Genotype and Phenotype of Adenosine Deaminase 2 Deficiency: a Report from Saudi Arabia.

Adenosine deaminase 2 deficiency (DADA2), a rare and potentially fatal systemic autoinflammatory disease, is characterized by low or lack of ADA2 activity due to ADA2 mutations. DADA2 symptoms are variable and include vasculitis, immunodeficiency, and cytopenia. Minimal data are available from Saudi Arabia. This retrospective study conducted at seven major tertiary medical centers examined the phenotypic and genotypic variabilities, clinical and diagnostic findings, and treatment outcomes among 20 Saudi patients with DADA2 from 14 families. The median age of the study cohort was 9.5 years (4-26 years). The clinical presentation was before the age of 5 months in 25% of patients. Homozygous c.1447-1451del mutation was the most frequent ADA2 alteration (40%), followed by c.882-2A:G (30%). All tested patients exhibited absent or near-absent ADA2 activity. Phenotypic manifestations included stroke (40%), hematological abnormalities (95%), lymphoproliferation (65%), and recurrent infection (45%). Five and three patients had extracranial vasculitis features and Hodgkin lymphoma, respectively. Atypical manifestations included growth retardation (30%) and transverse myelitis. Anti-tumor necrosis factor (anti-TNF) therapy was the main treatment. Some patients underwent blood transfusion, splenectomy, cyclosporine and colony-stimulating factor therapies, and hematopoietic stem cell transplantation due to anti-TNF therapy failure. Fulminant hepatitis and septic multiorgan failure caused mortality in three patients. Thus, this study revealed the variability in the molecular and clinical characteristics of DADA2 in the study cohort with predominant aberrant hematological and immunological characteristics. Consensus diagnostic criteria will facilitate early diagnosis and treatment. Additionally, disease registries or large prospective studies are needed for evaluating rare disease complications, such as cancer.

Effects of COVID-19 on Pediatric Cancer Care: A Multicenter Study of 11 Middle Eastern Countries.

During the COVID-19 pandemic, major challenges are facing pediatric cancer centers regarding access to cancer centers, continuity of the anti-cancer therapy, hospital admission, and infection protection precautions. Pediatric oncologists actively treating children with cancer from 29 cancer centers at 11 countries were asked to answer a survey from May 2020 to August 2020 either directly or through the internet. COVID-19 pandemic affected the access to pediatric cancer care in the form of difficulty in reaching the center in 22 (75.9%) centers and affection of patients' flow in 21 (72.4%) centers. Health care professionals (HCP) were infected with COVID-19 in 20 (69%) surveyed centers. Eighteen centers (62%) modified the treatment guidelines. Care of follow-up patients was provided in-hospital in 8(27.6%) centers, through telemedicine in 10 (34.5%) centers, and just delayed in 11 (38%) centers. Pediatric oncologists had different expectations about the future effects of COVID-19 on pediatric cancer care. Seventy-six percent of pediatric oncologists think the COVID-19 pandemic will increase the use of telemedicine. Fifty-five percent of pediatric oncologists think if the COVID-19 pandemic persists, we will need to change chemotherapy protocols to less myelosuppressive ones. Collaborative studies are required to prioritize pediatric cancer management during COVID-19 era.

Epidemiology, clinical characteristics and risk factors of COVID-19 among children in Saudi Arabia: a multicenter chart review study.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) has affected over 100 million cases worldwide. Children accounted for 1-5% of all cases with less reported symptoms and better prognosis compared to adults. This study aimed to describe the epidemiological characteristics and outcomes of pediatric COVID-19 cases in Saudi Arabia in addition to identifying risk factors associated with disease severity. METHODS: This was a multicenter, cross-sectional retrospective study that included confirmed SARS-CoV-2 infection among pediatric patients (< 14 years) from the time of initial identification in March 2020 to the end of July 2020 in 6 centers across the country. Patients were classified based on clinical severity. Study outcomes included time to recovery, need for invasive ventilation, and mortality. Multivariate logistic regression analysis was conducted to explore factors associated with increased disease severity. RESULTS: The study enrolled 567 children with (51.5%) were males, and (44.6%) aged from 6 to 14 years old. Asymptomatic patients accounted for 38.98% of the cases: while 319 patients (56%) had mild disease, and 27 patients (4.76%) had moderate-to-severe disease. Only 10 patients (1.76%) required Pediatric Intensive Care Unit admission. The calculated case-fatality was 0.7%. After performing multivariate regression analysis, chronic lung conditions [adjusted OR = 12.73, 95% CI (2.05-79.12)] and decreased red blood cells (RBCs) count [adjusted OR = 2.43, 95% CI (1.09-5.41] were found to be significant predictors for moderate-to-severe disease (p = 0.006 and 0.030, respectively). CONCLUSION: Most COVID-19 cases in the current study had a benign course of illness and carried an excellent prognosis. Children with chronic lung conditions or low RBCs count are at higher risk to develop moderate-to-severe COVID-19 disease.

Vaginal preparation with different antiseptic solutions before cesarean section for preventing postoperative infections: A systematic review and network meta-analysis.

AIMS: We aimed to investigate the effect of various vaginal wash solutions on reducing risks of post-cesarean endometritis, wound infections, fever, and hospital stay duration. METHODS: Scopus, Web of Science, PubMed, and Cochrane Library were searched for randomized clinical trials that compared different vaginal wash solutions to each other or to "no vaginal cleaning"; without restriction on the age of parturients or site where trials were conducted. We analyzed this frequentist network meta-analysis using the netmeta package in R software version 4.1.2; synthesized data as mean difference or risk ratio with their 95% confidence intervals. RESULTS: Our network meta-analysis included 29 RCTs with a total sample size of 9311 women undergoing CS. Regarding post-cesarean endometritis, we found that povidone-iodine had the highest significant risk reduction compared to "no vaginal cleaning" (RR = 0.08, 95% CI [0.01, 0.69]). While regarding post-cesarean reduction of wound infection, fever, and hospital stay duration, we found that chlorhexidine 4% (RR = 0.17, 95% CI [0.05, 0.65]), saline 0.9% (RR = 0.12, 95% CI [0.03; 0.48]), and saline 0.9% (MD = -1.29, 95% CI [-2.18; -0.39]), respectively, had the highest significant risk reduction compared to "no vaginal cleaning." CONCLUSION: Vaginal wash solutions were associated with a significant reduction of post-cesarean endometritis, wound infection, fever, and hospital stay duration. Since povidone-iodine had the highest significant reduction of post-cesarean endometritis, we recommend setting povidone-iodine as the standard practice as pre cesarean vaginal wash solution; consistent practice guidelines of Enhanced Recovery After Surgery (ERAS).

Lemierre Syndrome Complicating Deep Neck Infection and Descending Mediastinitis Secondary to Methicillin resistant Staphylococcus aureus (MRSA) Infection.

Lemierre syndrome (LS) is an oropharyngeal infection, followed by bacteremia, thrombosis of the internal jugular vein and subsequent hematogenic metastasis via septic emboli. We report a case of Lemierre syndrome complicated by descending necrotizing mediastinitis due to a Methicillin-resistant Staphylococcus aureus (MRSA) infection in a 5-month-old Saudi boy.

Efficacy of daprodustat for patients on dialysis with anemia: systematic review and network meta-analysis.

Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl hydroxylase of hypoxia-inducible factor, recombinant human erythropoietin (rhEPO), and iron supplements. We conducted this study to test our postulation; daprodustat is superior to rhEPO and other conventional treatments respecting efficacy and safety parameters. We made systematic search through PubMed, Web of Science, Scopus, and Cochrane. Seven unique trials were eventually included for systematic review; six of them with a sample size of 759 patients entered our network meta-analysis (NMA). Daprodustat 25-30 mg was associated with the greatest change in serum hemoglobin (MD=1.86, 95%CI= [1.20; 2.52]), ferritin (MD= -180.84, 95%CI= [-264.47; -97.20]), and total iron binding capacity (TIBC) (MD=11.03, 95%CI= [3.15; 18.92]) from baseline values. Dialysis-dependent patients with anemia had a significant increment in serum Hemoglobin and TIBC and a reduction in serum ferritin, in a dose-dependent manner, when administered daprodustat.

Vancomycin-Induced Fever and Neutropenia in an Immunocompetent Patient With Complicated Community-Acquired Pneumonia.

Drug-induced fever can be caused by many medications through several mechanisms. One of the most common mechanisms is an immunologic reaction mediated by drug-induced antibodies. Herein, we report the case of a rare adverse reaction with vancomycin. A six-year-old girl being treated for necrotizing pneumonia with vancomycin developed mild neutropenia, skin rash, and fever two weeks into her therapy. These resolved after stopping vancomycin, with noted reversal of neutropenia and leukopenia. Upon rechallenging the patient with vancomycin, she developed a fever in less than 24 h from the administration. Vancomycin-induced fever was made as a diagnosis of exclusion after all other possible causes were ruled out.

Kikuchi-Fujimoto Disease: A Rare Benign Cause of Lymphadenopathy That Mimics Malignant Lymphoma.

Kikuchi-Fujimoto disease (KFD), also called histiocytic necrotizing lymphadenitis, is a benign self-limited disease involving lymph node enlargement with unclear causes and high fever. It was first seen in Japan and has wide array of differentials, and thus it can be confused with other causes of lymphadenitis leading to an incorrect treatment. We describe a case of a 34-year-old man with prolonged painless cervical lymphadenopathy and fever, in whom KFD, that is histiocytic necrotizing lymphadenitis, was diagnosed after the gold standard test of lymph node biopsy. Physical examination, history, and other relevant investigations were performed to rule out infectious and autoimmune causes. For management, prednisone 80mg and hydroxychloroquine were given, which lead to an uneventful full recovery. Our findings were compared to other similar studies conducted in the past. KFD is a self-limited condition that usually resolves by itself. KFD should be considered in the differential diagnosis of lymphadenopathy. An accurate diagnosis requires close collaboration between clinicians and pathologists. Early diagnosis of KFD allows reducing stress caused by alarming symptoms and avoiding unnecessary treatment.

Efficacy of Different Doses of Daprodustat for Anemic Non-dialysis Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

(1) Background: Anemia affects about 40% of patients with chronic kidney disease (CKD). Daprodustat improves serum hemoglobin in anemic patients by inhibiting prolyl hydroxylase of hypoxia-inducible factor. We conducted a network meta-analysis to investigate the direct and indirect effects of different doses of daprodustat compared to each other and erythropoietin and placebo. (2) Methods: We searched PubMed, Cochrane Library, Web of Science, and Scopus, for randomized clinical trials (RCTs) reporting data about different doses of daprodustat for anemia in nondialysis of CKDs. (3) Results: We eventually included five RCTs with a total sample size of 4566 patients. We found that the higher the dose of daprodustat, the greater the change in serum total iron binding capacity (TIBC), hemoglobin, and ferritin from baseline. Compared to placebo, daprodustat 25-30 mg was associated with the highest significant increase in serum hemoglobin (MD = 3.27, 95% CI = [1.89; 4.65]), a decrease in serum ferritin (MD = -241.77, 95% CI = [-365.45; -118.09]) and increase in serum TIBC (MD = 18.52, 95% CI = [12.17; 24.87]). (4) Conclusion: Higher daprodustat doses were associated with a higher impact on efficacy outcomes as serum total iron-binding capacity (TIBC), hemoglobin, and ferritin. However, data about the safety profile of different doses of daprodustat is still missing.

Multiple Autoimmune Syndrome With Alopecia Universalis and Immune Thrombocytopenic Purpura.

Multiple autoimmune syndrome (MAS) is a condition characterized by three or more autoimmune disorders in the same individual. The development of MAS involves genetic, immunological, and infectious factors. Here we report a case of a 40-year-old man who presented with four autoimmune diseases, namely autoimmune hypothyroidism, alopecia universalis, celiac disease, and immune thrombocytopenic purpura (ITP), which leads to a diagnosis of MAS. However, the patient does not fit in any category of MAS classification. In addition to the need for continued surveillance for the development of new autoimmune disease in predisposed patients, this case report suggests an additional fourth category of the classification of MAS that includes autoimmune hypothyroidism, alopecia universalis, celiac disease, and ITP.

Vitamin B12 Deficiency Presenting With Microangiopathic Hemolytic Anemia.

Vitamin B12 has essential roles in DNA synthesis, red blood cell development, and neurologic functions. Vitamin B12 deficiency is relatively common, particularly in people aged over 60 years. Among hematological disturbances, microangiopathic hemolytic anemia with thrombocytopenia or so-called pseudo-thrombotic microangiopathy (pseudo-TMA) is a particularly rare but significant clinical complication in patients with vitamin B12 deficiency. We herein describe a case of an elderly patient with pseudo-TMA whose lack of vitamin B12 was misdiagnosed as thrombotic thrombocytopenic purpura (TTP). The patient was admitted as a case of pancytopenia with a hemolytic picture. The initial impression was TTP versus acute promyelocytic leukemia M3. After examination of laboratory tests and bone marrow examination, we deduced that the patient had a B12 deficiency. The condition of the patient improved with B12 replacement. This report should remind physicians to widen their differential diagnoses when patients present with microangiopathic hemolysis or in patients who are not responsive to standard treatments for TTP.

A Novel Variant of Adenosine Deaminase 2 Deficiency Presented With Chronic Thrombocytopenia, Anemia, and Early-Onset Stroke.

Deficiency of adenosine deaminase 2 (DADA2) is a rare recessive disorder caused by the bi-allelic loss-of-function pathogenic variants in the ADA2 gene (MIM: 607575, also known as CECR1, cat eye syndrome chromosome region, candidate 1). Based on the Human Gene Mutation Database (HGMD®), 53 different disease-causing variants have been identified in this gene to date. This case report aims to describe a new vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome (VAIHS) case caused by a novel pathogenic variant. A four-year-old boy was referred to our hospital with anemia, thrombocytopenia, and stroke, but no skin manifestations. The patient had a significant phenotypic overlap with VAIHS. Molecular genetic analysis via whole exome sequencing identified a homozygous deleterious variant in ADA2. To our knowledge, the identified variant has never been described in the literature. Screening for ADA2 pathogenic variants should be considered in the differential diagnosis of pediatric patients manifesting with chronic thrombocytopenia or early-onset stroke for an accurate diagnosis and appropriate treatment choices.

COVID-19 in Saudi Patients With Sickle Cell Disease: A Retrospective Multi-Center Study.

Background The prevalence of sickle cell disease (SCD) within Saudi Arabia is relatively high, with an estimated 145/10,000 cases. There is an urgent need for researching many aspects of the Coronavirus disease of 2019 (COVID-19) due to the widespread of the virus among SCD patients in Saudi Arabia. The aim of this study is to determine how COVID-19 affects SCD patients in order to reach the best strategy for their management protocols. Methods This is a retrospective chart review study from a multi-center in Saudi Arabia that evaluated a total of 33 patients with sickle cell anemia/disease who were confirmed to have COVID-19. The diagnosis of COVID-19 was confirmed by using the reverse transcription-polymerase chain reaction (RT-PCR) tests based on the nasopharyngeal swabs of the included patients. Results The mean age of patients was 10.75+9.11 years, and nearly all patients (n= 32; 96.9%) were Saudi, and 48.4% of them were females. Twenty-two patients were admitted (59.5%); the main reasons for admission included vaso-occlusive crisis (VOC) only (n= 6; 27.3%), fever (n= 6; 27.3%), acute chest syndrome (n= 5; 22.7%), and VOC combined with other conditions (n= 4; 18.2%). During hospitalization, 54.1% of the patients received at least one medication, while antibiotics (54.1%), analgesia (32.4%), anticoagulants (16.2%), and steroids (16.2%) were the most commonly administered drugs. The mean length of hospitalization was 7.6±4.5 days, with only one patient (2.7%) requiring intensive care unit admission and assisted ventilation. Conclusion The overall prognosis was good since only one patient has passed away, while all others recovered and, subsequently, were discharged. Manifestations, laboratory investigations, and management modalities should be utilized promptly to enhance the prognosis and obtain better outcomes.

Inherited Platelet Function Disorder From Novel Mutations in RAS Guanyl-Releasing Protein-2 Confirmed by Sanger Sequencing.

Inherited platelet disorders (IPDs) are genetically heterogeneous rare disorders due to quantitative and/or qualitative abnormalities of the platelet. IPDs are often predisposed to significant medical complications. RAS guanyl-releasing protein-2 (RASGRP2) was recently identified as a gene affected in patients with platelet function defects and a bleeding complication. RASGRP2 codes for the protein CalDAG-GEFI RAS (guanyl-releasing protein-2), a guanine nucleotide exchange factor for small guanosine triphosphate(GTP)ase Rap1. We used Sanger sequencing to identify a novel function-disrupting homozygous mutation in RASGRP2 responsible for bleeding diathesis and platelet dysfunction in a patient.