Newborn Pulse Oximetry Screening for Detecting Congenital Heart Disease: Experience at a Tertiary Care Center.

Background: Congenital heart disease (CHD) remains the number one birth defect worldwide. Pulse oximetry screening (POS) is a widely used CHD screening modality effective in detecting critical lesions. This study is aimed at assessing the accuracy and cost-effectiveness of POS in a cohort of term well-babies admitted to a regular nursery in a tertiary care center. Methods: We reviewed the charts of term babies admitted to our regular nursery over a period of one year. The results of POS and the findings of echocardiography were collected. Similarly, we explored the records of our fetal echocardiography program to identify the fetuses screened for CHD during the same period. Results: 900 term babies were born and admitted to newborn nursery at our center, and 69 fetuses were evaluated by our fetal cardiology team during the study period. None of our term babies had a positive POS at birth or 24 hours of age. However, 56 babies had a cardiac echo before hospital discharge due to suspicious findings on physical examination or a family history of CHD. A simple noncritical CHD was noted in 10 of them. Additionally, 53 babies underwent echocardiography within the first five years of life; a simple CHD was noted in 6 of them. In parallel, 21 of our fetuses were found to have CHD: 16 simple CHD and 5 critical CHD (CCHD). Conclusion: Despite its cost-effectiveness and efficacy in screening for CCHD, POS is suboptimal for detecting simple CHD. In the absence of a proper prenatal screening and fetal echocardiography program, POS remains a cost-effective modality for detecting CCHD.

Uncovering a novel role of focal adhesion and interferon-gamma in cellular rejection of kidney allografts at single cell resolution.

Background: Kidney transplant recipients are currently treated with nonspecific immunosuppressants that cause severe systemic side effects. Current immunosuppressants were developed based on their effect on T-cell activation rather than the underlying mechanisms driving alloimmune responses. Thus, understanding the role of the intragraft microenvironment will help us identify more directed therapies with lower side effects. Methods: To understand the role of the alloimmune response and the intragraft microenvironment in cellular rejection progression, we conducted a Single nucleus RNA sequencing (snRNA-seq) on one human non-rejecting kidney allograft sample, one borderline sample, and T-cell mediated rejection (TCMR) sample (Banff IIa). We studied the differential gene expression and enriched pathways in different conditions, in addition to ligand-receptor (L-R) interactions. Results: Pathway analysis of T-cells in borderline sample showed enrichment for allograft rejection pathway, suggesting that the borderline sample reflects an early rejection. Hence, this allows for studying the early stages of cellular rejection. Moreover, we showed that focal adhesion (FA), IFNg pathways, and endomucin (EMCN) were significantly upregulated in endothelial cell clusters (ECs) of borderline compared to ECs TCMR. Furthermore, we found that pericytes in TCMR seem to favor endothelial permeability compared to borderline. Similarly, T-cells interaction with ECs in borderline differs from TCMR by involving DAMPS-TLRs interactions. Conclusion: Our data revealed novel roles of T-cells, ECs, and pericytes in cellular rejection progression, providing new clues on the pathophysiology of allograft rejection.

2-Nucleobase-substituted 4,6-Diaminotriazine Analogs: Synthesis and Anti-cancer Activity in 5-Fluorouracil-sensitive and Resistant Colorectal Cancer Cells.

BACKGROUND: Cancer continues to be the second leading cause of death worldwide, with colorectal cancer (CRC) being the third most common type. Despite significant advances in cancer therapies, the current treatment of CRC remains suboptimal. In addition, the effectiveness of available chemotherapeutic drugs such as 5-Fluorouracil (5-FU) is limited by CRC-acquired resistance. METHODS: In this study, we provide innovative approaches employed in synthesizing four novel nucleobase analogs. Equally, we describe the effects of these compounds on proliferation, migration, aggregation, and adhesion of 5-FU-sensitive (HCT116) and -resistant (5-FU-R-HCT116) human CRC cells. In either cell type, our synthesized novel analogs significantly inhibited cell viability in a concentration- and time-dependent manner. This highlights the higher potency of these novel analogs. In addition, these compounds attenuated migration and adhesion of both cell types while they promoted homotypic cell-cell interaction. RESULTS: These changes were reflected by the downregulation of matrix metalloproteases (MMP-2 and MMP-9). Furthermore, our analogs exhibited potent anti-angiogenic activity in vivo. CONCLUSION: These novel nucleobase analogs reduced the level of secreted vascular endothelial growth factor (VEGF) and nitric oxide (NO) production in both 5-FU-sensitive and -resistant CRC cells. Taken together, our data highlight the potential chemotherapeutic properties of our novel analogs against CRC, including the 5-FU-resistant form.

Nanoparticles: Attractive tools to treat colorectal cancer.

Colorectal Cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Despite the notable advances achieved over the last few decades, CRC remains a hard-to-treat deadly disease in many patients. This is attributed mainly to chemo- and immuno-resistance, which frequently emerge soon after treatment with conventional therapeutics. Systemic treatments are also constrained by their many undesired and serious side effects. More recently, nanomedicine has emerged as an attractive modality that can overcome issues of therapeutic resistance, improper delivery, or suboptimal targeting of tumor cells. Many nanomaterials, having already been examined in pre-clinical and clinical studies, are now considered biocompatible and relatively safe. Indeed, around 50 nano-formulations have so far been approved as diagnostic and therapeutic agents in humans. Here, in this review, we describe a set of imperative nanoparticles (NPs) involved in diagnosing and treating CRC. In particular, we discuss the theragnostic roles of quantum dots, iron oxide NPs, Polylactide-co-glycolic acid (PLGA) NPs, dendrimer NPs, carbon nanotubes, liposomes, and gold NPs. We dissect the molecular and clinical evidence supporting the use of these NPs in CRC. We also highlight their implications in targeted drug delivery as well as their anti-tumorigenic properties and effects on the cardinal hallmarks of CRC. We conclude by highlighting the notion that nanomedicine is emerging as an attractive approach to address the unmet needs in managing several diseases, including CRC.

Aspirin in COVID-19: Pros and Cons.

Since its emergence, the COVID-19 pandemic has been ravaging the medical and economic sectors even with the significant vaccination advances. In severe presentations, the disease of SARS-CoV-2 can manifest with life-threatening thromboembolic and multi-organ repercussions provoking notable morbidity and mortality. The pathogenesis of such burdensome forms has been under extensive investigation and is attributed to a state of immune dysfunction and hyperinflammation. In light of these extraordinary circumstances, research efforts have focused on investigating and repurposing previously available agents that target the inflammatory and hematological cascades. Aspirin, due to its well-known properties and multiple molecular targets, and ought to its extensive clinical use, has been perceived as a potential therapeutic agent for COVID-19. Aspirin acts at multiple cellular targets to achieve its anti-inflammatory and anti-platelet effects. Although initial promising clinical data describing aspirin role in COVID-19 has appeared, evidence supporting its use remains fragile and premature. This review explores the notion of repurposing aspirin in COVID-19 infection. It delves into aspirin as a molecule, along with its pharmacology and clinical applications. It also reviews the current high-quality clinical evidence highlighting the role of aspirin in SARS-CoV-2 infection.

Pre-operative assessment of pediatric congenital heart disease patients in the COVID-19 era: lessons learned.

BACKGROUND: Equal to COVID-19 patients, non-COVID-19 patients are affected by the medical and social drawbacks of the COVID-19 pandemic. A significant reduction in elective life-changing surgeries has been witnessed in almost all affected countries. This study discusses an applicable and effective pre-operative assessment protocol that can be applied during the COVID-19 era. METHODS: Our study is a descriptive retrospective observational study that involves children with CHD requiring open-heart surgeries at our tertiary care centre between March and November, 2020. We reviewed the charts of eligible patients aged 18 years and below. We identified the total numbers of scheduled, performed, and postponed surgeries, respectively. A thorough description of the clinical and physical presentation of the postponed cases, who tested positive for SARS-CoV-2, is provided. RESULTS: Sixty-eight open-heart surgeries were scheduled at our centre between March and November, 2020. Three surgeries (4%) were postponed due to COVID-19. The three patients were asymptomatic COVID-19 cases detected on routine SARS-CoV-2 polymerase chain reaction testing. No symptoms of cough, chest pain, dyspnea, rhinorrhea, diarrhea, abdominal pain, anosmia, and ageusia were reported by our patients. All patients were afebrile and hemodynamically stable. Owing to the pre-operative assessment protocol that was implemented after the first case was detected, only three healthcare workers were at risk of COVID-19 transmission and were imposed to infectious evaluation and home quarantine. CONCLUSIONS: Adopting our discussed preoperative COVID-19 assessment protocol for CHD patients is an effective method to detect COVID-19 infections, optimise patient care, and ensure healthcare workers' safety.

COVID-19: potential therapeutics for pediatric patients.

The global spread of COVID-19 has imparted significant economic, medical, and social burdens. Like adults, children are affected by this pandemic. However, milder clinical symptoms are often experienced by them. Only a minimal proportion of the affected patients may develop severe and complicated COVID-19. Supportive treatment is recommended in all patients. Antiviral and immunomodulatory medications are spared for hospitalized children with respiratory distress or severe to critical disease. Up till now, remdesivir is the only USFDA-approved anti-COVID-19 medication indicated in the majority of symptomatic patients with moderate to severe disease. Dexamethasone is solely recommended in patients with respiratory distress maintained on oxygen or ventilatory support. The use of these medications in pediatric patients is founded on evidence deriving from adult studies. No randomized controlled trials (RCTs) involving pediatric COVID-19 patients have assessed these medications' efficacy and safety, among others. Similarly, three novel monoclonal anti-SARS-CoV-2 spike protein antibodies, bamlanivimab, casirivimab and imdevimab, have been recently authorized by the USFDA. Nonetheless, their efficacy has not been demonstrated by multiple RCTs. In this review, we aim to dissect the various potential therapeutics used in children with COVID-19. We aspire to provide a comprehensive review of the available evidence and display the mechanisms of action and the pharmacokinetic properties of the studied therapeutics. Our review offers an efficient and practical guide for treating children with COVID-19.

Ivabradine: A Potential Therapeutic for Children With Refractory SVT.

Background: In April 2015, ivabradine was approved by the Food and Drug Administration for the treatment of patients with coronary artery disease and heart failure (HF). The use of this medication has been linked with improved clinical outcomes and reduced rates of hospitalization in patients with symptomatic HF and a baseline heart rate of 70 bpm and above. Nonetheless, little is known about the use of ivabradine in pediatric patients with supraventricular tachycardia (SVT). This use is not well-studied and is only endorsed by a few case reports and case series. Aim: This study discusses the off-label utilization of ivabradine in pediatric patients with SVT, and highlights its efficacy in treating treatment-resistant (refractory) SVT. Methods: We conducted a retrospective single-center observational study involving pediatric patients with SVT treated at our center between January 2016 and October 2020. We identified the total number of patients with SVT, and the number of patients with refractory SVT treated with Ivabradine. Similarly, we performed a thorough review of the databases of PubMed, Medline and Google Scholar to compare the clinical course of our patients to those described in the literature. Results: Between January 2016 and October 2020, 79 pediatric patients with SVT were seen and treated at our center. A treatment-resistant SVT was noted only in three patients (4%). Ivabradine was used in these patients as a single or combined therapy. The rest (96%) were successfully treated with conventional anti-arrhythmics such as ß-blockers, flecainide, and other approved medications. In the ivabradine group, successful reversal to sinus rhythm was achieved in two of the three patients (66%), one patient was treated with a combination therapy of amiodarone and ivabradine, and the other patient was treated only with ivabradine. Conclusion: Overall, promissory results are associated with the use of ivabradine in pediatric patients with refractory SVT. Ivabradine appears to be a safe and well-tolerated medication that can induce adequate suppression of SVT, complete reversal to sinus rhythm, and effective enhancement of left ventricular function.

Cardiac Manifestations in COVID-19 Patients: A Focus on the Pediatric Population.

BACKGROUND: SARS-CoV-2 is a new strain of the coronavirus family that emerged by the end of 2019 and led to the unpreceded COVID-19 pandemic. The virus affects multiple organs simultaneously and leads to a high rate of morbidity and mortality in all age groups. The cardiovascular system is one of the major affected organ systems. Various mechanisms including direct myocardial injury contribute to the cardiac manifestations of COVID-19 patients. METHODS: We performed a comprehensive and updated search on the cardiac manifestations of COVID-19. Our search included laboratory and imaging evaluations. In addition, we added a unique section on the effect of SARS-CoV-2 on the cardiovascular system in the pediatric population. RESULTS: COVID-19 might have an effect on the cardiovascular system at various levels leading to myocardial ischemia, arrhythmia, heart failure, myocarditis, and multisystem inflammatory syndrome in children. The incidence of cardiovascular complications varies among patients. This paper also provides a comprehensive summary of all the reported pediatric cases with cardiac manifestations. CONCLUSION: Multidisciplinary teams are crucial for adequate management of patients with COVID-19 regardless of age. Timely diagnosis is critical in reducing mortality.

Metal-based nanoparticles: Promising tools for the management of cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of death worldwide. A search for more effective treatments of CVD is increasingly needed. Major advances in nanotechnology opened new avenues in CVD therapeutics. Owing to their special properties, iron oxide, gold and silver nanoparticles (NPs) could exert various effects in the management and treatment of CVD. The role of iron oxide NPs in the detection and identification of atherosclerotic plaques is receiving increased attention. Moreover, these NPs enhance targeted stem cell delivery, thereby potentiating the regenerative capacity at the injured sites. In addition to their antioxidative and antihypertrophic capacities, gold NPs have also been shown to be useful in the identification of plaques and recognition of inflammatory markers. Contrary to first reports suggestive of their cardio-vasculoprotective role, silver NPs now appear to exert negative effects on the cardiovascular system. Indeed, these NPs appear to negatively modulate inflammation and cholesterol uptake, both of which exacerbate atherosclerosis. Moreover, silver NPs may precipitate bradycardia, conduction block and sudden cardiac death. In this review, we dissect the cellular responses and toxicity profiles of these NPs from various perspectives including cellular and molecular ones.

COVID-19 in the MENA Region: Facts and Findings.

INTRODUCTION: Our study aims to assess the prevalence of COVID-19 in the Middle East and North Africa (MENA) region. It aims also to examine the various factors that have led to the unequal distribution of the confirmed cases among the different MENA countries. METHODOLOGY: Data was retrieved from the World Health Organization situation reports issued between January 29 and June 5, 2020. It included the numbers of cumulative cases, new cases, and cumulative deaths reported by MENA countries. Similarly, we searched for relevant articles in PubMed and Medline. RESULTS: A total of 481,347 cases and 11,851 deaths occurred in the MENA region, accounting for 7.37% and 3.06% of the global cases and deaths respectively. Iran had the highest number of cases and deaths accounting for 34.1% and 68.1% of the MENA cases and deaths respectively. Together the Gulf Cooperation Council (GCC) countries accounted for 52.2% and 10.6% of MENA cases and deaths respectively. Egypt had the highest number of confirmed cases and deaths among the African countries of the region. Syria, Libya and Yemen (countries at war) had the lowest numbers of reported cases. The MENA region overall case fatality rate (CFR) was estimated at 2.46%. The highest CFR (22.75%) occurred in Yemen, and the lowest (0.07%) in Qatar. CONCLUSIONS: The unequal distribution of wealth among the MENA countries, the lack of sociopolitical stability, and the high number of undetected and underreported cases in some of them have resulted in varied incidences of COVID-19 related morbidity and mortality.

The Era of the Coronavirus Disease 2019 Pandemic: A Review on Dynamics, Clinical Symptoms and Complications, Diagnosis, and Treatment.

Coronavirus disease 2019 (COVID-19) displays a broad spectrum of clinical presentations ranging from lack of symptoms to severe multiorgan system complications and death. Various laboratory assays have been employed in the diagnosis of COVID-19, including: nucleic acid-based tests; antigen tests; and serum testing for anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies. The disease can also be diagnosed based on suggestive clinical features and radiological findings. Until now, remdesivir is the only medication approved for the treatment of COVID-19 by the U.S. Food and Drug Administration (FDA); however, it is anticipated that several anti-SARS-CoV-2 monoclonal antibodies will gain soon approval. Other methods of treatment include supportive care directed toward treating the symptoms. Nevertheless, many studies have recently emerged, showing controversial preliminary results with the off-label medication hydroxychloroquine. Given that all results are still preliminary, including those seen by remdesivir, additional evidence and research are required to identify effective medications that are broadly effective and well tolerated. Importantly, two RNA-based vaccines have recently gained approval from Pfizer and Moderna, with many others still in clinical trials. This article reviews various aspects of COVID-19, including its epidemiology; its evolution and mutational spectrum; and its clinical dynamics, symptoms and complications, diagnosis, and treatment.

Balloon Valvuloplasty for Congenital Aortic Stenosis: Experience at a Tertiary Center in a Developing Country.

BACKGROUND: Aortic valve stenosis accounts for 3-6% of congenital heart disease. Balloon aortic valvuloplasty (BAV) is the preferred therapeutic intervention in many centers. However, most of the reported data are from developed countries. MATERIALS AND METHODS: We performed a retrospective single-center study involving consecutive eligible neonates and infants with congenital aortic stenosis admitted for percutaneous BAV between January 2005 and January 2016 to our tertiary center. We evaluated the short- and mid-term outcomes associated with the use of BAV as a treatment for congenital aortic stenosis (CAS) at a tertiary center in a developing country. Similarly, we compared these outcomes to those reported in developed countries. RESULTS: During the study period, a total of thirty patients, newborns (n = 15) and infants/children (n = 15), underwent BAV. Left ventricular systolic dysfunction was present in 56% of the patients. Isolated AS was present in 19 patients (63%). Associated anomalies were present in 11 patients (37%): seven (21%) had coarctation of the aorta, two (6%) had restrictive ventricular septal defects, one had mild Ebstein anomaly, one had Shone's syndrome, and one had cleft mitral valve. BAV was not associated with perioperative or immediate postoperative mortality. Immediately following the valvuloplasty, a more than mild aortic regurgitation was noted only in two patients (7%). A none-to-mild aortic regurgitation was noted in the remaining 93%. One patient died three months after the procedure. At a mean follow-up of 7 years, twenty patients (69%) had more than mild aortic regurgitation, and four patients (13%) required surgical intervention. Kaplan-Meier freedom from aortic valve reintervention was 97% at 1 year and 87% at 10 years of follow-up. CONCLUSION: Based on outcomes encountered at a tertiary center in a developing country, BAV is an effective and safe modality associated with low complication rates comparable to those reported in developed countries.

Hydroxychloroquine in COVID-19 Patients: Pros and Cons.

The pandemic of COVID-19, caused by SARS-CoV-2, has recently overwhelmed medical centers and paralyzed economies. The unparalleled public distress caused by this pandemic mandated an urgent quest for an effective approach to manage or treat this disease. Due to their well-established anti-infectious and anti-inflammatory properties, quinine derivatives have been sought as potential therapies for COVID-19. Indeed, these molecules were originally employed in the treatment and prophylaxis of malaria, and later in the management of various autoimmune rheumatic and dermatologic diseases. Initially, some promising results for the use of hydroxychloroquine (HCQ) in treating COVID-19 patients were reported by a few in vitro and in vivo studies. However, current evidence is not yet sufficiently solid to warrant its use as a therapy for this disease. Additionally, the therapeutic effects of HCQ are not without many side effects, which range from mild gastrointestinal effects to life-threatening cardiovascular and neurological effects. In this review, we explore the controversy associated with the repurposing of HCQ to manage or treat COVID-19, and we discuss the cellular and molecular mechanisms of action of HCQ.

COVID-19 in Pediatric Patients: A Focus on CHD Patients.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 virus. As of the 30th of September 2020, around 34,000,000 cases have been reported globally. Pediatrics with underlying congenital heart disease represent a small yet a critical proportion of these patients. In general, the majority of infected children experience mild to moderate disease with significant interindividual variability in laboratory and radiographic findings. Nevertheless, in healthy children with COVID-19, cardiac involvement has been documented and is attributed to various causes. Myocarditis, arrhythmias, cardiogenic shock, and serious multisystem inflammatory syndrome in children are all encountered. Since COVID-19 is a recent novel disease and based on previous experience with respiratory infections, children with underlying congenital heart disease should be given special attention. To date, little data is available about COVID-19 presentation, complications, and appropriate treatment in this population. However, variable and inconsistent disease presentation and severity have been observed. This paper discusses COVID-19 course of illness in pediatric population with a special emphasis on the cardiac manifestations of the disease in healthy population and also on the disease course in congenital heart disease patients in particular.