Evaluation of the effectiveness of mother milk exosomes in the experimental corrosive esophagitis model.

PURPOSE: We aimed to examine the effectiveness of mother milk exosomes in treating corrosive esophageal burns. MATERIALS AND METHODS: 32 rats were separated into four equal groups and weighed individually before the procedure. A corrosive esophageal burn model was created with 12.5% sodium hydroxide by a 3F Fogarty catheter. Group 1 did not apply any process or treatment, Group 2 was burned, and no treatment was performed. Group 3 was burned, and then 0.5 cc/day of mother milk exosome extract was given. Group 4 was not applied any process, and 0.5 cc/day mother milk exosome extract was given. All rats were weighed again and sacrificed. Biopsy samples were sent to the pathology laboratory for histopathological examination (in terms of inflammation, fibrosis, and necrosis).Kindly check and confrm all email ids.The e-mail addresses and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. RESULTS: A significant difference was found in the results of inflammation and fibrosis. There was a meaningful difference in fibrosis between the 2nd and 3rd groups. There was weight gain in groups 1, 3 and 4. Statistical evaluations for each group were significant. CONCLUSION: It was observed that breast milk exosomes may be effective in inflammation and fibrosis formation in treating corrosive esophageal burns. This suggested that breast milk exosomes reduce stricture formation due to esophageal corrosion.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [specify authors given name] Last name [specify authors last name]. Also, kindly confirm the details in the metadata are correct.The names and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. Also we confirm the details in the metadata.

Severe esophagitis induced by antituberculosis drugs: a case report.

Tuberculosis stands as one of humanity's oldest afflictions, intrinsically intertwined with social disparities. This formidable disease spares no age group and remains the prevailing cause of infection-induced mortality worldwide, particularly in developing nations. We present a case of a 56-year-old woman with diabetes who was diagnosed with Pulmonary Tuberculosis. After receiving antituberculosis drugs as part of her treatment, she experienced a range of systemic manifestations and suffered from severe ulcerative esophagitis. This adverse reaction led to uncontrollable gastrointestinal intolerance, tragically resulting in her untimely demise. The incident underscores the potential seriousness of adverse reactions that can arise from tuberculosis treatment medications.

Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial.

INTRODUCTION: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure. METHODS: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed. RESULTS: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm. DISCUSSION: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).

Long-term gastrointestinal adverse effects of doxycycline.

INTRODUCTION: Doxycycline is an antibiotic with known gastrointestinal (GI) adverse effects. Esophagitis is the most pronounced among these effects, and might be associated with a prolonged duration of therapy. The aim of this study is to evaluate the incidence of esophagitis and other GI side effects in adults who received doxycycline for at least a month. METHODOLOGY: This retrospective descriptive study included adults who received oral doxycycline for at least one month between 2016 and 2018. The primary outcome was the frequency of esophagitis. The secondary outcomes were frequency of and discontinuation due to GI adverse effects. RESULTS: A total of 189 subjects were included with a median age of 32 years. The median duration of doxycycline use was 44 days (interquartile range 30-60). Twelve patients (6.3%) reported having GI adverse effects resulting in doxycycline discontinuation in five of them (2.6%), and three patients (1.6%) had esophagitis. The incidence of GI adverse effects was significantly higher in patients who were ≥ 50 years than < 50 years old (8/50 vs. 4/139; p = 0.003) and in those who received a daily dose of 200 mg than 100 mg (12/93 vs. 0/96; p < 0.001). CONCLUSIONS: GI adverse events, including esophagitis, are not rare with long-term use of oral doxycycline, particularly in older age and a higher dose of 200 mg/day. Future large and randomized studies are needed to compare the efficacy and safety of different doxycycline doses.

Tetracycline-, Doxycycline-, Minocycline-Induced Pseudotumor Cerebri and Esophageal Perforation.

Tetracyclines are a class of broad-spectrum bacteriostatic antibiotics used to treat many infections, including methicillin-resistant Staphylococcus aureus (MRSA), acne, pelvic inflammatory disease, chlamydial infections, and a host of zoonotic infections. These drugs work by inhibiting protein synthesis in bacterial ribosomes, specifically by disallowing aminoacyl-tRNA molecules from binding to the ribosomal acceptor sites. While rare, tetracycline antibiotics, particularly minocycline and doxycycline, are associated with an increased risk of developing esophageal perforation and pseudotumor cerebri (PTC, or idiopathic intracranial hypertension). Since tetracyclines are a commonly prescribed class of medications, especially in adolescents for acne treatment, it is important for clinicians to appreciate significant side effects that can result in morbidity and mortality. This paper aims to consolidate and to emphasize current research on the association between tetracycline antibiotics and the development of esophageal perforation, and PTC. PTC is a neurological syndrome consisting of increased intracranial pressure, headache, and vision changes without evidence of the contributing source, such as mass lesion, infection, stroke, or malignancy. Esophageal perforation, while rare, can be the result of pill esophagitis. Pill-induced injuries occur when caustic medicinal pills dissolve in the esophagus rather than in the stomach. Most patients experience only self-limited pain (retrosternal burning discomfort, heartburn, dysphagia, or odynophagia), but hemorrhage, stricture, and perforation may occur. Tetracycline use can lead to pill esophagitis. In summary, clinicians should appreciate the potential risks of tetracycline compounds in clinical practice.

Analysis of the clinical characteristics of dabigatran-induced oesophagitis.

OBJECTIVES: Dabigatran-induced oesophagitis has emerged in recent years. However, the incidence and clinical characteristics of patients with dabigatran-induced oesophagitis have not yet been clarified. The aim of this study was to examine the clinical characteristics of the disease. METHODS: A retrospective analysis was undertaken of the literature on dabigatran-induced oesophagitis in Chinese and English from 2008 onwards. RESULTS: There were 20 men (74.07%) and seven women (25.93%) in the study; their median age was 75 years (range 37-90). The main clinical symptoms were dysphagia (42.31%), odynophagia (26.92%), retrosternal pain (23.08%) and heartburn (23.08%). Endoscopy mainly showed sloughing mucosal casts (14 cases, 56%), ulcers (8 cases, 32%) and erosion (6 cases, 24%). The main injury sites were the mid to lower oesophagus (32%) and the mid oesophagus (32%). Withdrawal of dabigatran or giving the correct medication regimen resulted in rapid recovery of clinical symptoms from 1 day in some patients and up to 4 weeks, and mucosal recovery (2-5 weeks) in a median time of 3 weeks (range 0.29-48) in all patients. CONCLUSIONS: Oesophagitis is a rare complication of dabigatran with a good prognosis. Patients should be given proper medication instructions to prevent the occurrence of dabigatran-induced oesophagitis.

Patient journey in erosive oesophagitis: real-world perspectives from US physicians and patients.

OBJECTIVE: Management of erosive oesophagitis (EE) remains suboptimal, with many patients experiencing incomplete healing, ongoing symptoms, and relapse despite proton pump inhibitor (PPI) treatment. The Study of Acid-Related Disorders investigated patient burden of individuals with EE in a real-world setting. DESIGN: US gastroenterologists (GIs) or family physicians (FPs)/general practitioners (GPs) treating patients with EE completed a physician survey and enrolled up to four patients with EE for a patient survey, with prespecified data extracted from medical records. RESULTS: 102 GIs and 149 FPs/GPs completed the survey; data were available for 73 patients (mean age at diagnosis, 45.4 years). Omeprazole was healthcare professional (HCP)-preferred first-line treatment (60.8% GIs; 56.4% FPs/GPs), and pantoprazole preferred second line (29.4% and 32.9%, respectively). Price and insurance coverage (both 55.5% HCPs) and familiarity (47.9%) key drivers for omeprazole; insurance coverage (52.0%), price (50.0%), familiarity (48.0%), initial symptom relief (46.0%), and safety (44.0%) key drivers for pantoprazole. Only 49.3% patients took medication as instructed all the time; 56.8% independently increased medication frequency some of the time. Despite treatment, 57.5% patients experienced heartburn and 30.1% regurgitation; heartburn was the most bothersome symptom. 58.9% patients believed that their symptoms could be better controlled; only 28.3% HCPs were very satisfied with current treatment options. 83.6% patients wanted long-lasting treatment options. Fast symptom relief for patients was a top priority for 66.1% HCPs, while 56.6% would welcome alternatives to PPIs. CONCLUSION: This real-world multicentre study highlights the need for new, rapidly acting treatments in EE that reduce symptom burden, offer durable healing and provide symptom control.

Two-year risedronate treatment for osteoporosis in patients with esophageal varices: a non-randomized clinical trial.

BACKGROUND: Bisphosphonates are the mainstay of osteoporosis treatment, but their use for patients with esophageal varices has been avoided due to the risk of esophagitis, which may cause variceal bleeding. Since most clinical trials assessing osteoporosis treatment last 2-3 years, this study aimed to evaluate a 2-year risedronate treatment for patients with esophageal varices and liver cirrhosis. METHODS: The study received Institutional Review Board approval, and the sample was divided into two groups according to bone mineral density (BMD). Cirrhosis severity and endoscopic findings at baseline were similar between the groups. The intervention group had 51 patients with osteoporosis, who received oral risedronate 35 mg weekly plus calcium and vitamin D supplements. The control group had 51 patients with osteopenia, receiving only the supplements. Scheduled esophagogastroduodenoscopies and BMD measurements were carried out. RESULTS: The adjusted esophagitis risk was higher in the intervention group; however, none of the subjects had digestive bleeding. Lumbar spine BMD increased in the intervention group (- 3.06 ± 0.71 to - 2.33 ± 0.90; p < 0.001) and in the control group (- 1.38 ± 0.77 to - 1.10 ± 1.05; p = 0.012). Femoral neck BMD did not change in the intervention group (- 1.64 ± 0.91 to - 1.71 ± 0.95; p = 0.220), but tended to decrease in the control group (- 1.00 ± 0.74 to - 1.09 ± 0.82; p = 0.053). CONCLUSION: Oral risedronate was effective and did not cause gastrointestinal bleeding in cirrhotic patients with esophageal varices under endoscopic surveillance.

Systemic antifungal therapy for oesophageal candidiasis - systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Oesophageal candidiasis is a common infection among individuals with immunosuppression, associated with significant morbidity. Available guidelines recommend fluconazole as the preferred treatment; however, data regarding its effectiveness in an era of increased fluconazole resistance has not been systematically compiled. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) addressing systemic antifungal therapy for oesophageal candidiasis was undertaken. The primary outcome was clinical response. Subgroup analysis was planned based on immune status and Candida spp. RESULTS: Twelve RCTs were included, of which six compared fluconazole with other azoles, four compared fluconazole with echinocandins, and two compared amphotericin deoxycholate with echinocandins. Most RCTs mainly included human-immunodeficiency-virus-positive individuals. No significant differences were found between fluconazole and comparators for the outcomes of clinical response or combined clinical and endoscopic response [relative risk (RR) 1.02, 95% confidence interval (CI) 0.97-1.07 and RR 1.06, 95% CI 0.98-1.15, respectively]. No differences were found between fluconazole and other azoles for other outcomes; however, compared with echinocandins, fluconazole had significantly higher mycological response rates and lower early relapse rates (RR 1.09, 95% CI 1.02-1.17 and RR 0.42, 95% CI 0.26-0.68, respectively). No significant differences were demonstrated between fluconazole and comparators for overall or severe adverse events. Information required for the planned subgroup analyses was not available. CONCLUSIONS: No differences in efficacy or safety were found between fluconazole and other azoles for the treatment of candida oesophagitis. The use of echinocandins resulted in lower mycological cure rates and higher relapse rates. Additional RCTs should evaluate these interventions among broader patient populations and a wider spectrum of Candida spp.

A Population Pharmacokinetic Model of Vonoprazan: Evaluating the Effects of Race, Disease Status, and Other Covariates on Exposure.

Vonoprazan, a potassium-competitive acid blocker, is under investigation in the United States and Europe for the treatment of erosive esophagitis and Helicobacter pylori infection. Population pharmacokinetic (popPK) analysis allows the identification of factors that could affect drug exposure in population subgroups. Here, we report a popPK model based on pooled data sets of available pharmacokinetic (PK) studies in healthy volunteers and patients with gastroesophageal reflux disease, including erosive esophagitis, from Asia and Europe. This model was used to evaluate the impact of different covariates, including race and disease status, on vonoprazan exposure. We analyzed PK data from 746 patients and 410 healthy volunteers from 15 clinical trials using a nonlinear mixed-effects approach to develop the popPK model. Model development focused on characterizing and quantifying the effects of clinical covariates of race (Asian vs non-Asian) and disease status (gastroesophageal reflux disease vs healthy volunteers) on vonoprazan exposure. Identified clinical covariates included fed/fasting status, race, sex, disease status, weight, serum creatinine, and age. The impact of variations in these clinical covariates on exposure to vonoprazan was smaller than the effect of halving or doubling the dose. PK parameters were similar in Asian and non-Asian populations. Variations in weight, age, and race are not predicted to have a clinically relevant impact on vonoprazan exposure or safety and require no changes in vonoprazan dosing. The limited impact of race on exposure suggests that efficacy and safety data for vonoprazan in Asian populations are translatable to non-Asian populations.

Clinicopathologic Features, Treatment Response, and Outcomes of Immune Checkpoint Inhibitor-Related Esophagitis.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) have provided practice-changing outcomes in treating many cancers, ICI-related gastrointestinal toxicity can limit their use. Upper gastrointestinal toxicity is not common nor as well described as lower gastrointestinal toxicity. We aimed to characterize the clinical presentation, endoscopic and histologic features, treatment response, and outcomes of ICI-related esophagitis. METHODS: We retrospectively studied patients at The University of Texas MD Anderson Cancer Center in whom esophagitis developed after receiving ICIs from June 2011 through January 2020. We included patients with endoscopic evidence of esophagitis and excluded those with other obvious causes of esophagitis. A chi-square test was used to assess associations between categorical variables. The Mann-Whitney U test was used to compare differences between continuous variables. RESULTS: Of 657 consecutive patients who underwent esophagogastroduodenoscopy (EGD) during or within 6 months of completing ICI-based therapy, 21 (3%) had esophagitis deemed to be from ICIs. Of these patients, 1 (5%) received an inhibitor of CTLA-4 alone, 15 (71%) received anti-PD-1 or PD-L1 monotherapy, and 5 (24%) received a combination of these. Median time from ICI initiation to onset of esophagitis was 4 months. Upon evaluation with EGD, only 3 patients (14%) had isolated esophageal involvement; 18 (86%) had concurrent involvement of the stomach, duodenum, or both. Most patients (67%) were treated with proton pump inhibitors, and 4 (19%) received steroids (prednisone or budesonide). The mortality rate was 38% (median follow-up, 15 months). CONCLUSIONS: Esophagitis associated with ICI use is rare. The diagnosis is one of exclusion because its clinical presentation appears similar to that of inflammation resulting from other causes. It often occurs in conjunction with other upper gastrointestinal toxicity. Symptoms are mild and respond well to nonimmunosuppressive treatment, with few severe complications.