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1.  Impact of Pediatric Inflammatory Bowel Disease on Linear Growth: Data from a National Cohort Study in Saudi Arabia 
Background/Aim:
Linear growth impairment (LGI) is one of the most important features peculiar to children with inflammatory bowel disease (IBD). The aim of this report is to define the impact of IBD on the linear growth of children in the Kingdom of Saudi Arabia (KSA).
Setting and Design:
Multicenter retrospective study.
Patients and Methods:
Data from a cohort of newly- diagnosed children with IBD from 2003 to 2012 were analyzed retrospectively. The diagnosis of IBD was confirmed in accordance with the published criteria. Length/height for age was measured at diagnosis. The World Health Organization (WHO) reference was used and LGI was defined by length/height for age <-2 standard deviation.
Results:
There were 374 children from 0.33 to 16 years of age, including 119 ulcerative colitis (UC) (32%), and 255 Crohn's disease (CD) (68%) patients. The prevalence of LGI was 26%, 28%, and 21% in IBD, CD, and UC, respectively. In children below 10 years, LGI was significantly more common in CD (P = 0.010), while in UC children, it was more common in older children (P = 0.011).
Conclusion:
This study demonstrates a prevalence of LGI consistent with that reported in the literature, but higher in CD children with early onset (<10 years) and in older children with UC, underscoring the importance of monitoring growth in children with IBD in the Saudi population. Prospective studies are needed to define the impact of IBD on growth velocity, puberty, and final adult stature.
doi:10.4103/1319-3767.178524
PMCID: PMC4817292  PMID: 26997215
Growth impairment; inflammatory bowel disease; Saudi children; short stature
2.  Correlation of HVPG Level with CTP Score, MELD Score, Ascites, Size of Varices, and Etiology in Cirrhotic Patients 
Background/Aim:
This study intends to determine the correlation of a patient's hepatic venous pressure gradient (HVPG) measurement with six factors: Child–Turcotte–Pugh (CTP) score, model for end-stage liver disease (MELD) score, presence of ascites, size of varices, presence of variceal bleeding, and an etiology of cirrhosis. The study also aims to identify the predictors of higher HVPG measurements that can indirectly affect the prognosis of cirrhotic patients.
Patients and Methods:
Thirty patients diagnosed with cirrhosis were enrolled prospectively and each patient's HVPG level was measured by the transjugular catheterization of the right or middle hepatic vein. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were measured using a 7F balloon catheter. The HVPG level was calculated as the difference between the WHVP and FHVP measurements.
Results:
The mean HVPG level was higher in alcoholic than in nonalcoholic cirrhosis (19.5 ± 7.3 vs 15.2 ± 4.5 mm Hg, P = 0.13). The mean HVPG was also higher in bleeders compared with nonbleeders (18.5 ± 5.3 vs 10.7 ± 3.1 mmHg, P = 0.001). Patients with varices had a higher mean HVPG level than those without varices (17.4 ± 5.8 vs 11.7 ± 3.9 mmHg, P = 0.04). The difference among the three categories of varices (small, large, and no varices) was statistically significant (P = 0.03). In addition, the mean HVPG level was higher in patients with ascites than in those without ascites (18.7 ± 4.7 vs 11 ± 5.3 mmHg, P = 0.002), and it was significantly higher in patients in CTP class C (21.8 ± 5.5 mmHg) as compared with those in CTP class B (16.9 ± 2.9 mmHg) and CTP class A (10.5 ± 4.1 mmHg; P ≤ 0.001).
Conclusion:
HVPG levels were significantly higher in patients in CTP class C as compared with those in CTP classes A and B, thereby indicating that an HVPG measurement correlates with severity of liver disease. A high HVPG level signifies more severe liver disease and can predict the major complications of cirrhosis.
doi:10.4103/1319-3767.164185
PMCID: PMC4817293  PMID: 26997216
Ascites; cirrhosis; Child–Turcotte–Pugh; hepatic venous pressure gradient; model for end-stage liver disease
3.  The Evaluation of Left Ventricular Functions with Tissue Doppler Echocardiography in Adults with Celiac Disease 
Background/Aim:
The aim of this study was to investigate the effects of celiac disease on cardiac functions using tissue Doppler echocardiography (TDE).
Patients and Methods:
The study included 30 patients with celiac disease (CD) and 30 healthy volunteers. Echocardiographic examinations were assessed by conventional echocardiography and tissue Doppler imaging. The peak systolic velocity (S'm), early diastolic myocardial peak velocity (E'm), late diastolic myocardial peak velocity (A'm), E'm/A'm ratio, myocardial precontraction time (PCT'm), myocardial contraction time (CT'm), and myocardial isovolumetric relaxation time (IVRT'm), E to E'm ratio were measured.
Results:
In pulsed wave Doppler echocardiography, mitral late diastolic flow (A) velocity and E to E'm ratio were significantly higher (P = 0.02 and P = 0,017), E/A ratio was significantly lower (P = 0.008) and IVRT was significantly prolonged (P = 0.014) in patients with CD. In TDE, S'm, E'm, and E'm/A'm ratio were significantly lower, IVRT'm was longer (P = 0.009) from septal mitral annulus and S'm, E'm, E'm/A'm ratio were significantly lower, PCT'm, PCT/ET ratio, IVRT'm were longer, and MPI was higher from lateral mitral annulus in celiac group than controls.
Conclusion:
Our study confirms that patients with CD have impaired diastolic function. More importantly, we also demonstrated an impairment of myocardial systolic function in patients with CD by TDE. We recommend using TDE in addition to conventional echocardiography parameters for the cardiovascular risk assessment of patients with CD.
doi:10.4103/1319-3767.164187
PMCID: PMC4817294  PMID: 26997217
Cardiac involvement; celiac disease; tissue Doppler echocardiography; ventricular functions
4.  Randomized Controlled Trial of Cholestyramine and Hydrotalcite to Eliminate Bile for Capsule Endoscopy 
Background/Aims:
Bile is the main cause of poor bowel preparation for capsule endoscopy (CE). We aimed to determine whether cholestyramine and hydrotalcite can eliminate bile in the bowel.
Patients and Methods:
Patients undergoing CE were randomized into two groups. Group A patients (n = 75) recieved 250 mL 20% mannitol and 1 L 0.9% saline orally at 20:00 hours on the day before and at 05:00 hours on the day of CE and 20 mL simethicone 30 min before CE. Group B patients (n = 73) were treated identically, except for taking oral cholestyramine and hydrotalcite, starting 3 days before CE. Greenish luminal contents were assessed by four tissue color bar segments using Color Area Statistics software. Bowel cleanliness was evaluated by visualized area percentage assessment of cleansing (AAC) score.
Result:
Bowel cleanliness (82.7% [62/75] vs 46.6% [34/73]; χ2 = 14.596, P = 0.000). and detected greenish luminal contents (20.0% [15/75] vs 8.2% [6/73]; χ2 = 4.217, P = 0.040) were significantly greater in Group A than in Group B. Greenish luminal contents in the two groups differed significantly in the captured small-bowel (t = −13.74, P = 0.000) segments and proximal small-bowel (t = −0.7365, P = 0.000) segments, but not for the distal small-bowel (t = −0.552, P = 0.581) segments.
Conclusions:
Cholestyramine and hydrotalcite were ineffective in eliminating bile and improving small-bowel preparation.
doi:10.4103/1319-3767.167185
PMCID: PMC4817295  PMID: 26997218
Bile; capsule endoscopy; cholestyramine; hydrotalcite; small-bowel cleansing; small-bowel preparation
5.  Adherence and Treatment Satisfaction in Liver Transplant Recipients 
Background/Aims:
Liver transplantation (LT) is a life-saving intervention for patients with liver failure. LT recipients' adherence to their therapeutic regimen is an essential element for graft survival. According to WHO, the impact of medication non-adherence in solid organ transplantation has shown to cost $15–100 million annually. The aim of the present study was to identify the factors that best predict medication adherence and to explore the relationship between treatment satisfaction and medication adherence in liver transplant recipients.
Patients and Methods:
Adult liver transplant patients at King Abdulaziz Medical City were included in the study. Patients completed the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4) in addition to several socio-demographic and transplant-related data.
Results:
A total of 154 patients were included in the study and of these 59.7% were adherent. Older age was a significant predictor of adherence (P < 0.05). The mean treatment satisfaction score was 91.9 ± 12.7 in Effectiveness, 80.0 ± 25.9 in Side Effects, 83.5 ± 15.7 in Convenience, and 94.6 ± 8.6 in Global Satisfaction. Further analysis indicated that patients in the adherent group had reported significantly higher satisfaction scores than those in the non-adherent group (P < 0.05) in all treatment satisfaction domains: Effectiveness (94.4 ± 10.4 vs. 88.6 ± 14.8), Side Effects (83.9 ± 22.0 vs. 74.2 ± 30.1), Convenience (87.0 ± 13.9 vs. 77.2 ± 16.1), and Global Satisfaction (96.9 ± 6.6 vs. 91.2 ± 8.6).
Conclusion:
Older patients and those who were more satisfied with their treatment tend to have better adherence to the prescribed medications. Therefore, increasing patients' satisfaction with their treatment should be an integral element of future care plans designed to improve treatment outcomes in liver transplant recipients.
doi:10.4103/1319-3767.164209
PMCID: PMC4817296  PMID: 26997219
Liver transplantation; medication adherence; treatment satisfaction
6.  Surface Gene Variants of Hepatitis B Virus in Saudi Patients 
Background/Aims:
Hepatitis B virus (HBV) continues to be one of the most important viral pathogens in humans. Surface (S) protein is the major HBV antigen that mediates virus attachment and entry and determines the virus subtype. Mutations in S gene, particularly in the “a” determinant, can influence virus detection by ELISA and may generate escape mutants. Since no records have documented the S gene mutations in HBV strains circulating in Saudi Arabia, the current study was designed to study sequence variation of S gene in strains circulating in Saudi Arabia and its correlation with clinical and risk factors.
Patients and Methods:
A total of 123 HBV-infected patients were recruited for this study. Clinical and biochemical parameters, serological markers, and viral load were determined in all patients. The entire S gene sequence of samples with viral load exceeding 2000 IU/mL was retrieved and exploited in sequence and phylogenetic analysis.
Patients and Methods:
A total of 123 HBV-infected patients were recruited for this study. Clinical and biochemical parameters, serological markers, and viral load were determined in all patients. The entire S gene sequence of samples with viral load exceeding 2000 IU/mL was retrieved and exploited in sequence and phylogenetic analysis.
Results:
A total of 48 mutations (21 unique) were recorded in viral strains in Saudi Arabia, among which 24 (11 unique) changed their respective amino acids. Two amino acid changes were recorded in “a” determinant, including F130L and S135F with no evidence of the vaccine escape mutant G145R in any of the samples. No specific relationship was recognized between the mutation/amino acid change record of HBsAg in strains in Saudi Arabia and clinical or laboratory data. Phylogenetic analysis categorized HBV viral strains in Saudi Arabia as members of subgenotypes D1 and D3.
Conclusion:
The present report is the first that describes mutation analysis of HBsAg in strains in Saudi Arabia on both nucleotide and amino acid levels. Different substitutions, particularly in major hydrophilic region, may have a potential influence on disease diagnosis, vaccination strategy, and antiviral chemotherapy.
doi:10.4103/1319-3767.167186
PMCID: PMC4817297  PMID: 26997220
Chronic hepatitis; hepatitis B virus; liver cirrhosis; phylogeny; sequence analysis; surface gene
7.  Association of Global DNA Hypomethylation with Clinicopathological Variables in Colonic Tumors of Iraqi Patients 
Background/Aim:
Colorectal cancer (CRC) ranks sixth among the most common 10 cancers in Iraq. It is a foremost public health dilemma and there is improved interest in understanding the fundamental principles of its molecular biology. DNA methylation in cancer has become the issue of passionate investigation. As compared with normal cells, the malignant cells show major disruptions in their DNA methylation patterns. We aimed to assess the association of global DNA hypomethylation in colonic adenomas and carcinomas of Iraqi patients, measured by immunohistochemistry of 5-methylcytosin, with different clinicopathological variables.
Patients and Methods:
Thirty tissue paraffin blocks from patients with colorectal adenomas, 30 tissue paraffin blocks from patients with colorectal adenocarcinomas, and 30 samples of apparently normal colonic tissue taken from autopsy cases as a control group were included in the present study. From each block, two sections of 5 μm thickness were taken, one section was stained with Hematoxylin and Eosin for revision of histopathological diagnosis and one section was immunohistochemically stained for 5-methylcytosine (5mC) and digitally analyzed by AperioImageScope software.
Results:
The mean digital value of 5mC immunohistochemical expression was sequentially decreased during neoplastic progression from normal colonic tissue into adenoma and then to carcinoma. The mean digital value of 5mC expression was significantly lower in large size adenomas (≥1 cm), and those with severe dysplasia. Concerning carcinoma cases, 5mC expression was significantly lower in stage C2.
Conclusions:
The immunohistochemical evaluation of 5mC yields refined information on colorectal tumor biology in adenoma and carcinoma. Global DNA hypomethylation reflected by low immunohistochemical expression of 5-mC is associated with advanced colorectal adenomatous polyps suggesting that it is an early event in colorectal carcinogenesis. Also this hypomethylation can reflect bad prognosis of patients with colorectal cancer by its correlation to higher tumor stage.
doi:10.4103/1319-3767.178525
PMCID: PMC4817298  PMID: 26997221
Colorectal adenoma; colorectal carcinoma; DNA hypomethylation; 5-methylcytocin
8.  Utility of Rectoscopy in the Assessment of Response to Neoadjuvant Treatment for Locally Advanced Rectal Cancer 
Background/Aims:
The management of locally advanced rectal cancer has changed substantially over the last few decades with neoadjuvant chemoradiotherapy. The aim of the present study is to compare the results between neoadjuvant post-treatment rectoscopy and the anatomopathological findings of the surgical specimen.
Patients and Methods:
We conducted a prospective study of 67 patients with locally advanced adenocarcinoma of the rectum (stages II and III). Two groups were established: One with complete clinical response (cCR) and one without (non-cCR), based on the findings at rectoscopy. Assessment of tumor regression grade in the surgical specimen was determined using Mandard's tumor regression scale.
Results:
Seventeen patients showed a cCR. Thirty-five biopsies were negative and 32 were positive for mailgnancy. All the cCR patients had a negative biopsy (P < 0.0001). All 32 positive biopsies revealed the presence of adenocarcinoma, and of the 35 negative biopsies, 18 had no malignancy and 17 were diagnosed with adenocarcinoma (P < 0.0001). Sixteen of the 17 cCR patients showed a complete pathological response and one patient showed the presence of adenocarcinoma. Of the 50 non-cCR patients 48 revealed the presence of adenocarcinoma and two had absence of malignancy. According to the Mandard classification, 16 of the 17 cCR patients were grade I and 1 grade II; 2 non-cCR patients were grade I, 7 grade II, 13 grade III, 19 grade IV, and 9 grade V.
Conclusions:
Endoscopic and histological findings could be determinants in the assessment of response to neoadjuvant treatment.
doi:10.4103/1319-3767.178526
PMCID: PMC4817299  PMID: 26997222
Complete clinical response; neoadjuvant chemoradiation; rectal cancer; rectoscopy
9.  Anatomical Predilection of Intestinal Metaplasia Based on 78,335 Endoscopic Cases 
Background/Aims:
Gastric intestinal metaplasia (IM) is an important risk factor for intestinal-type gastric carcinoma, and successful treatment critically depends on its timely detection. In order to guide appropriate endoscopic surveillance, objective knowledge on the anatomical predilection of intestinal metaplasia development is urgently needed.
Materials and Methods:
A total of 78,335 cases who underwent gastroduodenoscopy from 2008 to 2013 in Jiangsu and Anhui provinces in China, were studied. Demographic and clinical characteristics, as well as biopsy location and histological results, were analyzed.
Results:
This study revealed that intestinal metaplasia incidence was 28.5% in angulus, 20.24% in lesser curvature of the antrum, and 25.48% in corpus; and all these were significantly higher than those observed in other sites (P < 0.01). Histological grading of intestinal metaplasia in the lesser curvature of the antrum and angulus was generally worse than the grading observed in the greater curvature of the antrum. For Helicobacter pylori-positive patients, acute inflammation was more severe in the lesser curvature of the antrum compared with the greater curvature. In the H. Pylori-negative group, both acute and chronic inflammations were more severe in the lesser curvature of the antrum.
Conclusions:
The angulus, lesser curvature in the antrum, and corpus are most prone to the development of intestinal metaplasia. Inflammation is most severe in the lesser curvature of the antrum, which corresponds to a higher predilection to develop intestinal metaplasia at this site. The lesser curvature of the antrum and corpus require the most attention during endoscopic biopsy surveillance.
doi:10.4103/1319-3767.178528
PMCID: PMC4817300  PMID: 26997223
Angulus; biopsy sites; gastric cancer; intestinal metaplasia; predilection sites
10.  Study of Biofilm Formation in C57Bl/6J Mice by Clinical Isolates of Helicobacter pylori 
Background/Aim:
Despite the significant number of studies on H. pylori pathogenesis, not much data has been published concerning its ability to form biofilm in the host stomach. This study aims to evaluate the potential of clinical isolates of H. pylori to form biofilm in C57BL/6J mice model.
Materials and Methods:
Two strains of H. pylori were selected from a collection of clinical isolates; one (19B), an efficient biofilm producer and the other (4B), with weak biofilm-forming ability. Mice infected through gastric avages were examined after one and two weeks. Colonization was determined by CFU and urease activity; the anti-H. pylori IgA was measured by ELISA, and chronic infections were evaluated by histopathology. Bacterial communities within mucosal sections were studied by immunofluorescence and scanning electron microscopy (SEM).
Results:
Successful infection was obtained by both test strains. Strain 19B with higher ability to form biofilm in vitro also showed a higher colonization rate in the mice stomach one week after infection. Difference (P < 0.05) in IgA titers was observed between the infected mice and the controls as well as between 19B and 4B infected mice, two weeks after the last challenge. Immunofluorescence and SEM results showed tightly colonizing H. pylori in stomach mucosal sections and in squamous and glandular epithelium.
Conclusion:
H. pylori is able to form biofilm in the mouse stomach and induce IgA production, reflecting the same potential as in humans. Firm attachment of coccoid form bacteria to host cells suggests the importance of this state in biofilm formation by H. pylori. Occurrence of biofilm in squamous and glandular epithelium of the mouse stomach proposes that H. pylori can all parts of the upper gastrointestinal tract.
doi:10.4103/1319-3767.178529
PMCID: PMC4817301  PMID: 26997224
Biofilm; C57BL/6J mice; chronic infection; coccoid form; Helicobacter pylori
12.  Treatment of Nonalcoholic Fatty Liver Disease: Where do we Stand? An Overview 
Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, the prevalence of which had progressively increased over the past 10 years where other liver diseases remained at the same prevalence rates or are expected to decrease as in the case of hepatitis C virus (HCV). The treatment of NAFLD is of prime concern to health care professionals and patients due to the significant mortality and morbidity it implies; the problem is further escalated by the fact that standard of care medications targeting NAFLD remain experimental and without evidence base. Treatment nowadays is focused on lifestyle modification and managing the comorbid associated diseases, with a possible role for some hepatic protective agents. This review presents all the medications that had been proposed and used for the treatment of NAFLD with or without scientific rationale and includes agents for weight loss, insulin sensitizers, drugs that reduce blood lipids, glucagon-mimetics, drugs that may reduce fibrosis, angiotensin receptor blockers, and medicines believed to reduce endoplasmic reticular stress such as vitamin E, ursodeoxycholic acid, and S-adenosyl methionine. A quick review of the newer agents that proved to be promising such as obeticholic acid and GFT505 and the medicines that are still in the pipeline is also presented.
doi:10.4103/1319-3767.178527
PMCID: PMC4817303  PMID: 26997214
Insulin sensitizers; liver protectors; Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis; Ursodeoxycholic acid; vitamin E
14.  Carbon Dioxide Insufflation or Warm-water Infusion for Unsedated Colonoscopy: A Randomized Controlled Trial in Patients with Chronic Constipation in China 
Aims:
The effect of carbon dioxide (CO2) insufflation and warm-water infusion during colonoscopy on patients with chronic constipation remains unknown. We evaluated CO2 insufflation and warm-water irrigation versus air insufflation in unsedated patients with chronic constipation in China.
Patients and Methods:
This randomized, single–center, controlled trial enrolled 287 consecutive patients, from January 2014 to January 2015, who underwent colonoscopy for chronic constipation. Patients were randomized to CO2 insufflation, warm-water irrigation and air insufflation colonoscopy insertion phase groups. Pain scores were assessed by the visual analog scale (VAS). The primary outcome was real-time maximum insertion pain, recorded by an unblinded nurse assistant. At discharge, the recalled maximum insertion pain was recorded. Meanwhile, patients were requested to select the VAS at 0, 10, 30, and 60 min after the procedure. In addition, cecal intubation and withdrawal time, total procedure time, and adjunct measures were recorded.
Results:
A total of 287 patients were randomized. The correlation between real-time and recalled maximum insertion pain ((Pearson coefficient r = 0.929; P < 0.0001) confirmed internal validation of the primary outcome. The mean real-time maximum pain scores during insertion 2.9 ± 2.1 for CO2, 2.7 ± 1.9 for water achieved a significantly lower pain score compared with air (5.7 ± 2.5) group (air vs CO2 P < 0.001; air vs water P < 0.001). However, no significant pain score differences were found between the patients in the CO2 and water groups (CO2 vs water, P = 0.0535). P values in painless colonoscopy and only discomfort colonoscopy (pain 1–2) were, respectively, 6 (6.4%) and 8 (8.5%) for air; 17 (17.7%) and 29 (30.2%) for CO2; 16 (16.5%) and 31 (31.9%) for water. At 0, 10, 30, and 60 min postprocedure, pain scores showed in the CO2 and water groups had significantly reduced than in air group. Insertion time was significantly different between air (10.6 ± 2.5) and CO2 (7.2 ± 1.4) (air vs CO2 P < 0.001), air and water (6.9 ± 1.3) (air vs water P < 0.001). However, CO2 and was not significantly different in cecum-intubated time (CO2 vs water, P = 0.404). CO2 and water group in extubation time were significantly different, respectively, CO2 (7.9 ± 1.1) and water (8.0 ± 1.1) (CO2 vs water, P = 0.707). CO2 or water group required less implementation of adjunct measures and more willingness to repeat the procedure.
Conclusions:
Compared with air, the CO2 or water-aided method reduced real-time maximum pain and cecum-intubated time for chronic constipated patients in unsedated colonoscopy. The CO2 insufflation or warm-water irrigation may be a simple and inexpensive way to reduce discomfort in unsedated patients with constipation. This study demonstrated an advantage of using CO2 insufflation and warm-water irrigation during colonoscopy in unsedated constipated patients in China.
doi:10.4103/1319-3767.173754
PMCID: PMC4763523  PMID: 26831602
Air insufflation; carbon dioxide insufflation; constipation; unsedated colonoscopy; warm–water infusion
15.  The Prognostic Value of UHRF-1 and p53 in Gastric Cancer 
Background/Aims:
This study aimed to examine whether UHRF-1 and p53 overexpression is a prognostic marker for gastric cancer.
Patients and Methods:
Sixty-four patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis.
Results:
The median age was 63 years (18-83 years) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and five (21.7%) patients with gastritis (P = 0.559). UHRF1 expression level in gastric cancer is more powerful than in gastritis (P = 0.046). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (P < 0.001). After a median follow-up of 12 months (1–110), the 2-year overall survival rates were 55% and 30% in negative and positive p53, respectively (P = 0.084). Also, the 2-year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (P = 0.132).
Conclusion:
According to this study, UHRF-1and p53 were not prognostic factors for gastric cancer, whereas they may have a diagnostic value for differantiating between gastric cancer and gastritis.
doi:10.4103/1319-3767.173755
PMCID: PMC4763524  PMID: 26831603
Gastric cancer; p53 genes; prognosis; survival; UHRF-1 protein
16.  The Implications of Oxidative Stress and Antioxidant Therapies in Inflammatory Bowel Disease: Clinical Aspects and Animal Models 
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by alternating phases of clinical relapse and remission. The etiology of IBD remains largely unknown, although a combination of patient's immune response, genetics, microbiome, and environment plays an important role in disturbing intestinal homeostasis, leading to development and perpetuation of the inflammatory cascade in IBD. As chronic intestinal inflammation is associated with the formation of reactive oxygen and reactive nitrogen species (ROS and RNS), oxidative and nitrosative stress has been proposed as one of the major contributing factor in the IBD development. Substantial evidence suggests that IBD is associated with an imbalance between increased ROS and decreased antioxidant activity, which may explain, at least in part, many of the clinical pathophysiological features of both CD and UC patients. Hereby, we review the presently known oxidant and antioxidant mechanisms involved in IBD-specific events, the animal models used to determine these specific features, and also the antioxidant therapies proposed in IBD patients.
doi:10.4103/1319-3767.173753
PMCID: PMC4763525  PMID: 26831601
Animal models; antioxidants; Crohn's disease; lipid peroxidation; reactive oxygen species; ulcerative colitis
17.  MicroRNA-155-enhanced Autophagy in Human Gastric Epithelial Cell in Response to Helicobacter Pylori 
Background/Aim:
MicroRNAs (miRNAs) are a class of small noncoding RNAs acting as posttranscriptional gene expression regulators in many physiological and pathological conditions. MiR-155 is one kind of miRNAs that plays an important role in causing various diseases. However, the precise molecular mechanism of the ectopic expression of miR-155 in Helicobacter pylori infection remains poorly understood. Autophagy has recently been identified as an effective way to control the intracellular bacterium survival. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-H. pylori response.
Patients and Methods:
Totally 86 H. pylori-positive patients together with 10 H. pylori-negative, healthy control subjects were included in the study. Correlation between immunohistochemical grades and miR-155 expression were determined. Molecular mechanism of miR-155 on regulation of autophagy and elimination of intracellular H. pylori were determined using the GES-1 cell model.
Results:
We found that overexpression of miR-155 by transfecting miR-155 mimics could significantly decrease the survival of intracellular H. pylori, and this process was through induction of autophagy. Furthermore, there was a significant correlation between miR-155 and immunohistochemical grades in H. pylori-positive patients, and miR-155 expression were decreased in the intestinal metaplasia group.
Conclusions:
The results have indicated that the miR-155 expression level plays a key role in immunity response against H. pylori and this might provide potential targets for the future treatment of H. pylori-related diseases.
doi:10.4103/1319-3767.173756
PMCID: PMC4763526  PMID: 26831604
Autophagy; Helicobacter pylori; intestinal metaplasia; microRNA
18.  Antiviral Efficacy of Entecavir versus Entecavir plus Adefovir for Hepatitis B Virus rtA181V/T Mutants Alone 
Background/Aims:
Hepatitis B virus (HBV) rtA181V/T mutants developed by long-term nucleos(t) ide analogue therapy are known to present cross-resistance for other nucleos (t) ide analogues, except entecavir (ETV). Some studies reported that HBV rtA181V/T mutants could induce cross-resistance to ETV and showed incomplete response as well as persistence of HBV DNA, despite rescue therapy by ETV. This study aimed to investigate the antiviral efficacy of ETV monotherapy and ETV plus adefovir (ADV) as rescue therapy for HBV rtA181V/T single mutation.
Patients and Methods:
A total of 30 patients who received ETV alone (1.0 mg/day, n = 16) or ETV plus ADV (10.0 mg/day, n = 14) over 48 weeks between April 2008 and October 2011 were enrolled. Virological, biochemical, and serological response at 48 weeks of rescue therapy were investigated retrospectively.
Results:
No significant difference in baseline characteristics was observed between the ETV group and the ETV plus ADV group. Virological response showed complete response (62.5 vs. 42.9%), partial response (6.3 vs. 28.6%), non-response (25.0 vs. 28.6%), and virological breakthrough (6.3 vs. 0%) in the two groups, respectively. Virological response did not statistically differ between both groups (P = 0.278). No significant difference in the mean reduction of serum HBV DNA and biochemical response was observed between both groups (4.3 ± 2.9 vs. 4.1 ± 1.8 log10 IU/ml; P = 0.294 and 88.9 vs. 100%; P = 1.000, respectively). In addition, no significant difference in HBeAg loss or seroconversion was observed between the two groups (26.7 vs. 28.6%; P = 1.000).
Conclusions:
ETV monotherapy and ETV plus ADV therapy were clinically effective and comparable as rescue therapy for HBV rtA181V/T mutants alone.
doi:10.4103/1319-3767.173757
PMCID: PMC4763527  PMID: 26831605
Adefovir; entecavir; hepatitis B virus; rescue therapy; rtA181V/T mutants
19.  Predictors of Incomplete Optical Colonoscopy Using Computed Tomographic Colonography 
Background/Aims:
Optical colonoscopy (OC) is the primary modality for investigation of colonic pathology. Although there is data on demographic factors for incomplete OC, paucity of data exists for anatomic variables that are associated with an incomplete OC. These anatomic variables can be visualized using computed tomographic colonography (CTC). We aim to retrospectively identify variables associated with incomplete OC using CTC and develop a scoring method to predict the outcome of OC.
Patients and Methods:
In this case–control study, 70 cases (with incomplete OC) and 70 controls (with complete OC) were identified. CTC images of cases and controls were independently reviewed by a single CTC radiologist. Demographic and anatomical parameters were recorded. Data was examined using descriptive linear statistics and multivariate logistic regression model.
Results:
On analysis, female gender (80% vs 58.6% P = 0.007), prior abdominal/pelvic surgeries (51.4% vs 14.3% P < 0.001), colonic length (187.6 ± 30.0 cm vs 163.8 ± 27.2 cm P < 0.001), and number of flexures (11.4 ± 3.1 vs 8.4 ± 2.9 P < 0.001) increased the risk for incomplete OC. No significant association was observed for increasing age (P = 0.881) and history of severe diverticulosis (P = 0.867) with incomplete OC. A scoring system to predict the outcome of OC is proposed based on CTC findings.
Conclusion:
Female gender, prior surgery, and increasing colonic length and tortuosity were associated with incomplete OC, whereas increasing age and history of severe diverticulosis were not. These factors may be used in the future to predict those patients who are at risk of incomplete OC.
doi:10.4103/1319-3767.173758
PMCID: PMC4763528  PMID: 26831606
Anatomy; colonoscopy; computed tomographic colonography; factors predicting incomplete colonoscopy; failed colonoscopy; scoring method; screening colonoscopy
20.  Healing Acceleration of Acetic Acid-induced Colitis by Marigold (Calendula officinalis) in Male Rats 
Background/Aim:
Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat.
Materials and Methods:
Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20%) were given. Two groups as positive controls were given asacol (enema) and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed.
Results:
A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05).
Conclusion:
Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats.
doi:10.4103/1319-3767.173759
PMCID: PMC4763529  PMID: 26831607
Histopathology; marigold; oxidative stress; ulcerative colitis
21.  Noninvasive Fibrosis Marker Can Predict Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation 
Background/Aims:
Tumor recurrence after curative therapy is common for patients with hepatocellular carcinoma (HCC). As fibrosis and chronic inflammation contribute to the progression of HCC, we aimed to identify the predictive value of inflammatory and fibrosis markers for HCC recurrence after curative therapy using radiofrequency ablation (RFA).
Materials and Methods:
We retrospectively reviewed the records of patients with HCC treated with RFA between October 2005 and September 2013. The median duration of follow-up was 40 months (4–95 months). Inflammatory and fibrosis markers and demographic and clinical data were analyzed by Cox proportional hazards model using univariate and multivariate analyses and longitudinal analysis.
Results:
A total of 98 patients were included for analysis. There were 54 cases of HCC recurrence (55.1%). The aspartate aminotransferase-to-platelet ratio index (APRI; 2.3 ± 1.8 vs. 1.3 ± 1.4, P = 0.018) was significantly higher in the recurrence group than in the recurrence-free group. In multivariate analysis, APRI (hazard ratio, 2.64; confidence interval, 1.488–4.714; P = 0.001) was an independent risk factor for tumor recurrence. In particular, patients with APRI >1.38 showed a higher recurrence rate than patients with APRI ≤1.38 (P < 0.001). Longitudinal analysis showed persistently higher APRI values when assessed 12 months after RFA in patients who developed recurrence during follow-up than those who remained recurrence-free.
Conclusions:
These findings show that a high APRI value is associated with HCC recurrence after RFA. Therefore, APRI could play an important role in predicting HCC recurrence after RFA.
doi:10.4103/1319-3767.173760
PMCID: PMC4763530  PMID: 26831608
Aspartate aminotransferase-to-platelet ratio index; hepatocellular carcinoma; radiofrequency ablation
22.  Factors Influencing Challenging Colonoscopies During Anesthesiologist-Assisted Deep Sedation 
Background/Aim:
Increased demand for colon cancer screening procedures can significantly impact on routine colonoscopy management at dedicated facilities, prompting a review of the factors that can negatively affect workflow. Although potential adverse effects and impact on costs of deep sedation have been documented elsewhere, this study focuses on variables that can influence performance of colonoscopy in deep sedation and interfere with normal procedure scheduling in settings where the presence of an anesthesiologist is mandatory.
Patients and Methods:
We performed a cross-sectional study of the activities of a colonoscopy screening unit, applying Bayesian Network (BN) analysis, designed to assess interdependencies among variables that can affect a process in complex, multidimensional systems. The study was performed at a teaching hospital where endoscopists and anesthesiologists of varying work experience operate on a rota basis. During a six-month period, we analyzed 1485 consecutive colonoscopies performed under deep propofol sedation, administered by an anesthesiologist via hand-controlled syringe. The BN was constructed with the variables: Gender, age, ASA status, bowel preparation, baseline blood pressure, endoscopist's experience, anesthesiologist's experience, presence of polypectomy, and the target node, “challenging procedure.” This previously undefined category refers to any events disrupting the scheduled rota.
Result and Conclusion:
Two distinct networks were identified. One deals mainly with relationships among the variables, patients’ demographic and clinical characteristics (procedures with polypectomy, ASA and baseline blood pressure). The other explains relationships among the variables, “challenging procedure,” bowel preparation, and endoscopist's experience. The factors associated with the anesthesiologist's activity do not influence challenging colonoscopies.
doi:10.4103/1319-3767.173761
PMCID: PMC4763531  PMID: 26831609
Bayesian network; colon cancer screening; colonoscopy; deep sedation colonoscopy
23.  Effect of Telmisartan on Histological Activity and Fibrosis of Non-alcoholic Steatohepatitis: A 1-Year Randomized Control Trial 
Background/Aim:
Telmisartan can attenuate two hit pathogenesis of non-alcoholic steatohepatitis (NASH). This study aimed to observe the effect of Telmisartan on non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and fibrosis score in NASH patients.
Patients and Methods:
A total of 50 NASH patients were randomized; 35 of group 1 were treated with Telmisartan 40/80 mg once daily with life style modification (TL) and 15 of group 2 underwent only life style modification (L) for 1 year. At the end, 20 of TL group and 10 of L group were analyzed. Those who showed NAS improvement ≥ 2 or NAS improvement ≥ 1 with fibrosis improvement ≥ 1 were considered as responders.
Results:
Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin resistance index, components of metabolic syndrome, age, and sex were similar in both groups. At the end of study, NAS improvement in TL and L groups was 2.15 ± 1.66 and 1.10 ± 0.57 (P = 0.017) and fibrosis improvement was 0.65 ± 0.93 and –0.30 ± 0.48 (P = 0.001), respectively. NAS improved by ≥ 2 in 13 (65%) and 2 (20%) patients and fibrosis score improved by ≥ 1 in 8 (40%) patients and none of the patients in TL group and L group, respectively. Telmisartan and life style modification could improve steatosis, ballooning, lobular inflammation, and fibrosis. Life style modification could improve ballooning only, but fibrosis deteriorated. TL group showed improvement in NAS and fibrosis score [P value: 0.035; odds ratio (OR) =92.07, confidence interval (CI) =1.39–6106] to the level of response by regression analysis. Weight reduction and improvement of metabolic syndrome did not influence the response. There were similar minor adverse events in both groups.
Conclusion:
Telmisartan improved NAS and fibrosis score in NASH with insignificant adverse events.
doi:10.4103/1319-3767.173762
PMCID: PMC4763532  PMID: 26831610
Bangladesh; fatty liver; fibrosis; histological activity; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; Telmisartan

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