Oral health-related quality of life in children with celiac disease.

PURPOSE: There is limited knowledge about oral health-related quality of life (OHRQoL) in children with celiac disease (CD). This study aimed to assess OHRQoL in children with CD compared to healthy controls. METHODS: This case-control study included children with CD and healthy controls. Three scales were used to assess OHRQoL in different age groups: 6-7 years, 8-10 years, and 11-14 years. The OHRQoL scores were compared between cases and controls to examine the possible associations between OHRQoL and demographics, socioeconomic status, and oral health. RESULTS: Overall, 104 children with CD and 104 healthy children (controls) were included. The mean age was 10.67 ± 2.39 years in CD patients and 10.69 ± 2.36 in controls (P = 0.971). Male and female children constituted 50% of each group. Children with CD had significantly higher OHRQoL scores than controls (P = 0.003). Low education levels of parents of children with CD and a higher number of siblings in controls were associated with high OHRQoL scores (P = 0.002, P < 0.020, and P = 0.010, respectively). Recurrent aphthous stomatitis (RAS) increased the OHRQoL scores by 7.5 on average (P = 0.016). CONCLUSION: Children with CD had poor OHRQoL compared with healthy controls. Poor OHRQoL in children with CD was associated with RAS and with lower parental income and education. RAS was an independent predictor of poor OHRQoL in children with CD.

Prevalence and Predictors of Reduced Bone Density in Child and Adolescent Patients With Crohn's Disease.

Reduced bone mineral density (BMD) has broadly been found to be associated with inflammatory bowel disease across a number of geographical locations and cultures. We aimed to estimate the prevalence of reduced BMD and identify clinical predictors in a cohort of Crohn's disease patients (CD) in Saudi Arabia. We conducted a retrospective study involving children and adolescents with CD between 2013 and 2018. BMD was evaluated using dual-energy X-ray absorptiometry scans of the spine and body. A multivariate analysis was performed for the detection of predictors of low BMD. Sixty-four patients were enrolled. The median age was 16 years (range, 8-19 years) and 55% of patients were males. Total body BMD scanning identified 25 patients (39%) with osteoporosis. Twenty patients (31.3%) were found to have z scores consistent with osteopenia. A multivariate regression analysis identified a low weight-for-age z score (B coefficient = 0.347, 95% confidence interval [CI] = 0.211-0.482, p < 0.001 for Spine BMD and B coefficient = 0.321, 95% CI = 0.170-0.472, p < 0.001 for total body BMD), a low height-for-age z score (B coefficient = 0.187, 95% CI = 0.035-0.338, p = 0.017 for spine BMD and B coefficient = 0.0.258, 95% CI = 0.089-0.427, p = 0.004 for total body BMD), a low 25-hyroxyvitamin D level (B coefficient = 0.026, 95% CI = 0.013-0.038, p < 0.001 for spine BMD and B coefficient = 0.016, 95% CI = 0.002-0.031, p = 0.026 for total body BMD), and a higher number of corticosteroid induction courses (B coefficient = -0.567, 95% CI = -0.923 to -0.212, p = 0.003 for spine BMD and B coefficient = -0.566, 95% CI = 0.963-0.169, p = 0.007 for total body BMD) as predictors of low BMD. In the spine BMD analysis, older age at the time of presentation was identified as a significant predictor for low bone density (B coefficient = 0.254, 95% CI = 0.141-0.368, p < 0.001). In conclusion, Saudi Arabian children and adolescents with CD have a high prevalence rate of low bone density compared to Western populations. Several clinical characteristics are identified as significant predictors for low BMD.

Body composition profile of children and adolescent patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Children with inflammatory bowel disease (IBD) generally show an alteration in their fat and soft tissue mass contents. These alterations may influence disease severity and increase the risk of post-operative complications. METHODS: This is a retrospective cross-sectional study of patients with IBD, diagnosed and followed up between 2013 and 2018, in Jeddah, Saudi Arabia, who had dual-energy x-ray absorptiometry (DXA) scans for bone density evaluation. Obesity was defined based on fat mass index (FMI) and myopenia based on appendicular skeletal muscle mass (SMMa). RESULTS: This study incorporated 95 child and adolescent patients (52% female) with IBD: 59 with Crohn's disease (CD) and 36 with ulcerative colitis (UC), mean age 11.8 ± 3.3 years and mean duration of illness 1.8 ± 1.9 years. The most common disease phenotype and behaviour for CD patients were ileocolonic (57.6%) and non-stricturing and non-penetrating (76.3%). Of UC patients, 75% had extensive disease (pancolitis). Body composition profile in the total IBD cohort was classified as normal in 49.5%, obese in 26.3%, myopenic in 23.2% and myopenic-obese in 1.1%. The use of biological therapy was identified as a negative predictor for both obesity (OR = 7.0, 95% CI: 1.3-37.9, P = .02) and myopenia (OR = 0.11, 95% CI:0.02-0.47, P = .003), and female gender was shown to predict myopenia (OR = 3.5, 95% CI: 1.0-11.8, P = .04). CONCLUSIONS: Saudi Arabian children with IBD showed comparable body composition profiles to adult patients with IBD. Biological therapy was associated with a decreased incidence of both obesity and myopenia, and female gender was found to predict myopenia.

Oral and dental manifestations of celiac disease in children: a case-control study.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy. CD may also involve complications with the oral cavity, which can result in various dental and oral pathologies. There are currently a limited number of studies on the oral manifestation of CD. This study aims to compare the oral manifestations of children with CD against healthy controls in Saudi Arabia. MATERIALS AND METHODS: This study includes 208 children aged 6-14 years, distributed equally into CD patients and healthy controls. A parent completed and validated the interview questionnaire, which included the child's personal information and medical history. A dental examination was undertaken to measure possible recurrent aphthous stomatitis (RAS), dental enamel defects (DEDs), dental caries experience, and dental malocclusion. Data were analyzed using descriptive statistics and bivariate and multivariate analysis. RESULTS: Two hundred and eight participants were included (104 CD patients and 104 controls). The mean age for CD patients was 10.67 ± 2.39 years and 10.69 ± 2.36 for the healthy controls. CD children had more RAS than controls (42.3% vs. 15.4%, P < 0.001) (OR = 4.03, 95% CI = 2.09-7.81) and more DEDs than healthy controls (70.2% vs. 34.6%, P < 0.001) (OR = 4.45, 95% CI = 2.48-7.97). No significant difference was found in the frequency of malocclusion between cases and controls. CONCLUSION: Saudi Arabian children with CD had a greater number of clinical findings of RAS and DEDs than healthy controls. Pediatric dentists should consider the possibility of CD in child patients presenting with RAS or DEDs.

Colon-Targeted Therapy of Tacrolimus (FK506) in the Treatment of Experimentally Induced Colitis.

BACKGROUND/AIMS: Inflammatory bowel disease is a chronic or remitting/relapsing intestinal inflammation, which comprises Crohn's disease and ulcerative colitis (UC). Severe UC is a life-threatening condition that requires corticosteroids (CS) as a first-line rescue therapy. Some patients are refractory to CS and may require alternative immunosuppressive therapy. Oral tacrolimus (FK506), an immunosuppressive agent, has been reported to be effective in the management of severe refractory UC, but it can cause serious adverse effects. This work aims to study the effect of tacrolimus delivered by a colon-targeted delivery system (CTDS) in a dextran sulfate sodium (DSS)-induced animal model of colitis. MATERIALS AND METHODS: We developed and evaluated an oral CTDS of tacrolimus (FK506) loaded pH-dependent polymeric microspheres, composed of Eudragit® S100 as a pH-sensitive polymer using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these microparticles in gastrointestinal tract (GIT) conditions were examined. A DSS-induced colitis rat model was used to evaluate the potential remedial and in vivo distribution of microspheres. RESULTS: The pH-microspheres prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the rat GIT demonstrated that pH-microspheres were successfully delivered to the inflamed colon. Moreover, it also demonstrated a significant decrease of disease activity and expression of proinflammatory cytokines, such as tumor necrosis factor α, interleukin-1ß (IL-1ß), and IL-6, and minimized the histological and morphometric changes. CONCLUSION: The results confirmed the efficacy of tacrolimus (FK506) CTDs in the management of DSS-induced colitis.

Dental maturity in children with celiac disease: a case-control study.

BACKGROUND: Celiac disease (CD) is an immune-related enteropathy triggered by gluten ingestion in susceptible individuals. Oral manifestations of CD have been frequently described, although reports on dental maturity (DM) are scant. Thus, the aim of this study is to assess the prevalence of DM in CD patients and to test for possible predictors. METHODS: This is a case-control study of children with CD and healthy controls between 2017 and 2020. A panoramic radiograph and comprehensive oral examination were performed for each participant. Dental age (DA) was measured according to Demirjian's method and DM was calculated by subtracting the chronological age (CA) from the DA. Statistical analysis was performed to compare the DM between CD patients and controls, and a multivariate analysis was utilized to look for predictors of DM. RESULTS: Two-hundred and eight participants (104 children with CD, and 104 healthy controls) were incorporated. The mean age for CD patients was 10.67 ± 2.40 years, and 10.69 ± 2.37 years for healthy controls (P = 0.971). CD patients had a higher prevalence of delayed DM than controls (62.5% vs. 3%, respectively). They also had a greater delay in DM than controls (- 7.94 ± 10.94 vs. 6.99 ± 8.77, P < 0.001). A multivariate analysis identified age between 6 and 7 years (ß ± SE = 16.21 ± 2.58, P < 0.001), as the only predictor for DM. CONCLUSIONS: CD patients had a greater prevalence of delayed DM than controls. No predictors for DM could be found, except young age.

Inflammatory bowel disease and restless leg syndrome.

OBJECTIVE: Inflammatory bowel disease (IBD) has been associated with restless leg syndrome (RLS). This study aims to explore the prevalence, clinical predictors, and severity of RLS in IBD patients compared to controls. METHODS: We conducted a case-control study between January and December of 2019 comparing IBD patients with controls. Assessment of RLS was performed using the previously validated diagnostic restless leg syndrome questionnaire (RLSQ). Logistic regression analyses were applied to investigate associations between patient demographics and clinical features and RLS diagnosis. RESULTS: A total of 218 IBD patients and 211 healthy controls were incorporated after excluding 6 patients with positional discomfort and 4 patients with habitual foot tapping. The mean age was 30.2+/-11.7 and 64% were females. The prevalence of RLS was 16/218 (7.34%) and 17/211 (8.06%) among cases and controls, respectively. Based on the RLSQ severity score, 6/16 (37.5%), 4/16 (25%) and 1/16 (6.3%) of the IBD patients with RLS had mild, moderate and severe RLS; respectively. The odds of IBD were lower among patients with confirmed RLS (OR=0.90, 95% CI=0.44-1.84, p=0.78). In the logistic regression analysis, only vitamin B12 deficiency (OR=10.20, 95% CI=1.40-74.10, p=0.022) was associated with RLS diagnosis among IBD patients. CONCLUSION: No difference was found in the prevalence of RLS between IBD patients and non-IBD controls. Vitamin B12 deficiency was associated with RLS diagnosis among patients with IBD.

An explanatory mixed methods study on the validity and validation of students' assessment results in the undergraduate surgery course.

BACKGROUND/PURPOSE: There is inadequate evidence of reported validity of the results of assessment instruments used to assess clinical competence. This study aimed at combining multiple lines of quantitative and qualitative evidence to support interpretation and use of assessment results. METHOD: This study is a mixed methods explanatory research set in two stages of data collection and analysis (QUAN : qual). Guided by Messick's conceptual model, quantitative evidences as reliability and correlation coefficients of various validity components were calculated using students' scores, grades and success rates of the whole population of students in 2012/2013 and 2013/2014 (n= 383; 326). The underlying values that scaffold validity evidences were identified via Focus Group Discussions (FGD) with faculty and students; sampling technique was purposive; and results were analyzed by content analysis. RESULTS: (1) Themes that resulted from content analysis aligned with quantitative evidences. (2) Assessment results showed: (a) content validity (table of specifications and blueprinting in another study); (b) consequential validity (positive unintended consequences resulted from new assessment approach); (c) relationships to other variables [a statistically significant correlation among various assessment methods; with combined score (0.64-0.86) and between mid and final exam results (r = 0.672)]; (d) internal consistency (high reliability of MCQ and OSCE: 0.81, 0.80); (3) success rates and grades distribution alone could not provide evidence to advocate an argument on validity of results. CONCLUSION: The unified approach pursued in this study created a strong evidential basis for meaningful interpretation of assessment scores that could be applied in clinical assessments.

Comprehensive Computational Analysis of GWAS Loci Identifies CCR2 as a Candidate Gene for Celiac Disease Pathogenesis.

Celiac disease (CD) is a gluten intolerance disorder with known genetic contribution. The recent fine mapping and genome-wide association studies (GWAS) have identified up to 57 non-HLA CD susceptibility SNPs, majority of which are non-coding variants lacking any functional annotation. Therefore, we adopted multidimensional computational approach for uncovering the plausible mechanisms through which these GWAS SNPs are connected to CD pathogenesis. At initial phase, we identified that 25 (43.85%) out of 57 CD-SNPs lies in evolutionarily constrained genetic element regions. In follow-up phases, through computational (CADD, GWAVA, and FATHMM algorithms) deleterious intensity measurements, we have discovered that 42 (3.94%) out of 1065 variants (57 CD-lead and 1008-linked SNPs; r2 ≥ 0.8) are differentially deleterious in nature to CD. Further functional scrutinization of these CD variants by public domain eQTL mapping, gene expression, knockout mouse model, and pathway analyses revealed that deleterious SNPs of CCR2 gene influences its expression levels and may also elicit a cascade of T-cell-mediated immunological events leading to intestinal gluten intolerance in genetically susceptible individuals. This study demonstrates the utility of integrated in silico analysis of annotations, gene expression, and pathways in prioritizing the potential complex disease variants from large-scale open source genomic data. J. Cell. Biochem. 118: 2193-2207, 2017. © 2017 Wiley Periodicals, Inc.

Expression of CD200R1 and its Ligand CD200 on T-helper Lymphocytes of Pediatric Patients with Ulcerative Colitis and Crohn's Disease.

BACKGROUND: CD200 and its receptor CD200R are both type I membrane glycoproteins that modulate the activity of myeloid and lymphoid cells, and their interaction is functionally important in the suppression of effector T-cell responses by regulatory T-cells. We aimed to investigate the extent of expression of CD200 and CD200R1 on CD4+ T-cells in blood of children with ulcerative colitis (UC) and Crohn's disease (CD) and to explore their correlations with effector T cell subsets, regulatory T cells (Treg), and routine clinical and serological markers. METHODS: The frequencies of blood CD4+ expressing CD200 and CD200R1 as well as T-helper CD4+CD25+Foxp3+ Treg, CD4+ IL-17+ (Th17), CD4+ IFN-γ + (Th1), and CD4+IL-4+ (Th2) were estimated by flow cytometry in 23 patients with CD, 14 with UC, and 14 healthy volunteers (HCs). The clinical and inflammatory markers were also investigated. RESULTS: IBD patients showed decreased CD4+CD200R1+ T-cells, whereas, CD4+CD200+ T-cells were significantly higher in patient groups compared with healthy controls. Treg cells were found significantly decreased in the patients with UC and CD compared with healthy controls (both at p < 0.01). The percentage of Th17 was found significantly increased in CD (p < 0.05) compared with UC patients and healthy subjects (p = 0.014). CD200+CD4+ T-cells showed significant positive correlations with ESR, Th1, and Th17 (r = 0.438, p < 0.05; r = 0.411, p < 0.05; r = 0.492, p < 0.01, respectively). CD200R1+CD4+ T-cells correlated positively with Th2 and Treg (r = 0.482, p < 0.01, and r = 0.457, p < 0.01, respectively) and negatively with ESR (r = -0.387, p < 0.01). CONCLUSIONS: Our study demonstrates an aberrant expression of CD200/CD200R1 on CD4+ T-cells in IBD patients and these data may have potent pathological significance in IBD pathophysiology.

Reduced Dendritic Cells Expressing CD200R1 in Children with Inflammatory Bowel Disease: Correlation with Th17 and Regulatory T Cells.

Loss of tolerance of the adaptive immune system towards indigenous flora contributes to the development of inflammatory bowel diseases (IBD). Defects in dendritic cell (DC)-mediated innate and adoptive immune responses are conceivable. The aim of this study was to investigate the expression of the inhibitory molecules CD200R1 and their ligand CD200 on DCs, to clarify the role of the DCs in the pathogenesis of IBD. Thirty-seven pediatric IBD patients (23 with Crohn's disease (CD) and 14 with ulcerative colitis (UC)) with mean age 13.25 ± 2.9 years were included. Fourteen age-matched healthy pediatric volunteers (five males and nine females) served as a control group (HC). The percentage of CD11c⁺ myeloid dendritic cells (mDCs) and CD123⁺ plasmacytoid DCs (pDCs) expressing CD200R1 and CD200 were evaluated in peripheral blood using flow cytometry and were correlated with routine biochemical, serological markers, serum levels of cytokines and with the percentages of circulating regulatory T cells (Treg) and CD4⁺ producing IL-17 (Th17). IBD patients showed a significant decrease in the percentage of pDCs and mDCs expressing CD200R1 compared to that of HC. Patients with UC showed increased expressions of the CD200 molecule on pDCs as compared to HC. DCs expressing CD200R1 were found to be correlated positively with Treg and negatively with TH17 and erythrocyte sedimentation rate (ESR). Our findings suggest that IBD is associated with dysregulation in the CD200R1/CD200 axis and that the decrease in DCs expressing CD200R1 may contribute to the imbalance of Th17 and Treg cells and in the pathogenesis of IBD.

Prevalence of Esophageal Eosinophilia, Eosinophilic Esophagitis, and Lymphocytic Gastritis in Children with Celiac Disease: A Saudi Tertiary Center Experience.

Background: Celiac disease (CD) is an immune-mediated enteropathy that has been associated with other immune-related gastrointestinal disorders, such as eosinophilic esophagitis (EoE) and lymphocytic gastritis (LG). To our knowledge, this is the first study in Saudi Arabia that has described such an association. Aim: To evaluate the prevalence of EoE and LG in children and adolescents with CD. Methods: This was a retrospective cross-sectional study of all pediatric patients (aged 0-18 years) with CD following up at King Abdulaziz University Hospital, between January, 2014, and December, 2021. The study examined clinical, demographic, endoscopic, and histopathological data. Results: Seventy-five patients with CD were included in the analysis. The median age was 12 years (range, 2-18 years). Male constituted 54.7% of the overall cohort (n = 41). The most common clinical symptoms were short stature (54.7%), weight loss (34.7%), abdominal pain (33.3%), abdominal distension (29.3%), anorexia (29.3%), diarrhea (24%), and vomiting (21.3%). The esophageal biopsy results reported were basal cell hyperplasia in 24 patients (32.9%), esophageal eosinophilia in 23 patients (31.5%), and EoE in 3 patients (4.1%). The gastric biopsy results were normal in 40 patients (53.3%). The most common abnormality was chronic inactive gastritis with no Helicobacter pylori (HP) infection (16%). LG was found in 3 patients (4%). Conclusions: The prevalence of EoE in this cohort of patients with CD was lower than the prevalence recorded in a number of other studies. Further studies are needed to determine the effects of a gluten-free diet (GFD) on EOE and LG.

Pediatric inflammatory bowel disease with cytoplasmic staining of antineutrophil cytoplasmic antibodies.

BACKGROUND: It is unusual for the antineutrophil cytoplasmic antibody with cytoplasmic pattern (cANCA) to present in patients with inflammatory bowel disease (IBD) without vasculitis. The purpose of this study was to describe the occurrence and characteristics of pediatrics IBD with cANCA. METHODS: A retrospective review of pediatric IBD associated with cANCA serology in patients from King Abdulaziz University Hospital, Saudi Arabia, between September 2002 and February 2012. RESULTS: Out of 131 patients with IBD screened for cANCAs, cANCA was positive in 7 (5.3%) patients of whom 4 had ulcerative colitis and 3 had Crohn's disease. The median age was 8.8 years (2-14.8 years). Six (86%) were males. Of the 7 patients, 5 (71%) were Saudi Arabians and 2 were of Indian ethnicity. The most common symptoms were diarrhea, abdominal pain, weight loss, and rectal bleeding. None had family history or clinical features suggestive of vasculitis involving renal and respiratory systems. No difference in the disease location or severity was observed between cANCA positive and cANCA negative patients apart from male preponderance in cANCA positive patients. CONCLUSION: The occurrence of cANCA in pediatric IBD is rare. Apart from male preponderance, there were no peculiar characteristics for the cANCA positive patients.

Adverse drug reactions in hospitalized pediatric patients of Saudi Arabian University Hospital and impact of pharmacovigilance in reporting ADR.

OBJECTIVES: Children are more vulnerable to ADRs, and this susceptibility is compounded due to hospitalization. There is a lack of local data regarding the potential risk of ADRs in hospitalized pediatric patients. Therefore, this study is designed to identify the frequent nature, severity of adverse drug reactions, drugs implicated and factors influencing ADRs. METHODS: Intensive monitoring study of ADRs was done in hospitalized pediatric patients of King Abdulaziz University Hospital, Jeddah from January to December 2011, with an analogous retrospective study for the preceding year to determine incidence rate, demographic aspects, causality appraisal, polypharmacy, body organs/systems involved and drugs implicated in ADR. Comparison of the two data was done to determine the impact of pharmacovigilance. RESULTS: Incidence rate of ADRs in retrospective study was (4.50%) and (8.2%) in prospective study. ADR was more in patients who received 5-6 drugs, which was (15.5%) in retrospective study and (22.1%) in prospective study. Regarding age, it was the highest in patients of 0-1 year of age which was (40.7%) in retrospective study and (38.8%) in prospective study. Anti-infective agents were the most frequently involved in ADR (40.8%) in prospective study and (48.2%) and retrospective study. This study also demonstrated that, there was high susceptibility of the skin to the ADR which was (37%) in retrospective study and (42.9%) in prospective study. None of the ADRs proved to be fatal. CONCLUSION: Well premeditated intensive monitoring approach in pharmacovigilance amplifies the ADR detection, which can persuade healthcare providers into more drug safety.

Incidence and clinical characteristics of pediatric inflammatory bowel disease in Oman.

Background: Pediatric inflammatory bowel disease (PIBD) has been documented all over the world, and there is now a large body of clinical, pathological, and treatment knowledge and protocols in place in many countries. There is currently limited knowledge on the prevalence and pathology of PIBD in Omani population. The aim of this study is to report the incidence and clinical features of PIBD in Oman. Methods: This was a retrospective, cross-sectional, multicenter study carried out on all children <13 years of age between January 1, 2010 and December 31, 2021. Results: Fifty-one children were identified, 22 males (43.1%) and 29 females (56.9%), who were mostly from the Muscat region of Oman. The median incidence in the country was 0.57 (confidence interval [CI]: 0.31-0.64) per 105 children for inflammatory bowel disease (IBD), 0.18 (CI: 0.07-0.38) per 105 children for ulcerative colitis (UC), and 0.19 (CI: 0.12-0.33) per 105 children for Crohn's disease (CD). There was a significant increase in the incidence of all PIBD types after the year 2015. Bloody diarrhea was the most common symptom, followed by abdominal pain. Perianal disease affected nine children (40.9%) with CD. Conclusion: The incidence of PIBD in Oman is lower than in some neighboring Gulf countries but similar to that of Saudi Arabia. An alarming upward trend was noted from the year 2015. Large-scale population-based studies are required to investigate the possible causes of this increasing incidence.

Inflammatory bowel disease in the elderly: A focus on disease characteristics and treatment patterns.

Background: As the population ages, the number of elderly inflammatory bowel disease (IBD) patients is expected to increase. The clinical features and therapeutic options for young and old patients may differ, as elderly IBD patients are likely to have different comorbidities and disease characteristics. The goal of this study was to examine the clinical aspects and therapeutic choices for elderly Saudi IBD patients. Methods: We conducted a retrospective study aimed at describing the demographic, clinical, and management characteristics of IBD in elderly patients (≥60 years) who followed up at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. The data was extracted from the KAUH inflammatory bowel disease information system (IBDIS) registry. The primary outcome was to describe disease characteristics in accordance with the Montréal classification and the secondary outcomes were to describe treatment patterns and identify significant clinical associations. Results: Our data were collected from 76 patients who fulfilled the study inclusion criteria. Females outnumbered males (53.9% vs 46.1%) and the mean age was 51.5 ± 9.7 years. Essential hypertension (26.3%) was the most common comorbidity followed by diabetes mellitus (23.6%), and malignant neoplasms (9.21%). More than half of the patients with Crohn's disease (CD) had disease onset after forty years of age. The most common form of disease distribution was ileocolonic disease (64.7%). Less than 17% of patients had a penetrating disease phenotype. About 88 percent of patients with UC presented >40 years of age. Approximately, half of the cohort had left-sided ulcerative colitis (UC) (48%), followed by pancolitis (40%). The most prescribed medication class for IBD was 5-aminosalicylic acid (5-ASA) derivatives (56.58%) followed by corticosteroids and immunosuppressive drugs. Conclusions: In Saudi Arabia, age-specific concerns including comorbidities and polypharmacy remain the major challenges in the management of elderly IBD patients.

Composition of the gut microbiota in patients with inflammatory bowel disease in Saudi Arabia: A pilot study.

Conclusions: The results of this study provide an overview of the variations in microbiota diversity present in Saudi IBD patients compared to healthy controls. Results: The key finding was three negative bacterial biomarkers, Paraprevotellaceae, the Muribaculaceae families of Bacteroidetes phylum, and the Leuconostocaceae family of Firmicutes phylum, which had a higher relative abundance in healthy individuals compared to IBD patients. It was also found that primary microbiota signatures at certain genera and species levels, including Prevotella copri, Bifidobacterium adolescentis, Ruminococcus callidus, Coprococcus sp., Ruminococcus gnavus, Dorea formicigenerans, Leuconostoc, Dialister, Catenibacterium, Eubacterium biforme, and Lactobacillus mucosae, were absent in almost all IBD patients, while Veillonella dispar was absent in all healthy individuals. Methods: After obtaining an informed consent, fecal samples were collected from 11 participants with IBD (patients) and 10 healthy individuals (controls). The bacterial components of the microbial population were identified by next-generation sequencing of partial 16S rRNA. Statistically significant dissimilarities were observed between samples for all metrics. Background: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition attributed to a complex interaction between imbalances in the gut microbiome, environmental conditions, and a deregulated immune response. The aim of the study was to investigate the composition of the gut microbiome of Saudi patients with IBD.

Protein structural insights into a rare PCSK9 gain-of-function variant (R496W) causing familial hypercholesterolemia in a Saudi family: whole exome sequencing and computational analysis.

Familial hypercholesterolemia (FH) is a globally underdiagnosed genetic condition associated with premature cardiovascular death. The genetic etiology data on Arab FH patients is scarce. Therefore, this study aimed to identify the genetic basis of FH in a Saudi family using whole exome sequencing (WES) and multidimensional bioinformatic analysis. Our WES findings revealed a rare heterozygous gain-of-function variant (R496W) in the exon 9 of the PCSK9 gene as a causal factor for FH in this family. This variant was absent in healthy relatives of the proband and 200 healthy normolipidemic controls from Saudi Arabia. Furthermore, this variant has not been previously reported in various regional and global population genomic variant databases. Interestingly, this variant is classified as "likely pathogenic" (PP5) based on the variant interpretation guidelines of the American College of Medical Genetics (ACMG). Computational functional characterization suggested that this variant could destabilize the native PCSK9 protein and alter its secondary and tertiary structural features. In addition, this variant was predicted to negatively influence its ligand-binding ability with LDLR and Alirocumab antibody molecules. This rare PCSK9 (R496W) variant is likely to expand our understanding of the genetic basis of FH in Saudi Arabia. This study also provides computational structural insights into the genotype-protein phenotype relationship of PCSK9 pathogenic variants and contributes to the development of personalized medicine for FH patients in the future.

Transition Readiness Into Adult Health Care in Children With Inflammatory Bowel Disease.

Background and aim Approximately 25% of inflammatory bowel disease (IBD) cases are diagnosed before the age of 18 years. Compared to adults, pediatric IBD is more aggressive and progresses rapidly. It is important to have a well-structured transition process in place when patients are transferred from pediatric to adult care. We aimed to evaluate the readiness of Saudi adolescents with IBD to be transitioned from pediatric to adult care using the Transition Readiness Assessment Questionnaire (TRAQ). Materials and methods This cross-sectional study was carried out at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, between January and December 2021. Pediatric patients aged between 12-18 with confirmed IBD were recruited. The mean TRAQ component and the overall scores were calculated and analyzed. Results A total of 54 patients with IBD were included. The overall mean TRAQ scores were moderately high (3.60±0.78), including high mean values for individual domains of the TRAQ. In terms of components of TRAQ, no significant differences between males and females were encountered; however, there was a trend for males having higher scores than females in tracking health issues (P=0.07). Patients older than 15 years had higher overall scores than younger patients (P=0.04). The level of child education was found to be the only independent variable that correlated with higher overall scores (P=0.005). Conclusions In this cohort of Saudi adolescents with IBD, patients showed moderately high overall mean TRAQ scores reflecting high readiness for transitioning. While males demonstrated a trend for higher scores compared to females in tracking health issues, patients older than 15 had higher total scores relative to younger patients. More studies are needed to examine the impact of better transition readiness on the long-term outcome of IBD.

Predictors of biliary atresia outcome: Saudi National Study (2000 - 2018).

Background: Outcomes in biliary atresia (BA) have been well-documented in large national cohorts from Europe, North America, and East Asia. Understanding the challenges that preclude success of the Kasai portoenterostomy (KPE) is the key to improve the overall outcomes of BA and implementing intervention strategies. Here, we analyzed the data from the Saudi national BA study (204 BA cases diagnosed between 2000 and 2018) to identify the prognostic factors of BA outcomes. Methods: One hundred and forty-three cases underwent KPE. Several prognostic factors (center case load, congenital anomalies, serum gamma-glutamyl transferase, use of steroids, ascending cholangitis post-operatively, and degree of portal fibrosis at time of KPE) were investigated and correlated with the primary outcomes of interest: 1) success of KPE (clearance of jaundice and total serum bilirubin <20 mmol/l after KPE), 2) survival with native liver (SNL), and 3) overall survival. Results: Use of steroids after KPE was associated with clearance of jaundice, 68% vs. 36.8% in the BA cases that did not receive steroids (P = 0.013; odds ratio 2.5) and a significantly better SNL rate at 2 - and 10-year of 62.22% and 57.77% vs. 39.47% and 31.57%, respectively (P = 0.01). A better 10-year SNL was observed in centers with caseload <1/year (group 1) as compared to centers that performed ≥1/year (group 2) [45.34% vs. 26.66%, respectively; P = 0.047]. On comparison of the 2 groups, cases in group 1 had KPE at significantly earlier age (median 59.5 vs. 75 days, P = 0.006) and received steroids after KPE more frequently than group 2 (69% vs. 31%, P < 0.001). None of the remaining prognostic variables were identified as being significantly related to BA outcome. Conclusion: Steroids use post-KPE predicted clearance of jaundice and better short- and long-term SNL. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize the pre- and post-operative clinical practices and facilitate clinical and basic research to evaluate factors that influence BA outcome.