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.

Effectiveness of phototherapy with and without probiotics for the treatment of indirect hyperbilirubinaemia in preterm neonates: a randomised controlled trial.

INTRODUCTION: Raised serum bilirubin levels can cause kernicterus, and premature infants are at increased risk owing to metabolic immaturity. The standard treatment for neonatal jaundice is phototherapy, but probiotics alone can reduce the duration of phototherapy and hospitalisation. OBJECTIVES: To determine the effectiveness of phototherapy with and without probiotics for the treatment of indirect hyperbilirubinaemia in preterm neonates. PATIENTS AND METHODS: The open-labelled randomised controlled trial was conducted from January 2022 to January 2023 in the neonatal unit of the University of Lahore Teaching Hospital, Pakistan. A total of 76 preterm neonates who fulfilled the selection criteria were included and divided into two groups. Both groups received standard phototherapy. In Group B, a probiotic (Saccharomyces boulardii) 125 mg, twice daily, orally (in 5 cc of whichever milk the infant was receiving) was given until discharge from hospital. The primary outcome measurements were the duration of phototherapy and the length of hospitalisation. RESULTS: The mean (SD) duration of phototherapy was 36.55 (14.25) hours in Group A and 24.61 (9.25) hours in Group B (p <0.05). The mean (SD) duration of hospital stay was 47.36 (16.51) hours in Group A and 33.13 (8.93) hours in Group B (p <0.05). CONCLUSION: Oral probiotics (Saccharomyces boulardii) have a significant effect on the duration of phototherapy for neonatal hyperbilirubinaemia, and they decrease the chances of nosocomial infection. Exploration of clinical outcomes by investigating faecal flora and undertaking large randomised controlled trials of various probiotics are needed. ABBREVIATIONS: ABE: acute bilirubin encephalopathy; CNS: central nervous system; GA: gestational age; IVIG: intravenous immunoglobulin; KSD: kernicterus; NNU: neonatal unit; RCT: randomised controlled trial; S. boulardii: Saccharomyces boulardii.

Prevalence and Risk Factors for IgE and IgG Cow's Milk Protein Allergies in Saudi Arabia.

Cow's milk protein allergies (CMPAs) particularly occur in infancy and early childhood due to an immunological allergic reaction to milk proteins. This issue is increasing in Saudi Arabia and requires research to improve health status and provide alternatives. Our study aims to investigate the important aspects of immunoglobulin E (IgE) and IgG CMPA in Saudi Arabia regarding its prevalence and association with demographic and health-related factors in both adult and pediatric populations. A descriptive retrospective cross-sectional study was conducted on 376 patients, comprising 314 adults aged between 19 and 86 years, and 62 pediatric patients aged between one and 12 years. The study focused on individuals who attended a private medical center in Jeddah city over the past five years. Laboratory results for food allergy of IgE and IgG tests, including cow's milk proteins (CMPs), serum 25-hydroxyvitamin D (25OHD), specific IgE inhalant allergy results, and other health-related factors were collected from an electronic record system. Results have shown that casein was the most common sensitizing allergen of CMPs in adults, whereas α-lactalbumin was the most common sensitizing allergen in pediatrics. The most frequent sensitizing allergen in IgG CMP was cow's milk in 54/92 (58.7%) adults, followed by cow's sour milk products 41 (44.6%). Cow's milk was the most common sensitizing allergen in 20/20 (100%) children. The rate of CMPA was significantly higher in children younger than five years old (P =0.003), while children who interacted with pets had a marginal significantly reduced rate (P = 0.054). Thus, cow's milk is the most sensitizing allergen in IgG CMPs in adults and pediatrics.

Rare variant burden analysis from exomes of three consanguineous families reveals LILRB1 and PRSS3 as potential key proteins in inflammatory bowel disease pathogenesis.

Background: Inflammatory bowel disease (IBD) is a chronic autoimmune disorder characterized by severe inflammation and mucosal destruction of the intestine. The specific, complex molecular processes underlying IBD pathogenesis are not well understood. Therefore, this study is aimed at identifying and uncovering the role of key genetic factors in IBD. Method: The whole exome sequences (WESs) of three consanguineous Saudi families having many siblings with IBD were analyzed to discover the causal genetic defect. Then, we used a combination of artificial intelligence approaches, such as functional enrichment analysis using immune pathways and a set of computational functional validation tools for gene expression, immune cell expression analyses, phenotype aggregation, and the system biology of innate immunity, to highlight potential IBD genes that play an important role in its pathobiology. Results: Our findings have shown a causal group of extremely rare variants in the LILRB1 (Q53L, Y99N, W351G, D365A, and Q376H) and PRSS3 (F4L and V25I) genes in IBD-affected siblings. Findings from amino acids in conserved domains, tertiary-level structural deviations, and stability analysis have confirmed that these variants have a negative impact on structural features in the corresponding proteins. Intensive computational structural analysis shows that both genes have very high expression in the gastrointestinal tract and immune organs and are involved in a variety of innate immune system pathways. Since the innate immune system detects microbial infections, any defect in this system could lead to immune functional impairment contributing to IBD. Conclusion: The present study proposes a novel strategy for unraveling the complex genetic architecture of IBD by integrating WES data of familial cases, with computational analysis.

The impact of COVID-19 on the sustainability of the environment, animal health and food security, and safety.

COVID-19 pandemic influenced the environment, animal health, and food security. Due to reduced human mobility, the air and water quality increased. Other environmental consequences were the personal protective types of equipment and their haphazard disposal. Atmospheric pollution could be a cofactor leading to an increased COVID-19 mortality rate. Lockdown, however, caused a reduction in air and water pollution. Noise pollution affects the health of individuals and communities in terms of cardiovascular disorders and sleeping problems. Meanwhile, the COVID-19 lockdown controls human activities that reduce noise pollution. Municipal waste affects the environment. Recycling has been reduced in some countries but not in Saudi Arabia. COVID-19 had a drastic effect on livestock production on national, regional, and global levels, affecting countries' capacities to prevent and control diseases of animals and increasing global poverty, becoming a threat to the sustainability of global food security and safety. Many lessons have been learned from the COVID-19 pandemic, so it is wise to study and analyze the previous lessons and shed some light on past pandemics such as the Spanish flu to understand the readings and earn experiences. This paper is focused on the interaction between the pandemic and environmental health from the public health concern rather than other health classifications.

Complex Inheritance of Rare Missense Variants in PAK2, TAP2, and PLCL1 Genes in a Consanguineous Arab Family With Multiple Autoimmune Diseases Including Celiac Disease.

Background: Autoimmune diseases (AIDs) share a common molecular etiology and often present overlapping clinical presentations. Thus, this study aims to explore the complex molecular basis of AID by whole exome sequencing and computational biology analysis. Methods: Molecular screening of the consanguineous AID family and the computational biology characterization of the potential variants were performed. The potential variants were searched against the exome data of 100 healthy individuals and 30 celiac disease patients. Result: A complex inheritance pattern of PAK2 (V43A), TAP2 (F468Y), and PLCL1 (V473I) genetic variants was observed in the three probands of the AID family. The PAK2 variant (V43A) is a novel one, but TAP2 (F468Y) and PLCL1 (V473I) variants are extremely rare in local Arab (SGHP and GME) and global (gnomAD) databases. All these variants were localized in functional domains, except for the PAK2 variant (V43A) and were predicted to alter the structural (secondary structure elements, folding, active site confirmation, stability, and solvent accessibility) and functional (gene expression) features. Therefore, it is reasonable to postulate that the dysregulation of PAK2, TAP2, and PLCL1 genes is likely to elicit autoimmune reactions by altering antigen processing and presentation, T cell receptor signaling, and immunodeficiency pathways. Conclusion: Our findings highlight the importance of exploring the alternate inheritance patterns in families presenting complex autoimmune diseases, where classical genetic models often fail to explain their molecular basis. These findings may have potential implications for developing personalized therapies for complex disease patients.

Clinical and manometric characteristics of Allgrove syndrome.

OBJECTIVE: The association of adrenocorticotropic hormone (ACTH) insensitivity with achalasia and alacrimia (Allgrove syndrome, 3A) constitutes a rare multisystem disorder. Its evolution is not well known. The aim of this study was to describe clinical and esophageal manometric characteristics and outcomes in Allgrove syndrome. PATIENTS AND METHODS: This multicenter retrospective study compared clinical and manometric characteristics at diagnosis and on follow-up of 9 children presenting with 3A (mean age at diagnosis 7.1 years) with those of 9 children with idiopathic achalasia (IA) (mean age at diagnosis 8.3 years). RESULTS: At the time of diagnosis, 3 children with 3A presented with no digestive or respiratory signs because they were identified during a family screening; 1 remained asymptomatic 8 years later. ACTH levels were high in patients with 3A. All of the patients with IA were symptomatic at diagnosis. No significant difference was observed when comparing any of the manometric parameters of the first esophageal manometry of 3A with those of IA. Seven children with 3A were operated on using the Heller procedure, completed by pneumatic esophageal dilation in 2 of these 7. One patient with 3A was treated only by nifedipine. Failure of treatment was observed in 3 children with 3A and 1 child with IA, partial success in 4 with 3A and 1 with IA, and total success in 2 with 3A and 7 with IA (P < 0.03). Control manometry showed that in the 3A group, partial success after surgery was always associated with abnormally low or normal lower esophageal sphincter (LES) pressure, whereas failure after surgery was associated with high LES pressure. CONCLUSIONS: Our data showed that 3A presented a more severe course than IA despite presymptomatic diagnosis in cases of family screening. The high LES pressure noted in some patients with 3A is suggestive of a peculiar pattern in 3A affecting the LES and the lower part of the esophagus.

The Prevalence and Trends of the Early Introduction of Cow Milk to Newborns at Tertiary Care Center: A Risk of Atopy.

Although all health organizations recommend exclusive breastfeeding (EBF), few neonates meet these recommended goals. The early intake of cow milk formulas (CMFs) has been linked to several childhood illnesses, including atopic diseases. Therefore, this study aimed to evaluate the prevalence of early exposure to CMFs in the nursery of a tertiary care hospital in Jeddah, Kingdom of Saudi Arabia. A retrospective review was conducted on the medical records of feeding practices of neonates born in King Abdulaziz University Hospital (KAUH) at Jeddah, Kingdom of Saudi Arabia. Two months from each year (May and December) were selected over the last five years. Approval from the ethical research committee at KAUH was obtained. Eight hundred and ninety-four different neonate files were reviewed. Four hundred and eighty-seven (54.5%) were males. Out of the total of 894, 838 (93.7%) newborns experienced an early introduction to CMFs, 797 (89.1%) received mixed CMF and breast milk, 41 (4.6%) received CMF only, and 56 (6.3%) received exclusive breastfeeding (EBF). Surprisingly, EBF has declined over time, from 39% in May 2016 to 1% in December 2020. The prevalence of early exposure to CMF was very high in newborns at KAUH nursery, and this prevalence was trending upwards. Extensive teaching programs on EBF and allergy prevention for mothers and related health care providers are highly recommended.

Liver function changes following the introduction of a gluten-free diet in patients with celiac disease.

Aim of the study: Disturbance in liver enzymes is a well-described observation in patients with celiac disease (CD). We aim to describe the prevalence of all liver function abnormalities in CD and assess their response to a gluten-free diet (GFD). Material and methods: This is a retrospective cross-sectional study of all CD patients diagnosed from 2007 to 2020 in King Abdulaziz University Hospital, Jeddah. Demographic, biochemical, and histologic patient data were collected. Results: The study included 132 patients with CD. The median age was 9.5 years (range, 1-18 years). Males constituted 56.1% (n = 74) of the whole cohort. The most common associated morbidities were type 1 diabetes (33%), thyroid disease (15.7%), and Down syndrome (7.6%). Ninety-seven percent of patients were determined to have a severe form of CD (Marsh score 3). Aspartate aminotransferase (AST) was high in 38 patients (28.8%), while alanine aminotransferase (ALT) was high in 10 (7.6%). Two patients (1.5%) had elevated γ-glutamyl transferase (GGT) levels, and 2 patients (1.5%) had elevated AST, ALT, and GGT levels. Albumin levels were low in 29 patients (22%), while bilirubin levels were elevated in 1 patient. Introduction of a GFD resulted in improvement in ALT levels at 6 months, and improvement in albumin levels both after 6 months and 12 months. Conclusions: Transaminase and albumin disturbances are frequently found in CD, with the most common abnormality being elevated AST. A decreased ALT level is the most pronounced response to a GFD.

TagSNP approach for HLA risk allele genotyping of Saudi celiac disease patients: effectiveness and pitfalls.

BACKGROUND: Celiac disease (CD) is a genetically complex autoimmune disease which is triggered by dietary gluten. Human leukocyte antigen (HLA) class II genes are known to act as high-risk markers for CD, where >95% of CD patients carry (HLA), DQ2 and/or DQ8 alleles. Therefore, the present study was conducted to investigate the distribution of HLA haplotypes among Saudi CD patients and healthy controls by using the tag single nucleotide polymorphisms (SNP). METHODS: HLA-tag SNPs showing strong linkage value (r2>0.99) were used to predict the HLA DQ2 and DQ8 genotypes in 101 Saudi CD patients and in 103 healthy controls by using real-time polymerase chain reaction technique. Genotype calls were further validated by Sanger sequencing method. RESULTS: A total of 63.7% of CD cases and of 60.2% of controls were predicted to carry HLA-DQ2 and DQ8 heterodimers, either in the homozygous or heterozygous states. The prevalence of DQ8 in our CD patients was predicted to be higher than the patients from other ethnic populations (35.6%). More than 32% of the CD patients were found to be non-carriers of HLA risk haplotypes as predicted by the tag SNPs. CONCLUSION: The present study highlights that the Caucasian specific HLA-tag SNPs would be of limited value to accurately predict CD specific HLA haplotypes in Saudi population, when compared with the Caucasian groups. Prediction of risk haplotypes by tag SNPs in ethnic groups is a good alternate approach as long as the tag SNPs were identified from the local population genetic variant databases.

COVID-19: pathogenesis, advances in treatment and vaccine development and environmental impact-an updated review.

Diseases negatively impact the environment, causing many health risks and the spread of pollution and hazards. A novel coronavirus, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has led to a recent respiratory syndrome epidemic in humans. In December 2019, the sudden emergence of this new coronavirus and the subsequent severe disease it causes created a serious global health threat and hazards. This is in contrast to the two aforementioned coronaviruses, SARS-CoV-2 (in 2002) and middle east respiratory syndrome coronavirus MERS-CoV (in 2012), which were much more easily contained. The World Health Organization (WHO) dubbed this contagious respiratory disease an "epidemic outbreak" in March 2020. More than 80 companies and research institutions worldwide are working together, in cooperation with many governmental agencies, to develop an effective vaccine. To date, six authorized vaccines have been registered. Up till now, no approved drugs and drug scientists are racing from development to clinical trials to find new drugs for COVID-19. Wild animals, such as snakes, bats, and pangolins are the main sources of coronaviruses, as determined by the sequence homology between MERS-CoV and viruses in these animals. Human infection is caused by inhalation of respiratory droplets. To date, the only available treatment protocol for COVID-19 is based on the prevalent clinical signs. This review aims to summarize the current information regarding the origin, evolution, genomic organization, epidemiology, and molecular and cellular characteristics of SARS-CoV-2 as well as the diagnostic and treatment approaches for COVID-19 and its impact on global health, environment, and economy.

Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients.

Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22-5.54; P < 0.01). This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05-2.28; P = 0.02) and additive (OR = 0.35; 95% CI: 0.17-0.71; P = 0.03) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0156). Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD.

Congenital glucose-galactose malabsorption: a descriptive study of clinical characteristics and outcome from Western Saudi Arabia.

BACKGROUND AND STUDY AIMS: Congenital glucose galactose malabsorption (CGGM) is a rare autosomal recessive disorder caused by a defect in the sodium-coupled transport of glucose and galactose across the intestinal brush border presenting with neonatal diarrhoea. The aim of this study was to report the clinical and laboratory characteristics of patients with CGGM from the Western Saudi Arabia. PATIENTS AND METHODS: This is a retrospective review of CGGM patients in three major hospitals in the city of Jeddah, Saudi Arabia, namely King Abdulaziz University Hospital, King Faisal Specialist Hospital and Research Centre, and Maternity Children Hospital in the period between November 2001 and October 2011. RESULTS: Twenty-four patients with CGGM have been described. The median age at diagnosis was 4.5 months. Twelve (50%) were males. Sixteen (66.7%) were Saudi and 8 (33.3%) were non Saudi (5 Arabs and 3 Asians). Parents of 21 patients were consanguineous. Nine (37.5%) had affected siblings with CGGM. All presented with diarrhoea resulted in dehydration. Hypernatremia was seen in 7 (29.2%) patients, renal tubular acidosis in 4 patients. Renal stones and nephrocalcinosis were detected in 3 (12.5%) patients at 8 months, 12 months and 7 years, respectively. The median follow up was 41.6 months. All but three demonstrated normal weight gain. Five patients reported one or more symptoms of bloating (n=3), diarrhoea (n=3) and abdominal pain (n=1) during follow up. All had normal development and none had neurological complications secondary to dehydration. CONCLUSION: Early recognition and management of this condition are crucial to prevent consequences of dehydration and death.