Kawarabi: Administrative Structuring of a Multicenter Research Collaborative to Study Kawasaki Disease in the Arab Countries.

Kawasaki disease (KD), the leading cause of acquired heart disease in children in developed countries, merits conducting detailed studies in Arab countries. We introduce Kawarabi, as a multicenter research collaborative effort dedicated to improving diagnosis, care, and outcome of children and adults with KD in the Arab world. During the COVID-19 pandemic, there emerged a new multisystem inflammatory syndrome in children; a disease similar to KD. This highlighted the challenges that Arab physicians face in diagnosing and managing children with KD and KD-like illnesses. Kawarabi brings together experts in North America and Arab nations to study this family of diseases in a not-for-profit, voluntary scientific collaborative setting. Bylaws addressing the vision, objectives, structure, and governance of Kawarabi were established, and vetted by the 45 organizing members in 2021. An initial scientific publication showed evidence of a decreased level of awareness of the disease in the general population, as well as the lack of access to resources available for physicians caring for children with KD in Arab countries. Kawarabi has since held several educational webinars and an inaugural yearly meeting. The groundwork for future initiatives targeted at increasing awareness and understanding of the management and the long-term outcomes of children with KD in the region was established. Data on KD in the Arab world are lacking. Kawarabi is a multicenter research collaborative organization that has the unique resources, diversified ethnic makeup, and energy, to accomplish significant advances in our understanding and management of KD and its variants.

Access to Care and Therapy for Kawasaki Disease in the Arab Countries: A Kawasaki Disease Arab Initiative (Kawarabi) Multicenter Survey.

Kawasaki Disease (KD) is still the most common acquired heart disease in children below the age of five years; it has been well described in the developed world; however, data from the Arab world are limited to case reports or single-center case series. In an effort of optimizing KD research in the Arab world, a group of physicians and researchers established the KD Arab Initiative (Kawarabi) in 2021, and published the first survey, which showed disparities in the availability of intravenous immunoglobulin (IVIG); this had prompted Kawarabi to assess the access to care and therapy of KD patients in Arab countries. A 32 structured questions survey was conducted in thirteen Arab countries and addressed KD patients' access to healthcare in urban and rural settings. The survey results showed that access to care was uniform across large, mid-size cities and rural areas in 7/13 (54%) countries, while in 6/13 (46%) countries, it was in favor of large and mid-size cities over rural areas. The quality of medical services received by children with KD in large cities was rated as excellent in 6/13 or good in 7/13 countries compared to fair in 4/13 or poor in 4/13 countries in rural areas. Availability of IVIG was limited (23%) in mid-size cities and almost impossible (23%) in rural areas. The KD patients in mid-size cities and rural areas have limited access to standard healthcare in the Arab world. This survey laid the foundation for future Kawarabi endeavors to improve the care of children with KD.

Reference centiles for left ventricular longitudinal global and regional systolic strain by automated functional imaging in healthy Egyptian children.

BACKGROUND: Two-dimensional speckle tracking echocardiography-derived left ventricular longitudinal systolic strain is an important myocardial deformation parameter for assessing the systolic function of the left ventricle. Strain values differ according to the vendor machine and software. This study aimed to provide normal reference values for global and regional left ventricular longitudinal systolic strain in Egyptian children using automated functional imaging software integrated into the General Electric healthcare machine and to study the correlation between the global longitudinal left ventricular systolic strain and age, body size, vital data, and some echocardiographic parameters. METHODS: Healthy children (250) aged from 1 to 16 years were included. Conventional echocardiography was done to measure the left ventricular dimensions and function. Automated functional imaging was performed to measure the global and regional peak longitudinal systolic strain. RESULTS: The global longitudinal strain was -21.224 ± 1.862%. The regional strain was -20.68 ± 2.11%, -21.06 ± 1.84%, and -21.86 ± 2.71% at the basal, mid, and apical segments, respectively. The mean values of the systolic longitudinal strain become significantly more negative from base to apex. Age differences were found as regard to global and regional longitudinal strain parameters but no gender differences. The global peak longitudinal systolic strain correlated positively with age. No correlations were found with either the anthropometric parameters or the vital data. CONCLUSIONS: Age-specific normal values for two-dimensional speckle tracking-derived left ventricular longitudinal regional and global systolic strain are established using automated functional imaging.

COVID-19-Related Multisystem Inflammatory Syndrome in Children Presenting With New-Onset Type 1 Diabetes in Severe Ketoacidosis: A Case Series.

OBJECTIVE: To report and describe cases of children presenting with coronavirus disease 2019 (COVID-19)-related multisystem inflammatory syndrome in children (MIS-C) with new-onset type 1 diabetes mellitus (T1DM) in severe diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS: This prospective observational study was conducted to characterize children with COVID-19-related MIS-C and new-onset T1DM who were in DKA. MIS-C was diagnosed if Centers for Disease Control and Prevention and World Health Organization criteria were fulfilled. RESULTS: Six cases were identified. The patients were critically ill and in nonfluid responsive shock (combined hypovolemic and cardiogenic or distributive shock). All had cardiac involvement. One patient had a Kawasaki shock-like presentation. All needed aggressive treatment with careful monitoring of fluid balance (because of associated cardiac dysfunction), early institution of vasoactive/inotropic supports, and use of methylprednisolone and intravenous immunoglobulins. The latter are better administered after DKA resolution to avoid undue volume overload and fluid shifts while the patients are in DKA. CONCLUSIONS: Awareness of MIS-C coexistence with DKA at T1DM onset is crucial for rapid proper management.

Treatment of MIS-C in Children and Adolescents.

Purpose of Review: Different treatment approaches have been described for the management of COVID-19-related multisystem inflammatory syndrome in children (MIS-C), the pathogenesis of which has not yet been fully elucidated. Here, we comprehensively review and summarize the recommendations and management strategies that have been published to date. Recent Findings: MIS-C patients are treated with different regimens, mostly revolving around the use of immunomodulatory medications, including IVIG and glucocorticoids as first-tier therapy. Refractoriness to IVIG and glucocorticoids warrants a step-up of immunomodulatory therapy to biologic agents such as anakinra, tocilizumab, and infliximab. Summary: We review the current evidence regarding the use of monotherapy versus combination therapy, as well as the current recommendations for assessing thrombotic risk and administering antiplatelet and anticoagulant therapy. We anticipate that future studies will provide evidence for management plans that maximize short- and long-term outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-021-00259-4.

The "Golden Hours" Algorithm For the Management of the Multisystem Inflammatory Syndrome in Children (MIS-C).

The global concern of increasing number of children presenting with multisystem inflammatory syndrome in children (MIS-C) related to the coronavirus disease (COVID-19) has escalated the need for a case-oriented clinical approach that provides timely diagnosis and management. The aim of this study is to share our experience in managing 64 MIS-C patients of North African ethnicity guided by a risk-based algorithm. Sixty-four patients met the inclusion criteria, 19 (30%) patients were categorized as mild and moderate risk groups and cared for in an isolation ward and 45 patients who belonged to the high-risk group (70%) were admitted to the pediatric intensive care unit (PICU). Positive laboratory evidence of COVID-19 was found in 62 patients. Fever and dysfunction in 2 or more organs were confirmed in all cases (100%). Fifty patients (78%) presented with gastrointestinal symptoms, meanwhile only 10 patients (16%) had respiratory manifestations. Cardiac involvement was reported in 55 (86%) cases; hypotension and shock were found in 45 patients (70%) therein circulatory support and mechanical ventilations were needed for 45 and 13 patients respectively. Intravenous immunoglobulins (IVIG) were used for all cases and methylprednisolone was used in 60 patients (94%). Fifty-eight (91%) patients were discharged home after an average of 9 days of hospitalization. The mortality rate was 9% (6 patients). Conclusion. A single Egyptian center experience in the management of MIS-C patients guided by a proposed bed side algorithm is described. The algorithm proved to be a helpful tool for first-line responders, and helped initiate early treatment with IVIG.

Detection of Early Myocardial Injury in Children with Ventricular Septal Defect Using Cardiac Troponin I and Two-Dimensional Speckle Tracking Echocardiography.

Children with ventricular septal defects (VSDs) are subjected to hemodynamic overload which causes myocardial injury and subsequent heart failure. Early stages of myocardial damage cannot be detected by conventional echocardiography. Two-dimensional speckle tracking echocardiography (2D-STE) and cardiac troponin I (cTnI) have been recently introduced as more accurate tools for early assessment of cardiovascular diseases. The purpose of this study is to evaluate the role of cardiac troponin I (cTnI) and 2D-STE in the early detection of VSD-induced myocardial injury. Thirty children with VSD (symptomatic and asymptomatic) and 30 controls were assessed serologically by measuring serum cTnI and by conventional echocardiography. STE was performed to measure the averaged global peak longitudinal systolic stain [G peak SL(AVG)]. Serum cTnI levels were significantly higher in patients when compared to controls (P < 0.05) and in the symptomatic group when compared to the asymptomatic group (P < 0.05). Serum cTn I level correlated positively with the left atrial (r = 0.37, P = 0.045) and left ventricular dimensions (r = 0.46, P = 0.01) and negatively with the G peak SL(AVG) (r = -0.39, P = 0.03). There were no statistically significant differences between patients and controls or between symptomatic and asymptomatic groups with regard to the G peak SL(AVG). The peak longitudinal systolic strain (measured by 2D-STE) is not affected despite the elevation of serum cTnI. Serum cTnI is a sensitive marker for early detection of myocardial injury in VSD patients even before the development of ventricular dilatation or dysfunction.

Predictors of transient left ventricular dysfunction following transcatheter patent ductus arteriosus closure in pediatric age.

OBJECTIVES: To evaluate the left ventricular function before and after transcatheter percutaneous patent ductus arteriosus (PDA) closure, and to identify the predictors of myocardial dysfunction post-PDA closure if present. INTERVENTIONS: Transcatheter PDA closure; conventional, Doppler, and tissue Doppler imaging; and speckle tracking echocardiography. OUTCOME MEASURES: To determine the feasibility and reliability of tissue Doppler and myocardial deformation imaging for evaluating myocardial function in children undergoing transcatheter PDA closure. PATIENTS AND METHODS: Forty-two children diagnosed with hemodynamically significant PDA underwent percutaneous PDA closure. Conventional, Doppler, and tissue Doppler imaging, and speckle-derived strain rate echocardiography were performed at preclosure and at 48 hours, 1 month, and 6 months postclosure. Tissue Doppler velocities of the lateral and septal mitral valve annuli were obtained. Global and regional longitudinal peak systolic strain values were determined using two-dimensional speckle tracking echocardiography. RESULTS: The median age of the patients was 2 years and body weight was 15 kg, with the mean PDA diameter of 3.11 ± 0.99 mm. M-mode measurements (left ventricular end diastolic diameter, left atrium diameter to aortic annulus ratio, ejection fraction, and shortening fraction) reduced significantly early after PDA closure (p < 0.001). After 1 month, left ventricular end diastolic diameter and left atrium diameter to aortic annulus ratio continued to decrease, while ejection fraction and fractional shortening improved significantly. All tissue Doppler velocities showed a significant decrease at 48 hours with significant prolongation of global myocardial function (p < 0.001) and then were normalized within 1 month postclosure. Similarly, global longitudinal strain significantly decreased at 48 hours postclosure (p < 0.001), which also recovered at 1 month follow-up. Preclosure global longitudinal strain showed a good correlation with the postclosure prolongation of the myocardial performance index. CONCLUSION: Transcatheter PDA closure causes a significant decrease in left ventricular performance early after PDA closure, which recovers completely within 1 month. Preclosure global longitudinal strain can be a predictor of postclosure myocardial dysfunction.

Galectin-3 in Children with Chronic Heart Failure with Normal and Reduced Ejection Fraction: Relationship to Disease Severity.

Heart failure (HF) progression has not been studied in pediatric patients as well as HF in patients with a normal ejection fraction (HFNEF). We aimed to evaluate galactin-3 in children with HFNEF and reduced ejection fraction (HFREF) and its correlation to disease severity and progression. This cross-sectional study involved 45 chronic HF patients taking G1a (23 HFNEF children) and G1b (22 HFREF children) compared to 45 age- and sex-matched controls (G2) subjected to history taking, Ross functional HF classification, conventional and tissue Doppler echocardiographic systolic and diastolic function assessment (FS%, E/A, S m, E m/A m, E/E m) and laboratory investigations [glomerular filtration rate, serum galactin-3 level (ELISA)]. The results showed that serum galactin was increased in patients compared to controls (p > 0.001); a cutoff value of 3.5 ng/ml was estimated for HF diagnosis HFNEF patients who had higher galactin-3 levels than HFREF patients, but it did not reach statistical significance (p = 0.194). Galactin-3 levels positively correlated to the Ross HF classification (p = 0.01) and E/E m (p = 0.032) and negatively correlated to FS%, S m and E m/A m (p = 0.028, 0.022, 0.043). Galactin-3 levels were significantly reduced in patients receiving spironolactone (p = 0.049). Galactin-3 can be a tool for chronic HF diagnosis and a marker of disease severity and staging in children with HFNEF and HFREF. The role of spironolactone in reducing galactin-3 in pediatric HF requires further research.

N-Terminal proBNP Levels and Tissue Doppler Echocardiography in Acute Rheumatic Carditis.

Background. Rheumatic heart disease (RHD) is a leading cause of heart failure in children and young adults worldwide. B-type natriuretic peptide (BNP) is a useful marker of critical pediatric heart disease, and its N-terminal peptide, NT-proBNP, is elevated in congenital and acquired heart disease in children. Aim. To measure NT-proBNP levels as a marker of carditis in children with acute rheumatic carditis, as compared to children with quiescent RHD and healthy controls. Methods. 16 children with acute rheumatic carditis, 33 children with quiescent RHD, and a cohort of 30 healthy children were studied. Transthoracic echocardiography was performed to assess valve and cardiac function. Tissue Doppler echocardiography was performed for E/E' (ratio between mitral inflow E wave and lateral mitral annulus E' wave) and systolic strain. Results. NT-proBNP levels were significantly higher in children with acute rheumatic carditis and dropped with its resolution. Strain and E/E' values were comparable among the three groups. Conclusion. NT-proBNP is significantly elevated in children with acute rheumatic carditis in the acute stage compared to children with quiescent RHD and healthy subjects, in the presence of comparable echocardiographic indices of LV systolic and diastolic function.

Can serum tenascin-C be used as a marker of inflammation in patients with dilated cardiomyopathy?

Background. Tenascin-C (TN-C) is an extracellular matrix glycoprotein that appears at sites of inflammation in cardiac pathologies. Aim of the Work. To evaluate the role of TN-C as a marker for active inflammation in children with dilated cardiomyopathy (DCM). Subjects and Methods. 24 consecutive patients with primary nonfamilial DCM aged 6-72 months (mean 45.19 ± 11.03) were divided into group I, twelve patients with acute onset DCM (<6 months duration), and group II, twelve patients with chronic DCM (>6 months duration), and compared to 20 healthy age- and sex-matched controls. Investigations included estimation of serum TN-C and echocardiographic evaluation using M-mode and 2D speckle tracking echocardiography (STE). Results. Serum TN-C showed a higher significant statistical elevation among patients than controls (P < 0.001) and in group I than group II (P < 0.001). EF was significantly decreased, and LVEDD and EDV increased in patients than controls and in GI than GII. STE showed a statistically significant difference in global peak strain longitudinal (GPSL) average in patients than controls (P < 0.05) and between GI and GII (P < 0.001). STE wall motion scoring showed normokinesia (33.5%), hypokinesia (8.33%), and akinesia (50%) in GI and hypokinesia (100%) in GII. There was a statistically significant positive correlation between serum TN-C and GPSL average. Conclusions. Increased serum TN-C can be used as a marker of inflammation in DCM and is associated with the severity of heart failure and LV dysfunction as detected by STE.

Atrial natriuretic peptide as a marker of heart failure in children with left ventricular volume overload.

AIM: To evaluate the role of atrial natriuretic peptide (ANP) in differentiating the aetiology of heart failure in children with left ventricular (LV) volume overload. METHODS: The study was conducted on 48 patients with LV volume overload (G one: rheumatic heart disease in failure; G2: compensated rheumatic heart disease; G3: congenital left to right shunt; and G4: dilated cardiomyopathy). Twelve healthy children served as a control group. New York Heart Association (NYHA) class, LV dimensions and functions using Vivid 7 dimensions were evaluated. Serum ANP was measured using the ELISA technique, before and 3 months after treatment with angiotensin converting enzyme inhibitor. RESULTS: ANP was raised in all patients as compared to controls (G one: 28.33 ± 5.78, G2: 26.5 ± 4.11, G3: 28.5 ± 6.6, G4: 29.25 ± 4.5 pg/mL, control group: 5.54 ± 1.4 pg/mL, P < 0.001 for all) and varied significantly between different NYHA classes regardless of the underlying cardiac lesion. It was significantly higher in group 1 than 2 (P < 0.05). It decreased significantly after treatment (G1: 15.3 ± 5.3, G2: 10.7 ± 2.5, G3: 11.5 ± 3.8, G4: 15.7 ± 10.7 pg/mL, P < 0.001). The rate of change of ANP correlated with that of LV end diastolic diameter (r = 0.3, P < 0.05) irrespective of the underlying cause. CONCLUSION: ANP increases in cases of LV volume overload irrespective of the aetiology of heart failure. It can differentiate between children in quiescent state from those in clinical failure even in the absence of echocardiographically detectable systolic dysfunction. Furthermore, it can monitor LV remodelling with treatment.

Antistreptolysin O titer in health and disease: levels and significance.

Over diagnosis of acute rheumatic fever (ARF) based on a raised antistreptolysin O titer (ASOT) is not uncommon in endemic areas. In this study, 660 children (aged 9.2 ±1.7 years) were recruited consecutively and classified as: G1 (control group, n=200 healthy children), G2 (n=20 with ARF 1(st) attack), G3 (n=40 with recurrent ARF), G4 (n=100 with rheumatic heart disease (RHD) on long acting penicillin (LAP)), G5 (n=100 with acute follicular tonsillitis), and G6 (n=200 healthy children with history of repeated follicular tonsillitis more than three times a year). Serum ASOT was measured by latex agglutination. Upper limit of normal (ULN) ASOT (80(th) percentile) was 400 IU in G1, 200 IU in G4, and 1600 IU in G6. Significantly high levels were seen in ARF 1st attack when compared to groups 1 and 5 (P<0.001 and P<0.05, respectively). ASOT was significantly high in children over ten years of age, during winter and in those with acute rheumatic carditis. ASOT showed significant direct correlation with the number of attacks of tonsillitis (P<0.05). Egyptian children have high ULN ASOT reaching 400 IU. This has to be taken into consideration when interpreting its values in suspected ARF. A rise in ASOT is less prominent in recurrent ARF compared to 1st attack, and acute and recurrent tonsillitis. Basal levels of ASOT increase with age but the pattern of increase during infection is not age dependent.

Group A B Hemolytic Streptococci in rheumatic patients receiving long acting penicillin.

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