Glucose control during Ramadan in a pediatric cohort with type 1 diabetes on MiniMed standard and advanced hybrid closed­loop systems: A pilot study.

BACKGROUND: Hybrid closed-loop (HCL) systems have revolutionized the treatment of diabetes, enabling doctors to cope with challenging conditions that were previously almost impossible to manage or were very risky and difficult. AIMS: To assess the efficacy and safety of a hybrid closed-loop (HCL) system during Ramadan fasting in a pediatric cohort with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Glucose control outcomes in older children and adolescents aged 8-16 years with automated insulin delivery for T1D were analyzed during Ramadan and 1 month before Ramadan. Participants on MiniMed standard HCL (670G) or advanced HCL (780G) systems of Medtronic were categorized as fasting or nonfasting. RESULTS: The average age of the 19 participants (8 and 11 were on standard and advanced HCL systems, respectively) was 11.35 ± 2 years. Eleven patients fasted during Ramadan. Pump setup and sensor statistics were the same during Ramadan and the month before; no significant difference was found between the two groups in terms of insulin and glucose control metrics, with practically the same coefficient of variation, time in range (TIR) and time spent in hypoglycemia, maintained within the international recommended targets. Total daily doses were paradoxically higher in patients who fasted during Ramadan (p = 0.01), without repercussions on glucose control metrics. CONCLUSIONS: Standard and advanced HCL use during Ramadan were safe and were associated with a maintained optimum TIR (>70 %) and no significant hypoglycemia in adolescents and older children with T1D.

Novel biomarkers for subtle myocardial involvement in type I diabetes mellitus.

BACKGROUND: Evaluation of certain biomarkers could be used to predict left ventricular (LV) and right ventricular (RV) function impairment in children with type 1 diabetes mellitus. The aim of this study was to determine the best cardiac biomarker for prediction of diabetic cardiomyopathy. METHODOLOGY: This study was designed as case-control study. A total of 55 children with type 1 diabetes mellitus (group/G1) and 55 healthy controls (G2) were subjected to echocardiography including 3D-Speckle Tracking Echocardiography and tissue Doppler imaging for assessment of RV and LV systolic and diastolic functions. As well as HbA1c, troponin I, brain natriuretic peptide (BNP), plasma cardiotrophin (CT-1), activin-A, transforming growth factor-ß, and human insulin-like growth factor binding protein-7 (IGFBP-7) measurements. RESULTS: Diabetic patients showed RV and LV systo-diastolic dysfunction compared to controls, the best predictor of LV systolic dysfunction was CT-1 (sensitivity: 69%, while IGFBP-7 was found to be the best predictor of RV systolic dysfunction (sensitivity: 63%). BNP was found to the best predictor of diastolic RV and LV dysfunction (sensitivity: 82% for both). CONCLUSION: CT-1 has proven to be a diagnostic superiority in LV systolic dysfunction whilst BNP continues to prove every day through our study and through many others that it is the chief marker of diastolic dysfunction and HFpEF. This potential accuracy and the increasing availability of BNP in the outpatient setting make it clear that it should be used as a screening test for diabetic patients.

Ficolin-1 gene (FCN1) -144 C/A polymorphism is associated with adverse outcome of severe pneumonia in the under-five Egyptian children: A multicenter study.

BACKGROUND: Pneumonia is the foremost cause of child death worldwide. M-ficolin is encoded by the FCN1 gene and represents a novel link between innate and adaptive immunity. OBJECTIVES: To investigate the FCN1 -144 C/A (rs10117466) polymorphism as a potential marker for pneumonia severity and adverse outcome namely complications or mortality in the under-five Egyptian children. METHODS: This was a prospective multicenter study that included 620 children hospitalized with World Health Organization-defined severe pneumonia and 620 matched healthy control children. Polymorphism rs10117466 of the FCN1 gene promoter was analyzed by PCR-SSP, while serum M-ficolin levels were assessed by ELISA. RESULTS: The FCN1 A/A genotype and A allele at the -144 position were more frequently observed in patients compared to the control children (43.4% vs 27.6%; odds ratio [OR]: 1.62; [95% confidence interval {CI}: 1.18-2.2]; for the A/A genotype) and (60.8% vs 52.5%; OR: 1.4; [95% CI: 1.19-1.65]; for the A allele); P < .01. The FCN1 -144 A/A homozygous patients had significantly higher serum M-ficolin concentrations (mean: 1844 ± 396 ng/mL) compared with those carrying the C/C or C/A genotype (mean: 857 ± 278 and 1073 ± 323 ng/mL, respectively; P = .002). FCN1 -144 A/A genotype was an independent risk factor for adverse outcomes in children with severe pneumonia (adjusted OR = 4.85, [95% CI: 2.96-10.25]; P = .01). CONCLUSION: The FCN1 A/A genotype at the -144 position was associated with high M-ficolin serum levels and possibly contributes to enhanced inflammatory response resulting in the adverse outcome of pneumonia in the under-five Egyptian children.

Revival and modification of the Mustard operation.

OBJECTIVE: The neonatal arterial switch operation is currently the procedure of choice for patients with transposition of the great arteries. However, a large number of patients present too late for the arterial switch operation and are best managed with the atrial switch operation. METHODS: We have used the Mustard operation in its original form or following a new modification designed to enhance the atrial functions and filling of the left ventricle in an attempt to improve long-term results. RESULTS: Between July 2013 and November 2018, a total of 101 patients underwent the Mustard operation, 86 with the new modification. The median age at operation was 16 months (6 months to 27 years). A total of 75 patients (74.3%) were male. Median preoperative oxygen saturation was 71%. There were no early deaths and there were 3 late deaths during a median follow-up period of 24.2 months (all in patients with large ventricular septal defect and established pulmonary vascular disease). At the latest follow-up, all patients were in stable sinus rhythm. There were no baffle leaks. Seven patients had asymptomatic narrowing of the superior baffle, and 1 patient required balloon dilatation. Follow-up is 100% complete and includes computed tomography and magnetic resonance imaging at regular intervals (75 patients to date). Computerized analysis of representative subsets showed enhanced rate and pattern of filling of the left ventricle in the modified operation compared with the classic operation. CONCLUSIONS: The use of the Mustard operation, particularly the modified technique should play an important role in treating late-presenting patients with transposition of the great arteries. Improving the pattern of filling of the left ventricle could enhance the long-term results of the Mustard operation.

IL-Iß+3954 C/T Polymorphism and Its Clinical Associations in Egyptian Sickle Cell Disease Patients.

Background: Sickle cell disease (SCD) is a hereditary disorder characterized by hemolytic anemia with different clinical manifestations. Patients with SCD exhibit a chronic inflammatory state and reduced length and quality of life. Interleukin-1 ß (IL-1ß) is important in acute and chronic diseases; and its single nucleotide polymorphisms (SNP) have been considered as predictors of prognosis in several inflammatory conditions. This study aimed at exploring IL-1ß (+3954C/T) SNP as a potential genetic modifier and/or predictor of SCD clinical and laboratory phenotypes. Materials and Methods: This cross-sectional study involved 50 SCD patients and 50 age, sex and ethnicity-matched healthy individuals. IL-1ß (+3954C/T) SNP was identified by PCR-RFLP. Associations between IL-1ß (+3954 C/T) SNP and the clinical and laboratory profiles of patients with SCD were studied. Results: It was found that the homozygous mutant genotype TT was significantly higher in cases compared to controls [13(26%) vs. 3(6%) respectively; p=0.006, OR (95%CI): 5.505(1.460-20.756)]. The homozygous mutant genotype TT was associated with a higher mean pulmonary arterial pressure when compared to the CC and CT genotype (42.62 vs. 33.49 mmHg, p<0.001). Conclusion: There is an increased prevalence of the mutant genotype of IL-1ß +3954 SNP in Egyptian SCD patients. Regarding disease complications, the mutant genotype was more prevalent in cases complicated by pulmonary hypertension. These findings point to the possible role of IL-1ß +3954 SNP in the pathophysiology of SCD and its manifestations.

Development of tissue Doppler-derived predictors of hemodynamically significant patent ductus arteriosus and the ability to incorporate it in targeted neonatal echocardiography protocol.

BACKGROUND: Hemodynamically significant (HS) patent ductus arteriosus (PDA) is a significant cause of mortality in preterm neonates. Early detection of HS PDA and pre-symptomatic closure may help in avoiding complications. For this to happen, easily performed predictors must be available; the aim of this paper is to test the reliability and repeatability of tissue Doppler-derived parameters for prediction of HS PDA. METHODS: Preterm neonates <32 weeks were screened with echocardiography at Day 3 of life; 80 neonates with PDA were classified into HS group and hemodynamically insignificant (HIS) group based on benchmark parameter namely left ventricular outflow to superior vena caval flow ratio (LVO/SVC), and a ratio ≥4 was considered predictive of HS PDA. Tissue Doppler-derived left ventricular myocardial systolic and diastolic velocities were also performed. RESULTS: In total, 105 neonates (55 among HS and 60 among HIS groups) were included in the study. Septal systolic velocity (S') proved of high sensitivity (100%) in the prediction of HS PDA; nevertheless, it proved to be more repeatable than the initially discriminating parameter (LVO/SVC) with a Kappa of 0.92. CONCLUSION: This study concludes that septal S' can be reliably used even by neonatologists for pre-symptomatic detection of HS PDA. This may also indicate the need of adding tissue Doppler parameters to the standard protocol of targeted neonatal echocardiography.

ASD device closure in pediatrics: 3-Dimensional transthoracic echocardiography perspective.

OBJECTIVE: Real-time three-dimensional echocardiography, using both reconstruction methods and RT3D, has been used as an extra helping tool in several forms of congenital heart diseases. Our aim was to understand the relation of the ASD device to all surrounding structures by 3-dimensional echocardiography (3D). METHODS: This prospective study included 37 patients diagnosed as ASD secundum by transthoracic (TTE) and transesophageal echocardiography (TEE) referred for transcatheter closure from October 2013 to July 2016. Follow-up for 1 year using 2D and 3D-echocardiography was performed to assess the relations of the device to the surrounding structures. RESULTS: Transcatheter ASD closure and echocardiographic examinations were successfully performed for all patients. By 3D echocardiography, 16 patients (43.24%) had their ASD device close to the aortico-mitral continuity plane without apparent regurgitation, while the rest of our patients (56.75%) the devices were away from this plane. The following variables were significantly different between the two groups; body surface area, atrioventricular rim (AV), device size, left disc size and ratio of left disc to interatrial septum. A cut-off AV rim length not less than 8 mm was found optimal to avoid device encroachment on the sensitive surrounding structures. New Formula was constructed to aid in device choice. CONCLUSION: Use of 3D before and after ASD closure is of value to determine the device relation to the surrounding structures. AV rim by TEE is an important rim to avoid eventual encroachment on the mitral valve and aorta.

Association of IL-4 (intron 3) and IL-10 (-1082) gene polymorphisms with risk of mitral valve disease in children with rheumatic heart disease.

UNLABELLED: Aim Rheumatic heart disease is an inflammatory disease of cardiac tissue. The underlying pathogenic mechanisms highlight a complex interplay of immunological, genetic, and environmental factors. The aim of the present study was to investigate whether IL-4 (intron 3) and IL-10 (-1082) gene polymorphisms could be associated with susceptibility and/or severity of rheumatic heart disease among patients from the Egyptian population. Materials and methods A cohort of 140 Egyptian children with rheumatic heart disease and 100 healthy controls were enrolled in this case-control study. Genotyping for IL-4 (intron 3) and IL-10 (-1082) gene polymorphisms was carried out for all patients using a polymerase chain reaction-based analysis. RESULTS: No significant difference in the distribution of genotypes and allelic frequencies between rheumatic heart disease cases and controls for IL-4 (intron 3) (p=0.17; OR 1.07, 95% CI 0.82-3.74) and IL-10 (-1082) (p=0.49; OR 1.03, 95% CI 0.65-2.71) gene polymorphisms was observed. Further categorisation of patients into mitral valve disease and combined valve disease subgroups showed that cases with mitral valve disease have significantly higher frequency of the RP2 allele of IL-4 (intron 3) (p=0.03; OR 2.98, 95% CI 1.93-6.15) and the G allele of IL-10 (-1082) (p=0.04; OR 2.14, 95% CI 1.62-4.95) when compared with controls. Discussion Our study shows that IL-4 (intron 3) and IL-10 (-1082) gene polymorphisms are not significantly associated with susceptibility to rheumatic heart disease, but they might play a role in the pathogenesis of patients with mitral valve disease.

Antegrade flow in Anomalous Left Coronary Artery from Pulmonary Artery: Clinical implications.

Anomalous origin of the left main coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly that usually presents in childhood. It results in left ventricular (LV) ischemia with resulting LV dysfunction. This ischemia results from retrograde flow into the pulmonary artery which can act as a coronary steal. We here report antegrade flow detected in ALCAPA caused by severe pulmonary hypertension. Anatomic correction of ALCAPA is the preferred surgical option and should be performed as early as possible.

Lessons from patient-specific 3D models of the cardiac chambers after the Mustard operation.

The recent ability to create detailed 3D models of the atrial and ventricular chambers using CT, MRI and rapid prototyping offers unique opportunities to study the size and shape of the different cardiac chambers both before and following operation for complex cardiac anomalies. We here describe the techniques for creating detailed 3D models of the heart and demonstrate the utility of these techniques in a patient studied after the Mustard operation. This can give important insights into the changes in size and shape of the different chambers and the patterns of blood flow from the pulmonary and systemic veins to the 'appropriate' ventricle. This information in turn could be extremely helpful in understanding and optimizing the overall hemodynamic function after the Mustard operation.