Nephrotic syndrome: Pretibial epidermolysis bullosa in a patient with CD151 tetraspanin defect: A case report.

Nephrotic syndrome (NS)-epidermolysis bullosa (EB) sensorineural deafness syndrome is an autosomal recessive rare genetic disease caused by a CD151 gene homozygous mutation on chromosome 11p15.5. In this report, we discuss a rare case related to a Saudi patient with genetic syndrome who presented with NS and EB. Whole genome sequencing results indicated a homozygous pathogenic variant identified in the CD151 gene (c.493C>T p.(Arg165*), which was consistent with a genetic diagnosis of autosomal recessive nephropathy with pretibial EB and deafness syndrome. The findings emphasize that even a single genotype can result in variable phenotypic expression, necessitating the assessment of the pleiotropic effects of the disease on the patient, which can range from severe to mild. This case report adds to the literature by highlighting the considerable phenotypic variation that can be present in patients with the CD151 mutation.

Breaking new ground: Exploring de novo chromosomal rearrangements in 1p36 microdeletion.

Chromosomal structural variations (SVs) are linked to a wide range of phenotypes and arise due to disruptions during DNA replication, which can affect gene function within the SV regions. This case report details a patient diagnosed with neurodevelopmental delay. Detailed investigation through array comparative genomic hybridization revealed two pathogenic SVs on chromosome 1, which align with a 1p36 microdeletion, and a microduplication at 2p35.3, the latter being classified as a variant of unknown significance. The patient's clinical presentation is consistent with the 1p36 deletion syndrome, characterized by specific developmental delays and physical anomalies. Further genetic analysis suggests that these terminal rearrangements might stem from an unbalanced translocation between the short arms of chromosomes 1 and 2. This case underscores the complexity of interpreting multiple concurrent SVs and their cumulative effect on phenotype. Ongoing research into such chromosomal abnormalities will enhance our understanding of their clinical manifestations and guide more targeted therapeutic strategies.

Paediatric Asthma and the Microbiome: A Systematic Review.

Evidence from the literature suggests an association between the microbiome and asthma development. Here, we aimed to identify the current evidence for the association between asthma and the upper airway, lower airway and/or the gut microbiome. An electronic systemic search of PubMed, EBSCO, Science Direct and Web of Science was conducted until February 2022 to identify the eligible studies. The Newcastle-Ottawa Scale and the Systematic Review Centre for Laboratory Animal Experimentation risk of the bias tools were used to assess quality of included studies. Twenty-five studies met the inclusion criteria. Proteobacteria and Firmicutes were identified as being significantly higher in the asthmatic children compared with the healthy controls. The high relative abundance of Veillonella, Prevotella and Haemophilus in the microbiome of the upper airway in early infancy was associated with a higher risk of asthma development later in life. The gut microbiome analyses indicated that a high relative abundance of Clostridium in early childhood might be associated with asthma development later in life. The findings reported here serve as potential microbiome signatures associated with the increased risk of asthma development. There is a need for large longitudinal studies to further identify high-risk infants, which will help in design strategies and prevention mechanisms to avoid asthma early in life.

Prevalence of Carbapenem Non-susceptible Gram-Negative Bacteria at Tertiary Care Hospitals in Saudi Arabia.

Background Antibiotics significantly increased life expectancy and decreased mortality rates due to infections. However, this trend is starting to fade with the rise of multidrug-resistant organisms (MDR); these strains are becoming a global burden on healthcare and the economy. The dramatic increase and spread of carbapenem-resistant gram-negative bacteria (CRGNB) has become a serious global public health concern. In this retrospective cross-sectional study, we aimed to estimate the rates of gram-negative bacteremia in five tertiary care hospitals in different geographical locations in Saudi Arabia for five years. Methods A retrospective cross-sectional study was conducted in five tertiary care hospitals in Saudi Arabia among patients with bacteremia due to CRGNB. Electronic medical records were used to retrieve data regarding patient demographics and antimicrobial susceptibility testing (AST) over five years between January 2016 and December 2020. Patients with positive blood cultures for carbapenem-resistant Escherichia (E.) coli, Klebsiella (K.) pneumonia, Pseudomonas (P.) aeruginosa, and Acinetobacter (A.) baumannii comprise the final study population. Results This retrospective multicentric study was conducted between 2016 and 2020 in five tertiary care hospitals across five cities in Saudi Arabia. E. coli (n=2190, 38.03%), K. pneumoniae (n=2154, 37.41%), P. aeruginosa (n = 918, 15.94%), and A. baumannii (n=496, 8.61%) constitute the 5758 gram-negative bacteria isolates. E. coli was the most frequently identified species in Riyadh, AlAhsa, Dammam, and Madinah (40%, 46.50%, 61.67%, and 43.66%, respectively), with a p-value of (p<0.001), except in Jeddah, where K. pneumoniae was the most prevalent (42%). The mean age of patients across Riyadh, AlAhsa, Dammam, and Madinah was 62.2 years (± 4.24). In contrast to Jeddah, where the majority of isolates (702; 41.8%) belonged to the adult age group. Most isolates were from male patients (3045; 52.9%), compared to 2713 (47.1%) from female patients. K. pneumoniae 1226 (40.3%) was the most prevalent isolate among male patients while E. coli (1135; 41.8%) was the most prevalent isolate among female patients. Conclusion Our study showed that the prevalence of carbapenem non-susceptible Gram-negative bacteria is relatively high, which therefore makes them very challenging to treat. The results show an urgent need for improved antibiotic stewardship strategies, including better surveillance and more effective infection control measures to reduce this issue. Further research into the molecular epidemiology and risk factors associated with these infections is necessary to guide public health policymakers in developing interventions to help control the spread of carbapenem-resistant Gram-negative bacteria.

The diagnostic yield of CGH and WES in neurodevelopmental disorders.

Background: Neurodevelopmental disorders are a group of conditions characterized by developmental delays leading to abnormal brain functions. The methods of diagnosis and treatment of these conditions are complicated, and their treatment involves a combination of various forms of therapy. In recent years, the development of high-resolution technologies has played an important role in revealing the microdeletions, microduplications, and single-nucleotide variants of the chromosomes and how they are linked to the development of neurodevelopmental disorders. The wide implementation and application of molecular methodologies have started to shed light on the functional importance of using the appropriate methods in detecting these genetic variations that are categorized as either pathogenic or benign. The study aimed to compare the diagnostic yield of comparative hybridization (CGH) and whole exome sequencing (WES) in neurodevelopmental disorders among children attending the King Abdullah Specialist Children Hospital, Riyadh, Saudi Arabia. Methods: A retrospective study was conducted between 2015 and 2018 on 105 patients diagnosed with neurodevelopmental disorders through array-based CGH (Array-CGH) and WES. Results: In a sample of 105 patients, 16% was the hit rate of copy number variations (CNVs). WES was requested for CNV-negative patients (n = 79), of which 30% was the hit rate of pathogenic or likely pathogenic single-nucleotide variants. There was a difference in the diagnostic yield between CGH (16%) and WES (30%). Conclusion: WES was a better approach than Array-CGH to detect various DNA mutations or variants. Our findings could guide clinicians, researchers, and testing laboratories select the most cost-effective and appropriate approach for diagnosing their patients.

The Intersection of Health Rehabilitation Services with Quality of Life in Saudi Arabia: Current Status and Future Needs.

Quality of life (QoL) is essential for maintaining a healthy, balanced lifestyle, especially among individuals with chronic diseases. Saudi Arabia (SA) launched a health sector transformation program as part of the nationwide Vision 2030 initiative to ensure the sustainable development of efficient healthcare services, aiming to improve health by increasing well-being and QoL. More investigation into the current status of health rehabilitation services provided to individuals with chronic diseases and future needs to optimize services and improve QoL is needed. This was narratively discussed by experts from different health rehabilitation services in SA. Comprehensive health rehabilitation services including orthopedic, occupational, cardiac, pulmonary, critical care, perioperative, hearing and speech, substance use disorders, and vocational rehabilitation services were addressed. Health rehabilitation services in SA, as in other countries, are suboptimal for individuals in health rehabilitation programs. To optimize the QoL of individuals with chronic diseases, health rehabilitation services should be tailored based on the unique requirements of each service and its serving patients. The shared need to improve health rehabilitation services includes the adoption of home-based and telehealth services, the integration of multi-governmental sectors, the empowerment and allocation of health rehabilitation specialists, public awareness campaigns, policy legislation and guideline development, and the implementation of a long-term follow-up system. This review is one of the first to address the intersection of health rehabilitation services and QoL in SA; urgent and holistic actions are paramount to address the pressing need to optimize SA's health rehabilitation services. The experts' recommendations in this study may be applicable to other countries' health systems, as health rehabilitation services are not well optimized globally.

Stenotrophomonas maltophilia Epidemiology, Resistance Characteristics, and Clinical Outcomes: Understanding of the Recent Three Years' Trends.

BACKGROUND: Stenotrophomonas maltophilia is an emerging pathogen classified as a public health concern, that infects critically ill patients and has expressed resistance against antimicrobial therapy. The aim of this study was to examine the epidemiological pattern, resistance characteristics and clinical outcomes of S. maltophilia infections in hospitalized patients. METHODS: The study included 393 S. maltophilia isolates from different clinical specimens as well as the clinical data of 209 Intensive Care Unit (ICU) patients. The patients' data were obtained from medical and laboratory files. Descriptive statistics and a univariate analysis were used to report and compare the demographics, clinical data, and outcomes. RESULTS: The S. maltophilia was mostly isolated from the respiratory specimens of ICU patients. The adult patients were more likely to develop serious infections and worse outcomes than were pediatric patients. The most common co-infecting pathogens were SARS-CoV2 and Pseudomonas aeruginosa. The death rate was 44.5% and increased to 47.1% in the case of a respiratory infection. Septic shock was the most significant predictor of mortality. Older age and mechanical ventilation were independent and significant risk factors that worsened the outcomes in patients with respiratory infections. CONCLUSIONS: The identification of S. maltophilia as a threat highlights the importance of surveillance studies in this region.

Coinfection of pulmonary tuberculosis with other lower respiratory tract infections: A retrospective cross-sectional study.

BACKGROUND: Little attention has been given to the development of lower respiratory tract infections (LRTIs) in patients with pulmonary tuberculosis (PTB) during their anti-tuberculosis (anti-TB) treatment and how that might affect patients' health status. Here, the prevalence and etiologies of other LRTIs in a cohort of PTB patients were determined, and the clinical features and outcomes were described. METHODS: Adult patients with PTB between 2015 and 2020 were recruited and monitored during their anti-TB treatment for the presence of LRTIs. Clinical data were retrospectively collected from patients' medical records. RESULTS: Data from 76 PTB patients (57 [75%] males) were reviewed. The median age was 61.0 (interquartile range 83.5-35.5) years, and other LRTIs were detected in 45 (59.2%) PTB patients. Of the 126 episodes of LRTIs, 84 (66.7%) were due to bacterial infections, 37 (29.4%) were due to fungal infections, and 5 (3.9%) were due to viral infections. The development of LRTIs was significantly more common in older (P = 0.012) and hypertensive patients with PTB (P = 0.019). Patients with PTB and LRTIs experienced significantly more frequent extrapulmonary infections (P = 0.0004), bloodstream infections (P = 0.001), intensive care unit stays (P = 0.001), and invasive mechanical ventilation use (P = 0.03) than patients who did not develop LRTI. CONCLUSIONS: The identification of host-related risk factors for LRTI development among patients with PTB could be used to develop a prediction model for LRTI development. Hence, initiating antimicrobials early, in parallel with appropriate anti-TB treatment, may mitigate PTB-related health and economic consequences.

Translation and cross-cultural validation of the non-invasive prenatal testing questionnaire in Arabic.

OBJECTIVES: To translate and cross-culturally adapt a Swedish questionnaire to Arabic to assess the awareness of pregnant women in Saudi Arabia regarding the availability of an accurate and safe prenatal screening procedure. METHODS: The study was conducted at the Obstetrics and Gynecology Clinic, King Abdulaziz Medical City, Riyadh, Saudi Arabia between December 2018 to April 2019. The non-invasive prenatal testing (NIPT) questionnaire, translated and validated in Arabic. Cronbach's alpha reliability testing was carried out to validate the Arabic version of the questionnaire. The sample size was 100 pregnant women, at any gestational period, from 20 to 44 years old. This is a prospective cross-sectional. RESULTS: An Arabic translated, and culturally validated questionnaire related to the attitudes, knowledge, and self-perceived probability of delivering a child with chromosomal abnormality.  Conclusion: We translated and validated the NIPT questionnaire to assess the attitude and awareness of pregnant women regarding the availability of the NIPT.