Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Effect of Helicobacter pylori eradication on metabolic profile: an international, multicenter, case-control study.

BACKGROUND: As a gram-negative and microaerophilic bacterium, Helicobacter pylori (HP) is the main cause of chronic gastritis. Therefore, considering the high prevalence of HP infection worldwide, as well as the increasing prevalence of metabolic disorders, the present study aimed to investigate the relationship between HP infection eradication and metabolic profile. METHODS: This prospective case-control study was performed on patients with HP infection whom referred to 7 medical centers in 3 countries (Iran, Egypt, and Vietnam) in 2020-2021. The metabolic profile of all of the participants evaluated before starting of treatment for HP eradication and 3 months after the treatment. Then changes of metabolic profile compared between those with successful HP eradication (group A) and subjects who failed to eradicate (group B). RESULTS: Overall, 199 patients, including 93 male (46.7%) with the mean age of 44.5 years (18-93 years) included. Based on response to treatment, the participants allocate into group A (those who respond to HP eradication): 164 cases (82.42%); or group B as those who failed to achieve eradication (35 cases, 17.58%). Racially 86.9% of participants were Caucasian and 89% diagnosed as non-ulcer dyspepsia (NUD). The most prevalent comorbidity include hypertension (11.5%) and hyperlipidemia (10%) which were more prevalent in group B (P = 0.002). Three months after therapy, average weight of participants among those who achieved eradication (group A) decreased from 73.1 to 71.4 kg (P = 0.01), but in comparison with group B, was non-significant (P = 0.171). The BMI of patients before and after treatment did not show any significant differences. The biochemical parameters of patients before and after treatment were not significantly different regardless of treatment success (P > 0.05). The levels of total cholesterol and VLDL cholesterol after treatment were not significantly different from baseline values in two groups. HDL and LDL cholesterol levels before and after treatment in the resistant group were significantly higher than the responding group. Average serum TG level decreased significantly after treatment in the group A (P < 0.0001), in contrast to the resistant group (P = 0.356). The liver transaminases (AST and ALT) before and after treatment were not significantly different between the two groups (P > 0.05). The results of logistic regression showed that the eradication of infection has no significant affect any of the metabolic profile parameters. CONCLUSION: HP infection treatment in individuals without significant metabolic disorders does not affect metabolic parameters up to 3 months after eradication. HP eradication among subjects with several comorbidities mandates eradication protocol intensification to avoid treatment failure.

Efficacy of Common Bile Duct Stenting on the Reduction in Gallstone Migration and Symptoms Recurrence in Patients with Biliary Pancreatitis Who Were Candidates for Delayed Cholecystectomy.

BACKGROUND: In patients with severe biliary pancreatitis, delayed cholecystectomy associated with a high risk of recurrence is recommended. The current study aimed to evaluate the effect of common bile duct (CBD) stenting on reducing gallstones migration and recurrence of symptoms in patients with pancreatitis and delayed cholecystectomy candidates. METHODS: To this purpose, the randomized, controlled clinical trial was performed on 40 patients with biliary pancreatitis who were candidates for delayed cholecystectomy. Patients were randomly divided into two groups of A and B that underwent CBD stenting after ERCP and received endoscopic treatment without stenting, respectively. A checklist recorded demographics and complications. Group A was followed up after four weeks to remove the stent and record the complications. Group B underwent MRCP to examine the migration of new gallstones as well as the complications. RESULTS: Of the 40 patients, 20 subjects (11 males and 9 females) were allocated to each group, matched for demographic variables. In the one-month follow-up, only one subject in group A manifested symptoms of gallstone migration and recurrence, while in group B, recurrence was observed in 6 patients (P = 0.037). There was no significant difference in the success rate of ERCP and the incidence of complications between the two groups. CONCLUSION: CBD stenting in patients with biliary pancreatitis and gallstone could reduce the risk of recurrence and remigration of gallstones in delayed cholecystectomy cases.

Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study.

BACKGROUND: The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. METHODS: This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. RESULTS: The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. CONCLUSIONS: Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021.

Endoscopic mucosal resection: still a reliable therapeutic option for gastrointestinal neuroendocrine tumors.

BACKGROUND: Neuroendocrine tumors (NETs), as a rare and heterogeneous category of solid tumors, feature various morphologies and behaviors. In recent years, the incidence of NETs has continued to increase. Endoscopic mucosal resection (EMR) is one of the therapeutic modalities for the treatment of gastric and rectal NETs. METHODS: We evaluated patients with well-differentiated NETs of the stomach, duodenum, or rectum between 2011 and 2018. In this study, all cases with tumors confined to the mucosal or submucosal layers and smaller than 20 mm were resected using the EMR technique. We used EUS, CT scan, or MRI to exclude patients with advanced disease. All patients were actively monitored for recurrence according to the recommended protocols. RESULTS: A total of 36 patients with NETs entered the study; 17 (47.2%) were female and the remaining 19 (52.8%) were male, with a total age range of 20-74 years (mean: 52.47 ± 13.47 years). Among the tumors, 31 cases (86.1%) were G1 and the remaining 5 (13.9%) were G2. Based on the pathology reports, 22 tumors (61.1%) were smaller than 1 cm, while the remaining 14 (38.9%) were between 1-2 cm. Twenty-two patients (61.1%) had a margin of specimen involved with the tumor. No recurrence was observed during the mean follow-up time of 63.5 ± 19.8 months (range: 39-103 months). All 36 cases survived during the study period. CONCLUSION: Conventional EMR procedure provides low chance of R0 (complete resection) achievement in gastrointestinal NETs smaller than 20 mm and limited to the mucosa or sub mucosa. However, it could be an option if patients are closely followed. Postoperative marginal involvement is not a reliable predictor of disease recurrence, which may be explained by the deleterious effect of heat coagulation and cauterization applied during tumor removal.

Clinical Manifestations of Gastrointestinal Symptoms in COVID-19 Patients: An Integrative Review.

After the outbreak of novel coronavirus disease 2019 (COVID-19) in Wuhan, China, its spread to other countries is rapidly increasing. In this integrative review, we report the prevalence of gastrointestinal symptoms in patients with COVID-19. For this purpose, available articles on gastrointestinal manifestations in patients with COVID-19, which were reported from China, were reviewed. All reviewed articles were searched from December 11, 2019, to June 20, 2020, based on specific key words. Related findings in these articles show that the main target of COVID-19 is lung tissue, as after the virus enters the body, it mainly causes respiratory symptoms in affected patients. But in addition to respiratory symptoms, it is possible that, over time, these patients present with other symptoms, the most obvious of which are gastrointestinal symptoms. It is well documented that diarrhea and vomiting are the most common gastrointestinal symptoms in COVID-19 patients. As part of this report, we also look at the incidence and frequency of gastrointestinal symptoms in COVID-19 patients in Iran. The results can be used by providers as a guideline for better management of gastrointestinal symptoms in these patients.

Adding ursodeoxycholic acid to the endoscopic treatment and common bile duct stenting for large and multiple biliary stones: Will it improve the outcomes?

BACKGROUND: The role of common bile duct (CBD) stenting in the establishment of bile stream in the elderly patients and the ones who are not good candidates for surgery due to not responding to treatments was well documented in previous studies. The current study aimed at investigating the effect of adding Ursodeoxycholic acid (UDCA) to CBD stenting alone in order to reduce the size of large and multiple CBD stones. METHODS: Clinical outcomes including success rates in CBD stones clearance, incidence of pancreatitis, perforation, bleeding, as well as, decrease in size of stones and liver enzymes after a two-month period were assessed in the UDCA + CBD stenting group. RESULTS: A total of 64 patients referring to Shahid Beheshti Hospital in Qom, Iran with multiple or large CBD stones (above three or larger than 15 mm) received standard endoscopic therapies and UDCA + CBD stenting (group B) and controls only received standard endoscopic therapies with only CBD stenting (group A). The mean reduction in the size of stones in group B was significantly higher than that of group A (3.22 ± 1.31 vs 4.09 ± 1.87 mm) (p = 0.034). There was no difference in the incidence rate of complications including pancreatitis, cholangitis, bleeding, and perforation between the two groups (P > 0.05). CONCLUSION: Adding UDCA to CBD stenting, due to decrease in the stone size and subsequently facilitation of the stones outlet, can be considered as the first-line treatment for patients with large and multiple CBD stones. Also, in the cases with large or multi stones may be effective in reducing size and subsequently stone retrieval. Trial registry The study protocol was approved by the Ethics Committee of Qom University of Medical Sciences (ethical code: IR.MUQ.REC.1397.075); the study was also registered in the Iranian Registry of Clinical Trials (No. IRCT20161205031252N8). This study adheres to CONSORT guidelines.

Atorvastatin in combination with conventional antimicrobial treatment of Helicobacter pylori eradication: A randomized controlled clinical trial.

BACKGROUND AND AIM: Helicobacter pylori is one of the main causes of digestive diseases, which is difficult to treat and requires the administration of several antimicrobial agents. Considering the anti-inflammatory and antibacterial effect of atorvastatin, the present study aimed at adding this agent to a four-drug regimen in order to eradicate H. pylori. METHODS: A total of 220 patients with H. pylori infection were included in the current randomized controlled clinical trial. In the current study, 110 patients in the control group received a 14-day regimen of amoxicillin, clarithromycin, bismuth, and esomeprazole, and 110 patients in the intervention group received 40 mg of atorvastatin daily plus the antibiotic regimen for 14 weeks. The treatment results were evaluated 1 month later using H. pylori stool antigen test. Data were collected using checklist and analyzed using chi-squared and Fisher's exact tests with spss version 18. RESULTS: Helicobacter pylori eradication rate in the intervention and control groups was 78.18% and 65.45%, respectively (P = 0.025), and there was a significant difference in terms of non-ulcer dyspepsia between the groups (P = 0.049), but there was no significant difference in age, gender, and body mass index between the two groups (P < 0.05). CONCLUSION: The present study results showed that adding atorvastatin to the four-drug regimen of omeprazole, clarithromycin, bismuth, and amoxicillin is effective in the eradication of H. pylori. Also, the addition of atorvastatin to H. pylori eradication therapy is more effective in patients with non-ulcer dyspepsia.

The combination of sofosbuvir and daclatasvir is effective and safe in treating patients with hepatitis C and severe renal impairment.

BACKGROUND AND AIM: Many of the treatment regimens available for hepatitis C include sofosbuvir. Unfortunately, sofosbuvir has not been recommended for use in patients with severe renal impairment leaving these group of patients with very few options. Nevertheless, there are many reports in which these patients have been treated with sofosbuvir-containing regiments without important adverse events. This study aims at determining the safety and effectiveness of a sofosbuvir-based treatment in patients with severe renal impairment, including those on hemodialysis. METHOD: We enrolled subjects with hepatitis C and estimated glomerular filtration rate under ml/min/1.73m2 from 13 centers in Iran. Patients were treated for 12 weeks with a single daily pill containing 400-mg sofosbuvir and 60-mg daclatasvir. Patients with cirrhosis were treated for 24 weeks. Response to treatment was evaluated 12 weeks after end of treatment (sustained viral response [SVR]). ClinicalTrials.gov identifier: NCT03063879. RESULTS: A total of 103 patients were enrolled from 13 centers. Seventy-five patients were on hemodialysis. Thirty-nine had cirrhosis and eight were decompensated. Fifty-three were Genotype 1, and 27 Genotype 3. Twenty-seven patients had history of previous failed interferon-based treatment. Three patients died in which cause of death was not related to treatment. Six patients were lost to follow-up. The remaining 94 patients all achieved SVR. No adverse events leading to discontinuation of medicine was observed. CONCLUSIONS: The combination of sofosbuvir and daclatasvir is an effective and safe treatment for patients infected with all genotypes of hepatitis C who have severe renal impairment, including patients on hemodialysis.

Radioprotective effects of montelukast, a selective leukotriene CysLT1 receptor antagonist, against nephrotoxicity induced by gamma radiation in mice.

PURPOSE: In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice. MATERIALS AND METHODS: Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99m Tc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant. RESULTS: The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR-treated group. Also, 99m Tc-DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group. CONCLUSIONS: According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy.

Prevalence of Endoscopic Retrograde Cholangiopancreatography Complications and Amylase Sensitivity for Predicting Pancreatitis in ERCP Patients.

Endoscopic retrograde cholangiopancreatography (ERCP) is a complex procedure that is widely used for diagnosis and treatment of biliary and pancreatic diseases. With respect to its growing application, the present study aims to evaluate ERCP outcomes and complications. This cross-sectional study was performed using the data from 824 patients who underwent ERCP during 2014-2017 in Qom Shahid Beheshti hospital. Data were collected by a checklist and analyzed using SPSS V22. Among 824 patients, 397 (48.18%) were male and 427 (51.82%) were female with a mean age of 47 ± 6 years. The most common indications for ERCP were choledocholithiasis (78.28%) and cholestasis (20.27%), respectively. Total prevalence of complications was 15.66% and mortality rate was 0.72%. The most common complications were pancreatitis (9.59%) and bleeding (3.28%), respectively. A serum amylase level of greater than 160 could predict pancreatitis with sensitivity of 93.3% and specificity of 90.3%. Endoscopic retrograde cholangiopancreatography-related complications are inevitable but can be controlled by early diagnosis and clinical experience. Severe complications and high-risk patients may increase the mortality of the procedure.

Migraine and gastric disorders: Are they associated?

BACKGROUND: Migraine is a common disorder which affects quality of life. There has been an increasing interest for discovering the association of gastrointestinal (GI) disorders with migraine during past years. This study aims to evaluate the association of Helicobacter pylori contamination, gastroesophageal reflux disease (GERD), gastric ulcer (GU), and duodenal ulcer (DU) with migraine in patients who underwent upper GI endoscopy due to refractory dyspepsia. MATERIALS AND METHODS: In this observational cross-sectional study, 341 dyspeptic patients who underwent upper GI endoscopy in Shahid Beheshti Hospital, Qom, Iran, included during 2016-2018. A checklist was used for collecting demographics, symptoms, and results from endoscopy and H. pylori testing. Diagnosis of migraine was made according to the International Headache Society criteria in patients who had headache. Data were analyzed using Chi-square and independent samples t-tests in SPSS 16 (SPSS Inc., Chicago, IL, USA) with P < 0.05 as significance level. RESULTS: Among 341 patients, 141 (% 41.3) were male and 200 (58.7%) were female. 149 (43.7%) patients were diagnosed with migraine, from which 48 (32.2%) were male and 101 (67.8%) were female. The observed difference in migraine prevalence among male and female was statistically significant (P = 0.003). 198 (58.06%) patients were H. pylori contaminated, among these 138 (69.7%) suffered from migraine. Among 143 H. pylori-negative patients, there were 11 (7.7%) migraineurs. The difference in the prevalence of migraine among H. pylori positive and negative patients was significant. H. pylori and GERD were associated with migraine with P < 0.001. Patients with DU were more commonly suffering from migraine (P = 0.001). The association in patients with GU was not statistically significant (P = 0.863). CONCLUSION: Migraine might be associated with GERD, H. pylori infection, and DU, and the treatment of the underlying GI disorder may control headaches.

Comparison of the Effects of Govarcin Herbal Capsule and Metoclopramide for Alleviating Gastrointestinal Symptoms in Patients with Functional Dyspepsia: A Randomized Double-blind Clinical Trial.

BACKGROUND: Functional dyspepsia (FD) is felt as a discomfort or pain on the center line or upper abdomen. In this study, we aimed to compare the effects of Govarcin herbal capsule and Metoclopramide for alleviating gastrointestinal symptoms in patients with FD. METHODS: Totally, 106 patients enrolled in a double-blind, clinical trial study. The participants had FD and were divided into two groups receiving Govarcin and Metoclopramide by block randomization. The patients were treated for four weeks, taking one Govarcin capsule or Metoclopramide tablet after each meal. The rate of improvement in patients was assessed by mitigation of clinical symptoms, including epigastric pain, fullness, discomfort, nausea, vomiting and heartburn. Also, before and after intervention, we used Nepin questionnaire and ROME III. SPSS statistics 25 software was used for data analyzing. RESULTS: Clinical symptom score changes between Govarcin and Metoclopramide patients' groups showed that there was no significant difference in any of the clinical symptom scores (except for heartburn, p-value=0.012) between the study groups. Nepean score in Govarcin group before and after treatment were 19.3±4.8 and 8.9±2.8, respectively (p-value<0.001). For Metoclopramide group, these values were 19.8±3.5 and 9.4±2.1 respectively (p-value<0.001). No significant difference was found in terms of Nepean score between the Govarcin and Metoclopramide groups (p-value=0.995). CONCLUSION: Govarcin herbal capsule can be used to remedy symptoms in patients with FD. It seems that Govarcin is as effective as Metoclopramide in fighting symptoms of FD as no significant difference in efficacy has been demonstrated between them.

Clinical Phenotype and Disease Course of Inflammatory Bowel Disease in Iran: Results of the Iranian Registry of Crohn's and Colitis (IRCC).

BACKGROUND: Data on the epidemiology of inflammatory bowel disease (IBD) in the Middle East are scarce. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the Middle East. METHODS: We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) from 2017 until 2022. We collected information on demographic characteristics, past medical history, family history, disease extent and location, extra-intestinal manifestations, IBD medications, and activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions history, history of colon cancer, and IBD-related surgeries. RESULTS: In total, 9746 patients with ulcerative colitis (UC) (n=7793), and Crohn's disease (CD) (n=1953) were reported. The UC to CD ratio was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. The male-to-female ratio was 1.28 in CD patients. A positive family history was observed in 17.9% of UC patients. The majority of UC patients had pancolitis (47%). Ileocolonic involvement was the most common type of involvement in CD patients (43.7%), and the prevalence of stricturing behavior was 4.6%. A prevalence of 0.3% was observed for colorectal cancer among patients with UC. Moreover,15.2% of UC patients and 38.4% of CD patients had been treated with anti-tumor necrosis factor (anti-TNF). CONCLUSION: In this national registry-based study, there are significant differences in some clinical phenotypes such as the prevalence of extra-intestinal manifestations and treatment strategies such as biological use in different geographical locations.