Comparison Between 10- and 14-Day Hybrid Regimens for Helicobacter pylori Eradication: A Randomized Clinical Trial.

BACKGROUND: Helicobacter pylori (H. pylori) eradication has always been a concern. In our previous study, 14-day hybrid regimen showed ideal results. Based on these findings, we decided to compare the efficacy of 10- and 14-day hybrid regimens for H. pylori eradication. METHODS: Two hundred and seventy patients with peptic ulcer disease and H. pylori infection were enrolled in the study. One hundred and thirty-four patients received 10-day hybrid regimen (PACT-10): pantoprazole, 40 mg, and amoxicillin, 1 g, both twice daily for 10 days; plus clarithromycin, 500 mg, and tinidazole, 500 mg, both twice daily just during the last 5 days. One hundred and thirty-six patients received 14-day hybrid regimen (PACT-14): pantoprazole, 40 mg, and amoxicillin, 1 g, both twice a day for 14 days; plus clarithromycin, 500 mg, and tinidazole, 500 mg, both twice daily just for the last 7 days. Eight weeks after treatment, (14) C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: Two hundred and fifty patients (124 patients in PACT-10 and 126 patients in PACT-14 regimens) completed the study. The intention-to-treat eradication rates were 77.6% (95% confidence interval (CI): 70.6-84.6%) and 86% (95% CI: 80-92%) for the two regimens, respectively (p = .17). Per-protocol eradication rates were 83.8% (95% CI: 80-86%) and 92.8% (95% CI: 88-96%), respectively (p < .01). There were no significant intergroup differences in compliance to treatment or discontinuation of therapy due to severe side effects. CONCLUSION: Ten-day hybrid regimen could not achieve acceptable eradication rate. However, 14-day hybrid regimen seems to be an acceptable option for H. pylori eradication in Iran.

Comparison of quadruple and triple Furazolidone containing regimens on eradication of helicobacter pylori.

BACKGROUND: The effectiveness of classic standard triple therapy regimen of helicobacter pylori (H. pylori) eradication has decreased to unacceptably low levels, largely related to development of resistance to metronidazole and clarithromycin. Thus successful eradication of H. pylori infections remains challenging. Therefore alternative treatments with superior effectiveness and safety should be designed and appropriately tested in all areas depending on the native resistance patterns. Furazolidone has been used successfully in eradication regimens previously and regimens containing furazolidone may be an ideal regimen. METHODS: H. pylori infected patients with proven gastric or duodenal ulcers and /or gastric or duodenal erosions at Imam Khomeini Hospital in Sari/Northern Iran, were randomly allocated into three groups: group A (OABF) with furazolidone (F) (200 mg bid.), group B (OABM-F) metronidazole (M) (500 mg bid.) for the first five days, followed by furazolidone (F) (200 mg bid.) for the second five days and group C (OAF) with furazolidone (F) (200 mg tid.). Omeprazole (O) (20 mg bid.) and amoxicillin (A) (1000 mg bid.) were given in all groups; bismuth (B) (240 mg bid.) was prescribed in groups A & B. Duration of all eradication regimens were ten days. Eight weeks after treatment, a 14C-urea breath test was performed for evaluation of H. pylori eradication. RESULTS: A total of 372 patients were enrolled in three groups randomly (124 patients in each group); 120 (97%) patients in group A (OABF), 120 (97%) in group B (OABM-F) and 116 (93%) in group C (OAF) completed the study. The intention-to-treat eradication rates were 83.7% (95% CI= 77.3-90.4), 79.8% (95% CI= 72.6-87), and 84.6% (95% CI= 78.2-91.1) and per-protocol eradication rates were 86.6% (95% CI= 80.5-92.8), 82.5% (95% CI= 75.6-89.4), and 90.5% (95% CI= 85.1-95.9) for groups OABF, OABM-F, and OAF, respectively. No statistical significant differences were found in case of severe drug adverse effects between the above mentioned three groups (p> 0.05). The most common side effects, namely nausea and fever, occurred in all groups, but more frequently in group C (OAF) (p< 0.05). CONCLUSION: In developing countries such as Iran, furazolidone-based regimens can substitute clarithromycinbased regimens for H. pylori eradication because of a very low level of resistance, low cost and high effectiveness. Considering per-protocol eradication rate of ten days OAF regimen, and the acceptable limit of ninety percent, we recommend this regimen in developing countries such as Iran to be substituted of classic standard triple therapy. In order to minimize rare serious adverse effects, one week high dose OAF regimen should be taken into consideration in other studies.

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.

Comparison of hybrid and sequential therapies for Helicobacter pylori eradication in Iran: a prospective randomized trial.

BACKGROUND: The eradication of Helicobacter pylori has been always a concern. In the present study, we aimed to compare two novel treatments in Iran. METHOD: Four hundred and twenty patients with peptic ulcer and naïve H. pylori infection were randomized in the study. Two hundred and ten patients received hybrid therapy: pantoprazole 40 mg/b.i.d. and amoxicillin 1 g/b.i.d. for 14 days plus 500 mg clarithromycin and 500 mg tinidazole, both twice daily for the last 7 days. The other 210 patients received sequential therapy: 40 mg pantoprazole/b.i.d. for 10 days and 1 g amoxicillin/b.i.d. for the first 5 days, followed by 500 mg clarithromycin/b.i.d. and 500 mg tinidazole/b.i.d. for the last 5 days. C¹4-urea breath test was performed 8 weeks after the treatment. RESULTS: Three hundred and ninety-six patients (197 patients in the hybrid group and 199 patients in the sequential group) completed the study. The compliance rates were 96.7 and 98.6% for the two groups, respectively. The intention-to-treat eradication rate was 89.5% (95% CI = 85.4-93.6) for the hybrid group and 76.7% (95% CI = 71-82.4) for the sequential group (p = .001), and the per-protocol eradication rates were 92.9% (95% CI = 89.2-96.5) and 79.9% (95% CI = 74.1-85.4) for the hybrid and sequential groups (p = .001), respectively. Severe adverse effects were observed in 2.4% of patients in the hybrid group and 3.8% of those in the sequential group. CONCLUSION: According to our results, sequential regimen does not seem to be an appropriate therapy for H. pylori eradication in the Iranian population, whereas hybrid therapy showed to be more effective. However, considering the high cost of clarithromycin in Iran, we recommend further studies to compare hybrid therapy with bismuth-containing regimens or to assess the effects of hybrid therapies with periods shorter than 14 days.

Evaluation of Circulating Leptin and Its Receptor (Ob-R) Tissue Expression in Colorectal Cancer, a Report From North of Iran.

Background & Objective: Leptin is an adipocyte-derived hormone with a critical role in energy balance. As demonstrated by previous investigations, leptin acts as a proliferative and angiogenic factor in cancer cells. However, results regarding its role in colorectal cancer are still inconclusive. We aimed to evaluate serum leptin and tissue expression of leptin receptor (Ob-R) in normal and malignant samples of colorectal. Methods: Serum and tissue samples from pathology-confirmed colorectal cancer patients and normal controls referring to a university hospital of Mazandaran were obtained during 2019-21. ELISA and immunohistochemistry were applied to determine leptin and Ob-R expression respectively. Results: A total of 90 samples belonging to 46 normal and 44 CRC patients were enrolled. Normal and CRC groups included 32 (69.56%) and 21 (47.72%) female subjects respectively. The average leptin concentration in the normal group was 115.80 and, in the patient, group was 124.47 ng/mL (P=0.897). CRC cases showed an insignificantly higher Ob-R detection rate (P=0.086). Conclusion: There was no significant difference in leptin and Ob-R expression between CRC patients and normal subjects. Thus, leptin and its receptor may not be useful as a biomarker of CRC.

Effects of 14-days bismuth- and tetracycline-containing quadruple therapy with concomitant regimen for the first line Helicobacterpylori eradication.

Background: Helicobacter pylori (H. pylori) has infected about 50% of the world's population and it is the main cause for peptic ulcer, gastric adenocarcinoma and even a major cause for gastric MALT lymphoma. Methods: This study was performed in Mazandaran, Sari, situated in North of Iran. Three-hundred and twenty-eight adult patients with endoscopically approved gastric or duodenal ulcers or erosions and H. pylori infection were randomly divided into 2 groups to receive either 14 days PABT (Pantoprazole 40 mg, Amoxicillin 1 g, Bismuth 425 mg (all twice daily) and Tetracycline 500 mg four times a day) and PACM (Pantoprazole 40 mg, Amoxicillin 1g, Clarithromycin 500 mg, and Metronidazole 500 mg, all twice daily). To evaluate H. pylori eradication, fecal H. pylori antigen test was performed 8 weeks after treatment. Results: The eradication rates were 94.51% in the PABT and 91.46% in PACM group based on the intention to treat analysis. Moreover, the eradication rates were 95.58% and 92.72% according to per-protocol analysis, respectively. Also, both groups had very low rates of severe side effects. Conclusion: Regarding the ideal eradication rates achieved by both treatment groups and the low rates of severe side effects, both treatment protocols can be prescribed for H. pylori eradication in North of Iran.

Epidemiological, Endoscopic, Clinical, and Pathological Features of Patients with Celiac Diseases in Southern Littoral of Caspian Sea.

Background: Celiac disease is an autoimmune disorder resulting from gluten consumption in genetically predisposed individuals. The present study investigated the epidemiological, endoscopic, and clinicopathological features of patients with celiac disease in the southern littoral of the Caspian Sea. Methods: 140 patients with celiac disease were interviewed and examined regarding demographic characteristics, clinical symptoms, and serologic, endoscopic, and pathological findings. Results: 44 (31.4%) of the patients were male and 68.6% were female. The mean age of the patients at diagnosis was 27.13±13.4 years (ranging from 2 to 60 years). The most common gastrointestinal (GI) symptoms were bloating (47.8%), abdominal pain (47.1%) and diarrhea (30.7%), respectively. Also, 17 (12.1%) patients did not complain of any GI symptoms.18 (12.8%) patients had aphthous stomatitis, 10.7% had dermatitis herpetiformis, 3.6% suffered from itching without a rash, two (1.4%) mentioned psoriasis and one (0.7%) had lichen planus. 19 (19.7%) of the female patients complained of menstrual bleeding disorders, 4% mentioned infertility, and 2% experienced primary amenorrhea. The most common comorbid condition was hypothyroidism in 16 (11.4%) patients. The most common endoscopic finding was duodenal scalloping (37.25%). In addition, 7.8% of the patients had a normal endoscopic appearance. 43 (30.7%) patients were classified as Marsh IIIC, 25.7% Marsh IIIB, 17.8% Marsh IIIA, 12.8% Marsh II and 12.8% were classified as Marsh I. Conclusion: Since celiac disease can present with non-GI manifestations and the majority of our patients had Marsh III classification, it seems that celiac disease must be considered as a routine screening test in GI clinics, and also, it should be kept in mind as a differential diagnosis in other specialty fields.

A comparison between sequential therapy and a modified bismuth-based quadruple therapy for Helicobacter pylori eradication in Iran: a randomized clinical trial.

BACKGROUND: Sequential regimens have been recently reported to be superior to the standard triple therapies in Helicobacter pylori eradication, but most of these studies were performed in Europe and data from developing countries are lacking. So we designed a study to compare a sequential regimen with a bismuth-based quadruple therapy that contains a short course of furazolidone, in Iran. METHODS: Two hundred and ninety-six patients with duodenal ulcer and naïve H. pylori infection were randomized into two groups: 148 patients received (PAB-F) pantoprazole (40mg-bid), amoxicillin (1g-bid), and bismuth subcitrate (240mg-bid) for 2weeks and furazolidone (200mg-bid) just during the first week. And 148 patients received (PA-CT) pantoprazole (40mg-bid) for 10days, amoxicillin (1g-bid) for the first 5days, and clarithromycin (500mg-bid) plus tinidazole (500mg-bid) just during the second 5days. C(14) -urea breath test was performed 8weeks after the treatment. RESULTS: Two hundred and sixty-one patients completed the study (137 patients in the PA-CT and 124 in the PAB-F group). The results were not statistically different between the two groups in the eradication rates and the severity of side effects. The intention to treat eradication rate was 80.4% in the PAB-F group and 83.7% in the PA-CT group. Per-protocol eradication rates were 88.7% and 89.1%, respectively. CONCLUSION: Because the two regimens showed acceptable and similar abilities in H. pylori eradication and because of much higher cost of clarithromycin in Iran, the furazolidone containing regimen seems to be superior. Further modifications of sequential therapies are needed to make them ideal regimens in developing countries.

Efficacy of 14-day concomitant quadruple therapy and 14-day high-dose dual therapy on H. pylori eradication.

Aim: We compared the efficacy of two different regimens for H. pylori eradication in areas with high antibiotic resistance. Background: Helicobacter pylori (H. pylori) is a gram-negative bacillus that has a strong association with chronic gastritis and peptic ulcer disease. Different regimens with varying degrees of effectiveness have been used for H. pylori eradication. Methods: The current randomized controlled trial (RCT) randomly assigned 217 patients who had indications for H. pylori eradication therapy to two groups. One group were administered concomitant quadruple therapy (pantoprazole 40 mg, amoxicillin 1 gr, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) for 14 days, and the second group received 14 days of high-dose dual therapy, consisting of esomeprazole 40 mg BID and amoxicillin 1g TDS. H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori eradication rates by PP analysis for 14 days concomitant quadruple therapy and high-dose dual therapy were 88.6% (95% CI, 80.3-92.8) and 82.2% (95% CI, 74.8-89.5), respectively (p = 0.19). According to intention-to-treat (ITT) analysis, the eradication rates were 81.6% (95% CI, 74.5-88.6) and 80.6% (95% CI, 73-88.1), respectively (p = 0.58). Overall drug side effects were 20.8% in high-dose dual therapy and 49.6% in concomitant quadruple therapy (p < 0.001). Conclusion: Fourteen days concomitant quadruple therapy can be considered as a relatively acceptable regimen for H. pylori eradication in areas with high clarithromycin and metronidazole resistance. It seems that high-dose dual therapy could be a promising alternative regimen in these areas.

Helicobacter pylori homB, but not cagA, is associated with gastric cancer in Iran.

While several distinct virulence factors of Helicobacter pylori have been shown to be associated with different clinical outcomes, there is still much to learn about the role of different bacterial factors in gastric carcinogenesis. This study looked at the distribution of the cagA, homA, and homB genes in strains isolated from patients suffering from gastroduodenal diseases in Iran and assessed if there was any association between disease state and the presence of the aforementioned virulence factors. Genomic DNA from 138 H. pylori strains was isolated and genotyped via PCR. Strains were obtained from dyspeptic patients (35 from gastritis patients, 62 from peptic ulcer patients, and 41 from gastric cancer patients) at the Teaching Touba Clinic and Imam Hospital of the Mazandaran University of Medical Sciences in Sari, Iran. The overall prevalence rates of cagA, homA, and homB were 58%, 54%, and 43%, respectively. Stratification of patients showed a significant difference in the prevalence of H. pylori virulence genes across the disease states. The frequency of homB was statistically significantly higher in gastric cancer patients (78%) than in patients suffering from peptic ulcers (20%) or gastritis (43%) (P < 0.0001). The presence of homB was also associated with the presence of cagA (r = 0.243). These data suggest that in this population the presence of homB may be a predictor of more virulent strains of H. pylori and influence the severity of disease manifestation.

Effectiveness of Buspirone in Patients with Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND Functional dyspepsia (FD) is a relatively common disorder whose pathogenesis has yet been poorly understood. There are still debates concerning definitions and the best possible treatments for this disorder. We aimed to assess the effectiveness of buspirone, a 5-hydroxytryptamine (HT)1A agonist, in improving the symptoms and quality of life (QoL) as well as psychological dimensions in patients with FD. METHODS This study was a randomized, double-blinded, placebo-controlled trial performed on 30 patients with FD, residing in the city of Sari, northern Iran, from December 2017 to October 2018. Consecutive patients referring to a tertiary hospital with a clinical diagnosis of FD, according to the Rome IV criteria, were recruited. All patients were ethnically Persian and had normal upper endoscopy and negative histological evaluation results for any gastrointestinal disease or helicobacter pylori (H. pylori) infection while evaluating biopsy samples endoscopically. Exclusion criteria were being diagnosed with major psychiatric disorders, suicidal thoughts, recent treatments with psychoactive drugs, as well as major cognitive impairments. Patients were randomly assigned to receive either buspirone (n=18) or placebo (n=12) for two months. The first group received buspirone 5mg three times a day for the first month and 10mg three times a day for the second month. During the treatment course, the patients were advised to report any adverse reactions. Also, both groups were evaluated by three questionnaires [demographic characteristics form, the 36-Item Short-Form Health Survey (SF-36), The Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) and Hospital Anxiety and Depression Scale(HADS)] at the baseline and at the end of the 8th week by a blinded psychologist. Finally, data were analyzed using SPSS software (version 18). P values <0.05 were considered statistically significant. RESULTS The most common symptoms of the patients were FD followed by heartburn. No significant differences were observed between buspirone and placebo groups regarding QoL (p=0.58), anxiety and depression (p =0.36), and severity and frequency of FD symptoms (p =0.22) before and after the intervention. In both groups, the overall QoL as well as HADS and SF-LDQ scores had significantly improved at the end of the study compared with the baseline. CONCLUSION Our findings indicate no significant effects associated with buspirone on the clinical course of FD, compared with placebo. More studies are needed to introduce effective therapies according to the pathophysiology of FD.

Psychomotor abilities in diagnostic upper gastrointestinal endoscopy derived from procedural task analysis techniques and expert review.

BACKGROUND: Any prediction of a person's ability to succeed in a motor skill depends on the detection and accurate measurement of the basic abilities for the performance of that skill. Task analysis is needed to determine the psychomotor skills and abilities required to perform an action. This study aimed to determine the components of psychomotor abilities for diagnostic upper gastrointestinal (GI) endoscopy through procedural task analysis (PTA) and expert review. MATERIAL AND METHODS: A multisource, multimethod task analysis was conducted in six metropolitan teaching hospitals affiliated with the adult gastroenterology and hepatology training centers in the Islamic Republic of Iran in 2019. Observation, video-recording, and think-aloud protocols were used while diagnostic upper GI endoscopy was performed. To confirm the accuracy of the PTA, the incorporated the views of the adult gastroenterology and hepatology subspecialty experts through the checklist of PTA assessment criteria. Finally, to determine the psychomotor abilities for each stage of the procedure, the study incorporated a panel of experts from occupational therapy, physical education, physical medicine, and adult gastroenterology and hepatology subspecialty. RESULTS: Of the 15 psychomotor abilities examined, 11 were determined for upper GI endoscopy procedure, of which six cases (including visuospatial and perceptual abilities, hand-eye coordination, multilimb coordination, finger dexterity, arm-hand steadiness, and manual dexterity) were the most frequent. CONCLUSIONS: PTA techniques and subsequent expert review were used to identify the components of psychomotor abilities for diagnostic upper GI endoscopy. It is suggested that PTA is performed for other procedures, and after psychomotor abilities are specified, proportional tests are developed.

Antibiotic resistance of Helicobacter pylori in Mazandaran, North of Iran.

BACKGROUND: The aim of this study was to investigate the prevalence of resistances in Helicobacter pylori against commonly used antibiotics including metronidazole, clarithromycin, amoxicillin, and tetracycline in Iranian patients. METHODS: H. pylori isolates were collected from gastric biopsies from patients referred for upper gastrointestinal endoscopy at Tooba Medical Center, Sari, Iran, from 2007 to 2010. None of them had been using antibiotics for at least 8 months. H. pylori was identified based on morphological shape and positive biochemical tests for catalase, oxidase, and urease activity. Antibiotic resistance for metronidazole, clarithromycin, amoxicillin, and tetracycline was investigated by using epsilometer test. Resistance was defined by minimal inhibitory concentration (MIC) > 0.5 mg/L for amoxicillin (AMX), >4 mg/L for tetracycline (TET), >8 mg/L for metronidazole (MTZ), and >1 mg/L for clarithromycin (CLR). RESULTS: Strains were collected from 132 patients, mean age 45.8 years, 52 (39%) were women. Patients had diverse diagnoses: gastritis 42 (31.8%), duodenal ulcer 45 (34%), gastric cancer 15 (11.3%), or gastric ulcer 30 (22.7%). The prevalences of resistance of H. pylori strains isolated from the patients were 73.4% for metronidazole, 30% for clarithromycin, 6.8% for amoxicillin, and 9% for tetracycline. Twenty-eight (21.2%) were double resistant to MTZ-CLR, 16 (12.1%) showed triple resistance to MTZ-CLR-AMX, and 8 (6%) were resistant to all four tested antibiotics (MTZ-CLR-AMX-TET). No associations were detected between multiple resistant strains and clinical manifestations (p > .05). CONCLUSIONS: The prevalence of H. pylori antibiotic resistance to metronidazole and clarithromycin was high in Iran consistent with the reported low success rates for H. pylori treatment in this country.

A Comparison between 10-day and 12-day Concomitant Regimens for Helicobacter Pylori Eradication: A Randomized Clinical Trial.

BACKGROUND Helicobacter pylori (H. pylori) infection is one of the most common bacterial infections worldwide, which is associated with peptic ulcer disease and gastric cancer. In this study, we compared the efficacy of 10-day versus 12-day concomitant therapy as the first-line treatment for H. pylori eradication in Iran. METHODS 218 patients with peptic ulcer disease and naïve H. pylori infection, were randomly divided into two groups to receive either 10-day or 12-day concomitant regimens, composed of pantoprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily. Eight weeks after treatment, H. pylori eradication was assessed by 14C- urea breath test. The trial was registered in the Iranian Registry of Clinical Trials (code: IRCT20170521034070N2). RESULTS 212 patients completed the study. According to the intention to treat analysis, the eradication rates were 83.6% (95% CI: 76.6-90.5) and 88.8% (95% CI: 82.8-94.7) in 10-day and 12-day concomitant therapy groups, respectively (p = 0.24). Per-protocol eradication rates were 85.9% (95% CI: 79.3-92.4) and 92.6% (95% CI: 87.6-97.5), respectively (p = 0.19). The rates of severe side effects were not statistically different between the two groups (3.6% vs. 8.1%; p = 0.428). CONCLUSION 12-day concomitant therapy could achieve ideal eradication rates by both intention to treat and perprotocol analyses. In order to reduce the cost of drugs and the rate of adverse effects of therapy, among 10-day and 12day regimens, 12-day concomitant therapy seems to be a good alternative to 14-day concomitant therapy that has been suggested by international guidelines.

Evaluation of the Additive Effect of Domperidone on Patients with Refractory Gastroesophageal Reflux Disease; A Randomized Double Blind Clinical Trial.

BACKGROUND Gastroesophageal reflux disease (GERD) is a common problem with annoying symptoms. It is associated with negative impact on quality of life. Prokinetic agents may be used in combination with acid suppression agents as an adjunctive in patients with GERD refractory to proton pump inhibitors (PPI) therapy, rather than as sole treatment. This study aimed to evaluate the efficacy of combination of PPI with domperidone (a prokinetic agent) compared with PPI alone in the treatment of patients with refractory GERD. METHODS This study was a double blind clinical trial on 29 patients with GERD refractory to PPI during the period of one month. By randomization, the patients were divided into two groups. Group A was treated by pantoprazole 40 mg twice daily and domperidone three times a day for a month, while group B was treated by pantoprazole 40 mg twice daily and placebo three times a day. In this study endoscopy was performed to evaluate the prevalence of erosive esophagitis, non-erosive reflux, and hiatal hernia. Manometry was conducted to study the prevalence of dysmotility. GERD symptom questionnaires including the Gastrointestinal Symptom Rating Scale (GSRS), Carlson Dennett, and the Medical Outcomes Study Short Form-36 health survey (SF36) were used before and after treatment for screening GERD and assessing treatment response. RESULTS There were 17 (58.62%) women and 12 (41.37%) men. The prevalence of erosive esophagitis and non-erosive reflux, was 10.34% and 89.66%, respectively. There was a significant difference comparing reflux symptoms before and after treatment between the two groups according to reflux and Carlson Dennett questionnaires. At the end of the study, symptoms of reflux significantly improved by treatment. Although, the quality of life questionnaire scores improved by treatment, there was no statistically significant difference in response to treatment between the two groups. CONCLUSION In this research, we showed that adding domperidone to PPI could not make any improvement in patients with refractory reflux regarding the quality of life and improving the symptoms.

Tim-3 Up-regulation in Patients with Gastric Cancer and Peptic Ulcer Disease

Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an inhibitory immunoregulatory receptor, has been recently implicated in tumor biology and tumor-associated immune suppression. In the present study, expression of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at both mRNA and protein levels. Methods: A total of 133 gastric tissue biopsies, comprising 43 from GC cases, 48 from PUD and 42 from non-ulcer dyspepsia (NUD) serving as controls were collected. Additionally, non-neoplastic adjacent tissue biopsies were also obtained from 6 patients with GC. Infection with Helicobacter pylori was determined by the rapid urease test for all participants and H&E staining was conducted for GC and PUD patients. Tim-3 relative mRNA expression was determined by SYBR Green based Real-Time PCR using ß-actin as a reference gene. Tim-3 protein expression was also studied by immunohistochemistry in 7 GC, 7 PUD and 10 NUD tissue samples. Results: Tim-3 was expressed at higher levels in GC (p=0.030) and PUD (p=0.022) cases compared to he NUD group. Among paired samples obtained from gastric cancer patients, tumor tissues showed elevated Tim-3 expression (p=0.019) in comparison with adjacent non-neoplastic biopsies. Tim-3 mRNA findings were supported by detection of more Tim-3 protein in cancerous (p=0.002) and ulcerative (p=0.01) tissues than in controls. Tim-3 was similarly expressed in H. pylori positive and negative cases.Conclusion: Higher Tim-3 expression in patients with gastric cancer and peptic ulcer implies that it might be involved in immune regulation and establishment of these gastrointestinal diseases. Targeted immunotherapy by blocking of inhibitory receptors like Tim-3 could be a promising approach for gastric cancer treatment.

A Comparison between Hybrid and Concomitant Regimens for Helicobacter Pylori Eradication: A Randomized Clinical Trial.

BACKGROUND Helicobacter pylori (H. pylori) is one of the most common bacterial infections worldwide. We designed a study to compare the efficacy of 14-day hybrid regimen with 10-day concomitant therapy for H. pylori eradication in Iran. METHODS 252 patients with naïve H. pylori infection were randomly divided to receive either hybrid regimen (pantoprazole 40 mg, and amoxicillin 1 gr twice daily for 14 days, accompanied by clarithromycin 500 mg, and metronidazole 500 mg, twice daily just during the last 7 days) or concomitant regimen (pantoprazole 40 mg, amoxicillin 1 gr, clarithromycin 500 mg, and metronidazole 500 mg, all twice daily for 10 days). 8 weeks after therapy, 14C- urease breath test was performed to confirm eradication. RESULTS According to intention to treat analysis, the eradication rates were 87.3% (95% CI: 81.4-93.1) and 80.9% (95% CI: 74-87.8) in hybrid and concomitant groups, respectively (p=0.38). Per-protocol eradication rates were 89.3% (95% CI: 83.8-94.7) and 83.1% (95% CI: 76.3-89.8), respectively (p=0.19). The rates of severe side effects were not statistically different between the two groups (4% vs. 8.7%). CONCLUSION 14-day hybrid therapy can be considered as a nearly acceptable regimen with few severe side effects in Iran. However, it seems that the efficacy of this therapy is decreasing as the resistance rates to antibiotics are increasing. We suggest further studies to assess the efficacy of a more prolonged concomitant therapy for H. pylori eradication in Iran.

Regulatory T Cells and Myeloid-Derived Suppressor Cells in Patients with Peptic Ulcer and Gastric Cancer.

BACKGROUND: Regulatory T Cells (Tregs) and Myeloid-Derived Suppressor Cells (MDSCs) are two main regulatory cells modulating the immune responses in inflammation and cancer. OBJECTIVE: To investigate and compare Tregs and MDSCs in peptic ulcer and gastric cancer. METHODS: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD, n=22), peptic ulcer disease (PUD, n=25), and gastric cancer (GC, n=27) according to their endoscopic and histopathological examinations. Helicobacter pylori infection was diagnosed by rapid urease test and histopathology. The number of peripheral blood CD4+CD25+FoxP3+Tregs and CD14+HLA-DR- MDSCs were determined in all patients, by flow cytometry. The number of FoxP3+ regulatory T cells was also determined by immunohistochemistry (IHC). RESULTS: The percentage of peripheral blood Treg cells in both PUD (0.81 ± 0.39, p<0.001) and GC groups (0.98 ± 0.65, p<0.001) were significantly higher than in NUD group (0.46 ± 0.10). These results were also confirmed by IHC. A significantly higher percentage of MDSCs in patients with PUD (0.73 ± 0.19, p<0.001) and GC (0.73 ± 0.16, p<0.001) was also observed when compared to NUD group (0.46 ± 0.16). There was no difference in the percentages of these two cell types between the PUD and GC groups. The percentages of Tregs and MDSCs in patients with PUD and GC were not significantly correlated. CONCLUSIONS: Both Tregs and MDSCs showed higher frequencies in PUD and GC. These results suggest that immune-modulation by the Tregs and MDSCs may play a role in the pathogenesis of PUD and GC.

Validation of the Persian version of the inflammatory bowel disease questionnaire (IBDQ) in ulcerative colitis patients.

BACKGROUND: Inflammatory bowel diseases (IBD) are a group of inflammatory conditions of the colon and small intestine that may have critical consequences on patient's quality of life (QOL). Many disease-specific QOL tools have been developed recently. The McMaster Inflammatory Bowel Disease Questionnaire (IBDQ) is one of them. The aim of this study was to translate the IBDQ from English to Persian and evaluate the validity and reliability of this version of the McMaster IBDQ. METHODS: 68 subjects with ulcerative colitis were recruited in this study. The original IBDQ was translated into Persian using back- translation method. The reliability of the subscales and the summary score of the Persian IBDQ was demonstrated by intraclass correlation coefficients, their validity was evaluated by their correlations with SF-36, visual analogue scale and colitis activity index. RESULTS: All dimensions of IBDQ met the standards of construct validity and were correlated well with SF-36, visual analog scale and colitis activity index. IBDQ was able to discriminate the different groups of patients. The intraclass correlation coefficient was very high and its value was close to one (P<0.05). All dimensional scores differed significantly between the baseline and the follow-up measurement. CONCLUSION: The findings of this study conclude that the Persian translation of IBDQ confers satisfactory psychometric and cultural properties when applied to a sample of Iranian population with inflammatory bowel disease. This questionnaire is recommended for use in clinical trials and in the assessment of efficacy of interventions and therapy.

The prognostic impact of EGFR, ErbB2 and MET gene amplification in human gastric carcinomas as measured by quantitative Real-Time PCR.

PURPOSE: Identification of critical genes which play pivotal roles in controlling tumor growth and survival will establish the basis for developing therapeutic targets. In this study, we focused on frequencies of EGFR, ErbB2 and MET gene amplification in gastric cancer patients to develop personalized medicine to improve the treatment. METHOD: EGFR, ErbB2 and MET gene amplification, and mRNA expression were analyzed by the quantitative Real-Time PCR in paraffin-embedded samples from 115 patients with gastric cancer. RESULTS: EGFR, ErbB2 and MET genes were amplified in 11.3 % (13/115), 6.1 % (7/115) and 19.1 % (22/115) of cancerous specimens, respectively. The correlation coefficient test clearly indicated that gene amplification in these three genes was positively correlated with mRNA transcription (EGFR: R = 0.631, p = 0.009; ErbB2: R = 0.652, p = 0.023; MET: R = 0.715, p < 0.001). EGFR and MET gene amplification was significantly associated with Ki-67 MI (p = 0.022 and p = 0.015). MET amplification was also significantly associated with age of ≥60 years (p = 0.021) and tumor size of ≥5 cm (p = 0.032). MET amplification, but not EGFR and ErbB2, was a significant prognostic factor in poor survival among patients with gastric cancer. CONCLUSIONS: EGFR, ErbB2 and MET genes are frequently amplified in gastric carcinoma. EGFR, ErbB2 and MET gene amplification is positively correlated with mRNA transcription. MET gene amplification correlates with a poor prognosis and poor survival in gastric carcinomas.