The Investigation of Therapeutic Implications of Mast Cell Stabilizer Cromolyn Sodium on Cholestasis and Cholestatic Pruritus in Experimental Cholestasis.

BACKGROUND: Relevant studies have indicated that hepatic mast cells may have potential roles in the progression of cholestasis and cholestasis-induced itch. We aimed to compare the effects of cromolyn sodium and other medications on cholestatic pruritus, serum biochemistry, histamine, total bile acids, autotaxin, liver histopathology, and mast cell distribution in tissues in an experimental cholestasis model conducted by bile duct ligation. METHODS: Rats received the determined treatment consecutively for 10 days in addition to bile duct ligation. On the 5th and 10th days of the experiment, the rats' itching behaviors were observed for 5 minutes. After 10 days, blood and tissue samples were taken. RESULTS: Significant decreases in serum histamine and autotaxin levels, plasma total bile acids, total bilirubin, and biliary enzymes were reported only in cromolyn sodium-treated rats compared to the control group. In immunohistochemistry of the liver samples, the peribiliary mast cells stained positive for autotaxin. Except for bile duct infarctus, all histopathological findings of cholestasis significantly improved only in cromolyn sodium-treated and sertraline-treated rats. The liver and peritoneal mast cells significantly decreased only in cromolyn sodium-treated rats compared to the control group. On the 10th day of the experiment, the mean duration of itching was significantly lower in all groups, except for naloxone- and ondansetron-treated rats. CONCLUSION: Cromolyn sodium has promising antipruritic efficacy and provides biochemical and histopathological recovery of the relevant parameters of cholestasis induced by bile duct ligation. For the first time in the literature, we showed that peribiliary mast cells can produce autotaxin, which is a very important pruritogenic signal in the setting of cholestasis.

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.

Post COVID-19 irritable bowel syndrome.

OBJECTIVES: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. DESIGN: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. RESULTS: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. CONCLUSION: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. TRIAL REGISTRATION NUMBER: NCT04691895.

Factors affecting survival in esophageal squamous cell carcinoma: Single-center experience.

OBJECTIVE: Squamous cell esophageal cancer (ESCC) is a highly fatal malignancy. This study aims to investigate the factors affecting survival in patients with metastatic and non-metastatic ESCC. METHODS: Between 2008 and 2016, 107 patients with ESCC who were followed up in an oncology clinic were included in the analysis. Patients were grouped based on the stage of disease as clinical-stage II to IV. RESULTS: Of the 107 patients, 55 (55.1%) of them were male and 52 (48.6%) of them were female. The mean age was 60.8 years. Based on the clinical-stage, 28 (26.2%) patients had stage II disease, 33 (30.8%) had stage III disease, and 46 (43.0%) had stage IV disease. Twenty-nine (27.1%) patients with the non-metastatic disease underwent surgery following neoadjuvant chemoradiotherapy (CRT), while 29 (27.1%) patients received definitive CRT. Twenty-six (56.5%) patients with metastatic disease received chemotherapy (CT). While median overall survival (mOS) could not be reached in patients who underwent surgery following neoadjuvant CRT, mOS for patients receiving definitive CRT versus patients treated with surgery alone-was 22.0 months and 24.0 months, respectively (p=0.008). In the metastatic stage, mOS was 8.0 months for the patients treated with a first-line CT and 3.0 months for patients receiving best supportive care (p<0.001). In multivariate analysis, factors predicting survival in patients with the non-metastatic disease were ECOG PS 3-4 (Hazard ratio [HR], 6.13), undergoing surgery (HR, 0.22), clinical-stage III disease (HR, 3.19), and presence of recurrence (HR, 24.12). For patients with metastatic disease, ECOG PS 3-4 (HR, 3.31), grade-III histology (HR, 3.39), liver metastasis (HR, 2.53), and receiving CT (HR, 0.15) were the factors associated with survival in multivariate analysis. CONCLUSION: In our study, surgery and early clinical-stage increased survival, whereas experiencing recurrence adversely affected survival in non-metastatic ESCC. In the metastatic stage, ECOG PS 3-4, grade-3 histology and liver metastasis adversely affected survival, while receiving CT significantly improved survival.