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.

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.

Outcomes of Endoscopic Closure of Respiratory Esophageal Fistula in Children Using the Esophageal Approach: A Case Series.

Repository-esophageal fistula (REF) in children includes congenital or acquired tracheoesophageal fistula (TEF) and pleuro-esophageal fistula (PEF). TEF is a well-known congenital anomaly that is managed surgically. Recurrent tracheoesophageal fistula (rTEF) occurring after surgical repair of TEF is not an uncommon complication and most of the time requires repeat surgery. The aim of this paper is to report the outcomes of endoscopic closure of REF in children in Oman. This is a retrospective case series describing the endoscopic closure of REF in children in the Royal Hospital (RH), Oman. Five cases were identified with one of them having acquired PEF while the rest had rTEF. All children had esophageal endoscopic closure of the esophageal fistula using endoclips, cauterization, and glue injection. The patient who had PEF had successful closure of the fistula and only one out of four with rTEF had successful endoscopic closure. Esophageal endoscopic approach is unsatisfactory in the closure of rTEF but could be effective in the closure of inflammatory PEF. An esophageal approach for the closure of rTEF may need to be consolidated with simultaneous bronchoscopic closure.

Granulomatous hepatitis in a Saudi child with IL2RA defect: a case report and literature review.

Interleukin-2 receptor alpha (IL2RA) defect (OMIM- # 606367) is an immune disease where affected patients are vulnerable to developing recurrent microbial infections in addition to lymphadenopathy and dermatological manifestations. This condition is known to be caused by pathogenic variants in the IL2RA gene, which are inherited in an autosomal recessive fashion. In this case report, we present a patient with IL2RA defect from Saudi Arabia who presented with chronic diarrhea, poor weight gain, mild villous atrophy, malnutrition, hepatomegaly, nonspecific inflammation, and an eczematous skin rash. His genetic analysis revealed a novel, homozygous, and likely pathogenic variant, that is, c.504 C>A (Cys168Ter), located in the exon 4of the IL2RA gene, which was inherited from his parents in an autosomal recessive mode of inheritance. This variant produces a 272-amino-acid shorter IL2RA protein chain, which most likely becomes degraded in the cytosol. Thus, we assume that the c.504 C>A is a null allele that abolishes the synthesis of IL2RA, malforms the IL-2 receptor complex, and eventually causes immunodeficiency manifestations. To our knowledge, this is the first time a person with IL2RA defect has shown signs of granulomatous hepatitis on a liver biopsy.

Magnetic resonance enterography and bowel ultrasonography in Saudi Arabian patients with Crohn's disease: A correlation study.

Background: Crohn's disease (CD) is a complex autoimmune disease that results in chronic inflammation of the gastrointestinal tract. CD activity is determined through clinical, laboratory, endoscopic, and radiological evaluations. Studies that examine the data of radiological modalities of evaluation are lacking, particularly in Saudi Arabia. This study compares magnetic resonance enterography (MRE) and ultrasonography (US) findings among patients diagnosed with CD, to uncover a possible correlation between these techniques. Methods: All patients were assessed for disease activity using MRE and US. Results: A total of 376 patients with CD were recruited. The mean age was 14.9 ± 4.3 years (range, 8-27 years), and males constituted 64% (n = 239) of the cohort. Overall, a strong positive correlation was found between US and MRE evaluations of disease activity (r = 0.83, P < 0.001). US activity correlated positively with MRE findings of enlarged lymph nodes (P < 0.001), bowel wall enhancement (P < 0.001), distal jejunal thickness (P < 0.001), and distal ileal thickness (P < 0.001). The mean difference in wall thickness was significant based on gender (P < 0.001), age in proximal jejunal thickness (P < 0.001), and distal ileal thickness (P = 0.011). Conclusions: MRE and US correlate significantly as imaging techniques for the assessment of CD activity.

Attributes of intestinal microbiota composition and their correlation with clinical primary non-response to anti-TNF-α agents in inflammatory bowel disease patients.

The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn's disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae-previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy.

Factors Affecting Ulcerative Colitis Flare-Ups: Associations With Smoking Habits and Other Patient Characteristics.

Background and study aims Currently, there are no studies conducted in the Kingdom of Saudi Arabia (KSA) that have assessed the relationship between ulcerative colitis (UC) flare-ups and smoking. The present study aims to assess the risk of UC flare-ups and evaluate the relationship between UC flare-ups and smoking in adult patients following up at King Abdulaziz University Hospital in Jeddah, KSA. Patients and methods This was a retrospective study involving patients with confirmed UC between January 2015 and December 2020. Various information was examined, including demographic, clinical, endoscopic, radiologic, and laboratory data. Descriptive statistics were used for summarizing findings and a logistic regression analysis was applied to test for possible associations. Results Eighty-nine patients with UC were included in the study. Almost half (48.3%) had recurrent UC flare-ups during follow-up. A non-significant relationship was found between recurrent UC flares and all types of smoking habits (cigarette smoking, P = 0.15; shisha smoking, P = 0.88; and vape smoking, P = 0.09). Participants who were underweight (P = 0.041), had family history of UC (P = 0.013), depression (P = 0.033), fecal incontinence (P = 0.003), iron deficiency anemia (P = 0.009), or a malignancy (P = 0.039) had a significantly higher probability of experiencing recurrent flares. Binary logistic regressions revealed that family history of UC (OR = 5.3, P = 0.007) and fecal incontinence (OR = 4.7, P = 0.006) were associated significantly with recurrent flares. Conclusion There was no clear association between smoking and recurrent UC flares identified in this cohort. Of the variables considered, UC patients with fecal incontinence or family history of UC were at the highest risk of developing recurrent flares.

Solitary rectal ulcer syndrome in children and adolescents: a descriptive clinicopathologic study.

Solitary rectal ulcer syndrome (SRUS) is an uncommon disorder of the rectum. While benign, it can cause concern for patients and affect quality of life. Reported studies on SRUS worldwide are scarce. The aim of this study is to describe the clinicopathologic characteristics of SRUS in a cohort of children based in Saudi Arabia. In this study, children with a confirmed diagnosis of SRUS at King Abdulaziz University Hospital (KAUH) were included, during the period November 2003 to November 2017. Data were collected from hospital medical records. The study comprised twenty-one patients: 17 males (81%) and 4 females (19%); the median age was 11.4 years (range, 5.43-17.9 years). The most common presenting symptoms were rectal bleeding in 21 patients (100%), passage of mucus in 16 (76.1%), abdominal pain in 14 (66.6%), constipation in 13 (61.9%), straining in 9 (42.9%), and rectal prolapse in 5 (23.8%). The most common finding at initial colonoscopy was a single ulcer in 7 patients (33.3%), multiple ulcers in 6 (28.5%), polypoid lesions in 5 (23.8%), and hyperemic mucosa in 3 (14.2%). All patients received medical treatment and 14 (81%) continued to manifest one or more of the symptoms following treatment, which required subsequent modification of the treatment course. None of the patients required surgery. In conclusion, the study found rectal bleeding to be the most common presentation, with a single ulcer being the most prevalent lesion in endoscopy. Treatment response was variable, but almost half of patients reported relief of symptoms following treatment.

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.

Bowel Damage at Diagnosis Using the Lémann Index Score in Saudi Arabian Patients With Crohn's Disease.

Background Advanced bowel damage caused by Crohn's disease (CD) in the form of strictures and penetrating lesions has been associated with future surgical resection. However, in general, the degree of bowel damage in patients with CD is not examined at the time of diagnosis, and the natural history of CD may differ phenotypically between patients from Arabic countries as compared to patients from Europe and North America. Thus, we aimed to assess the degree of structural bowel damage in Saudi Arabian CD patients at diagnosis. We used the Lémann Index (LI) score, an instrument that measures cumulative digestive tissue damage by magnetic resonance enterography (MRE) and endoscopy, to establish any possible association between the duration of symptoms and the degree of bowel damage. Method This retrospective study was conducted by reviewing the data of all CD patients following up at King Abdulaziz University Hospital (KAUH) that were investigated by endoscopy and MRE at baseline. MRE-LI was calculated by scoring previous surgery, disease location and extension, and intestinal complications. A LI score of >2.0 was set as the cut-off point for bowel damage. Descriptive statistics were used to provide an overview of demographic and clinical characteristics, and hypothesis testing was applied to identify associations. Result Eighty-three patients with CD were included in this study. Fifty point six percent (50.6%) of the cohort comprised females and the median age was 27 years. With regards to CD location and extension, 34.9% showed ileal disease (L1), 9.6% showed colonic CD (L2), whereas 55.4% had ileocolonic involvement (L3). Moreover, 48.2% of patients presented with non-complicated behavior (B1), 25.3% had at least one stricture (B2), and 26.5% showed a penetrating phenotype (B3). Perianal CD was observed in 2.4% of subjects and 62.7% had undergone bowel resection. Mean LI was 2.4 (±2.6) with 34 patients (39.8%) exhibiting an LI score indicative of advanced bowel damage at the time of diagnosis. The duration of symptoms did not correlate with the degree of bowel damage according to the LI score. Conclusion A significant proportion of patients with CD presented with advanced bowel damage at the time of diagnosis, suggesting that a severe form of CD may be endemic in Saudi Arabia.

The Efficacy of Anti-Tumor Necrosis Factor Alpha for Symptomatic Stricturing Small Bowel Crohn's Disease.

Introduction Crohn's disease (CD) is a chronic inflammatory disease. Current treatment aims to prevent complications and the need for surgical intervention. In patients with symptomatic complications, such as strictures, the possible benefits of anti-tumor necrosis factor-alpha (anti-TNF-α) therapy are currently the subject of considerable debate. This study aims to determine whether anti-TNF-α therapy could decrease the need for or delay the time until surgery in patients with CD presenting with symptomatic strictures of the small bowel in the King Abdulaziz University Hospital (KAUH), Saudi Arabia. Methods We conducted a retrospective, single-center study that assessed the need for surgical treatment in adult patients with symptomatic stricturing CD who were treated conventionally or with TNF-α inhibitors. Simple logistic regression was used to examine the association between surgical resection and biologics therapy and stepwise elimination logistic regression analysis was used to identify predictors of surgical resection. Results In total, 75 patients fulfilled the study criteria with 50 in the anti-TNF-α arm and 25 in the conventional arm. Surgical resection was required for six patients (12.2%) in the anti-TNF-α treatment arm and one patient (4%) in the conventional treatment arm (P=0.26). Endoscopic balloon dilatation was performed in two patients (4%) in the anti-TNF-α arm and one patient (4%) in the conventional arm (P=0.69). No statistically significant association was observed between surgical resection and treatment with biologic therapy (odds ratio [OR]=0.50, 95% CI: 0.16-1.53, P=0.22). Stepwise elimination identified age (OR=4.54, 95% CI: 0.79-25.11, P=0.09) and disease duration (OR=1.01, 95% CI: 1.00-1.02, P=0.004) as significant predictors of surgery. Conclusions In this cohort, anti-TNF-α therapy did not provide additional benefits with regards to avoiding or delaying surgery in CD patients with stricturing of the small bowel.

Prevalence of Celiac Disease in Children and Adolescents With Inflammatory Bowel Disease.

Introduction The association between inflammatory bowel disease (IBD) - particularly its two main subtypes, ulcerative colitis (UC) and Crohn's disease (CD) - and celiac disease (CeD) has been attributed to an overlap in the mechanism of immune dysregulation that characterizes these conditions. Owing to the paucity of studies that have explored this condition in pediatric patients, we examined the prevalence of CeD in children with IBD. Materials and methods This is a cross-sectional study of children aged two to 18 years with IBD that were diagnosed between 2016 and 2018. Clinical, demographic, laboratory, and endoscopic data were analysed. Serology for CeD measured the immunoglobulin A tissue transglutaminase (IgA-tTG) antibodies, and the diagnosis was confirmed histologically through small bowel biopsies. Results The study included 101 patients with IBD (83.2% with UC and 16.8% with CD). The mean age was 8.7±4.0 years. Males constituted 59.4% of the cohort, and only 3% had perianal disease. Ileocolonic involvement was reported in 64.7% and non-stricturing and non-penetrating behaviour in 76.7% of CD patients. Pancolitis constituted 45.2% of UC patients. Ten patients (9.9%) had positive serology based on IgA-tTG antibodies, three (approximately 3%) had CeD based on biopsy findings, two patients (2%) had CD, and one patient (1%) had UC. Patients with confirmed CeD had a significantly higher frequency of symptoms of gaseous sensation and bloating (P=0.003) and abdominal distension (P=0.04). Conclusions The prevalence of CeD in Egyptian children with IBD is higher than previously reported in a number of similar studies. Abdominal bloating and gaseous sensation were identified as associated symptoms.

Deamidated gliadin peptide and tissue transglutaminase antibodies in children with coeliac disease: A correlation study.

BACKGROUND AND STUDY AIMS: Serological tests for coeliac disease (CD) are important in the clinical diagnosis and monitoring of response to a gluten free diet (GFD). The tests differ in their sensitivity, specificity, and diagnostic accuracy. In this study, tissue transglutaminase (IgA) (tTG-IgA) antibody was compared with the deamidated gliadin peptide (DGP), of both IgG (DGP-IgG) and IgA (DGP-IgA) types, in patients with CD. PATIENTS AND METHODS: This cross-sectional study was conducted over a period of 2 years, between 2016 and 2018, at King Abdulaziz University Hospital in children 18 years of age or younger with biopsy-proven CD. Patients' sera were tested for DGP-IgA, DGP-IgG, and tTG-IgA antibodies using enzyme-linked immunosorbent assay (ELISA). A Pearson correlation coefficient and Cohen's kappa coefficient were performed to analyse the serological tests. RESULTS: The study included 26 patients with CD, with a median age of 15 years (range, 5-18 years). Seventeen patients (65.4%) were males. The median disease duration was 5 years (range, 3-14 years). Fifteen patients (57.7%) reported good adherence to a GFD. The patients' serological tests showed a mean ± SD tTG-IgA titer of 149.8 ± 75 u/ml, a mean DGP-IgG titer of 62.5 ± 36.5, and a mean DGP-IgA of 32 ± 23.3 µ/ml. We found a significant correlation between tTG-IgA and DGP-IgG (r = 0.69, P < 0.001), tTG-IgA and DGP-IgA (r = 0.67, P < 0.001), and DGP-IgG and DGP-IgA (r = 0.83, P < 0.001). Cohen's kappa coefficient (k) showed substantial agreement between tTG-IgA and DGP-IgG (k = 0.71, P < 0.001) and DGP-IgG and DGP-IgA (k = 0.69, P < 0.001), but moderate agreement between tTG-IgA and DGP-IgA (k = 0.45, P = 0.006). CONCLUSION: We found a good correlation between tTG-IgA and DGP-IgG and tTG-IgA and DGP-IgA, and substantial agreement between tTG-IgA and DGP-IgG, but moderate agreement between tTG-IgA and DGP-IgA. These results indicate that DGP-IgG was comparable to tTG-IgA and may be useful as an alternative to tTG-IgA in the diagnosis and follow-up of patients with CD.

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.

Short children with impaired growth hormone secretion. Do they have celiac disease?

OBJECTIVES: To determine the prevalence of celiac disease (CeD) in children with short stature (SS) and growth hormone deficiency (GHD). METHODS: This is a retrospective study of patients with isolated SS and GHD, diagnosed during the period 2002 to 2016. Their medical records were reviewed and serum tissue transglutaminase (tTG) antibody results retrieved. Patients with positive serology results underwent upper gastrointestinal endoscopy and small bowel biopsy to confirm the diagnosis of CeD. Clinical, anthropometric, and laboratory data were recorded for all patients. RESULTS: Of the 351 patients identified with GHD, 199 (56.7%) were male. The mean age±SD was 9.0±3.7 years (range: 2-17.6 years), and the mean±SD height-for-age z score was -2.9±1.3. Partial GHD constituted 42.2% and severe GHD constituted 57.8% of GHD diagnoses. The mean growth hormone (GH) peak level was 5.8±3.9 ng/ml. Forty-seven patients (13.4%) had positive serology, and 14 (4%) had biopsy-proven CeD. No predictors could be identified through binary logistic regression analysis. CONCLUSION: A prevalence of CeD seropositivity was found in 13.4% and overt CeD in 4% of children with GHD. The finding of GHD should not preclude the search for CeD, because the majority will potentially improve on a gluten-free diet (GFD).

Celiac disease in Saudi children with isolated short stature: is it rare or are we not screening rigorously enough?

Background Celiac disease (CeD) is an immune-mediated enteropathy induced by gluten exposure in individuals with genetic susceptibility. Short stature (SS) can be the sole clinical manifestation of CeD, in the absence of gastrointestinal (GI) symptoms. This study aimed to determine the prevalence of CeD in Saudi Arabian children with SS. Patients and methods Medical records were reviewed in a total number of 275 retrospective cases (during the period 2002-2014) of children with isolated SS from King Abdulaziz University Hospital, Jeddah. Their serum samples were tested with tissue transglutaminase (tTG) antibodies. Patients with a positive serology were scheduled for an upper endoscopy and intestinal biopsy to confirm CeD diagnosis before starting a gluten-free diet (GFD). Clinical, anthropometric and laboratory data were recorded for all patients. Results A total of 275 children with SS were included. The mean age ± standard deviation (SD) was 9.4 ± 4.0 years (range, 2.6-16.9 years) and males constituted the predominant gender group (151/275; 54.9%) over females (124/275; 45.1%). The mean ± SD height for age z score (HAZ) was -2.9 ± 1.0.Thirty-eight (13.8%) had positive serology, and 16 (5.8%) had biopsy-proven CeD. Apart from the difference in duration of delayed bone age between CeD patients and CeD-negative serology subjects (mean ± SD, 39.6 ± 10.5 vs. 18.6 ± 16.8, p = 0.02), no other major difference in other clinical or laboratory parameters was evident. Conclusions The prevalence rate of CeD in Saudi Arabian SS children was 5.8%, which is comparable to published reports of a number of other countries. Regular screening of children with SS is therefore justifiable.

Diagnostic delay of pediatric inflammatory bowel disease in Saudi Arabia.

BACKGROUND/AIM: Delay in the diagnosis of inflammatory bowel disease (IBD) is associated with complications. Our aim was to describe the pattern and risk factors associated with delay in the diagnosis of IBD in Saudi children. PATIENTS AND METHODS: This was a multicenter study with a retrospective/prospective design. Data on diagnostic delay in children with Crohn's disease (CD) and ulcerative colitis (UC) were retrieved from physician's notes. Multivariate regression analysis was used to assess the risk factors associated with long delay in diagnosis. RESULTS: There were 240 and 183 Saudi children with CD and UC, respectively. The median delays in diagnosis were 8 and 5 months in CD and UC, respectively, significantly longer in children with CD than UC (P < 0.001). Long diagnostic delays (>75th percentile) were 24 and 8.8 months for CD and UC, respectively. Ileal location was a significant risk factor in CD and the age of onset above 10 years was protective in UC. CONCLUSIONS: Long diagnostic delay in IBD was mainly due to the longer delay in gastroenterologist consultation. Review of the referral system is needed to focus on measures to reduce long delays in diagnosis. The ileal location as a risk factor in CD and age older than 10 years as protective in UC should help recognition and early referral.

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.

Whole exome sequencing of a consanguineous family identifies the possible modifying effect of a globally rare AK5 allelic variant in celiac disease development among Saudi patients.

Celiac disease (CD), a multi-factorial auto-inflammatory disease of the small intestine, is known to occur in both sporadic and familial forms. Together HLA and Non-HLA genes can explain up to 50% of CD's heritability. In order to discover the missing heritability due to rare variants, we have exome sequenced a consanguineous Saudi family presenting CD in an autosomal recessive (AR) pattern. We have identified a rare homozygous insertion c.1683_1684insATT, in the conserved coding region of AK5 gene that showed classical AR model segregation in this family. Sequence validation of 200 chromosomes each of sporadic CD cases and controls, revealed that this extremely rare (EXac MAF 0.000008) mutation is highly penetrant among general Saudi populations (MAF is 0.62). Genotype and allelic distribution analysis have indicated that this AK5 (c.1683_1684insATT) mutation is negatively selected among patient groups and positively selected in the control group, in whom it may modify the risk against CD development [p<0.002]. Our observation gains additional support from computational analysis which predicted that Iso561 insertion shifts the existing H-bonds between 400th and 556th amino acid residues lying near the functional domain of adenylate kinase. This shuffling of amino acids and their H-bond interactions is likely to disturb the secondary structure orientation of the polypeptide and induces the gain-of-function in nucleoside phosphate kinase activity of AK5, which may eventually down-regulates the reactivity potential of CD4+ T-cells against gluten antigens. Our study underlines the need to have population-specific genome databases to avoid false leads and to identify true candidate causal genes for the familial form of celiac disease.