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.

Mebendazole, an anti-helminth drug, suppresses inflammation, oxidative stress and injury in a mouse model of ulcerative colitis.

Mebendazole (MBZ) is an efficacious anthelmintic with known anti-inflammatory and fibrinolytic properties. In this study, we aimed to explore the protective effects of this FDA-approved drug against DSS-induced colitis in a murine model either alone or in combination with Sulfasalazine (SSZ), a standard therapy for ulcerative colitis. We found that MBZ significantly improved colitis disease activity index as assessed by changes in body weight, degree of stool consistency, rectal bleeding, and prolapse. We also found that MBZ ameliorated the colon histopathological score by attenuating crypt loss, mucosal damage, and inflammation score in colitis tissues. Similarly, DSS-induced colon shortening, colon weight loss, and increase in spleen weight were all abrogated in the presence of MBZ. Moreover, MBZ decreased inflammation, possibly by reducing oxidative stress markers, suppressing inflammatory cell infiltration, and down-regulation of inflammatory genes in colon tissues. Furthermore, MBZ potently reduced fibrosis by decreasing collagen deposition and down-regulating pro-fibrotic genes including Col 1a1 and Col 1a2 in colitis tissue homogenates. In conclusion, our study showed that this broad-spectrum anthelminthic could be repurposed as a novel therapy for ulcerative colitis without any observed side effects, however, regarding the concerns about the potential toxicity of MBZ in UC patients, future experiments on MBZ therapy in other models of UC is needed to completely address the toxicity concerns.

High prevalence of SARS-Coronavirus-2 in patients with inflammatory bowel disease and the role of soluble angiotensin converting Enzyme2.

Context: Patients with inflammatory bowel disease (IBD) were found to have the higher intestinal expression of Angiotensin-Converting Enzyme2 (ACE2) that could consequently increase susceptibility to COVID-19 infection.Objective: This study reports the outcomes of COVID-19 infection in a large cohort of IBD patients. We compare levels of serum ACE and IFN-α between COVID19 patients with and without IBD. We performed a cross-sectional retrospective multicenter study.Methods: We enrolled patients with IBD screened for SARS-COV-2 in six medical centres in Iran from June to November 2020. The blood samples were drawn to measure COVID-19 IgM and IgG, and serum levels of sACE2, sACE1, and interferon-α, regardless of suspicious symptoms have done the molecular test.Results: A total of 534 IBD patients were included in the study. Of these, 109 (20.0%) cases had detectable IgG and IgM against SARS-CoV-2. sACE2 levels were higher in IBD patients than controls, whereas ACE1and IFN-α levels were similar among groups.

Serological response to SARS-CoV-2 is attenuated in patients with inflammatory bowel disease and can affect immunization.

In this study we indicated that impaired serological responses to SARS-CoV-2 infection among patients with IBD, could have significant implications for this group of patients and should be considered in vaccination program.

Explaining the Disease Management Experiences of Patients With Inflammatory Bowel Disease: A Qualitative Study.

Inflammatory bowel disease is an unpredictable, chronic, recurrent gastrointestinal disorder with a wide range of social, physical, and psychological problems experienced by patients. The identification of these concerns is important to provide better healthcare. The purpose of this study was to understand the experiences and concerns of these patients. This study was conducted using a qualitative content analysis approach. The participants were 20 inflammatory bowel disease patients. Data were collected through unstructured interviews with purposive sampling and continued until data saturation. Data were comparatively analyzed continuously and simultaneously with data collection. Data analysis revealed two themes of "tension due to possible recurrence" and "fear of decline and deterioration." The integration of these concepts suggested that patients experience "sinking into the marsh of recurrence" as a major concern that disrupts their successful management of inflammatory bowel disease. Identifying the concerns of inflammatory bowel disease patients regarding their cultural and social context is of paramount importance. The integration of such concerns into treatment can improve patients' coping abilities and improve their quality of life.

Reconstruction of individual, social, and professional life: Self-management experience of patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) experience wide range of physical and psychological problems experience. The use of strategies to improve disease management by patients is of has special importance in solving these problems. The aim of present study was to discover the strategies and behaviors of patients to manage their disease. MATERIALS AND METHODS: The present study was conducted with a qualitative research approach and a qualitative content analysis method. The research participants included 20 patients with IBD referred to gastrointestinal wards in 2020 in Mashhad. Data were collected through unstructured interviews and purposeful sampling method and continued until data saturation. Data analysis was performed continuously and simultaneously with data collection and comparatively. RESULTS: Data analysis provided five themes of "Improving self-efficacy and problem-solving skills," "Coexistence with disease," "Reviewing and modifying of interactions," "Adjusting job and professional conditions" and "Commitment to self-care." The combination of these concepts indicated that is the main theme in disease management for these patients. CONCLUSIONS: Reconstruction of individual, social, and professional life can improve self-regulation and problem-solving skills in these patients and make them a sense of control on their lives and disease.

A review of non-alcoholic fatty liver disease in non-obese and lean individuals.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of hepatic disorders. It represents a wide range of chronic liver diseases in patients with no history of significant alcohol consumption, starting with simple steatosis and progressing towards non-alcoholic steatohepatitis, cirrhosis, and ultimately hepatocellular carcinoma. NAFLD is usually associated with type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, and obesity. This disease has mostly been studied in obese individuals; however, it has been widely reported and studied among the lean/non-obese population in recent years. The pathogenesis of NAFLD in non-obese patients is associated with various genetic predispositions, particularly a patatin-like phospholipase domain-containing protein 3 G allele polymorphism, which results in the accumulation of triglyceride in the liver and resistance to insulin. Additionally, dietary factors such as high fructose consumption seem to play a substantial role in the pathology of non-obese NAFLD. Although there is not enough evidence on the treatment of NAFLD in non-obese patients, the standard approach is to advise altering one's lifestyle in order to diminish visceral adiposity. Dietary modification, weight loss, and increased physical activity are highly recommended. We aimed to review and summarize the existing information on the prevalence, pathogenesis, genetic predispositions, diagnosis, and treatment of NAFLD in non-obese patients according to the latest literature.

Fibrin Glue in Postlaryngectomy Fistula-A Case Report.

INTRODUCTION: One of the most common complications following total laryngectomy is pharyngocutaneous fistula (PCF). Various methods have been proposed to treat this disorder in recent studies, including a range of simple and conservative treatments to more aggressive therapies, such as various surgical procedures. One of the most innovative and least developed methods is the use of plasma-rich compounds, such as fibrin glue. CASE REPORT: The patient was a 55-year-old woman with a transglottic squamous cell carcinoma of the T3N0M0 stage and PCF development following total laryngectomy surgery with total thyroidectomy and bilateral elective cervical lymph node dissection level I-IV. In spite of conservative treatment, the fistula was not recovered after 3 weeks. It was decided to perform fibrin glue injection into the fistula tract via the endoscopic approach. One month after the fibrin glue injection, no evidence of contrast extravasation was observed on barium swallow test, and the fistula was completely closed. CONCLUSION: No PCF has been treated with fibrin glue using only the endoscopic technique. The present study showed that fibrin glue can be used as an effective way to treat chronic fistulas in head and neck surgeries.

Association Between Gastric Lymphoid Follicles (Precursor Of MALT Lymphomas) And H. pylori Infection At A Referral Hospital In Iran.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) is the most common endoscopic finding in Helicobacter pylori positive patients that can progress to MALT lymphoma after a prolonged antigenic contact. This study was aimed to evaluate the prevalence of lymphoid follicles and aggregates (precursors of MALT lymphomas) in gastric mucosal biopsies and their correlation with H. pylori infection. PATIENTS AND METHODS: In this study, 100 patients who had undergone an upper gastrointestinal endoscopy were enrolled. Five biopsy specimens were taken each patient through screening endoscopy and histopathological changes were evaluated and graded using the Wotherspoon System. The clinical background and H. pylori infection status were also investigated. RESULTS: Among the 100 cases in our series, 79 patients (79%) showed evidence of MALT in at least one biopsy specimen taken from the stomach and 21 cases (21%) had no evidence of MALT. H. pylori infection was detected in 74 (74%) patients. Lymphoid follicles were detected more frequently in H. pylori-positive patients (59%) compared to H. pylori-negative cases (3%) (P<0.001). CONCLUSION: The frequency of lymphoid follicles and aggregates in gastric mucosal is associated with H. pylori infection. Further community-based studies in larger sample sizes using a combination of microscopic methods and PCR assay are required for effective monitoring of H. pylori infection.

Iranian Registry of Crohn's and Colitis: study profile of first nation-wide inflammatory bowel disease registry in Middle East.

BACKGROUND/AIMS: A recent study revealed increasing incidence and prevalence of inflammatory bowel disease (IBD) in Iran. The Iranian Registry of Crohn's and Colitis (IRCC) was designed recently to answer the needs. We reported the design, methods of data collection, and aims of IRCC in this paper. METHODS: IRCC is a multicenter prospective registry, which is established with collaboration of more than 100 gastroenterologists from different provinces of Iran. Minimum data set for IRCC was defined according to an international consensus on standard set of outcomes for IBD. A pilot feasibility study was performed on 553 IBD patients with a web-based questionnaire. The reliability of questionnaire evaluated by Cronbach's α. RESULTS: All sections of questionnaire had Cronbach's α of more than 0.6. In pilot study, 312 of participants (56.4%) were male and mean age was 38 years (standard deviation=12.8) and 378 patients (68.35%) had ulcerative colitis, 303 subjects (54,7%) had college education and 358 patients (64.74%) were of Fars ethnicity. We found that 68 (12.3%), 44 (7.9%), 13 (2.3%) of participants were smokers, hookah and opium users, respectively. History of appendectomy was reported in 58 of patients (10.48%). The most common medication was 5-aminosalicylate (94.39%). CONCLUSIONS: To the best of our knowledge, IRCC is the first national IBD registry in the Middle East and could become a reliable infrastructure for national and international research on IBD. IRCC will improve the quality of care of IBD patients and provide national information for policy makers to better plan for controlling IBD in Iran.

Severe Abdominal Pain Caused by Lead Toxicity without Response to Oral Chelators: A Case Report.

A 19-year-old woman was referred to the Emergency Surgery Department with severe abdominal pain, icterus, and anemia. The patient's clinical and paraclinical findings in addition to her occupational and social history, convinced us to assay blood lead level (BLL), which was 41/5 µg/dL. Therefore toxicology consult was performed to treat lead toxicity. Recheck of the BLL showed the level as 53/7 µg/dL. So oral chelator with succimer was started. Despite consumption of oral chelator, there was no response and the pain continued. Because our repeated evaluations were negative, we decided to re-treat lead poisoning by intravenous and intramuscular chelators. Dimercaprol (BAL) + calcium EDTA was started, and after 5 days, the pain relieved dramatically and the patient was discharged. We recommend more liberal lead poisoning therapy in symptomatic patients, and also suggest parenteral chelator therapy, which is more potent, instead of oral chelators in patients with severe symptoms.

Emerging Epidemic of Inflammatory Bowel Disease in a Middle Income Country: A Nation-wide Study from Iran.

BACKGROUND: The burden of inflammatory bowel disease (IBD) hasn't been reported in Iran. We aimed to estimate the prevalence and incidence of IBD and its trend in Iran at national and subnational level from 1990 to 2012. METHODS: We conducted a systematic review of English and Persian databases about the epidemiology of IBD. We also collected outpatient data from 17 provinces of Iran using almost all public and private referral gastroenterology clinics. Prevalence and incidence rate was calculated at national and subnational levels. The Kriging method was used to extrapolate provinces with missing data and GPR model to calculate time trends of rates at subnational level. RESULTS: We found 16 case series, two population-based studies, and two review articles. We collected 11,000 IBD cases from outpatient databases. Among them, 9,269 (84.26%) had ulcerative colitis (UC), 1,646 (14.96%) had Crohn's disease (CD), and 85 had intermediate colitis (IC). A total of 5,452 (49.56%) patients were male. Mean age at diagnosis was 32.80 years (CI: 13 - 61) for UC and 29.98 years (CI: 11 - 58) for CD. Annual incidences of IBD, UC, and CD in 2012 were 3.11, 2.70, and 0.41 per 100,000 subjects respectively. Prevalence of IBD, UC, and CD in 2012 were 40.67, 35.52, and 5.03 per 100,000 subjects respectively. The incidence of UC and CD showed a significant increase during the study period (P for trend < 0.05). CONCLUSIONS: The incidence and prevalence of IBD are increasing in Iran. Establishing a national IBD registry seems necessary for comprehensive care of IBD patients in Iran.

Gastrointestinal Stromal Tumors in Northeastern Iran: 46 Cases During 2003-2012.

BACKGROUND Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. They are usually C-kit positive and seen slightly more common in men. These tumors are seen in the GI tract from the esophagus to the anus with occasional invasion or metastasis. METHODS In this retrospective study, we evaluated the prevalence of c-kit positive stromal tumors of the GI tract based on age, site of involvement, size of tumor, local invasion, and Immunohistochemical markers. The study was conducted in Mashhad University of Medical Sciences in Iran during 2003-2012. RESULTS Of the total 46 patients, 18 (39.1%) were men and 28(60.9%) were women with a mean age of 58.07 years (range: 18-93). Common sites of tumor were stomach, small intestine, esophagus and rectum, respectively. The number of mitoses per 50 HPF varied between zero and 160 mitoses. Overall, 23 cases had 5 mitoses 50/HPF (50%) and 23 tumors expressed <5 mitoses/50 HPF (50%). Local invasion and metastasis were observed in seven cases with extension to liver, pancreas, pregastric tissue, omentum, mesentery and appendix. Positive reaction for CD34, S100, actin and desmin was seen in 47.8%, 13%, 21.7%, and 4.3% of the patients, respectively. CONCLUSION Most patients were women. The prevalence of tumors in the esophagus was higher than the rectum. Invasion and metastasis did not correlate with mitotic rate, site and size of tumor. We suggest evaluation of genetic, racial and geographical or other unknown risk factors.

Causes of Persistently Elevated Alanine Aminotransferase Levels in Patients who Presented to Two Referral Hospitals in Mashhad, Iran during 2011.

BACKGROUND Worldwide, chronic liver disease is a major cause of morbidity and mortality. Causes of elevated serum alanine aminotransferase (ALT) levels vary depending on the population under study. The aim of this study is to evaluate the frequency and causes of persistently elevated ALT levels in patients of the Gastroenterology (GI) Clinics in Ghaem and Emam Reza Hospitals in Mashhad, Iran. METHODS A total of 100 consecutive patients with persistently elevated ALT levels that referred to the GI Clinics at Ghaem and Emam Reza Hospitals in 2011 were studied. Elevated levels were defined as ALT ≥40 U/L at least twice within six months. A comprehensive history that included previous surgeries, transfusion, alcohol consumption and medications was obtained. Patients underwent physical examinations, laboratory analyses and ultrasonography studies. When necessary, liver biopsies were performed. RESULTS Patients' mean age was 44.4 ± 11.83 years. Females comprised 62% of cases. Patients presented with the following conditions: non-alcoholic fatty liver disease (NAFLD, 55%), hepatitis B (17%), autoimmune hepatitis (13%), hepatitis C (4%), autoimmune hepatitis and hepatitis C (2%), overlapping autoimmune disease (2%), Wilson disease (1%), celiac disease (1%), alcoholiche patitis (1%), primary biliary cirrhosis (PBC, 1%), primary sclerosing cholangitis (PSC, 1%), and cryptogenic (2%). CONCLUSION NAFLD was the most common cause of persistently elevated serum ALT levels in this study.

Diagnostic value of carcinoembryonic antigen in malignancy-related ascites: systematic review and meta-analysis.

BACKGROUND AND STUDY AIMS: There is a common misconception that malignant ascites is equivalent to peritoneal carcinomatosis. It seems that malignancy-related ascites is a more appropriate description of malignant ascites, which is difficult to confirm. Carcinoembryonic antigen, a glycoprotein tumor marker shed by malignant cells, increases in a wide range of gastrointestinal malignancies. We carried out the current meta-analysis to determine carcinoembryonic antigen accuracy in the diagnosis of malignancy-related ascites. PATIENTS AND METHODS: Pubmed/Medline and SCOPUS were searched using these search terms: malignan* AND ascites AND (CEA OR carcinoembryonic). The outcome of interest was carcino-embryonic antigen accuracy in the differentiation of malignancy-related ascites and nonmalignant ascites. RESULTS: Seven studies were included in this systematic review. Pooled diagnostic indices using random-effects model were as follows: sensitivity 43.1% [381-48.3]; specificity 95.5% [93-97.3]; LR+ (positive likelihood ratio) 7.33 [4.58-11.73]; LR- (negative likelihood ratio) 0.6 [0.54-0.68]; and DOR (diagnostic odds ratio) 12.93 [7.58-22]. CONCLUSIONS: Carcinoembryonic antigen of the ascitic fluid does not seem to be sensitive enough to diagnose malignancy-related ascites. However, due to high specificity, the positive predictive value of this marker is high and the higher the level of carcino-embryonic antigen, the more likely it is to be malignancy-related. Nevertheless, a negative test result cannot definitely rule out the malignancy.

An epidemiological study of gastroesophageal reflux disease and related risk factors in urban population of mashhad, iran.

BACKGROUND: Gastroesophageal Reflux Disease (GERD) is a chronic and common disease, which is characterized by heartburn and regurgitation. In the last couple of decades, GERD has received much attention and studies have shown an increase in its prevalence. Although there have been a few studies on the prevalence of GERD in Iran, no study has yet been done in the northeastern part of the country. The aim of our study was to evaluate the prevalence of GERD and its risk factors in a population from Mashhad. OBJECTIVES: To evaluate the epidemiology of GERD based on a population study in Mashhad. PATIENTS AND METHODS: This was a cross sectional descriptive study conducted in 2010. In total, 2500 participants were selected based on cluster sampling. Modified and validated Mayo Clinic questionnaire for GERD was used for data collection. Overall, 1685 questionnaires were retrieved. Fifty-one participants were excluded because of pregnancies, history of abdominal surgery and being less than 18 years old. We analyzed data using the SPSS software version 16. Prevalence of GERD and significant risk factors (P value < 0.05) were determined. RESULTS: In total, 420 participants (25.7%) had GERD symptoms. Risk factors with significant effects consisted of smoking, consumption of non-steroidal anti-inflammatory drugs (NASIDs), overeating, chronic diseases, tea and coffee consumption and GERD in spouse. CONCLUSIONS: The prevalence of GERD among people living in Mashhad was above the average prevalence in other cities of Iran. However, risk factors seemed to be similar to those reported by other studies.