A novel mutation in ATM gene in a Saudi female with ataxia telangiectasia.

Ataxia telangiectasia is a hereditary multisystem disorder with a wide range of symptoms and signs. It is inherited in an autosomal recessive manner due to a mutation in the ataxia telangiectasia mutated (ATM) gene, which encodes a protein kinase with a domain related to a phosphatidylinositol 3-kinase (PI-3 kinase) proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell cycle control. The characteristics of the disease include progressive cerebellar ataxia beginning between ages one and four years, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctiva, immunodeficiency with frequent infections, and an increased risk for malignancy. In this article, we report a novel homozygous missense variant c.1516G > T, p.(Gly506Cys) in the ATM gene causing ataxia telangiectasia in a Saudi female. This variant led to the development of a later onset disease (at the age of 14 years) and the classical neurodegenerative process both clinically and on imaging. However, no immune system dysfunction or endocrine abnormalities were present. This is the second novel mutation in this gene so far reported from Saudi Arabia. The novel mutation described in the present study widened the genetic spectrum of ATM-associated diseases, which will benefit studies addressing this disease in the future.

Characteristics of visits and predictors of admission from a paediatric emergency room in Saudi Arabia.

BACKGROUND: The Emergency Repartment (ER) is one of the most used areas in healthcare institutions. Problems with over utilisation and overcrowding have been reported worldwide. This study aims at examining the characteristics of paediatric ER visits, the rate of hospital admissions and its associated predictors at King Fahd Hospital of the University in the Eastern Province of Saudi Arabia. METHODS: This is a retrospective, medical record-based study. Variables included gender, age group, nationality, complaints, Triage level, shifts and seasons. Descriptive statistics were reported as frequencies/percentages. P-values were obtained through a Chi-Squared test while unadjusted and adjusted odds ratios were estimated by binary logistic regression, where admission was considered as the outcome. RESULTS: The total number of paediatric patients included was 46,374, and only 2.5% were admitted. Males comprised 55.4% while females comprised 44.6%. The most common age group were toddlers, and 92.4% of the total sample were Saudis. The most common complaint was fever (26.9%) followed by respiratory symptoms (24.9%). Only 7 patients (0.02%) were classified as triage I (Resuscitation), and most were triage IV (Less urgent) (71.0%). Most visits occurred during the winter months. Adjusted ORs showed that neonates had higher odds of admission (OR = 3.85, 95%CI = 2.57-5.76). Moreover, those presenting with haematological conditions showed an OR of 65.49 (95%CI = 47.85-89.64), followed by endocrine conditions showing an OR of 34.89 (95%CI = 23.65-51.47). Triage I had a very high odds of admission (OR = 19.02, 95%CI = 2.70-133.76), whereas triage V was associated with a very low odds of admission (OR = 0.30, 95%CI = 0.23-0.38). CONCLUSIONS: A low rate of hospital admission was found in comparison with other rates worldwide. This was mostly attributed to an alarmingly high number of non-urgent ER visits. This further emphasises the problem with improper use of ER services, as these cases should be more appropriately directed towards primary healthcare centres. Further studies to examine the impact of prioritising patients in the ER based on the identified predictors of hospital admission, in addition to the standard triage system, are suggested.

Molecular and enzoinformatics perspectives of targeting Polo-like kinase 1 in cancer therapy.

Cancer is a disease that has been the focus of scientific research and discovery and continues to remain so. Polo-like kinases (PLKs) are basically serine/threonine kinase enzymes that control cell cycle from yeast to humans. PLK-1 stands for 'Polo-like kinase-1'. It is the most investigated protein among PLKs. It is crucial for intracellular processes, hence a 'hot' anticancer drug-target. Accelerating innovations in Enzoinformatics and associated molecular visualization tools have made it possible to literally perform a 'molecular level walk' traversing through and observing the minutest contours of the active site of relevant enzymes. PLK-1 as a protein consists of a kinase domain at the protein N-terminal and a Polo Box Domain (PBD) at the C-terminal connected by a short inter-domain linking region. PBD has two Polo-Boxes. PBD of PLK-1 gives the impression of "a small clamp sandwiched between two clips", where the two Polo Boxes are the 'clips' and the 'phosphopeptide' is the small 'clamp'. Broadly, two major sites of PLK-1 can be potential targets: one is the adenosine-5'-triphosphate (ATP)-binding site in the kinase domain and the other is PBD (more preferred due to specificity). Targeting PLK-1 RNA and the interaction of PLK-1 with a key binding partner can also be approached. However, the list of potent small molecule inhibitors targeting the PBD site of PLK-1 is still not long enough and needs due input from the scientific community. Recently, eminent scientists have proposed targeting the 'Y'-shaped pocket of PLK-1-PBD and encouraged design of ligands that should be able to concurrently bind to two or more modules of the 'Y' pocket. Hence, it is suggested that during molecular interaction analyses, particular focus should be kept on the moiety in each ligand/drug candidate which directly interacts with the amino acid residue(s) that belong(s) to one of the three binding modules which together create this Y-shaped cavity. This obviously includes (but it is not limited to) the 'shallow cleft'-forming residues i.e. Trp414, H538 and K540, as significance of these binding residues has been consistently highlighted by many studies. The present article attempts to give a concise yet critically updated overview of targeting PLK-1 for cancer therapy.

A Novel Heterozygous Variant in Exon 19 of NOTCH3 in a Saudi Family with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL; OMIM #125310) is the most common cause of monogenic familial cerebral small vessel disease. It typically manifests at middle adulthood with highly variable clinical features including migraine with aura, recurrent transient ischemic attacks or ischemic strokes, mood disorders, and progressive cognitive decline. It is caused by mutations in the NOTCH3 gene, which maps to the short arm of chromosome 19 and encode for epidermal growth factor-like repeats. In this article, we report a 40-year-old male patient who presented with a two-year history of progressive cognitive decline including impaired attention, memory, executive functions, and processing speed whose family history was strongly positive for young-onset ischemic stroke and memory impairment. His father, uncle, and grandfather died due to ischemic strokes and cognitive impairment (similar condition). A whole exome sequencing to the patient (proband II-1) revealed a novel heterozygous missense variant c.3009G>T, p.(Trp1003Cys) (chr19;15291625; hg19) in exon 19 of the NOTCH3 gene. Sanger sequencing was used to confirm the variant in other family members. This variant has not been described in the literature so far. The novel mutation described in the present study widened the genetic spectrum of NOTCH3-associated diseases, which will benefit studies addressing this disease in the future. CADASIL remains a disabling disorder leading to medical retirement in our patient due to late clinical presentation, lack of family history taking prior to joining the military, and lack of curative therapy. Further research for therapeutic options is needed including stem cell therapy .

Whole exome sequencing reveals a homozygous nonsense mutation in HEXA gene leading to Tay-Sachs disease in Saudi Family.

OBJECTIVE: To study the causative variants in affected member of a Saudi family with Tay-Sachs disorder. This disorder includes paralysis, decreasing in attentiveness, seizures, blindness, motor deterioration progresses rapidly leading to a completely unresponsive state and a cherry-red spot visible on the eye. METHODS: Whole exome sequencing (WES) and Sanger sequencing was performed to study the variant leading to the disease. RESULTS: WES data analysis and Sanger sequencing validation, identifies a homozygous nonsense mutation c.1177C>T, p.Arg393Ter as a result in protein change. This mutation was also studied in 100 unrelated healthy controls. CONCLUSIONS: We detected homozygous mutation in HEXA gene that may lead to cause Tay-Sachs disorder. Moreover, explain the possibility that HEXA gene may play important role for multiple aspects of normal human neurodevelopment.

A novel homozygous nonsense mutation in CCDC88A gene cause PEHO-like syndrome in consanguineous Saudi family.

Progressive encephalopathy, edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an unusual Mendelian phenotype of unidentified origin that causes profound intellectual disability, optic nerve/cerebellar atrophy, epileptic seizures, developmental progress, pedal edema, and early death. Uncharacteristic affected individuals are often classified as having PEHO-like syndrome, although they may be misdiagnosed as having epileptic encephalopathy, a potential result of early birth. In this study, we report a consanguineous Saudi family with a novel homozygous nonsense mutation of the CCDC88A gene causing PEHO-like syndrome. The children were suffering from developmental delay, epilepsy, mental disability, optic nerve/cerebellar atrophy, and pedal edema. Whole exome sequencing was conducted for the members of the family who have the disorder to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation, identified a novel homozygous nonsense mutation c. 1292G > A, which was caused by p.Trp431* stop gain. This mutation was ruled out in 100 unrelated healthy controls. The nonsense homozygous mutation detected in this study has not yet been reported as pathogenic in the literature or various databases. In conclusion, a complete loss of protein function due to premature stop gain was caused by a mutation in exon 12 of CCDC88A. This loss may lead to PEHO phenotype. CCDC88A gene may therefore play an important and critical role for multiple aspects of normal human neurodevelopment.

Novel compound heterozygous mutations in WDR62 gene leading to developmental delay and Primary Microcephaly in Saudi Family.

OBJECTIVE: Primary microcephaly (MCPH) is a rare autosomal recessive disorder characterized by impaired congenital reduction of brain size along with head circumference and intellectual disability. MCPH is a heterogeneous disorder and more than twenty four genes associated with this disease have been identified so far. The objective of this study was to find out the novel genes or mutations leading to the genetic defect in a Saudi family with primary microcephaly. METHODS: Whole exome sequencing was carried out to find the novel mutation and the results was further validated using Sanger sequencing analysis. This study was done in the Center of excellence in Genomic Medicine and Research, King Abdulaziz University under KACST project during 2017 and 2018. RESULTS: We report a novel compound heterozygous mutations c.797C>T in exon 7 and c.1102G>A in exon 9 of the WD repeat domain 62 (WDR62) (OMIM 604317) gene in two affected siblings in Saudi family with intellectual disability, speech impediments walking difficulty along with primary microcephaly. Two rare, missense variants were detected in heterozygous state in the WDR62 gene in these two affected individuals from the heterozygous parents. CONCLUSIONS: A compound heterozygous mutations c.797C>T in exon 7 and c.1102G> A in exon 9 of the WDR62 gene was identified. WDR62 gene is very important gene and mutation can lead to neuro developmental defects, brain malformations, reduced brain and head size. These results should be taken into consideration during prognostic discussions and mutation spectrum with affected patients and their families in the Saudi population.

Identification of De Novo and Rare Inherited Copy Number Variants in Children with Syndromic Congenital Heart Defects.

Congenital heart defects (CHDs) are the most common birth defects in neonatal life. CHDs could be presented as isolated defects or associated with developmental delay (DD) and/or other congenital malformations. A small proportion of cardiac defects are caused by chromosomal abnormalities or single gene defects; however, in a large proportion of cases no genetic diagnosis could be achieved by clinical examination and conventional genetic analysis. The development of genome wide array-Comparative Genomic Hybridization technique (array-CGH) allowed for the detection of cryptic chromosomal imbalances and pathogenic copy number variants (CNVs) not detected by conventional techniques. We investigated 94 patients having CHDs associated with other malformations and/or DD. Clinical examination and Echocardiography was done to all patients to evaluate the type of CHD. To investigate for genome defects we applied high-density array-CGH 2 × 400K (41 patients) and CGH/SNP microarray 2 × 400K (Agilent) for 53 patients. Confirmation of results was done using Fluorescent in situ hybridization (FISH) or qPCR techniques in certain cases. Chromosomal abnormalities such as trisomy 18, 13, 21, microdeletions: del22q11.2, del7q11.23, del18 (p11.32; p11.21), tetrasomy 18p, trisomy 9p, del11q24-q25, add 15p, add(18)(q21.3), and der 9, 15 (q34.2; q11.2) were detected in 21/94 patients (22%) using both conventional cytogenetics methods and array-CGH technique. Cryptic chromosomal anomalies and pathogenic variants were detected in 15/73 (20.5%) cases. CNVs were observed in a large proportion of the studied samples (27/56) (48%). Clustering of variants was observed in chromosome 1p36, 1p21.1, 2q37, 3q29, 5p15, 7p22.3, 8p23, 11p15.5, 14q11.2, 15q11.2, 16p13.3, 16p11.2, 18p11, 21q22, and 22q11.2. CGH/SNP array could detect loss of heterozygosity (LOH) in different chromosomal loci in 10/25 patients. Array-CGH technique allowed for detection of cryptic chromosomal imbalances that could not be detected by conventional cytogenetics methods. CHDs associated with DD/congenital malformations presented with a relatively high rate of cryptic chromosomal abnormalities. Clustering of CNVs in certain genome loci needs further analysis to identify candidate genes that may provide clues for understanding the molecular pathway of cardiac development.

Novel compound heterozygous mutations in MCPH1 gene causes primary microcephaly in Saudi family.

OBJECTIVE: To identify genetic variation involved in primary microcephaly. METHODS: In present study we identified 4 generation Saudi family showing primary microcephaly. We performed whole exome sequencing along with Sanger sequencing to find the genetic defect in this family. This study was conducted in King Abdulaziz University started from 2016 and the results presented in this manuscript are from one of the family. RESULTS: Two novel missense variants (c.982G>A and c.1273T>A) were identified in heterozygous state in exon 8 of MCPH1 gene. The detected missense variants cause a tyrosine to asparagine substitution of residue 425 and a valine to isoleucine substitution at residue 310. MCPH1 gene encodes a DNA damage response protein. The encoded protein play a role in G2/M DNA damage checkpoint arrest via maintenance of inhibitory phosphorylation of cyclin-dependent kinase 1. The respective mutation was ruled out in 100 control samples. CONCLUSION: We found novel compound heterozygous mutation in Saudi family that will help to build database for genetic mutations in population and pave way to devise strategies to tackle such disorders in future.

Synthesis and Characterization of Cefotaxime Conjugated Gold Nanoparticles and Their Use to Target Drug-Resistant CTX-M-Producing Bacterial Pathogens.

Multidrug-resistance due to "ß lactamases having the expanded spectrum" (ESBLs) in members of Enterobacteriaceae is a matter of continued clinical concern. CTX-M is among the most common ESBLs in Enterobacteriaceae family. In the present study, a nanoformulation of cefotaxime was prepared using gold nanoparticles to combat drug-resistance in ESBL producing strains. Here, two CTX-M-15 positive cefotaxime resistant bacterial strains (i.e., one Escherichia coli and one Klebsiella pneumoniae strain) were used for testing the efficacy of "cefotaxime loaded gold-nanoparticles." Bromelain was used for both reduction and capping in the process of synthesis of gold-nanoparticles. Thereafter, cefotaxime was conjugated onto it with the help of activator 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide. For characterization of both unconjugated and cefotaxime conjugated gold nanoparticles; UV-Visible spectroscopy, Scanning, and Transmission type Electron Microscopy methods accompanied with Dynamic Light Scattering were used. We used agar diffusion method plus microbroth-dilution method for the estimation of the antibacterial-activity and determination of minimum inhibitory concentration or MIC values, respectively. MIC values of cefotaxime loaded gold nanoparticles against E. coli and K. pneumoniae were obtained as 1.009 and 2.018 mg/L, respectively. These bacterial strains were completely resistant to cefotaxime alone. These results reinforce the utility of conjugating an old unresponsive antibiotic with gold nanoparticles to restore its efficacy against otherwise resistant bacterial pathogens. J. Cell. Biochem. 118: 2802-2808, 2017. © 2017 Wiley Periodicals, Inc.

Copy number variations in Saudi family with intellectual disability and epilepsy.

BACKGROUND: Epilepsy is genetically complex but common brain disorder of the world affecting millions of people with almost of all age groups. Novel Copy number variations (CNVs) are considered as important reason for the numerous neurodevelopmental disorders along with intellectual disability and epilepsy. DNA array based studies contribute to explain a more severe clinical presentation of the disease but interoperation of many detected CNVs are still challenging. RESULTS: In order to study novel CNVs with epilepsy related genes in Saudi family with six affected and two normal individuals with several forms of epileptic seizures, intellectual disability (ID), and minor dysmorphism, we performed the high density whole genome Agilent sure print G3 Hmn CGH 2x 400 K array-CGH chips analysis. Our results showed de novo deletions, duplications and deletion plus duplication on differential chromosomal regions in the affected individuals that were not shown in the normal fathe and normal kids by using Agilent CytoGenomics 3.0.6.6 softwear. Copy number gain were observed in the chromosome 1, 16 and 22 with LCE3C, HPR, GSTT2, GSTTP2, DDT and DDTL genes respectively whereas the deletions observed in the chromosomal regions 8p23-p21 (4303127-4337759) and the potential gene in this region is CSMD1 (OMIM: 612279). Moreover, the array CGH results deletions and duplication were also validated by using primer design of deleted regions utilizing the flanked SNPs using simple PCR and also by using quantitative real time PCR. CONCLUSIONS: We found some of the de novo deletions and duplication in our study in Saudi family with intellectual disability and epilepsy. Our results suggest that array-CGH should be used as a first line of genetic test for epilepsy except there is a strong indication for a monogenic syndrome. The advanced high through put array-CGH technique used in this study aim to collect the data base and to identify new mechanisms describing epileptic disorder, may help to improve the clinical management of individual cases in decreasing the burden of epilepsy in Saudi Arabia.

Microcephaly-capillary malformation syndrome: Brothers with a homozygous STAMBP mutation, uncovered by exome sequencing.

We describe two brothers from a consanguineous family of Egyptian ancestry, presenting with microcephaly, apparent global developmental delay, seizures, spasticity, congenital blindness, and multiple cutaneous capillary malformations. Through exome sequencing, we uncovered a homozygous missense variant in STAMBP (p.K303R) in the two siblings, inherited from heterozygous carrier parents. Mutations in STAMBP are known to cause microcephaly-capillary malformation syndrome (MIC-CAP) and the phenotype in this family is consistent with this diagnosis. We compared the findings in the present brothers with those of earlier reported patients. © 2016 Wiley Periodicals, Inc.

Genome wide analysis of novel copy number variations duplications/deletions of different epileptic patients in Saudi Arabia.

BACKGROUND: Epilepsy is genetically complex neurological disorder affecting millions of people of different age groups varying in its type and severity. Copy number variants (CNVs) are key players in the genetic etiology of numerous neurodevelopmental disorders and prior findings also revealed that chromosomal aberrations are more susceptible against the pathogenesis of epilepsy. Novel technologies, such as array comparative genomic hybridization (array-CGH), may help to uncover the pathogenic CNVs in patients with epilepsy. RESULTS: This study was carried out by high density whole genome array-CGH analysis with blood DNA samples from a cohort of 22 epilepsy patients to search for CNVs associated with epilepsy. Pathogenic rearrangements which include 6p12.1 microduplications in 5 patients covering a total region of 99.9kb and 7q32.3 microdeletions in 3 patients covering a total region of 63.9kb were detected. Two genes BMP5 and PODXL were located in the predicted duplicated and deleted regions respectively. Furthermore, these CNV findings were confirmed by qPCR. CONCLUSION: We have described, for the first time, several novel CNVs/genes implicated in epilepsy in the Saudi population. These findings enable us to better describe the genetic variations in epilepsy, and could provide a foundation for understanding the critical regions of the genome which might be involved in the development of epilepsy.

Thyroid Disorders Spectrum in Pediatric Endocrine Clinic; Seven-Year Experience of a Teaching Hospital in Saudi Arabia.

Thyroid disorders constitute one of the major endocrine disorders in pediatric service. It includes a range of congenital versus acquired anatomic and/or functional thyroid diseases in growing children that has a spectrum of severity from severe intellectual disability effect to subclinical mild pathologies. This study was designed to analyze the demographic characteristics, clinical pattern, and severity of thyroid disorders in the pediatric endocrine clinic patients at the teaching hospital of the university over a 7-year duration. A total number of 148 patients with thyroid disorders were seen in pediatric Endocrine clinic during the time between January 2015 and December 2021. Female patients constitute 64% of them. Acquired Hypothyroidism was the commonest disorder; 34% of the cases followed by the congenital hypothyroidism (CH), then Hashimoto's thyroiditis, and 5.8% for others. While a very small percentage was acquired hyperthyroidism. The majority of referrals were from dermatology and other service for the screening of thyroid disease as association with other autoimmune diseases with percentage of 28.3%. Next was neck swelling manifestation in 22.6%. Thyroid disorders in children, both congenital and acquired, constitute an important medical issue for pediatricians to be aware of its variable presentations, and its potential serious health consequences on the affected children if not diagnosed and treated earlier. Acquired hypothyroidism constitutes more percentage of the thyroid disorders followed in the pediatric endocrinology outpatient clinics. Congenital hypothyroidism is the second most common thyroid disorder in the outpatient unit, having the most potential complications. These results support the international studies with the female predominance in most of thyroid disorders.

A Clinical and Biochemical Comparative Study Of Diabetic Ketoacidosis (DKA) in Newly Diagnosed Vs Known Cases of Type 1 Diabetic Children.

Objectives: We aimed to study the characterizing clinical and biochemical profiles of Diabetic Ketoacidosis (DKA) in children with newly diagnosed Type 1 Diabetes Mellitus (Type 1DM) compared to children with established diagnosis of Type 1DM presenting with DKA admitted to the pediatric intensive care unit of a large university hospital in the eastern region of Saudi Arabia. Methods: We retrospectively reviewed the medical records of 211 patients who were admitted to the pediatric intensive care unit with diabetic ketoacidosis between 2010 and 2019. The diagnosis of diabetic ketoacidosis was based on symptoms of polydipsia, polyurea, weight loss, vomiting, dehydration, abdominal pain, breathing problems, lethargy or coma, biochemical hyperglycemia (blood glucose level of >200 mg/dL), venous pH of <7.3, serum bicarbonate level of ≤15 mEq/L, and ketonemia (blood ß -hydroxybutyrate concentration of ≥3 mM) or moderate or severe ketonuria (diagnosed as newly acquired type 1 diabetes). Results: The rate of newly diagnosed Type 1 DM with DKA was 41.7%, out of them who got severe and moderate diabetic ketoacidosis were 61.6% and 38.4%, respectively. We observed significantly increased heart and respiratory rates in patients newly diagnosed with diabetic ketoacidosis and in those with severe diabetic ketoacidosis (p<0.001) compared to known cases with Type 1DM presenting with DKA. We also identified significantly increased biochemical indices including HbA1c, random blood sugar, serum osmolality, blood urea nitrogen, creatinine, chloride, lactate, and anion gap in relation to severe diabetic ketoacidosis and newly diagnosed type 1 diabetes (p ≤ 0.05). Conclusions: We found that the clinical and biochemical profiles of patients with newly diagnosed Type 1 DM children were significantly affected compared to children who were known Type 1DM presenting with DKA.

Diabetic Ketoacidosis and its Severity Predictors in Type 1 Diabetic Children; A 10-year Experience of A Teaching Hospital in Saudi Arabia.

OBJECTIVE: Our objective was to determine the trend and precipitating factors of the severity of diabetic ketoacidosis (DKA) in the population admitted to the Pediatric Intensive Care Unit (PICU) in a large teaching hospital in the Eastern region of Saudi Arabia. METHODS: We conducted a retrospective, analytical study at King Fahad Hospital, Imam Abdulrahman Bin Faisal University, Alkhobar, Saudi Arabia. We retrieved the complete medical records of 2234 children who were admitted to the PICU during the 10-year period of 2010 through 2019. The children included those with polydipsia, polyurea, abdominal pain, vomiting, dehydration, and weight loss, as well as breathing disturbances due to acidosis and CNS issues such as lethargy or coma and elevated blood glucose level, > 200 mg/dL [> 11.1 mmol/L], venous pH 7.3, serum total CO2 15 mmol/L, and blood- hydroxybutyrate concentration 3 mmol/L or moderate or severe ketonuria. RESULTS: Out of 2234 PICU admissions, 211 (9.4%) were diagnosed with DKA. A persistent increase in the rate of DKA ended up at 14.1% in 2019 (p = .005). The incidence of DKA was 88/2234 (3.93%). The severity of DKA was as follows: 130 (61.6%) had severe and 81 (38.4%) had moderate DKA. Excessive sweet intake without adding insulin in 83 (39.3%) patients and unhealthy lifestyles (35.1%) were the best predictors of severe DKA (p = .001). CONCLUSION: Over a 10-year period, the DKA pattern was persistently rising and slightly falling, which ended up at the significantly highest rate of 14.1% in 2019. URTI, pneumonia, unhealthy lifestyle, and excess sweet intake were significant precipitating factors associated with severe DKA.

Myocarditis in Children: Impact of Early Presentation on Disease Outcomes at a Single Tertiary Center in Saudi Arabia.

Purpose: Myocarditis is the inflammation of the heart muscle and can be caused by a variety of infections, incendiary diseases, and pollutants. It is challenging for an emergency pediatrician to have a sufficiently high degree of suspicion for myocarditis to avoid diagnostic delay given the broad overlap of myocarditis symptoms with other disease processes. The study aimed to evaluate the impact of early presentation and diagnosis on the outcomes of acute myocarditis in children. Patients and Methods: We performed a retrospective analysis of the complete records of 80 pediatric patients diagnosed with acute myocarditis between 2015 and 2019 at a single tertiary center in Saudi Arabia. Patients were two weeks to 14 years of age and were admitted to the pediatric intensive care unit (PICU) for various sequelae of myocarditis. Data from routine clinical and laboratory investigations were collected. Results: The incidence of delayed presentation at the hospital after the onset of symptoms of myocarditis was 42.5%. A total of 22 (27.5%) patients expired during their hospital stay. There was marginally significant association of earlier presentation with in-hospital survival (80.4% vs 61.8%) and delayed presentation with higher proportion of in-hospital mortality (38.2% vs 19.6%, p=0.064). The rate of mechanical ventilator was also marginally significant in delayed presentation (p=0.068). Shock and multisystem organ failure were the significantly associated manifestations of delayed acute myocarditis presentations. Length of stay in PICU was also significant in delayed presentation group. The impact of presenting symptoms, ECG findings, and use of mechanical ventilator was not significantly associated with delayed presentation. Conclusion: An earlier presentation may have a substantial impact on overall prognosis and length of PICU stay and may lead to comparatively lesser frequency of mechanical ventilation use.

Innovative Method to Digitize a Web-Based OSCE Evaluation System for Medical Students: A Cross-Sectional Study in University Hospital in Saudi Arabia.

PURPOSE: The Objective Structured Clinical Examination (OSCE) is a standard academic assessment tool in the field of medical education. This study presents an innovative method for digitizing OSCE evaluation system for medical students and explores its efficacy compared to the traditional paper-based system, through the analysis of a User Satisfaction Survey. METHODS: A cross-sectional, questionnaire-based study involving a User Satisfaction Survey to evaluate assessors' attitudes toward and acceptance of the Computerized Web-based OSCE Evaluation System (COES) was used. Fifth-year medical students at a College of Medicine were assessed clinically through their 2019 end-of-year OSCE examination by 30 examiners in five different OSCE stations. The traditional paper-based stations were converted into an online electronic version using QuestionPro software. Answers were filled in using smart tablets (iPads). QR codes were used for students' identification at each station to fully digitize the process and save time. After the completion of the exam, a User Satisfaction Survey was sent electronically to all examiners to evaluate their experiences with the new system. RESULTS: The response rate for the survey was 100% with an internal consistency of 0.83. Almost all the examiners (29, 97%) were satisfied with the application of the COES. Further, 72% of the examiners indicated that the electronic system facilitated the evaluation of the students' skills, and 84% found using a smart device (iPad) was easier than using a paper form. All examiners expressed their preference for using the electronic system in the future. CONCLUSION: Users were satisfied with the utilization of the customized COES. This concept of fully digitizing the OSCE assessment process shortened the time needed for both the analysis of results and providing students with feedback. Further observational studies are needed to assess examiners' behaviors when using this methodology.