Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review.

BACKGROUND: Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken. OBJECTIVES: To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness. METHODS: For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction. RESULTS: Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases. CONCLUSION: Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).

Characteristics of chest pain among children presenting to the pediatric emergency department.

Chest pain in pediatric patients is a common concern in pediatric emergency departments (ED). In most cases, benign conditions are related to noncardiac causes, and only a minority of the cases are caused by heart disease. This research aimed to evaluate the causes and characteristics of chest pain among children in a pediatric emergency department. This retrospective study evaluated children younger than 14 years of age who presented to the emergency department of a general pediatric hospital in the Eastern area of Saudi Arabia with non-traumatic chest pain between 2017 and 2022. The data included socioeconomic information, physical examination findings, and the results of basic investigations, such as chest X-ray and electrocardiogram. The Chi-square test was performed to compare various etiologies, with a 5% significant level. The study evaluated 310 patients with a mean age of 9.1±2.7 years. The majority of children presenting with chest pain had normal physical examinations, except 3.3% who showed respiratory and cardiac findings. The diagnostic tests indicated pneumonia in 2.9% and arrhythmia in 2.1% of children. Most patients were discharged with a diagnosis of idiopathic or muscular chest pain. The majority of patients (95%) were treated symptomatically in outpatient settings, with just one patient requiring hospitalization. The most common cause of chest pain prompting a child to visit the ED was idiopathic chest pain. Therefore, this study highlights the significance of obtaining a comprehensive medical history and physical examination to reveal important clues and help avoid unnecessary tests.

Prevalence, frequency, and disability of migraine headaches and tension headaches among the general population in the Eastern Region of Saudi Arabia.

A tension-type headache (TTH) is a recurrent headache that is mild to moderate in intensity, unlike migraine (MH), which is accompanied by crippling effects of nausea, vomiting, photophobia, or phonophobia. TTH is more frequent than migraine, but it is less likely to cause severe pain and physical dysfunction. TTHs account for more lost workdays due to their prevalence. The study aimed to evaluate the prevalence, frequency, and disability of MHs and TTHs among the general population in the Eastern Region of Saudi Arabia. A cross-sectional study was employed using a validated questionnaire. The questionnaire implemented the HARDSHIP algorithm to diagnose MH and TTH and questions to correlate their prevalence to socio-demographic data, measurement of the level of disability, headache management, and treatment effectiveness using the chi-square test. The study reviewed 877 subjects (46.6% males vs. 53.4% females). 52.9% of the participants experienced headaches during the previous three months, and 35.6% experienced headaches recently. The most common type of headache was a probable MH (32.1%), followed by a TTH (26.9%), probable TTH (19.5%), and MH (15%). It was reported that some disability was attributed to 47% of MHs and 26% of TTHs. The most commonly used headache medication was paracetamol (53.5%). This study revealed that TTH and MH are common illnesses in Saudi Arabia's Eastern Region. TTH and MH are correlated with significant individual and social burdens, particularly for MH. Headache sufferers mostly manage their headaches using conventional over-the-counter methods.

Intussusception and COVID-19 in Children: A Systematic Review and Meta-Analysis.

Background: Intussusception (ISN) post-COVID-19 infection in children is rare but can occur. SARS-CoV-2 may play a role in the pathogenesis of ISN and trigger immune activation and mesenteric adenitis, which predispose peristaltic activity to "telescope" a proximal bowel segment into the distal bowel lumen. Objectives: To estimate the prevalence of SARS-CoV-2 infection in ISN children and analyze the demographic parameters, clinical characteristics and treatment outcomes in ISN pediatric patients with COVID-19 illness. Methods: We performed this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies reporting on the incidence of ISN post-SARS-CoV-2 infection in children, published from 1 December 2019 until 1 October 2022, in PROQUEST, MEDLINE, EMBASE, PUBMED, CINAHL, WILEY ONLINE LIBRARY, SCOPUS and NATURE, with a restriction to articles available in the English language, were included. Results: Of the 169 papers that were identified, 34 articles were included in the systematic review and meta-analysis (28 case report, 5 cohort and 1 case-series studies). Studies involving 64 ISN patients with confirmed COVID-19 (all patients were children) were analyzed. The overall pooled proportions of the ISN patients who had PCR-confirmed SARS-CoV-2 infection was 0.06% (95% CI 0.03 to 0.09, n = 1790, four studies, I2 0%, p = 0.64), while 0.07% (95% CI 0.03 to 0.12, n = 1552, three studies, I2 0%, p = 0.47) had success to ISN pneumatic, hydrostatic and surgical reduction treatment and 0.04% (95% CI 0.00 to 0.09, n = 923, two studies, I2 0%, p = 0.97) had failure to ISN pneumatic, hydrostatic and surgical reduction treatment. The median patient age ranged from 1 to 132 months across studies, and most of the patients were in the 1−12 month age group (n = 32, 50%), p = 0.001. The majority of the patients were male (n = 41, 64.1%, p = 0.000) and belonged to White (Caucasian) (n = 25, 39.1%), Hispanic (n = 13, 20.3%) and Asian (n = 5, 7.8%) ethnicity, p = 0.000. The reported ISN classifications by location were mostly ileocolic (n = 35, 54.7%), and few children experienced ileo-ileal ISN (n = 4, 6.2%), p = 0.001. The most common symptoms from ISN were vomiting (n = 36, 56.2%), abdominal pain (n = 29, 45.3%), red currant jelly stools (n = 25, 39.1%) and blood in stool (n = 15, 23.4%). Half of the patients never had any medical comorbidities (n = 32, 50%), p = 0.036. The approaches and treatments commonly used to manage ISN included surgical reduction of the ISN (n = 17, 26.6%), pneumatic reduction of the ISN (n = 13, 20.2%), antibiotics (n = 12, 18.7%), hydrostatic reduction of the ISN (n = 11, 17.2%), laparotomy (n = 10, 15.6%), intravenous fluids (n = 8, 12.5%) and surgical resection (n = 5, 7.8%), p = 0.051. ISN was recurrent in two cases only (n = 2, 3.1%). The patients experienced failure to pneumatic (n = 7, 10.9%), hydrostatic (n = 6, 9.4%) and surgical (n = 1, 1.5%) ISN treatment, p = 0.002. The odds ratios of death were significantly higher in patients with a female gender (OR 1.13, 95% CI 0.31−0.79, p = 0.045), Asian ethnicity (OR 0.38, 95% CI 0.28−0.48, p < 0.001), failure to pneumatic or surgical ISN reduction treatment (OR 0.11, 95% CI 0.05−0.21, p = 0.036), admission to ICU (OR 0.71, 95% CI 0.83−1.18, p = 0.03), intubation and placement of mechanical ventilation (OR 0.68, 95% CI 0.51−1.41, p = 0.01) or suffering from ARDS (OR 0.88, 95% CI 0.93−1.88, p = 0.01) compared to those who survived. Conclusion: Children with SARS-CoV-2 infection are at low risk to develop ISN. A female gender, Asian ethnicity, failure to ISN reduction treatment (pneumatic or surgical), admission to ICU, mechanical ventilation and suffering from ARDS were significantly associated with death following ISN in pediatric COVID-19 patients.

Global Coinfections with Bacteria, Fungi, and Respiratory Viruses in Children with SARS-CoV-2: A Systematic Review and Meta-Analysis.

Background: Coinfection with bacteria, fungi, and respiratory viruses has been described as a factor associated with more severe clinical outcomes in children with COVID-19. Such coinfections in children with COVID-19 have been reported to increase morbidity and mortality. Objectives: To identify the type and proportion of coinfections with SARS-CoV-2 and bacteria, fungi, and/or respiratory viruses, and investigate the severity of COVID-19 in children. Methods: For this systematic review and meta-analysis, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus, and Nature through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies on the incidence of COVID-19 in children with bacterial, fungal, and/or respiratory coinfections, published from 1 December 2019 to 1 October 2022, with English language restriction. Results: Of the 169 papers that were identified, 130 articles were included in the systematic review (57 cohort, 52 case report, and 21 case series studies) and 34 articles (23 cohort, eight case series, and three case report studies) were included in the meta-analysis. Of the 17,588 COVID-19 children who were tested for co-pathogens, bacterial, fungal, and/or respiratory viral coinfections were reported (n = 1633, 9.3%). The median patient age ranged from 1.4 months to 144 months across studies. There was an increased male predominance in pediatric COVID-19 patients diagnosed with bacterial, fungal, and/or viral coinfections in most of the studies (male gender: n = 204, 59.1% compared to female gender: n = 141, 40.9%). The majority of the cases belonged to White (Caucasian) (n = 441, 53.3%), Asian (n = 205, 24.8%), Indian (n = 71, 8.6%), and Black (n = 51, 6.2%) ethnicities. The overall pooled proportions of children with laboratory-confirmed COVID-19 who had bacterial, fungal, and respiratory viral coinfections were 4.73% (95% CI 3.86 to 5.60, n = 445, 34 studies, I2 85%, p < 0.01), 0.98% (95% CI 0.13 to 1.83, n = 17, six studies, I2 49%, p < 0.08), and 5.41% (95% CI 4.48 to 6.34, n = 441, 32 studies, I2 87%, p < 0.01), respectively. Children with COVID-19 in the ICU had higher coinfections compared to ICU and non-ICU patients, as follows: respiratory viral (6.61%, 95% CI 5.06−8.17, I2 = 0% versus 5.31%, 95% CI 4.31−6.30, I2 = 88%) and fungal (1.72%, 95% CI 0.45−2.99, I2 = 0% versus 0.62%, 95% CI 0.00−1.55, I2 = 54%); however, COVID-19 children admitted to the ICU had a lower bacterial coinfection compared to the COVID-19 children in the ICU and non-ICU group (3.02%, 95% CI 1.70−4.34, I2 = 0% versus 4.91%, 95% CI 3.97−5.84, I2 = 87%). The most common identified virus and bacterium in children with COVID-19 were RSV (n = 342, 31.4%) and Mycoplasma pneumonia (n = 120, 23.1%). Conclusion: Children with COVID-19 seem to have distinctly lower rates of bacterial, fungal, and/or respiratory viral coinfections than adults. RSV and Mycoplasma pneumonia were the most common identified virus and bacterium in children infected with SARS-CoV-2. Knowledge of bacterial, fungal, and/or respiratory viral confections has potential diagnostic and treatment implications in COVID-19 children.

Indications and complications for surgical management of thyroid diseases: A single center experience.

Background: Thyroid disorders are one of the most common endocrine disorders. Thyroid disorders are highly prevalent in the Saudi population. There are many approaches to treat thyroid disorders, varying from conservative to surgical, depending on the severity of each condition. There are many indications for surgical management of thyroid diseases, including carcinoma, hyperthyroidism, and local compression symptoms. Materials and methods: This is a retrospective study included subjects operated upon for a thyroid disorder over 6 years period in the eastern province of Saudi Arabia. Results: The clinical manifestations and postoperative characteristics of the patients are given in Table 2. It can be observed that the most dominant clinical presentation was neck mass (76.4%), while the most common indication of surgery was the suspicion of cancer (54.5%). Furthermore, the most common histopathology was papillary thyroid cancer (41.8%), whereas the most common complication after the surgery was hypocalcemia (9.1%). Likewise, total thyroidectomy was the most commonly sought surgical intervention (70.9%). Additionally, Bethesda class III constitutes 35.1%, while Bethesda class II constitutes 29.7%. Conclusion: Suspicion of cancer was the most prominent indication for surgical intervention. The most prevalent postoperative complications were hypocalcemia. Furthermore, papillary thyroid carcinoma was the most common histological findings, which raises several questions since it contrasts with previous studies done in Saudi Arabia. We believe that the number of thyroid procedures in our region is underreported, and more research is needed to validate this.

Towards a Security Reference Architecture for NFV.

Network function virtualization (NFV) is an emerging technology that is becoming increasingly important due to its many advantages. NFV transforms legacy hardware-based network infrastructure into software-based virtualized networks. This transformation increases the flexibility and scalability of networks, at the same time reducing the time for the creation of new networks. However, the attack surface of the network increases, which requires the definition of a clear map of where attacks may happen. ETSI standards precisely define many security aspects of this architecture, but these publications are very long and provide many details which are not of interest to software architects. We start by conducting threat analysis of some of the NFV use cases. The use cases serve as scenarios where the threats to the architecture can be enumerated. Representing threats as misuse cases that describe the modus operandi of attackers, we can find countermeasures to them in the form of security patterns, and we can build a security reference architecture (SRA). Until now, only imprecise models of NFV architectures existed; by making them more detailed and precise it is possible to handle not only security but also safety and reliability, although we do not explore those aspects. Because security is a global property that requires a holistic approach, we strongly believe that architectural models are fundamental to produce secure networks and allow us to build networks which are secure by design. The resulting SRA defines a roadmap to implement secure concrete architectures.

Retained Presumed Intraocular Cotton Fiber after Implantable Collemer Lens Implantation: A Case Report.

Retained intraocular foreign body is a known complication of ophthalmic surgery. The presence of intraocular cotton fibers after ophthalmic surgery is well-documented in different procedures including cataract and vitreoretinal surgeries. This report describes a case of retained cotton fiber after implantable collamer lens (ICL) implantation. This report describes a case of a 23-year-old female who was diagnosed with high myopia and mild astigmatism. The patient was selected to undergo ICL implantation in her right eye. The postoperative examination was done a few hours after the procedure, and a cotton fiber was incidentally found to be attached to the posterior surface of the ICL without causing visual disturbances or any other abnormal findings. This patient was followed up closely within the 2 postoperative weeks, and a 1-year follow-up did not reveal any change in the cotton fiber place or position, nor was there any other complication. In conclusion, cotton fibers are typically inert and usually do not lead to major complications. The decision of whether to surgically remove these fibers or not should only be made after weighing the benefits against the risks of such intervention. Recurrent inflammatory reactions or iridocyclitis related to the presence of cotton fibers could validate surgical intervention; however, the presence of cotton fibers solely does not necessitate early surgical removal.

Management Approach of Pediatric Constipation.

Constipation is a common challenge in pediatrics. Abdominal radiographs are frequently taken in the pediatric emergency department for diagnosis despite their inadequate reliability to detect the pathology or the degree of constipation. Misdiagnosis of constipation may cause multiple vague physician visits, deployment of emergency medical services, use of radiation, unnecessary laboratory tests, and even surgical procedures. The primary evidence-based suggestions are based on published guidelines that include management of constipation in children divided into three stages of therapy: (1) disimpaction, (2) maintenance therapy, and (3) behavior modification, and special care should be given to neonates and to children with pre-existing medical problems.

Hydroxyurea usage awareness among patients with sickle-cell disease in Saudi Arabia.

BACKGROUND AND AIM: Hydroxyurea (HU) plays an essential role in the complex pathophysiology alteration of sickle-cell disease (SCD), which translates clinically into the enhanced quality of life and increased survival. This research examines adult patients with SCD's attitudes and awareness toward HU, as well as underutilization consequences. METHOD: A cross-sectional research was performed in Saudi Arabia, and adult patients with SCD were interviewed. The survey includes patient demographics, attitudes, and knowledge of HU and clinical data. The chi-square was applied through SPSS version 23 for assessing any association with outcome variables and demographic characteristics. RESULTS: HU is known to 72 (67.3%) of the 107 patients. The hydroxyurea treatment was initiated in 46 patients (63%). Of these, 23 (50%) discontinue HU, with the key factors being pregnancy preparation and side effects development. For those who were unaware of HU, 13 (37.1%) were admitted to the intensive care unit because of acute chest syndrome, 29 (82.8%) required a frequent blood transfusion and 12 (34.2%) with frequent hospitalizations. However, there was no significant relationship between awareness and education level (P value is .078 > .05). In addition, there was no significant relationship between the level of awareness and age and gender of participants (P value is .68 and .44, respectively). CONCLUSION: HU is a long-established and effective disease-modifying agent for SCD patients, but it is underutilized. The causality of underuse is bidirectional between patients and healthcare providers. It is essential to educate healthcare providers and patients with SCD about hydroxyurea role in modifying disease severity, resolving adverse events, and achieving full benefits.

Knowledge of Thyroid Disease Manifestations and Risk Factors Among Residents of the Eastern Province, Saudi Arabia.

BACKGROUND: Thyroid disorders are worldwide common endocrine disorders. These disorders are frequently under-diagnosed. In general, lack of knowledge and understanding of thyroid disorder effects can lead patients to go undiagnosed. This study aims to figure out the level of the general knowledge about thyroid disease manifestations, risk factors, and preventive behaviors among the general population.  Method: This cross-sectional study was conducted among 882 participants in the Eastern province of Saudi Arabia from July 2020 to October 2020, and were selected randomly. The representative sample included Saudi and non-Saudi males and females of different age groups (18-60 years). RESULT: The overall mean knowledge score was 8.67 (SD 3.69) with 44.7%, 41.2%, and 14.2% were classified into low, average, and high knowledge, respectively. In the comparison of mean knowledge score among the socio-demographic profiles and previous history of thyroid disease, the current study shows that being a female, living in Al Ahsa, being a student, those with a previous history of thyroid disease, family history of the disease, and those who underwent thyroid gland examination were significantly more associated with having better knowledge toward thyroid diseases. CONCLUSION: Nearly, half of the studied sample has low awareness scores regarding thyroid disease manifestations and its risk factors. The health authorities should hold more successful health education methods to improve the public and their caregivers' awareness of the various aspects of thyroid disorders and the value of their early detection and adequate control.

Awareness of diabetic retinopathy among Saudis with diabetes type 2 in Riyadh city.

OBJECTIVE: To assess awareness of diabetic retinopathy (DR) for Saudis with diabetes mellitus (DM) type 2 in Riyadh City. METHODS: A cross-sectional study that used self-administered questionnaires conducted in primary healthcare centers in Riyadh City between October and December 2019. RESULTS: There were 267 Saudi participants with diabetes mellitus type 2 visiting primary healthcare clinics. (52.4%) were aged 40 years or above at time of diagnosis with diabetes. (73%) had diabetes for at least 5 years. Most of the participants have a good blood glucose control and they do home measurements. In regard to DR, (64.4%) of participants had no subjective or objective indicators of retinopathy, and (70%) had visited ophthalmology clinics. Majority of the participants were advised about DR or referred to an ophthalmologist by their primary physician, with the percentages being (64.8%) and (59.6%), respectively. Regarding other risk factors of DR, (19.5%) had a family history of DR, (23.2%) of participant are smokers and (41.6%) were hypertensives. Majority of the participants were aware about all the aspects of DR, its consequences, and appropriate management except the laser therapy. In terms of area of living and education respondents, who lived in the center of Riyadh City and the secondary level or less educated participants had the lowest level of education. CONCLUSIONS: Awareness of DR is acceptable but should not lead this information to reduced awareness and educational programs. Outreach researchers' efforts should cover other directions instead awareness of DR.

The value of 18F-FDG PET-CT and 131I-norcholesterol scintigraphy in the characterization of high-risk adrenal masses.

PURPOSE: To assess the value of F-FDG PET-computed tomography (CT) and I-norcholesterol scintigraphy in noninvasive characterization of high-risk adrenal lesions using surgical pathology as the gold standard. METHODS: We retrospectively reviewed clinical cases referred to the adrenal multidisciplinary team in a tertiary centre over the last 6 years. Inclusion criteria were the presence of indeterminate adrenal lesions and performance of combined imaging with 2-deoxy-2-[fluorine-18] fluoro- D-glucose Positron emission tomography/ computed tomography and I-norcholesterol scans. The accuracy of CT, PET-CT and I-norcholesterol findings was assessed by comparison with the postoperative histopathological outcome. RESULTS: Sixteen patients fulfilled the inclusion criteria. Ten underwent unilateral adrenalectomy, and six had clinical follow-up. The number of cases categorized as concerning on the basis of unenhanced CT, F-FDG PET-CT and I-norcholesterol was 11, 9 and 2, respectively. The mean diameter of adrenal lesions was 4.5 ± 1.9 cm. Average SUVmax of the FDG-avid adrenal lesions was 5.0 ± 2.0 (range 3.5-9.7). Fourteen adrenal masses showed I-norcholesterol uptake. All adrenal masses turned out to be benign lesions. CONCLUSION: Conventional CT and FDG PET parameters are not adequately specific for determination of a benign lesion in this selected cohort of high-risk patients. Use of I-norcholesterol in this patient cohort may provide additional value.

The serious complications of frontal sinusitis, a case series and literature review.

The aim of this study is to illustrate the managements of different clinical and radiological presentations of serious complications of frontal sinusitis diagnosed and managed at the tertiary referral hospital. A case series study conducted at the tertiary referral in the period from 2012 to 2019. Four different cases of serious complications of frontal sinusitis namely orbital abscess, frontal meningitis, subdural empyema and frontal lobe abscess will be presented and discussed. Despite the generous use of antibiotics, the serious complications of frontal sinusitis still develop. The serious complications of frontal sinusitis ranges from orbital abscess to frank frontal lobe abscess. The management is a combination of systemic antibiotics and surgical drainage with excellent outcomes.