Diagnostic strategy of irritable bowel syndrome: a low- and middle-income country perspective.

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder associated with substantial impairment which considerably burdens healthcare systems worldwide. Research on IBS has largely been conducted in high-income countries posing barriers to the application of diagnostic strategies in low- and middle-income countries (LMICs) due to differences in disease characteristics, healthcare resources, and socioeconomic factors. This review discusses the diagnostic issues associated with LMICs. We present a concise overview of the relevant approaches and propose a diagnostic strategy based on the latest evidence. A positive diagnostic strategy that relies on appropriate symptom-based criteria is crucial within the diagnostic framework. A combination of complete blood count, fecal occult blood test, and complete stool test may reliably identify individuals with suspected IBS who are more likely to have organic diseases, thus justifying the necessity for a colonoscopy. Eventually, we developed a diagnostic algorithm based on a limited setting perspective that summarizes the available evidence and may be applied in LMICs.

Erratum: Potassium intake is associated with nutritional quality and actual diet cost: a study at formulating a low sodium high potassium (LSHP) healthy diet - CORRIGENDUM.

[This corrects the article DOI: 10.1017/jns.2021.104.].

The Prevalence, Etiology and Treatment of Gastroduodenal Ulcers and Perforation: A Systematic Review.

(1) Background: Gastroduodenal perforation (GDP) is a life-threatening condition caused by a spontaneous or traumatic event. Treatment should be based on the mechanism of damage, timing, location, extent of the injury, and the patient's clinical condition. We aimed to examine several etiologic factors associated with gastroduodenal perforation and to search for the best method(s) for its prevention and treatment. (2) Methods: We conducted extensive literature reviews by searching numerous studies obtained from PubMed, Science Direct, and Cochrane for the following keywords: gastroduodenal perforation, Helicobacter pylori, NSAIDs' use, side effects of GDP, laparoscopy, and surgery. The primary outcome was the reported occurrence of GDP. (3) Results: Using keywords, 883 articles were identified. After applying the inclusion and exclusion criteria, 53 studies were eligible for the current analyses, with a total number of 34,692 gastroduodenal perforation cases. Even though the risk factors of gastroduodenal perforation are various, the prevalence of H. pylori among patients with perforation is considerably high. As technology develops, the treatment for gastric perforation will also improve, with laparoscopic surgery having a lower mortality and complication rate compared to open surgery for GDP treatment. (4) Conclusions: H. pylori infection plays the most significant role in GDP, more than NSAIDs, surgery, chemotherapy, or transplantation. Treatment of H. pylori infection is essential to decrease the prevalence of GDP and speed up its recovery. However, urgent cases require immediate intervention, such as laparoscopic or open surgery.

Diagnosis and Management of Hepatic Hydrothorax.

Hepatic hydrothorax is a pleural effusion (typically ≥500 mL) that develops in patients with cirrhosis and/or portal hypertension in the absence of other causes. In most cases, hepatic hydrothorax is seen in patients with ascites. However, ascites is not always found at diagnosis and is not clinically detected in 20% of patients with hepatic hydrothorax. Some patients have no symptoms and incidental findings on radiologic examination lead to the diagnosis of the condition. In the majority of cases, the patients present with symptoms such as dyspnea at rest, cough, nausea, and pleuritic chest pain. The diagnosis of hepatic hydrothorax is based on clinical manifestations, radiological features, and thoracocentesis to exclude other etiologies such as infection (parapneumonic effusion, tuberculosis), malignancy (lymphoma, adenocarcinoma) and chylothorax. The management strategy involves a stepwise approach of one or more of the following: Reducing ascitic fluid production, preventing fluid transfer to the pleural space, fluid drainage from the pleural cavity, pleurodesis (obliteration of the pleural cavity), and liver transplantation. The complications of hepatic hydrothorax are associated with significant morbidity and mortality. The complication that causes the highest morbidity and mortality is spontaneous bacterial empyema (also called spontaneous bacterial pleuritis).

Predictive factors and prognosis of upper gastrointestinal bleeding in gastric cancer: A large population-based study (UGIB-GC trial).

BACKGROUND: Gastric cancer remains the fourth leading cause of cancer-related death worldwide. Significant number of gastric cancer patients presented with bleeding. OBJECTIVE: This study aimed to identify risk factors and overall survival rates of bleeding gastric cancer patients. METHODS: This retrospective cohort study was conducted between 2007-2022 at tertiary care center in Thailand. Clinical information, endoscopic findings and histological type were extensively reviewed and were compared between bleeders and non-bleeders. Patients were monitored for at least 5 years. RESULTS: There were 20,981 patients who underwent upper gastrointestinal endoscopy during study period. Total of 201 gastric cancer patients were included in this study, 21 were excluded due to incomplete medical records. 180 gastric cancer patients were included with mean age of 60.5±14.3 years. There were 65 (36.1%) patients with gastrointestinal bleeding. Hypertension and chronic kidney disease were significantly more common in bleeders than non-bleeders (43.1% vs 23.5%, OR2.51, 95%CI 1.14.-5.52, p = 0.022; and 16.9% vs 5.2%, OR2.00, 95%CI 1.56-6.63, p = 0.025, respectively). current H. pylori infection was also significantly more common in bleeders than non-bleeders (84.6% vs. 55.7%, OR 4.39, 95%CI 1.90-10.12, p<0.001). Median overall survival of bleeders was significantly lower than non-bleeders (7±0.93 vs 10±2.10 months, p = 0.001). CONCLUSIONS: Bleeding gastric cancer was not an uncommon condition. Majority of patients presented at advanced stage with grave prognosis. Male gender, hypertension, chronic kidney disease, and current H. pylori infection were reliable predictors for bleeding. Early diagnosis and prompt treatment are the key to improve clinical outcome.

Comparison of RDQ and GERDQ for Predicting Erosive Esophagitis in Patients with Typical GERD Symptoms.

Background/Aims: The management decisions regarding gastroesophageal reflux disease (GERD) may differ according to the presence of erosive esophagitis. On the other hand, the availability of upper endoscopy in Indonesia is relatively limited. This study compared the Reflux Disease Questionnaire (RDQ) and the GERD questionnaire (GERDQ) performance in predicting the presence of clinically significant erosive esophagitis and determined the validity and reliability of the Indonesian-translated version of RDQ. Methods: Ninety-two adults with GERD suspicion were recruited. All patients completed RDQ and GERDQ. Receiver operating curve analysis was conducted on RDQ and GERDQ to evaluate their performance in discriminating LA GERD B or higher esophagitis from others. The translated RDQ preserved its main structure and was culturally adapted. Results: The patients were 66.3% female and 73.9% Javanese. Only 22 (23.9%) patients presented with LA grade B or higher erosive esophagitis. The RDQ showed a higher AUC than the GERDQ (0.602 vs. 0.589). A cutoff point of 20 was selected for the RDQ with sensitivity and specificity of 73% and 50%, respectively, whereas the optimal cutoff point of GERDQ was 8, with a sensitivity and specificity of 77% and 43%, respectively. The r-value greater than the critical value table (r>0.205, p<0.01) confirmed the construct validity of our translated RDQ. The questionnaire also demonstrated excellent reliability (α=0.900) and moderate similarity with the Indonesian version of GERDQ (κ=0.459, p<0.01). Conclusions: The RDQ is slightly superior to GERDQ in predicting the presence of clinically significant erosive esophagitis (LA grade B or higher). The Indonesian-translated RDQ is valid and reliable.

Real-world practice of Helicobacter pylori management: A survey among physicians in Southeast Asia.

BACKGROUND: Multidrug-resistant Helicobacter pylori strains are emerging in Southeast Asia. This study evaluates the region's real-world practice in H. pylori management. MATERIALS AND METHODS: Physicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real-world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide. RESULTS: There were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non-GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first-line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second-line therapy, the most common regimen was bismuth-based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first-line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first-line treatment. In countries with high clarithromycin resistance, the most common first-line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non-GI physicians than GI physicians (40.1% vs. 16.2%, p < 0.001). CONCLUSIONS: Choosing inappropriate regimens containing antibiotics with high resistance rates is not uncommon in Southeast Asia, especially among non-GI physicians. In countries with high clarithromycin resistance, the PBMT regimen is underutilized.

Global Antimicrobial Resistance Gene Study of Helicobacter pylori: Comparison of Detection Tools, ARG and Efflux Pump Gene Analysis, Worldwide Epidemiological Distribution, and Information Related to the Antimicrobial-Resistant Phenotype.

We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then analyzed their correlation with clinical antibiogram data from dozens of patients across countries. This revealed that combining multiple tools and databases, followed by manual selection of ARG from the annotation results, produces more conclusive results than using a single tool or database alone. After curation, the results showed that H. pylori has 42 ARG against 11 different antibiotic classes (16 genes related to single antibiotic class resistance and 26 genes related to multidrug resistance). Further analysis revealed that H. pylori naturally harbors ARG in the core genome, called the 'Set of ARG commonly found in the Core Genome of H. pylori (ARG-CORE)', while ARG-ACC-the ARG in the accessory genome-are exclusive to particular strains. In addition, we detected 29 genes of potential efflux pump-related AMR that were mostly categorized as ARG-CORE. The ARG distribution appears to be almost similar either by geographical or H. pylori populations perspective; however, some ARG had a unique distribution since they tend to be found only in a particular region or population. Finally, we demonstrated that the presence of ARG may not directly correlate with the sensitive/resistance phenotype of clinical patient isolates but may influence the minimum inhibitory concentration phenotype.

Validity and Reliability of the Reflux Symptoms Index Translated into Indonesian: The Role of Upper Endoscopy in Assessing Extra-Esophageal Gastroesophageal Reflux Disease Symptoms.

Background/Aims: The Reflux Symptom Index (RSI) is a questionnaire that evaluates the severity of extra-esophageal symptoms and is one of the most widely used measures to evaluate LPR. This study assessed the validity and reliability of the RSI questionnaire in Bahasa Indonesia and investigated the association between each extra-esophageal symptom reported in the questionnaire and the severity of erosive esophagitis as determined by endoscopic findings. Methods: 85 adult patients with GERD symptoms had an upper endoscopy examination and were asked to complete the translated RSI. The validity and reliability of the questionnaire were assessed. Results: The construct validity of the RSI translated into Bahasa Indonesia was verified with the r value of each question being higher than the crucial table value (r>0.213, p<0.05). Our questionnaire had a Cronbach alpha value of 0.81, which indicates an acceptable level of internal consistency. At least one extra-esophageal symptom was seen in 91.7% of patients with Los Angeles (LA) grade B or higher-grade esophagitis. In addition, the presence of extra-esophageal symptoms was associated with significant mucosal erosion (p=0.20). The symptoms of cough after eating or lying down and chronic cough were associated with the severity of esophageal mucosal erosion (p<0.05). Conclusions: The version of RSI translated into Bahasa Indonesia is a valid and reliable tool for assessing extra-esophageal GERD symptoms. The occurrence of extra-esophageal symptoms in patients with typical GERD symptoms is associated with endoscopic findings of LA grade B or erosive esophagitis of higher severity.

Genetic determinants of Biofilm formation of Helicobacter pylori using whole-genome sequencing.

BACKGROUND: Infection with Helicobacter pylori as the cause of gastric cancer is a global public health concern. In addition to protecting germs from antibiotics, biofilms reduce the efficacy of H. pylori eradication therapy. The nucleotide polymorphisms (SNPs) related with the biofilm forming phenotype of Helicobacter pylori were studied. RESULTS: Fifty-six H. pylori isolate from Bangladeshi patients were included in this cross-sectional study. Crystal violet assay was used to quantify biofilm amount, and the strains were classified into high- and low-biofilm formers As a result, strains were classified as 19.6% high- and 81.4% low-biofilm formers. These phenotypes were not related to specific clades in the phylogenetic analysis. The accessories genes associated with biofilm from whole-genome sequences were extracted and analysed, and SNPs among the previously reported biofilm-related genes were analysed. Biofilm formation was significantly associated with SNPs of alpA, alpB, cagE, cgt, csd4, csd5, futB, gluP, homD, and murF (P < 0.05). Among the SNPs reported in alpB, strains encoding the N156K, G160S, and A223V mutations were high-biofilm formers. CONCLUSIONS: This study revealed the potential role of SNPs in biofilm formation and proposed a method to detect mutation in biofilm from whole-genome sequences.

Gastric microbiome changes in relation with Helicobacter pylori resistance.

INTRODUCTION: Inadequate antimicrobial treatment has led to multidrug-resistant (MDR) bacteria, including Helicobacter pylori (H. pylori), which one of the notable pathogens in the stomach. Antibiotic-induced changes in the microbiota can negatively affect the host. This study aimed to determine the influence of H. pylori resistance on the diversity and abundance of the stomach microbiome. METHODS: Bacterial DNA was extracted from biopsy samples of patients presenting dyspepsia symptoms with H. pylori positive from cultures and histology. DNA was amplified from the V3-V4 regions of the 16S rRNA gene. In-vitro E-test was used to detect antibiotic resistance. Microbiome community analysis was conducted through α-diversity, ß-diversity, and relative abundance. RESULTS: Sixty-nine H. pylori positive samples were eligible after quality filtering. Following resistance status to five antibiotics, samples were classified into 24 sensitive, 24 single resistance, 16 double resistance, 5 triple resistance. Samples were mostly resistant to metronidazole (73.33%; 33/45). Comparation of four groups displayed significantly elevated α-diversity parameters under the multidrug resistance condition (all P <0.05). A notable change was observed in triple-resistant compared to sensitive (P <0.05) and double-resistant (P <0.05) groups. Differences in ß-diversity by UniFrac and Jaccard were not significant in terms of the resistance (P = 0.113 and P = 0.275, respectively). In the triple-resistant group, the relative abundance of Helicobacter genera was lower, whereas that of Streptococcus increased. Moreover, the linear discriminant analysis effect size (LEfSe) was associated with the presence of Corynebacterium and Saccharimonadales in the single-resistant group and Pseudomonas and Cloacibacterium in the triple-resistant group. CONCLUSION: Our results suggest that the resistant samples showed a higher trend of diversity and evenness than the sensitive samples. The abundance of H. pylori in the triple-resistant samples decreased with increasing cohabitation of pathogenic bacteria, which may support antimicrobial resistance. However, antibiotic susceptibility determined by the E-test may not completely represent the resistance status.

Management of dyspepsia and Helicobacter pylori infection: the 2022 Indonesian Consensus Report.

Dyspepsia still becomes a major challenge in upper gastrointestinal disease in Indonesia. This disease often correlated with Helicobacter pylori infection. However, the prevalence of this bacterium is generally low in Indonesia. Therefore, several considerations should be taken into consideration during the management of dyspepsia and H. pylori infection. "Management of dyspepsia and H. pylori infection in Indonesia: The Indonesian consensus report" comprises information gathered from 22 gastroenterology centers across Indonesia. The experts gathered to evolve a consensus, that consists of the statements, grades of recommendations, evidence levels, and rationales for the dyspepsia and H. pylori infection management for daily clinical practice. The report explains several aspects from the updated epidemiology information to comprehensive management therapy. After the experts worked together on all statements in the recommendations, the results are presented with the final agreement as a consensus to help clinicians in understanding, diagnosing, and treating dyspepsia and H. pylori infection patients in daily clinical practice in Indonesia.

High levels of fecal calprotectin and C-reactive protein in patients with colitis.

Inflammatory bowel disease (IBD) with a poor prognosis may be due to persistent colitis. According to the latest guidelines, monitoring has become a part of the treatment process for colitis. Adequate monitoring of the patient's condition is necessary to determine the course of the disease to prevent the worsening of the condition and suppress the subclinical inflammatory process. This analytical study with a cross-sectional design was conducted to evaluate the activity of colitis using the results of C-reactive protein (CRP) and fecal calprotectin (FC) assays. FC levels were analyzed by ELISA, while CRP levels were analyzed using Siemens Flex particle-enhanced turbidimetric immunoassay. In 30 subjects with endoscopy and biopsy of colitis, 16 men and 14 women had a median age of 52.5 (18-70) years. The median FC value increased by 67 (7.3-722 g/g) and was positive (≥50 g/g) in 20 subjects (66.7%), and the mean CRP value was 13.64 mg/L, positive (10-15 mg/L) in 13 subjects (43.33%), and negative (<10 mg/L) in 17 subjects (56.67%). This study demonstrated that FC had a significant relationship with CRP (r=0.57; p<0.001) in patients with colitis. Assessing the levels of FC and CRP among patients with colitis can be useful to assess the worsening of symptoms early and reduce mortality and morbidity.

High socioeconomic status is associated with stroke severity among stroke patients in the National Brain Centre Hospital, Jakarta, Indonesia.

Rapid economic growth has widened the gap between the rich and the poor, contributing to inequalities in socioeconomic status (SES) in Indonesia and possibly inequalities in health care. Here, we aimed to assess the potential association between SES and stroke severity in Indonesia, one of the largest low- and middle-income countries. Patients diagnosed with stroke at National Brain Centre (NBC) Hospital, Jakarta, Indonesia, in 2020 were included in the study. SES was measured based on marital status, occupation, education level, source of payment, and hospitalized class with smoking status and sex as confounder. Stroke severity was classified based on the National Institutes of Health Stroke Scale score into minor stroke (Adams et al., 1993, Amarenco et al., 2014, Andersen and Olsen, 2018, Austin and Steyerberg, 2017) and moderate to severe stroke (>4). A total of 2,443 patients with moderate to severe stroke (58%) were analyzed. Currently employed patients had a lower adjusted OR (aOR) of 0.65 (95% confidence interval [CI], 0.51-0.83) than unemployed patients. Patients with the highest education level, at least a diploma degree, had a lower aOR of 0.67 (95% CI, 0.49-0.92) than those with an elementary or no education. Our findings showed that patients with a higher SES had a lower risk of more severe stroke than those with a lower SES. Hence, we must focus on improving SES as part of stroke management.

Long-Term Resistance-Endurance Combined Training Reduces Pro-Inflammatory Cytokines in Young Adult Females with Obesity.

A sedentary lifestyle and an unhealthy diet increase the risk of obesity. People with obesity experience adipocyte hypertrophy and hyperplasia, which increases the production of proinflammatory cytokines, thereby increasing the risk of morbidity and mortality. Lifestyle modification using non-pharmacological approaches such as physical exercise prevents increased morbidity through its anti-inflammatory effects. The purpose of this study was to examine the effects of different types of exercise on decreased proinflammatory cytokines in young adult females with obesity. A total of 36 female students from Malang City aged 21.86 ± 1.39 years with body mass index (BMI) of 30.93 ± 3.51 kg/m2 were recruited and followed three different types of exercise interventions: moderate-intensity endurance training (MIET), moderate-intensity resistance training (MIRT), and moderate-intensity combined training (MICT). The exercise was performed at a frequency of 3x/week for 4 weeks. Statistical analysis was performed using the Statistical Package for Social Science (SPSS) version 21.0, using the paired sample t-test. The results revealed that serum IL-6 and TNF-α levels were significantly decreased between pre-training and post-training in the three types of exercise (MIET, MIRT, and MICT) (p ≤ 0.001). The percentage change in IL-6 levels from pre-training in CTRL was (0.76 ± 13.58%), in MIET was (-82.79 ± 8.73%), in MIRT was (-58.30 ± 18.05%), in MICT was (-96.91 ± 2.39%), and (p ≤ 0.001). There was a percentage change in TNF-α levels from pre-training in CTRL (6.46 ± 12.13%), MIET (-53.11 ± 20.02%), MIRT (-42.59 ± 21.64%), and MICT (-73.41 ± 14.50%), and (p ≤ 0.001). All three types of exercise consistently reduced proinflammatory cytokines such as serum levels of IL-6 and TNF-α.

Single 30 min treadmill exercise session suppresses the production of pro-inflammatory cytokines and oxidative stress in obese female adolescents.

OBJECTIVES: Regular treadmill exercise may result in changes in pro-inflammatory cytokines and oxidative stress. However, the way acute treadmill exercise mechanisms affect the changes in pro-inflammatory cytokines and oxidative stress in obese has not been comprehensively exposed. This study aimed to analyze the pro-inflammatory cytokines and oxidative stress between 30 min before treadmill exercise and 24 h after treadmill exercise in obese adolescents. METHODS: A total of 20 obese females aged 19-24 years were recruited from female students and given one session of treadmill exercise with an intensity of 60-70% HRmax. Thiobarbituric acid reactive substance (TBARS) was used to analyze serum levels of MDA, while enzyme-linked immunosorbent assay (ELISA) was used to analyze serum levels of TNF-α and IL-6. Moreover, the independent samples t-test with a significance level of 5% was employed to have the statistical analysis. RESULTS: The results on 24 h after treadmill exercise and delta (Δ) between CTRL and TREG showed a significant difference (p<0.001). CONCLUSIONS: This study found a decrease in pro-inflammatory cytokines and oxidative stress 24 h after treadmill exercise in obese adolescents. Therefore, treadmill exercise can be a promising strategy for preventing adolescents from obesity as well as preventing disease risks associated with oxidative stress and chronic inflammation.

Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh.

Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, early detection and understanding of the underlying mechanism of this resistance are necessary. This study evaluated the mutations in the genes related to the Antimicrobial Resistance (AMR) of the clinical isolates from Bangladeshi subjects. Whole-genome sequencing was performed on 56 isolates and the genes (such as pbp1a, rdxA, ribF, fur, gyrA, gyrB, 23S rRNA, and infB) were extracted. The reads were assembled, and the SNPs were extracted by the latest pipeline for antibiotic mutation analysis, ARIBA. The mutations and the association with the antibiotic phenotypes were evaluated using Fisher's exact test. In this study, the clarithromycin resistance rate was high, 39.3% (22/56), with the median MIC 24 mg/L ranging from 2 to 128 mg/L. The mutation of A2147G was significantly associated with resistance (p = 0.000018) but not in locus A2146G (p = 0.056). Levofloxacin also posed a high resistance. We observed that the mutation of D91N (but not D91Y) (p = 0.002) and N87K (p = 0.002) of gyrA was associated with levofloxacin resistance. Mutations in locus A343V (p = 0.041) of gyrB also showed a significant association. Meanwhile, in the pbp1a gene, several mutations might explain the resistance; they were G594fs (p = 0.036), K306R (p = 0.036), N562Y (p = 0.0006), and V45I (p = 0.018). The prevalence of metronidazole was exceptionally high (96.4%), and numerous mutations occurred in rdxA genes, including the truncation of genes. These results imply that the mutation in genes encoding the target protein of antibiotics remains the critical resistance mechanism in H. pylori.

Low-grade intestinal metaplasia in Indonesia: Insights into the expression of proinflammatory cytokines during Helicobacter pylori infection and unique East-Asian CagA characteristics.

Helicobacter pylori infection is a major cause of intestinal metaplasia. In this study, we aimed to understand the reason underlying the low grade and incidence of intestinal metaplasia in Indonesia, based on the expression of genes encoding proinflammatory cytokines in gastric biopsy specimens. The possible reasons for the lesser virulence of the East-Asian-type CagA in Indonesia than that of the Western-type CagA, which is not common in other countries, were also investigated. The mRNA expression of cytokines was evaluated using real-time PCR. CagA characteristics were analyzed using in silico analysis. The expression of cytokines was typically not robust, among H. pylori-infected subjects in Indonesia, despite them predominantly demonstrating the East-Asian-type CagA. This might partially be explained by the characteristics of the East-Asian-type CagA in Indonesia, which showed a higher instability index and required higher energy to interact with proteins related to the cytokine induction pathway compared with the other types (p < 0.001 and p < 0.05, respectively). Taken together, besides the low prevalence of H. pylori, the low inflammatory response of the host and low CagA virulence, even among populations with high infection rates, may play an essential role in the low grade and low incidence of intestinal metaplasia in Indonesia. We believe that these findings would be relevant for better understanding of intestinal metaplasia, which is closely associated with the development of gastric cancer.

A comprehensive evaluation of an animal model for Helicobacter pylori-associated stomach cancer: Fact and controversy.

Even though Helicobacter pylori infection was the most causative factor of gastric cancer, numerous in vivo studies failed to induce gastric cancer using H. pylori infection only. The utilization of established animal studies in cancer research is crucial as they aim to investigate the coincidental association between suspected oncogenes and pathogenesis as well as generate models for the development and testing of potential treatments. The methods to establish gastric cancer using infected animal models remain limited, diverse in methods, and showed different results. This study investigates the differences in animal models, which highlight different pathological results in gaster by literature research. Electronic databases searched were performed in PubMed, Science Direct, and Cochrane, without a period filter. A total of 135 articles were used in this study after a full-text assessment was conducted. The most frequent animal models used for gastric cancer were Mice, while Mongolian gerbils and Transgenic mice were the most susceptible model for gastric cancer associated with H. pylori infection. Additionally, transgenic mice showed that the susceptibility to gastric cancer progression was due to genetic and epigenetic factors. These studies showed that in Mongolian gerbil models, H. pylori could function as a single agent to trigger stomach cancer. However, most gastric cancer susceptibilities were not solely relying on H. pylori infection, and numerous factors are involved in cancer progression. Further study using Mongolian gerbils and Transgenic mice is crucial to conduct and establish the best models for gastric cancer associated H. pylori.