outcomes Partnership-Common Data Model version for a cohort study based on large-scale propensity score matching. Results: In the PPI co-prescription group, recurrent hospitalization with stroke occurred in 17.6% of the 8201 patients with history of stroke, and recurrent MI occurred in 17.1% of the 1216 patients with history of MI within1 year. According to the self-controlled case series, the overall relative risk (RR) of recurrent stroke was 2.09 (95% confidence interval (CI); 1.83–2.38); the RR showed an increasing trend parallel to the time from the beginning of PPI co-prescription. In the cohort study, there was a higher incidence of recurrent stroke in the PPI co-prescription group (Hazard ratio (HR): 1.34, 95% CI: 1.01–1.76, p = 0.04). The overall RR of recurrent MI was 1.47 (95% CI; 1.02–2.11) in the self-controlled case series; however, there was no statistically significant difference in recurrent MI in the cohort study (HR:1.42, 95% CI:0.79–2.49, p = 0.23). The impact of individual PPIs on stroke and MI showed different patterns. Conclusions: A PPI co-prescription >4 weeks with clopidogrel was associated with hospitalization of recurrent stroke within 1 year of initial diagnosis; however, its association with recurrent MI remains inconclusive. The influence of individual PPIs should be clarified in the future. [ABSTRACT FROM AUTHOR]

Background: Endoscopic resection (ER) is widely applied to treat early colorectal cancer (CRC). Predicting the invasion depth of early CRC is critical in determining treatment strategies. The use of computer-aided diagnosis (CAD) algorithms could theoretically make accurate and objective predictions regarding the suitability of lesions for ER indication based on invasion depth. This study aimed to assess diagnostic test accuracy of CAD algorithms in predicting the invasion depth of early CRC and to compare the performance between the CAD algorithms and endoscopists. Methods: Multiple databases were searched until June 30, 2022 for studies that evaluated the diagnostic performance of CAD algorithms for invasion depth of CRC. Meta-analysis of diagnostic test accuracy using a bivariate mixed-effects model was performed. Results: Ten studies consisting of 13 arms (13,918 images from 1472 lesions) were included. Due to significant heterogeneity, studies were stratified into Japan/Korea-based or China-based studies. For the former, the area under the curve (AUC), sensitivity, and specificity of the CAD algorithms were 0.89 (95% CI 0.86–0.91), 62% (95% CI 50–72%), and 96% (95% CI 93–98%), respectively. For the latter, AUC, sensitivity, and specificity were 0.94 (95% CI 0.92–0.96), 88% (95% CI 78–94%), and 88% (95% CI 80–93%), respectively. The performance of the CAD algorithms in Japan/Korea-based studies was not significantly different from that of all endoscopists (0.88 vs. 0.91, P = 0.10) but was inferior to that of expert endoscopists (0.88 vs. 0.92, P = 0.03). The performance of the CAD algorithms in China-based studies was better than that of all endoscopists (0.94 vs. 0.90, P = 0.01). Conclusion: The CAD algorithms showed comparable accuracy for prediction of invasion depth of early CRC compared to all endoscopists, which was still lower than expert endoscopists in diagnostic accuracy; more improvements should be achieved before it can be extensively applied to clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To study the outcomes and complications of per-oral endoscopic myotomy (POEM) in patients with esophageal achalasia. Materials and Methods: This retrospective observational study reviewed the medical records of esophageal achalasia patients who underwent POEM between March 2013 and September 2022. One hundred and eight cases were included. Results: A total of 108 consecutive patients were included in this study and classified into 4 groups: 30 (27.8%) as type I; 53 (49.1%) as type II; 5 (4.6%) as type III; and 20 (18.5%) as unspecified due to unsuccessful catheter placement across the esophagogastric junction. The mean patient age was 46.10±16.59, 77 (71.3%) patients were female. Ten (9.3%) of the patients had undergone prior treatment, including balloon dilation, POEM, Heller myotomy, and nitroglycerine. Technical success was achieved in 106 (98.1%) cases, clinical success was evaluated only in 88 patients who follow up more than 6 month and the median follow-up time was 20.50 months (range 6-110 months). The clinical success was accomplished in 82 (93.2%), and 26 (24.1%) patients experienced perioperative complications which were significantly associated with anterior myotomy and probably operator learning curve. One patient (1.1%) had recurrent symptoms at 24-month follow up. Gastroesophageal reflux disease (GERD) was found in 19 (21.6%) patients, all of whom responded well to proton pump inhibitors (PPIs). Conclusion: POEM is effective and safe in long-term treatment of achalasia. Although the incidence of symptomatic GERD was slightly high, the cases were not severe and were well controlled with medication. [ABSTRACT FROM AUTHOR]

Purpose of review: In decades prior, eosinophilic esophagitis was considered a rare diagnosis. For reasons that cannot be fully explained by an increase in disease recognition alone, eosinophilic esophagitis is rising in incidence and prevalence. This article will highlight the most up-to date literature for emerging medical therapy for this disease. Recent findings: It is estimated that nearly one-third of patients with eosinophilic esophagitis will not respond to traditional pharmacologic therapies which include proton-pump inhibitors and swallowed topical corticosteroids. The need for more effective therapy has led to an explosion of research for targeted biologic therapies, and there are several promising molecules in the pipeline. Summary: A number of Phase II and III clinical trials are underway and show propitious results for treatment in eosinophilic esophagitis. In 2022, the Food and Drug Administration approved the first treatment for eosinophilic esophagitis, dupilumab. This approval satisfies an unmet need for a growing number of patients with eosinophilic esophagitis. It is likely that in the future, there will be multiple therapeutic options for the management of eosinophilic esophagitis. [ABSTRACT FROM AUTHOR]

Background. Proton pump inhibitors (PPIs) are currently the reference drugs for gastroesophageal reflux disease (GERD), but symptoms often recur after their withdrawal. Moreover, whether prokinetics or barrier drugs used alongside PPIs are more effective remains under debate. Objectives. The aim of the study was to assess the efficacy of different therapeutic approaches to GERD treatment. Materials and methods. We enrolled 211 grade A reflux esophagitis patients who consented to participate in this non-randomized, open-label trial. The study consisted of 6 sequentially administered medical treatments for GERD, lasting 2 months, with a 3-week washout period between each drug schedule: Group A: PPI (esomeprazole 40 mg/day before breakfast); Group B: mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, 3 times daily after a meal); Group C: prokinetics (levosulpiride 25 mg or domperidone 10 mg, 3 times daily before a meal); Group D: barrier drug (alginate 3 times daily after a meal); Group E: PPI (esomeprazole 40 mg/day before breakfast) and mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, before sleep); Group F: PPI (esomeprazole 40 mg/day before breakfast) and prokinetics (levosulpiride 25 mg or domperidone 10 mg before lunch and dinner). Symptoms were evaluated using the visual analogue scale (VAS) and global symptomatic score (GSS), as follows: heartburn: 0-3; retrosternal chest pain: 0-3; regurgitation: 0-3. Results. All but 2 treatments (groups C and D) significantly improved VAS and GSS, with group E showing the most significant GSS improvement. Group C had the highest number of dropouts due to treatment failure and reported more side effects. Conclusions. Using PPIs and mucosal protective drugs resulted in significant symptom alleviation. However, the administration of prokinetics caused higher dropouts due to treatment failure. [ABSTRACT FROM AUTHOR]

Despite the advances made in treatment, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal, even in the locoregional and locally advanced stages, with high relapse rates after surgery. PDAC exhibits a chemoresistant and immunosuppressive phenotype, and the tumor microenvironment (TME) surrounding cancer cells actively participates in creating a stromal barrier to chemotherapy and an immunosuppressive environment. Recently, there has been an increasing use of interventional radiology techniques for the treatment of PDAC, although they do not represent a standard of care and are not included in clinical guidelines. Local approaches such as radiation therapy, hyperthermia, microwave or radiofrequency ablation, irreversible electroporation and high-intensity focused ultrasound exert their action on the tumor tissue, altering the composition and structure of TME and potentially enhancing the action of chemotherapy. Moreover, their action can increase antigen release and presentation with T-cell activation and reduction tumor-induced immune suppression. This review summarizes the current evidence on locoregional therapies in PDAC and their effect on remodeling TME to make it more susceptible to the action of antitumor agents. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an antigen-mediated chronic inflammatory disease of the esophagus, the prevalence of which has steadily increased in recent years. The pathogenesis of EoE is not yet well-defined; however, recent studies have demonstrated that the esophageal microbiota is an essential regulator of physiological and pathological processes of EoE. Currently, research on EoE and microbiota is an emerging field of study that is receiving increasing attention. Here, we review existing EoE-related esophageal microbiota studies to explore the potential mechanisms underlying esophageal microbiota-mediated EoE. The esophageal microbiome is altered in patients with EoE. Although α diversity is usually not significantly different, an increase in Haemophilus and a decrease in Firmicutes were observed in EoE patients. The role of microbiota in initiating and perpetuating inflammation is not fully understood. Current evidence suggests that the penetration of microbiota leads to the activation of epithelial cells as well as innate and adaptive immune cells, with the subsequent release of cytokines, leading to immune responses and inflammation. The involvement of toll-like receptors in EoE also supports the potential role of the microbiota in the progression of this disease. While EoEinduced inflammation can also lead to alterations in the local microbiome. Moreover, dietary modifications, proton pump inhibitors, and corticosteroids can modulate the esophageal microbiota; however, definitive conclusions about the alterations of microbes after treatment cannot be drawn. These findings provide promising avenues for future studies. [ABSTRACT FROM AUTHOR]

The expression of miR-223-3p, miR-17-5p, and miR-24-3p was evaluated in hepatitis C virus (HCV) patient serum samples, collected before DAA treatment and after a sustained virological response (SVR). Fifty HCV patients were stratified based on their liver damage stages into three different subgroups (21 with chronic hepatitis—CH, 15 with cirrhosis, and 14 with hepatocellular carcinoma—HCC). Considering the entire HCV population, the miRNA expression levels were significantly downregulated after the SVR compared to pre-treatment ones (p < 0.05). Stratifying the patients based on liver damage, the post-SVR values of the three miRNAs were significantly downregulated compared to the pre-treatment levels for both cirrhosis and HCC patients. No significant differences emerged from the analysis of the CH group. To our knowledge, this is the first study to detail the behavior of miR-223-3p, miR-17-5p, and miR-24-3p levels in patients with HCV-related CH, cirrhosis, and HCC after DAA therapy. Our findings show that HCV-infected patients have different miRNA profiles before and after treatment with DAAs, strongly suggesting that miRNAs may be involved in the pathogenesis of HCV-related damage. In this respect, the correlation observed among the three studied miRNAs could imply that they share common pathways by which they contribute the progression of HCV-induced chronic liver damage. [ABSTRACT FROM AUTHOR]

Artificial-intelligence-based computer-aided diagnosis (CAD) systems have developed remarkably in recent years. These systems can help increase the adenoma detection rate (ADR), an important quality indicator in colonoscopies. While there have been many still-image-based studies on the usefulness of CAD, few have reported on its usefulness using actual clinical videos. However, no studies have compared the CAD group and control groups using the exact same case videos. This study aimed to determine whether CAD or endoscopists were superior in identifying colorectal neoplastic lesions in videos. In this study, we examined 34 lesions from 21 cases. CAD performed better than four of the six endoscopists (three experts and three beginners), including all the beginners. The time to lesion detection with beginners and experts was 2.147 ± 1.118 s and 1.394 ± 0.805 s, respectively, with significant differences between beginners and experts (p < 0.001) and between beginners and CAD (both p < 0.001). The time to lesion detection was significantly shorter for experts and CAD than for beginners. No significant difference was found between experts and CAD (p = 1.000). CAD could be useful as a diagnostic support tool for beginners to bridge the experience gap with experts. [ABSTRACT FROM AUTHOR]

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

Stroke, a neurological disorder, is intricately linked to the gut microbiota, influencing microbial composition and elevating the risk of ischemic stroke. The neuroprotective impact of short-chain fatty acids (SCFAs) derived from dietary fiber fermentation contrasts with the neuroinflammatory effects of lipopolysaccharide (LPS) from gut bacteria. The pivotal role of the gut-brain axis, facilitating bidirectional communication between the gut and the brain, is crucial in maintaining gastrointestinal equilibrium and influencing cognitive functions. An in-depth understanding of the interplay among the gut microbiota, immune system, and neurological outcomes in stroke is imperative for devising innovative preventive and therapeutic approaches. Strategies such as dietary adjustments, probiotics, prebiotics, antibiotics, or fecal transplantation offer promise in modulating stroke outcomes. Nevertheless, comprehensive research is essential to unravel the precise mechanisms governing the gut microbiota's involvement in stroke and to establish effective therapeutic interventions. The initiation of large-scale clinical trials is warranted to assess the safety and efficacy of interventions targeting the gut microbiota in stroke management. Tailored strategies that reinstate eubiosis and foster a healthy gut microbiota hold potential for both stroke prevention and treatment. This review underscores the gut microbiota as a promising therapeutic target in stroke and underscores the need for continued research to delineate its precise role and develop microbiome-based interventions effectively., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Peroral endoscopic myotomy (POEM) is an effective and safe treatment for achalasia, but often leads to posttreatment gastroesophageal reflux disease. The aim of this study was to examine the incidence and severity of reflux esophagitis after POEM and to identify associated predictive factors., Methods: Patients who underwent POEM between August 2011 and December 2022 were included. Multivariate logistic regression was used to assess predictive factors for reflux esophagitis after POEM., Key Results: In total, 252 patients were included; of which, 46% were female and age ranged between 18 and 87 years. Reflux esophagitis within 1 year after POEM was observed in 131 patients (52%), which was severe in 29 patients (LA grade C/D, 12%). Length of full-thickness myotomy (cm; OR 1.11, 95% CI 1.02-1.21), Eckardt scores before POEM (OR 0.84, 95% CI 0.74-0.96), previous pneumatic dilation (OR 0.51, 95% CI 0.29-0.91), and previous laparoscopic Heller myotomy (LHM; OR 0.44, 95% CI 0.23-0.86) were associated with reflux esophagitis after POEM. Alcohol use (none vs > 7 units per week; OR 3.51, 95% CI 1.35-9.11) and overweight (BMI ≥25 kg/m 2 ; OR 2.67, 95% CI 1.17-6.09) were positive predictive factors and previous LHM (OR 0.13, 95% CI 0.02-0.95) was a negative predictive factor for severe reflux esophagitis after POEM (LA grade C/D)., Conclusion: About half of the patients develop reflux esophagitis after POEM and 12% is graded as severe. Recognizing predictive factors of reflux esophagitis after POEM treatment leads to better patient selection before POEM and provides an opportunity to take preventive measures or start preemptive treatment., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Many women grow up dreaming of becoming doctors, preferring specialties that allow more focus on time outside the hospital and on family life. Nowadays, specialties, like gastroenterology, have still a significant gender gap., Methods: Based on this known discrepancy, a web-based questionnaire was designed by the Young Component of the Scientific Committee of the Federation of Italian Scientific Societies of Digestive Diseases 2023 (FISMAD) to examine the current situation of female gastroenterologists in Italy. The survey, designed specifically for this study, was sent by email to all female gastroenterologists and residents gastroenterologists, members of the three major Italian societies of Gastroenterology., Results: A total of 423 female physicians responded to the survey: 325 (76.8%) had full-time employment, and only a few had an academic career (7.2%). The main occupations were outpatient clinics (n = 288, 68%) and diagnostic endoscopy (n = 289, 68.3%); only 175 (41.3%) performed interventional endoscopy. One hundred and forty-seven (34.7%) had the chance to attend a master in advanced or interventional endoscopy, while 133 (31.4%) faced disadvantages that enabled them to attend. Of the 244 (58%) who reported feeling underappreciated, 194 (79.5%) said it was due to gender bias. We found that women doctors considered themselves disadvantaged compared with men doctors due to career opportunities (n = 338), salary negotiations (n = 64), and training opportunities (n = 144)., Conclusions: In conclusion, gastroenterology still has a long way to go before approaching greater gender parity., (© 2024. The Author(s).)

Irritable bowel syndrome (IBS), one of the most prevalent functional gastrointestinal disorders, is characterized by recurrent abdominal pain and abnormal defecation habits, resulting in a severe healthcare burden worldwide. The pathophysiological mechanisms of IBS are multi-factorially involved, including food antigens, visceral hypersensitivity reactions, and the brain-gut axis. Numerous studies have found that gut microbiota and intestinal mucosal immunity play an important role in the development of IBS in crosstalk with multiple mechanisms. Therefore, based on existing evidence, this paper elaborates that the damage and activation of intestinal mucosal immunity and the disturbance of gut microbiota are closely related to the progression of IBS. Combined with the application prospect, it also provides references for further in-depth exploration and clinical practice., (© 2024 John Wiley & Sons Ltd.)

The beneficial effects of probiotics, postbiotics, and paraprobiotics have already been registered in managing ischemic stroke-generated neuroinflammation and gut dysbiosis. Herein, we examined the impact of cell-free supernatant (CFS) obtained from probiotics (Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01) in a rat transient middle cerebral artery occlusion (MCAO) model of focal cerebral injury. Pre-MCAO supplementation of probiotics (2 × 10 9  CFU/mL) for 21 days or CFS (1 mL/rat) for 7 days protect the MCAO-induced somatosensory and motor impairments recorded at 24 h and 72 h after reperfusion in foot-fault, rotarod, adhesive removal, and vibrissae-evoked forelimb placing tests. We also noted the reduced infarct area and neuronal degradation in the right hemisphere of probiotics- and CFS-recipient MCAO-operated animals. Moreover, MCAO-induced altered concentrations of glial-fibrillary acidic protein, NeuN, zonula occludens-1 (ZO-1), TLR4, IL-1β, IL-6, and TNF-α, as well as matrix metalloproteinase-9 (MMP9) were reversed in the treatment groups. Probiotics and CFS treatment ameliorated the elevated levels of IL-6, IL-1β, and MMP9 in the blood plasma of rats. The disrupted microbial phyla, Firmicutes-to-Bacteroides ratio, villi/crypt ratio, and decreased mucin-producing goblet cells, ZO-1, and occludin in the colon of MCAO-operated rats were recovered following probiotics and CFS treatment. NMR characterization of CFS and rat blood plasma revealed the presence of several important bacterial metabolites. These findings suggest that the CFS obtained from Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01 has the propensity to improve MCAO-generated neurological dysfunctions in rats by dampening neuroinflammation and modulating the gut-brain axis modulators., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Benign esophageal strictures are commonly encountered in clinical practice. The principal etiologies of benign esophageal strictures include long term acid reflux, caustic injuries, eosinophilic esophagitis, anastomotic strictures or endoscopic therapy. Dysphagia is most prominently present in esophageal strictures along with a variety of other symptoms which depend on the stricture etiology. Benign esophageal strictures can be categorized into two groups: simple or complex depending on their structure. Most strictures can be treated successfully with endoscopic dilation by bougies or balloons dilators. In some cases, treatment is more challenging, involving a higher risk of the patient developing recurrent or refractory strictures. To improve symptoms in these patients, other endoscopic treatments such as steroid injection, incisional therapy and stent placement should be considered. In this manuscript, we provide a comprehensive review of the main treatment options currently available to manage recurrent benign esophageal strictures.