Cost-Consequence Analysis of Colon Cancer Screening among Patients with Long-Standing Ulcerative Colitis: 11 Years' Experience of Saudi Population.

Background: Clinical guidelines recommend that patients with long-standing ulcerative colitis (UC) should undergo periodic surveillance colonoscopy. However, the cost and clinical value of performing annual colonoscopy among high-risk patient populations is largely unknown in the Middle East. Therefore, this study aimed to examine the cost and consequence of annual colonoscopy among high-risk UC patients in Saudi Arabia. Methods: A retrospective cohort study was conducted on UC patients who had UC for ≥ 8 years or had primary sclerosing cholangitis (PSC) at any time during their disease,and underwent colonoscopy surveillance between 2010 and 2021 at a university-affiliated tertiary care center. Patients who underwent annual screening were considered adherent, and those who did not were considered non-adherent. The dysplasia detection rate (%) and the costs were expressed in United States Dollars (USD). To generate the 95 % confidence intervals for annual cost and clinical consequence, nonparametric bias-corrected accelerated bootstrapping with 10,000 simulations were conducted. Results: Two-hundred and sixty-one UC patients met the inclusion criteria and were included. Most of the patients 54 % (141 patients), were non-adherent to annual screening, and the patients' mean age and duration of illness were 45 years and 15 years, respectively. The mean annual direct medical costs were USD 10,210.6 for patients who adhered to the annual screening program and USD 6,191.77 for those who did not adhere. The mean rates of dysplasia detection were 1.66 % and 7.09 % for patients who adhered and patients who did not adhere to annual colonoscopy, respectively. The difference in costs and rates of dysplasia detections between those who adhered to the annual screening and those who did not were USD 4,018.88 (95 % CI: 3097.46 - 6,798.06) and -5.43 % (95 % CI: -10.019 - -1.58730), respectively, resulting in an incremental cost-effectiveness ratio (ICER) of USD 740.125 per 1 % reduction in the rates of dysplasia. According to the bootstrap cost effectiveness distributions, adherence to the annual screening for UC patients would result in higher cost and lower rates of dysplasia development with more than 99 % confidence level. Conclusion: Adherence to annual colonoscopy screening detects more dysplasia in UC patients but with an increased cost. Considering the low rate of progression to colorectal cancer among UC patients, the annual screening might not be cost effective.

Using single-operator cholangioscopy for endoscopic evaluation of indeterminate biliary strictures: results from a large multinational registry.

BACKGROUND: Peroral cholangioscopy (POCS) of indeterminate biliary strictures aims to achieve a diagnosis through visual examination and/or by obtaining targeted biopsies under direct visualization. In this large, prospective, multinational, real-life experience of POCS-guided evaluation of indeterminate biliary strictures, we evaluated the performance of POCS in this difficult-to-manage patient population. METHODS: This prospective registry enrolled patients, with indeterminate biliary strictures across 20 centers in Asia, the Middle East, and Africa. The primary end points were the ability to visualize the lesion, obtain histological sampling when intended, and an assessment of the diagnostic accuracy of POCS for malignant strictures. Patients were followed for 6 months after POCS or until a definitive malignant diagnosis was made, whichever occurred first. RESULTS: 289 patients underwent 290 POCS procedures with intent to biopsy in 182 cases. The stricture/filling defect was successfully visualized in 286/290 (98.6 %), providing a visual diagnostic impression in 253/290 (87.2 %) and obtaining adequate biopsies in 169/182 (92.9 %). Procedure-related adverse events occurred in 5/289 patients (1.7 %). POCS influenced patient management principally by elucidating filling defects or the causes of bile duct stricture or dilation. The visual impression of malignancy showed 86.7 % sensitivity, 71.2 % specificity, 65.8 % positive and 89.4 % negative predictive value, and 77.2 % overall accuracy compared with final diagnosis. Histological POCS-guided samples showed 75.3 % sensitivity, 100 % specificity, 100 % positive and 77.1 % negative predictive value, and 86.5 % overall accuracy. CONCLUSION: In this large, real-life, prospective series, POCS was demonstrated to be an effective and safe intervention guiding the management of patients with indeterminate biliary strictures.

Cholangioscopy-guided lithotripsy for difficult bile duct stone clearance in a single session of ERCP: results from a large multinational registry demonstrate high success rates.

BACKGROUND: Peroral cholangioscopy (POCS) can be useful for difficult bile duct stone clearance. Large prospective multinational data on POCS-guided lithotripsy for clearing difficult bile duct stones in a single session of endoscopic retrograde cholangiopancreatography (ERCP) are missing. METHODS: Patients with difficult bile duct stones (defined as one or more of: largest stone diameter ≥ 15 mm, failed prior attempt at stone clearance, impacted, multiple, hepatic duct location, or located above a stricture) were enrolled at 17 centers in 10 countries. The principal endpoint was stone clearance in a single ERCP procedure using POCS. RESULTS : 156 patients underwent 174 sessions of POCS-guided electrohydraulic or laser lithotripsy. Stone clearance had failed in a previous ERCP using traditional techniques in 124/156 patients (80 %), while 32 /156 patients (21 %) were referred directly to POCS-guided therapy based on preprocedural assessment of the difficulty of stone clearance. In 101/156 patients (65 %), there were impacted stones. POCS-guided stone clearance was achieved in a single POCS procedure in 125 /156 patients (80 %, 95 % confidence interval [CI] 73 % - 86 %), and was significantly more likely for stones ≤ 30 mm compared with > 30 mm (odds ratio 7.9, 95 %CI 2.4 - 26.2; P = 0.002). Serious adverse events occurred in 3/156 patients (1.9 %, 95 %CI 0.4 % - 5.5 %), and included pancreatitis, perforation due to laser lithotripsy, and cholangitis (n = 1 each), all resolved within 1 week. CONCLUSION: POCS-guided lithotripsy is highly effective for clearance of difficult bile duct stones in a single procedure and successfully salvages most prior treatment failures. It may also be considered first-line therapy for patients with difficult choledocholithiasis to avoid serial procedures.

Drug utilization and cost associated with inflammatory bowel disease management in Saudi Arabia.

BACKGROUND: There has been an increase in incidence and prevalence of inflammatory bowel disease (IBD) outside the western countries. Treatment costs are an essential component for healthcare planning and priority setting. The utilization patterns and annual administration and cost of IBD medications are largely unknown in countries with an increasing incidence of disease, Saudi Arabia being an example. AIM: To evaluate the use of non-biologic and biologic agents and their associated annual administration costs in a sample of patients with Crohn's disease (CD) and ulcerative colitis (UC) in Saudi Arabia. METHODS: Single-center retrospective chart review was performed to determine the use of biologic and non-biologic medications among IBD patients in a tertiary care hospital in Riyadh, Saudi Arabia. Daily and the annual acquisition cost of different IBD therapeutic agents was calculated. The utilization rates and cost of each type of medication by CD and UC patients were compared. RESULTS: Data of 258 CD patients and 249 UC patients were analyzed. Infliximab and adalimumab were the most commonly prescribed biologics among the study sample, however, their utilization rates were significantly higher among CD than UC patients (36.82% vs. 11.24%, and 20.54% vs. 9.64%, respectively, P < 0. 01). Azathioprine utilization rate was also higher among CD patients compared to their UC counterparts (71.71% vs. 40.16%, respectively, P < 0.01). However, the utilization rate of mesalazine in the UC patients was significantly higher than their CD counterparts (85.53% vs. 14.34% for CD, P < 0.01). The annual cost of biologics (including administration and lab test cost) ranged from 5572 USD for ustekinumab to 18,424 USD for vedolizumab. On the other hand, the annual cost of non-biologics ranged from 16 USD for prednisone to 527 USD for methotrexate. CONCLUSION: Biologics are extensively used in the management of IBD, particularly CD, and their utilization costs are significantly higher than non-biologics. Future studies should examine the cost effectiveness of IBD medications especially in countries with increasing incidence such as Saudi Arabia.

The effectiveness of vedolizumab in advanced therapy-experienced ulcerative colitis patients: Real world data from the Inflammatory Bowel Disease of the Middle East (IBD-ME) Registry group.

BACKGROUND: Vedolizumab is an approved ulcerative colitis (UC) treatment. Multiple large randomized clinical trials have demonstrated the drug's efficacy and safety. However, real-world data from Middle Eastern countries are spare. The study aims to evaluate the clinical efficacy of vedolizumab (VDZ) therapy in advanced therapy experienced UC patients. METHODS: A retrospective electronic chart review of a cohort study of 153 moderately to severely active UC patients who failed or were intolerant to TNF antagonists and received vedolizumab from two large tertiary care centers was performed. Rates of clinical response and remission were retrospectively evaluated at 3,6, and 12 months post VDZ therapy using Patient Simple Clinical Colitis Activity Index (P-SCCAI); clinical response was defined as a decrease in P-SCCAI ≥3, and clinical remission was defined as a P-SCCAI score of ≤3 points. Logistic regression analysis was used to identify predictors of response to vedolizumab. RESULTS: A total of 153 UC patients had sufficient data for analysis. Clinical remission rates were 61.9% for patients on vedolizumab every 8 weeks and 89.3% for those receiving every 4 (Q4) weeks dosing. A significant reduction in CRP and improvement of albumin post vedolizumab treatment were observed, and corticosteroids were stopped in most patients. In a multiple logistic regression analysis, several factors were found to influence the clinical effectiveness of VDZ in inducing remission. Female gender was associated with a higher likelihood of remission [OR =3.09, 95% CI = (1.05-9.13), P = 0.04]. Conversely, a greater number of biologics used prior to VDZ treatment was associated with a lower likelihood of remission [OR =0.418, 95% CI = (0.203-0.859), P = 0.017]. Patients with extensive disease (E3) had an increased likelihood of remission [OR =3.81, 95% CI = (1.32-10.97), P = 0.0129]. Additionally, a VDZ dosing frequency of Q4 weeks was associated with a significantly higher likelihood of remission [OR =6.08, 95% CI = (1.73-21.39), P = 0.0049]. No significant safety signals were reported. CONCLUSIONS: In this current real-world study, vedolizumab effectively achieved clinical response and remission in most advanced therapy experienced UC patients treated for up to 12 months. Future studies with larger sample sizes and more robust study designs should be conducted to further validate the results of this study.

LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency.

BACKGROUND: Clinical immunology has traditionally relied on accurate phenotyping of the patient's immune dysfunction for the identification of a candidate gene or genes for sequencing and molecular confirmation. Although this is also true for other branches of medicine, the marked variability in immune-related phenotypes and the highly complex network of molecules that confer normal host immunity are challenges that clinical immunologists often face in their quest to establish a specific genetic diagnosis. OBJECTIVE: We sought to identify the underlying genetic cause in a consanguineous family with chronic inflammatory bowel disease-like disorder and combined immunodeficiency. METHODS: We performed exome sequencing followed by autozygome filtration. RESULTS: A truncating mutation in LPS-responsive beige-like anchor (LRBA), which abolished protein expression, was identified as the most likely candidate variant in this family. CONCLUSION: The combined exome sequencing and autozygosity mapping approach is a powerful tool in the study of atypical immune dysfunctions. We identify LRBA as a novel immunodeficiency candidate gene the precise role of which in the immune system requires future studies.

The Prevalence and Knowledge of Digital Eye Strain Among the Undergraduates in Riyadh, Saudi Arabia.

Aim/background Digital eye strain, also called computer vision syndrome (CVS), is a group of symptoms resulting from prolonged computer, tablet, e-reader, and cell phone use. The level of discomfort and the severity of these symptoms appear to increase with the amount of digital screen use. These symptoms include eyestrain, headaches, blurred vision, and dry eyes. This study aims to assess the changes in the prevalence of digital eye strain among college students in Riyadh, Saudi Arabia. Methods A cross-sectional study was conducted among university students at different college institutions in Riyadh, Saudi Arabia. Subjects were interviewed, and the data were collected using an online questionnaire. The questionnaire was composed of student demographic data, students' general knowledge and risk perception of digital eye strain, and the assessment of CVS symptoms questionnaire. Results Of the 364 university students, 55.5% were females, and 96.2% were aged between 18 and 29 years. A significant proportion of university students (84.6%) were using digital devices for five hours or more. The proportion of university students who were aware of the 20-20-20 rule was 37.4%. The overall prevalence of positive for CVS symptoms was 76.1%. Independent risk factors for CVS symptoms were gender female, ocular disorders, and using digital devices at a shorter distance. Conclusion There was a high prevalence of CVS symptoms among university students in our region. Female students with an ocular disease were more likely to exhibit CVS symptoms than other university students, but using a digital device at a longer distance could alleviate the symptoms of CVS. A longitudinal study is needed to establish the effect of CVS symptoms among university students, especially during the post-pandemic era.

The Long-Term Clinical Effectiveness of Ustekinumab in Antitumor Necrosis Factor-Experienced Crohn's Disease Patients.

Background Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) of unknown etiology. Ustekinumab (UST), an interleukin (IL)-12 and IL-23 antibody, has been approved in the recent years to treat IBD, both Crohn's disease and ulcerative colitis. This study clarifies the long-term effectiveness of ustekinumab (UST) in antitumor necrosis factor (anti-TNF) refractory Crohn's disease in Middle Eastern patients. Methods A retrospective review study, including 30 refractory or medication-intolerant patients with Crohn's disease, was conducted at a tertiary care center in Riyadh, Saudi Arabia. The patients were started on ustekinumab and followed up for at least 52 weeks. Follow-up was performed on weeks 12, 24, and 52. Data related to demographic and laboratory parameters, the dosing schedule of ustekinumab administration, and the Harvey-Bradshaw index (HBI) were collected. Clinical remission and response rates were assessed. Statistical analysis was performed using SPSS Statistics version 28.0 (IBM Corp., Armonk, NY, USA). A statistical significance threshold of p < 0.05 was adopted. Results The mean age of the study subjects was 34.2 ± 17.9 years (95% confidence interval (CI): 27.5-40.9), with a mean disease duration of 10.6 ± 4.9 years (95% CI: 8.8-12.5). Of our cohort, 56.7% failed two biologics during their disease course, and about 20% failed three different biologics. The percentage of patients who used thiopurines was 76.7%, while 6.7% used methotrexate. Concurrent immunomodulators were used by 58.6% of the patients. Corticosteroids were given to 13.3% of the patients. Intravenous induction of UST at 6 mg/kg was used for 90% of the patients, while only 10% used a 260 mg subcutaneous dose. At week 12, 73.3% of the patients had a clinical response, and 66.7% achieved clinical remission. Corticosteroid-free remission, clinical response, and clinical remission showed a decreasing percentage trend between weeks 12 and 24 compared to week 52 where a spike was observed in all aforementioned parameters. The clinical response rate at week 52 was 76.7%. The p-values from cross-tabulation were significant for clinical response and remission when comparing week 12 to weeks 24 and 52. Conclusion Ustekinumab presents a safe and effective treatment option in moderate to severe Crohn's disease patients with previous exposure to multiple biologics.

Rate and risk factors of postoperative endoscopic recurrence of moderate- to high-risk Crohn's disease patients - A real-world experience from a Middle Eastern cohort.

Background: Crohn's disease (CD) frequently recurs after intestinal resection. Azathioprine (AZA) and biological therapies have shown efficacy in preventing postoperative recurrence (POR). Data on POR from Middle Eastern populations is lacking. This study aimed to evaluate the rate of endoscopic POR in a cohort of CD patients who underwent ileocecal resection (ICR), and to assess the effectiveness of AZA and biological therapies in reducing the risk of disease recurrence. Methods: We performed a retrospective cohort study on 105 CD patients followed at our center, who underwent ileal resection and were at moderate to high risk for POR. Clinical and laboratory data were collected; the primary endpoint was post ICR endoscopic recurrence at 24 months defined by Rutgeerts' score of i2 or more despite treatment. Results: In total, 105 patients with Crohn's disease met our inclusion criteria; 76.2% were in remission and did not have endoscopic POR at 24 months. Further, 41.9% were on biological therapy, and 34.3% were mainly on AZA. Out of the 28.2% who had POR, approximately 15% were on biological therapies. Penetrating phenotype was the only predictive factor for decreasing POR (OR = 0.19, 95% CI: 0.04-0.98, P = 0.04) as identified in multiple logistic regression analysis. Conclusions: The use of biological therapies post-surgery was not superior than AZA in reducing the endoscopic POR for mod- high risk CD patients. Only penetrating behavior of the CD was associated with significantly lower risk of endoscopic recurrence. This finding is worth further investigation in more robust study designs and among larger samples of patients.

Predictors of Anti-TNF Therapy Failure among Inflammatory Bowel Disease (IBD) Patients in Saudi Arabia: A Single-Center Study.

BACKGROUND: The advent of monoclonal antibodies (mAbs) has revolutionized the management of many immune-mediated diseases such as inflammatory bowel disease (IBD). Infliximab and adalimumab were the first mAbs approved for the management of IBD, and are still commonly prescribed for the treatment of both Crohn's disease (CD) and ulcerative colitis (UC). Although mAbs have demonstrated high effectiveness rates in the management of IBD, some patients fail to respond adequately to mAbs, resulting in disease progression and the flare-up of symptoms. OBJECTIVE: The objective was to explore the predictors of treatment failure among IBD patients on infliximab (INF) and adalimumab (ADA)-as demonstrated via colonoscopy with a simple endoscopic score (SES-CD) of ≥1 for CD and a Mayo score of ≥2 for UC-and compare the rates of treatment failure among patients on those two mAbs. METHODS: This was a prospective cohort study among IBD patients aged 18 years and above who had not had any exposure to mAbs before. Those patients were followed after the initiation of biologic treatment with either INF or ADA until they were switched to another treatment due to failure of these mAbs in preventing the disease progression. Univariate and multiple logistic regressions were conducted to examine the predictors and rates of treatment failure. RESULTS: A total of 146 IBD patients (118 patients on INF and 28 on ADA) met the inclusion criteria and were included in the analysis. The mean age of the patients was 31 years, and most of them were males (59%) with CD (75%). About 27% and 26% of the patients had penetrating and non-stricturing-non-penetrating CD behavior, respectively. Patients with UC had significantly higher odds of treatment failure compared to their counterparts with CD (OR = 2.58, 95% CI [1.06-6.26], p = 0.035). Those with left-sided disease had significantly higher odds of treatment failure (OR = 4.28, 95% CI [1.42-12.81], p = 0.0094). Patients on ADA had higher odds of treatment failure in comparison to those on INF (OR = 26.91, 95% CI [7.75-93.39], p = 0.0001). CONCLUSION: Infliximab was shown to be more effective in the management of IBD, with lower incidence rates of treatment failure in comparison to adalimumab.

Prevalence, severity and associated factors of restless leg syndrome in inflammatory bowel disease patients.

BACKGROUND: The association between restless leg syndrome (RLS) and inflammatory bowel disease (IBD) has often been an under-investigated and clinically misdiagnosed entity. An emphasis should be made on the severity and associated factors, as the prevalence of both entities is on the rise globally. In this study we aimed to investigate the prevalence, severity and associated risk factors of RLS in patients with IBD. METHODS: A multi-center, prospective cross-sectional study was conducted with age and gender matched controls in the ratio of 1:3. Cases of IBD were confirmed according to European Crohns and Colitis Organization guidelines. The study recruited 377 cases and 1131 age and gender-matched controls. RLS severity and prevalence was determined using a validated International Restless Legs Syndrome Study Group questionnaire. The anthropometric and blood biochemical measurements were retrieved from the patient's medical records. Associated factors were analyzed by regression analysis. RESULTS: The prevalence of RLS in patients with IBD and non-IBD control groups was 21.5% and 9.7%, respectively (P = 0.001). The severity index of RLS symptoms in all the three categories of mild, moderate and severe RLS was higher in the IBD group (P = 0.001). Obesity (BMI >30 Kg/m2) was more prevalent in patients with IBD with RLS than without RLS (21.9%: 10.3%, P = 0.009). Ages between 46 and 59 years (OR = 18.7 [2.6-29.4], P = 0.008), obesity (OR = 22 [2.6-29.4], P = 0.005), higher TSH levels (OR = 1.7 [1.0-3.0], P = 0.033), and lower hemoglobin levels (P = 0.028) showed a greater risk associated with RLS. CONCLUSION: Prevalence and severity of RLS was higher in patients with IBD. The risk factors for RLS in IBD include increasing age, obesity, higher TSH, and lower hemoglobin.

Time trends of causes of upper gastrointestinal bleeding and endoscopic findings.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a frequent cause for emergency endoscopy and, in a proportion, requires the application of endotherapy. We aim to evaluate the proportion of variceal and nonvariceal upper gastrointestinal bleeding (NVUGIB), the endoscopic findings that were detected, as well as the temporal trends of endoscopic findings over a period of 13 years. METHODS: This is a retrospective study of patients who underwent an esophagogastroduodenoscopy with an indication of UGIB or presented with hematemesis, melena, or both, as well as those who had hematochezia, from January 2004 to December 2016 (13 years). RESULTS: A total of 2075 patients were included with a mean age of 56.8 years (range 18-113) and males constituted 67.9%, while 65.9% had at least one comorbidity. Symptoms on presentation included hematemesis (52.5%), melena (31.2%), both hematemesis & melena (15.1%), and hematochezia (1.2%). The majority of UGIB were from a NVUGIB source (80.5%) and a variceal source was found in 13.1%, while no endoscopic findings were found in 6.4% of cases. The most common endoscopic diagnosis was gastroduodenal erosions (23.8%), duodenal ulcers (23.5%), reflux esophagitis (16.0%), esophageal varices (12.1%), and gastric ulcers (10.8%). There was no change in the endoscopic findings over the time period of the study. A third of duodenal ulcers (33.3%) as well as 21.9% of gastric ulcers were actively bleeding at the time of endoscopy, while 3.3% of duodenal ulcers had an adherent clot. CONCLUSIONS: NVUGIB composed the majority of cases presenting with UGIB and variceal bleeding was lower than that described in prior studies, but there were no clear trends in the proportion of causes of UGIB during the study duration.

Clinical characteristics, natural history, and outcomes of Crohn's-related intra-abdominal collections.

BACKGROUND: Intra-abdominal collections in the form of abscesses or matted bowel loops, called phlegmons, might occur in patients with Crohn's disease (CD). The clinical characteristics and management of such conditions are not well described. We aim to characterize CD-related intra-abdominal collections clinically, and identify predictors of need for surgical interventions and the time to surgery. METHODS: We utilized the Saudi Inflammatory Bowel Disease Information System (IBDIS) database to identify all patients treated for radiologically proven intra-abdominal abscesses or phlegmons since inception. Demographics, clinical data, clinical course, and treatment outcomes were recorded. Logistic regression analysis and survival analysis were used to identify predictors of surgical resection and differences in time to surgery between patient subgroups, respectively. RESULTS: A total of 734 patients with a diagnosis of CD were screened and 75 patients were identified. The mean age was 25.6 ± 9.9 years and 51% were males. Nearly 60% of patients had abscesses larger than 3 cm while 13% had smaller abscesses and 36% had phlegmons. On presentation, the most commonly reported symptom was abdominal pain (99%) followed by weight loss (27%). About 89% of patients were treated with antibiotics during hospitalization for an average of 2.7 weeks. Steroids were prescribed for 52% of patients and tumor necrosis factor alpha (TNF-alpha) antagonists for 17%. Surgical resection was required for 33 patients (44% of the cohort) while 51% were managed with antibiotics and/or percutaneous drainage. The most common surgical intervention was ileocecal resection (45%). Although patients who underwent follow-up imaging were more likely to require early surgical intervention (P = 0.04), no statistically significant predictor of surgery could be identified from this cohort. Time to surgery varied numerically according to abscess size (HR = 1.18, 95% CI = 0.62-2.27, P = 0.61). CONCLUSIONS: Although the majority of patients with CD-related intra-abdominal collections underwent surgical resection in this cohort, no obvious predictors of surgical intervention could be identified. The decision to perform early surgery appeared to be influenced by the findings observed on cross-sectional imaging during the follow-up of these collections.

Impact of infliximab therapeutic drug level monitoring on outcomes of patients with inflammatory bowel disease: A real-world experience from a Middle Eastern cohort.

BACKGROUND AND STUDY AIM: Therapeutic drug monitoring (TDM) through measurement of infliximab (IFX) trough levels and antibodies to infliximab (ATI) is performed to guide IFX intensification strategies and improve its efficacy. We conducted this study to explore the relationship between clinical and endoscopic/radiological remission and IFX and ATI levels in patients with inflammatory bowel disease (IBD) treated with IFX and to evaluate the appropriateness of treatment decision post TDM. PATIENTS AND METHODS: This was a cross-sectional study of a cohort of adult patients with IBD. Serum IFX trough concentrations and ATI were measured. RESULTS: A total of 129 patients [104] with ulcerative colitis (UC) and 25 with Crohn's disease (CD)] were included in this study, of whom 61.2% were men. The mean disease duration was 6.7 years, and 72% of patients with UC had extensive colitis. The mean serum IFX trough level was 4.1 µg/mL; the IFX trough levels were subtherapeutic in 75 patients (58%), therapeutic in 37 patients (29%), and supratherapeutic in 17 patients (13%). Positivity to ATI was found in 16 patients (12.4%). Only 43 patients (33.3%) underwent an appropriate change in therapy after TDM, patients with penetrating CD disease had low IFX levels and higher C-reactive protein levels at 12 months before TDM. CONCLUSIONS: Patients with IBD with therapeutic IFX levels tend to have increased endoscopic/radiological remission rates. However, an appropriate change in management based on TDM was absent in the majority of patients, potentially reflecting the need to have a dashboard to support and guide clinicians in decision-making.

NOTCH Single Nucleotide Polymorphisms in the Predisposition of Breast and Colorectal Cancers in Saudi Patients.

Breast cancer (BC) is a heterogeneous disease and is one of the most common malignancy affecting women worldwide while colorectal cancer (CRC) is estimated to be the third common cancer and second leading cause of cancer related death globally. Both BC and CRC involve multiple genetic and epigenetic alterations in genes belonging to various signaling pathways including NOTCH that has been implicated in the development of these cancers. We investigated four single nucleotide polymorphisms, each in genes encoding NOTCH1-4 receptors for their role in susceptibility to breast and colorectal cancers in Saudi population. In this case-control study, TaqMan genotypic analysis of rs3124591 in NOTCH1 and rs3820041 in NOTCH4 did not exhibit association with breast as well as colorectal cancers. However, a strong association of rs11249433 which is in close proximity to NOTCH2 was observed with breast cancer susceptibility especially with those having an early onset of the disease. Interestingly, the rs1043994 located in NOTCH3 showed gender preference and was found to be significantly associated with colorectal cancers in males. Validation of these findings in bigger populations of different ethnicities may prove beneficial in identifying rs11249433 and rs1043994 as genetic screening markers for early detection of breast and colorectal carcinomas, respectively.

Expression and Polymorphism of TSLP/TSLP Receptors as Potential Diagnostic Markers of Colorectal Cancer Progression.

Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer-related mortality worldwide. Inflammation is considered as a critical driver for CRC development and growth. We investigated the association between polymorphisms/expression levels of thymic stromal lymphopoietin (TSLP) /TSLP receptors and CRC risk in Saudi population. DNA samples were isolated from blood samples from 220 participants. Case subjects were 112 patients diagnosed with CRC, while control subjects were 108 healthy individuals, who were not diagnosed with any type of malignancy. We selected two single nucleotide polymorphisms (SNPs) located in the thymic stromal lymphopoietin gene (rs10043985 and rs2289276), three SNPs in TSLP receptor gene (TSLPR; rs36139698, rs36177645, and rs36133495), and two other SNPs in interleukin-7 receptor gene (IL-7R; rs12516866 and rs1053496), and designated these SNPs for a case-control genotyping study. The gene expression was analyzed using quantitative RT-PCR and immunohistochemistry assays array on 20 matching colorectal cancer/normal tissues. mRNA expressions and protein levels of TSLP, TSLPR-α subunit, and IL-7R-α subunit showed a 4-fold increase in colon cancer tissues when compared to normal colon tissues. Furthermore, two SNPs (rs10043985 of TSLP and rs1053496 of IL-7R) showed statistically significant correlations with CRC susceptibility. Interestingly, only rs10043985 showed a statistically significant association (p < 0.0001) in the genotypic and phenotypic levels with CRC for all clinical parameters (age, gender, and tumor location) tested. However, IL-7R rs1053496 genotyping results presented a significant correlation (p < 0.05) in male CRC patients and in individuals under 57 years of age. TSLP rs2289276, IL-7R rs12516866, and all TSLPR variants did not display any significant genotypic or phenotypic correlations in all tested clinical parameters. This study identified that TSLP rs10043985 and IL-7R rs1053496 SNPs, and the expression levels of TSLP and TSLPR-α subunit, can be used as markers for CRC development and treatment. However, additional investigations are required on larger group of patients from diverse ethnicities to confirm the genetic association of these variants to CRC.

Upper gastrointestinal bleeding: Causes and patient outcomes.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) remains a healthcare burden and is associated with considerable morbidity and mortality. We aim to describe the presentation, clinical, and laboratory characteristics of patients presenting with UGIB as well as important patient outcomes. METHODS: This is a retrospective study performed at a tertiary care university hospital in Riyadh. Electronic endoscopic reports of patients undergoing gastroscopies for the indication of UGIB from January 2006 to January 2015 were included. Demographic data, past medical conditions, medications used, symptoms on presentation, as well as the patients' hemodynamic status, laboratory investigations on presentations, the need for blood products, the need for admission to an intensive care unit, rebleeding, and in-hospital mortality rates were retrieved from medical records. RESULTS: Two hundred fifty-nine patients were included with a mean age of 57.1 years and males constituted 66.8% of the study cohort. At least one comorbidity was present in 88.2%, while 20.7% had a history of prior UGIB, 12.6% had a history of peptic ulcer disease, and 9.2% had known esophageal varices. A nonvariceal source represented 80.1% of the causes (95% CI: 75.4 to 85.3%), 15.5% required admission to the intensive care unit (ICU), the rebleeding rate was 8.9% (95% CI; 5.7% to 12.2%) while the in-hospital mortality was 4.4% (95% CI; 2.4% to 6.9%). The mean pre-endoscopic Rockall score was 2.6 (range: 0 to 5), while the total Rockall score was 4.4 (range: 1 to 9). There was no association between the pre-endoscopic Rockall score and rebleeding (3.0 vs. 2.5, P = 0.27) or need for ICU admission (3.2 vs. 2.4, P = 0.08), the total Rockall score and rebleeding (5.0 vs. 4.4, P = 0.58) or need for ICU admission (5.0 vs. 4.3, P = 0.36). CONCLUSION: Causes of UGIB in this patient population were predominantly nonvariceal and the rebleeding and mortality rates resembled those of other studies.

Association of HER1 and HER2 Gene Variants in the Predisposition of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is a major health concern worldwide. A series of sequential accumulation of genetic and epigenetic changes are responsible for the initiation and progression of diseases via the normal > adenoma > carcinoma sequence. Genetic variants in crucial cancer-causing genes are known to mediate the risk of cancer. OBJECTIVE: In this case-control study, we examined single nucleotide polymorphism (SNP) in HER1 (rs763317 and rs3752651) and HER2 (rs1136201 and rs1058808) genes to assess their role in the susceptibility of CRC in a Saudi population. METHODS: TaqMan allelic discrimination assay was utilized to identify the genotypes in 163 normal and 143 CRC patients. RESULTS: In the overall analysis, the rs3752651 and rs1136201 were significantly associated with the risk of CRC. Although none of the examined SNPs had any impact on the age at which CRC was diagnosed, interestingly, three SNPs showed a significant association based on gender. The rs3752651 conferred significant protection only in men, whereas rs1136201 diminished the risk and rs1058808 considerably increased the susceptibility of CRC only in women. CONCLUSIONS: Our result suggests that these SNPs in HER1 and HER2 after validation in larger cohorts of different ethnicities may be utilized as genetic screening markers for predicting colorectal cancer predisposition.

Seroprevalence rates of Helicobacter pylori and viral hepatitis A among adolescents in three regions of the Kingdom of Saudi Arabia: is there any correlation?

BACKGROUND: The seroprevalence rate of Helicobacter pylori in the Kingdom of Saudi Arabia (KSA) was reported to be in the range of 50-80% among mostly symptomatic patients in non-community-based studies. However, the seroprevalence of viral hepatitis A (HAV) underwent a marked decline in the last two decades from over 50% in 1989 to 25% in 1997 among Saudi children under the age of 12 years. The aim of this paper was to study seroprevalence rates of H. pylori and HAV among the adolescent population in three regions of KSA and to determine whether there was any correlation between them. MATERIALS AND METHODS: We randomly selected 1200 16-18-year-old students from three regions around KSA. Demographic data, including socioeconomic status (SES), were recorded, and each student was tested for the presence of H. pylori-IgG antibodies and anti-HAV-IgG. RESULTS: The results indicate a high H. pylori infection rate (47%) among this age group. Boys had a higher prevalence than girls (p = .03), and the Al-Qaseem region had the highest prevalence (51%, p = .002). SES did not contribute to the high prevalence rates (p = .83). A cross-tabulation of data showed that 88 (8%) of the teenagers were seropositive and that 512 (44%) were negative for both H. pylori and HAV antibodies (χ(2) = 0.03, OR = 0.97, CI = 0.70-1.34). The agreement between H. pylori and HAV seropositivity was lower than would be predicted by chance (κ = -0.03). The variables that were independently associated with seropositivity to H. pylori were being female (OR = 0.75, 95% CI = 0.60-0.95) and living in the Madinah region (OR = 0.72, 95% CI = 0.55-0.94). CONCLUSION: The prevalence of H. pylori in this group of adolescents was high. However, there was no correlation between H. pylori and HAV infection rates. Hence, factors contributing to the transmission source and route seem to be different.