Patients with chronic liver disease (CLD) and liver transplant recipients are at increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19). Although several studies demonstrated the safety and efficacy of COVID-19 vaccines in the general population, data in CLD patients and liver transplant recipients are lacking. Two COVID-19 vaccines were approved by the Saudi Food and Drug Authority and rolled out to several million recipients in Saudi Arabia. These vaccines are mRNA-based vaccine BNT162b2 from Pfizer/BioNTech and adenovirus-based AZD1222 from Oxford/AstraZeneca from three manufacturing sites (EU Nodes, Serum Institute of India, and South Korea Bio). The Saudi Association for the Study of Liver diseases and Transplantation (SASLT) has reviewed the available evidence and issued interim recommendations for COVID-19 vaccination in CLD and liver transplant recipients. Since there is no evidence contradicting the safety and immunogenicity of the currently approved COVID-19 vaccines in patients with CLD and hepatobiliary cancer and liver transplant recipients, the SASLT recommends vaccination in those patient populations. CLD and hepatobiliary cancer patients and liver transplant recipients should be prioritized depending on the risk factors for severe COVID-19. In transplant recipients, the optimal timing of vaccination remains unknown; however, immunization is recommended after the initial immunosuppression phase. Patients with CLD and liver transplant candidates or recipients should be closely monitored after COVID-19 vaccination. These patient populations should be included in future clinical trials to provide further evidence on the efficacy and safety of COVID-19 vaccines.

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In contrast to previous perceptions that inflammatory bowel disease (IBD) patients are generally malnourished and underweight, there is mounting evidence to suggest that rates of obesity in IBD now mirror that of the general population. IBD is an immune-mediated condition that appears to develop in individuals who have not only a genetic predisposition to immune dysregulation but also likely exposure to various environmental factors which further potentiate this risk. With the surge in obesity alongside the rising incidence of IBD, particularly in developing nations, the role that obesity may play, not only in the pathogenesis but also in the natural history of disease has become a topic of growing interest. Currently available data exploring obesity's impact on the natural history of IBD are largely conflicting, potentially limited by the use of body mass index as a surrogate measure of obesity at varying time points throughout the disease course. While there are pharmacokinetic data to suggest possible detrimental effects that obesity may have on the response to medical therapy, results in this realm are also inconsistent. Moreover, not only is it unclear whether weight loss improves IBD outcomes, little is known about the safety and efficacy of available weight-loss strategies in this population. For these reasons, it becomes increasingly important to further understand the nature of any interaction between obesity and IBD.

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Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. RNA-binding proteins (RBPs) regulate essential biological processes and play essential roles in a variety of cancers. The present study screened differentially expressed RBPs, analyzed their function and constructed a prognostic model to predict the overall survival of patients with CRC. Methods: We downloaded CRC RNA-sequencing data from the Cancer Genome Atlas (TCGA) portal and screened differentially expressed RBPs. Then, functional analyses of these genes were performed, and a risk model was established by multivariate Cox regression. Results: We obtained 132 differentially expressed RBPs, including 66 upregulated and 66 downregulated RBPs. Functional analysis revealed that these genes were significantly enriched in RNA processing, modification and binding, ribosome biogenesis, post-transcriptional regulation, ribonuclease and nuclease activity. Additionally, some RBPs were significantly related to interferon (IFN)-alpha and IFN-beta biosynthetic processes and the Toll-like receptor signaling pathway. A prognostic model was constructed and included insulin like growth factor 2 messenger ribonucleic acid binding protein 3 (IGF2BP3), poly (A) binding protein cytoplasmic 1 like (PABPC1L), peroxisome proliferator activated receptor gamma coactivator 1 alpha (PPARGC1A), peptidyl- transfer ribonucleic acid hydrolase 1 homolog (PTRH1) and tudor domain containing 7 (TDRD7). The model is an independent risk factor for clinicopathological characteristics. Conclusion: Our study provided novel insights into the pathogenesis of CRC and constructed a prognostic gene model, which may be helpful for determining the prognosis of CRC.

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Background: Colorectal cancer (CRC) screening is cost-effective in many Western countries, and many have successfully implemented CRC screening programs. For countries with a lower CRC incidence, like Saudi Arabia, the value of CRC screening is less evident and requires careful weighing of harms, benefits, and costs. Methods: We used the MISCAN-Colon microsimulation model to simulate a male and female cohort with life expectancy and CRC risk as observed in Saudi Arabia. For both cohorts, we evaluated strategies without screening, with annual or biennial faecal immunochemical testing (FIT), and with 10-yearly or once-only colonoscopy. We also considered different start and end ages of screening. For both cohorts, we estimated lifetime costs and effects of each strategy. We then identified a set of potentially cost-effective strategies using incremental cost-effectiveness ratios (ICERs) defined as the additional cost per additional quality-adjusted life year (QALY). Results: Without CRC screening, an estimated 14 per 1,000 males would develop CRC during their lifetime and 9 would die from CRC. Several strategies proved potentially cost-effective including biennial FIT at ages 55-65 (ICER of $7,400), once-only colonoscopy at age 55 (ICER of $7,700), and 10-yearly colonoscopy at ages 50–65, 45–65, and 45–75 (ICERs of $34,000, 71,000, and 375,000, respectively). For females, risk of CRC was lower and CRC screening was therefore less cost-effective, but efficient strategies were largely similar. Conclusions: Despite low CRC incidence in Saudi Arabia, some FIT or colonoscopy screening strategies may meet reasonable thresholds of cost-effectiveness. The optimal strategy will depend on multiple factors including the willingness to pay per QALY, the colonoscopy capacity, and the accepted budget impact.

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Background: Infliximab (IFX) and calcineurin inhibitors (cyclosporine [CYS] and tacrolimus [TAC]) were considered as rescue therapy in steroid-refractory ulcerative colitis (UC). The objective of our study was to perform a meta-analysis evaluating the short-term and long-term efficacy and safety of IFX and calcineurin inhibitors in steroid-refractory UC. Methods: We systematically searched the databases from inception to September 2020 that evaluated IFX, CYS, and TAC in steroid-refractory UC. The primary outcome was the response rates, remission rates, mucosal healing rates, and colectomy rates after therapy initiation. The secondary outcomes were the rates of adverse events (AE), serious adverse events (SAE), and mortality. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated. Results: Nineteen studies comprising 1323 Acute severe ulcerative colitis (ASUC) patients were included in the meta-analysis. Among the non-randomized studies, a significantly higher therapeutic response rate was seen with IFX treatment, with a pooled OR of 3.15 (95% CI 2.26–4.40). Among non-randomized studies, IFX was associated with a significantly lower first-year OR (0.46 [95% CI 0.27–0.79]), second-year (OR 0.53 [95% CI 0.28–0.97]), third-year (OR 0.43 [95% CI 0.24–0.75]) colectomy rate. But the randomized controlled trials (RCTs) did not suggest any difference between IFX and CYS as rescue therapies for steroid-refractory UC. There were no significant differences among IFX, CYS, and TAC in the rates of AE, SAE, or mortality. Conclusion: Our meta-analysis suggested a better treatment response rate and lower risk of colectomy in the first, second and third year, with IFX, compared with CYS in steroid-refractory UC patients. There was no significant difference among IFX and calcineurin inhibitors in AE, SAE, and mortality.

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Background: The utilization rate of different treatment regimens for Helicobacter pylori infection is believed to be high; however, the cost-effectiveness of these regimens has not been examined before. Therefore, the aim of this study was to examine the cost-effectiveness of the two commonly prescribed treatments for H. pylori infection. Methods: The data of an open-label, single-center, randomized trial that compared the efficacy of sequential therapy (SQT) (i.e., esomeprazole 20 mg twice daily for 10 days, amoxicillin 1000 mg twice daily for 5 days, then clarithromycin 500 mg and tinidazole 500 mg twice daily for 5 days) to standard triple therapy (STT) (i.e., esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 twice daily for 14 days) in the eradication of H. pylori, as confirmed by the negative urea breath test (UBT), were used. Propensity score matching bin bootstrapping, with 10,000 replications and bias correction was conducted to generate the 95% confidence limits. Moreover, probabilistic sensitivity analysis was conducted by varying both the eradication rates and the costs of treatment regimens. Results: There were 82 and 88 patients who were on SQT and STT, respectively. Patients' mean age was 47 years, and approximately 55% of them were females. The mean treatment costs were SAR 2,075.51 (USD 553.47) and SAR 2,629.26 (USD 701.14) for SQT and STT, respectively. The mean eradication rates for SQT and STT were 63.41% and 67.05%, respectively. The mean difference in costs and eradication rates for SQT versus STT were SAR − 550.75 (95% CI: −563.84- −537.69) and − 3.64% (95% CI: −6.98- 5.88). The use of SQT was more likely to be cost saving and more effective with 56.25% confidence level, in comparison to STT. Conclusion: The use of SQT in the treatment of H. pylori seems to be more cost-effective than STT.

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Background: Nucleotide-binding oligomerization domain-containing two (NOD2/CARD15) gene polymorphisms are implicated in the pathogenesis of Crohn's disease (CD). Aim: To describe the allelic frequency of NOD2/CARD15 gene variants among Kuwaiti patients with CD and investigate potential genotype/phenotype associations. Methods: Adult Kuwaiti citizens with an established diagnosis of CD and healthy controls were enrolled from October 2018 to May 2020. Three common NOD2/CARD15 polymorphisms (R702W, G908R, and L1007fs) and P268S and IVS8⁺¹⁵⁸ polymorphisms were screened by polymerase chain reaction/restriction analysis length polymorphism (PCR/RFLP). Results: Ninety adult Kuwaiti patients with CD and 210 healthy subjects (as controls) were recruited. P268S, IVS8⁺¹⁵⁸, G908R, and R702W minor alleles were identified in 38.9%, 21.1%, 12.2%, and 4.4% of CD patients, respectively. NOD2/CARD15 polymorphisms coexisted in 35 healthy controls (16.7%) and 21 CD patients (23.3%). Individuals with either a single or multiple polymorphism were approximately two times more likely to have CD than those with no polymorphism. Patients with multiple polymorphisms had significantly more stricturing and penetrating disease. Conclusion: NOD2/CARD15 gene polymorphisms were significantly associated with an increased risk of disease and aggressive phenotypes among the Kuwaiti CD population.

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Background: The aim of this study was to compare the efficacy and tolerability of polyethylene glycol (PEG) in single- or split-dose regimens for colonoscopy bowel preparation. Methods: This is a prospective, randomized, endoscopist blinded, single-center study, that included adult patients who underwent colonoscopy during the period from December 2017 to October 2018. Two groups were enrolled in the same period: One group used 4 L of PEG (Nulytely) in a single-dose preparation, administered a day before the procedure, and the other group received a split-dose regimen of 2 L PEG (Nulytely), given a day before the procedure and 2 L on the day of the procedure in the early morning. The Boston Bowel Preparation Scale (BBPS) was used for bowel preparation adequacy; scales 0 and 1 were considered inadequate, and scales 2 and 3 were considered adequate preparation. Results: Two hundred and forty patients were enrolled, 120 (50%) using the split-dose regimen and 120 (50%) using the single-dose regimen, for bowel preparation. Males constituted 51.6% of the study cohort. In the single-dose group, 62.5% achieved adequate bowel preparation compared to 89.2% in the split-dose group (p< 0.001). In addition, polyp detection in the split-dose group was 23.3% in comparison to 10.8% in the single-dose group (P = 0.016). We also found hypertension and diabetes as significant predictors of bowel preparation inadequacy, while sex and age were not related to bowel preparation adequacy. Conclusions: Split-dose bowel preparation for colonoscopy with PEG (Nulytely) is better than routine single-dose, in terms of adequate bowel preparation and polyp detection.

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Background: Mutations in NOD2/CARD15 gene have been linked to an increased risk of Crohn's disease (CD). The objective of this study is to determine NOD2/CARD15 gene mutations, and their association with the risk of CD in Arabs in Kuwait. Methods: Four NOD2 gene mutations, including Pro268Ser (SNP5), Arg702Trp (SNP8), Gly908Arg (SNP12), and Leu1007FsinsC (SNP13) were examined in Arab CD patients (n = 103) and control subjects (n = 100). The genomic DNA was isolated and used in polymerase chain reaction (PCR) with four sets of specific primers. The PCR-amplified DNA fragments were sequenced and analyzed for the NOD2 mutations. Logistic regression was used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results: Of the four genotyped variants, the Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) variants were not informative in our study sample due to minor allele frequency of <1%. The Pro268Ser (SNP5) mutation was detected in 17 (16.5%) CD patients and 32 (32.0%) controls. The Gly908Arg (SNP12) mutation was observed in 24 (23.3%) patients and 10 (10.0%) controls. In the dominant genetic risk model (i.e. carrying at least one minor allele), CD patients compared to controls were less likely to carry either the “CT” or “TT” genotype of variant Pro268Ser (SNP5; aOR = 0.43, 95% CI: 0.22–0.84). In contrast, CD patients compared to controls were more likely to carry the homozygous for the minor allele or the heterozygous genotypes of variant Gly908Arg (SNP12; aOR = 2.67, 95% CI: 1.19–5.97). Conclusions: In this Arab population, carrying at least one copy of the minor allele of Gly908Arg (SNP12) mutation in NOD2 gene was associated with increased susceptibility to CD, while having the heterozygous or homozygous for the minor allele genotype of the Pro268Ser (SNP5) mutation provided protection against CD. Mutations in Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) were not detected in this sample of the Arab population in Kuwait.

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