A new variant of MYCN gene as a cause of Feingold syndrome.

Feingold syndrome 1 (FS1) is a rare disorder that is inherited in autosomal dominant manner with full penetrance but with variable expressivity. The most common phenotypical features described are finger and toe anomalies, microcephaly, short stature, and intestinal atresia. Dysmorphic features, intellectual disability and other organ anomalies are less frequently described. Here, we present a 7-year-old boy with severe intellectual disability who is diagnosed with FS1 syndrome caused by a new heterozygous variant of MYCN gene.

Complete revascularization for patients with multivessel coronary artery disease and ST-segment elevation myocardial infarction after the COMPLETE trial: A meta-analysis of randomized controlled trials.

BACKGROUND: The recently published COMPLETE trial has demonstrated that patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), who underwent successful percutaneous coronary intervention (PCI) of both culprit and non-culprit (vs. culprit-only) lesions had a reduced risk of major adverse cardiac events (MACE), but not of cardiovascular or total mortality. The aim of this meta-analysis was to assess the efficacy of complete revascularization on cardiovascular or total mortality reduction using available randomized controlled trials (RCTs) including the COMPLETE trial, in hemodynamically stable STEMI patients with MVD. METHODS: PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL and ClinicalTrials.gov databases search identified 10 RCTs of 7033 patients with STEMI and MVD which compared complete (n = 3420) vs. only culprit lesion (n = 3613) PCI for a median 27.7 months follow-up. Random effect risk ratios were used to estimate for efficacy and safety outcomes. RESULTS: Complete revascularization reduced the risk of MACE (10.4% vs.16.6%; RR = 0.59, 95% CI: 0.47 to 0.74, p < 0.0001), CV mortality (2.87% vs. 3.72%; RR = 0.73, 95% CI: 0.56 to 0.95, p = 0.02), reinfarction (5.1% vs. 7.1%; RR = 0.67, 95% CI: 0.52 to 0.86, p = 0.002), urgent revascularization (7.92% vs.17.4%; RR = 0.47, 95% CI: 0.30 to 0.73, p < 0.001), and CV hospitalization (8.68% vs.11.4%; RR = 0.65, 95% CI: 0.44to 0.96, p = 0.03) compared with culprit only revascularization. All-cause mortality, stroke, major bleeding events, or contrast induced nephropathy were not affected by the revascularization strategy. CONCLUSION: The findings of this meta-analysis suggest that in patients with STEMI and MVD, complete revascularization is superior to culprit-only PCI in reducing the risk of MACE outcomes, including cardiovascular mortality, without increasing the risk of adverse safety outcomes.

Exaggerated systolic hypertensive response to exercise predicts cardiovascular events: a systematic review and meta-analysis.

INTRODUCTION: The pathophysiology of exaggerated systolic hypertensive response to exercise (SHRE) is not fully understood, with contradictory data on its role in predicting cardiovascular (CV) events. OBJECTIVES: The aim of this review and meta­analysis was to assess the association of SHRE with CV clinical outcomes in healthy normotensive individuals. PATIENTS AND METHODS: We searched PubMed (MEDLINE), Cochrane Library, RefWorks, and Google Scholar to identify clinical studies that reported data on CV event rates and outcomes for patients with SHRE on exercise stress testing. Sensitivity and specificity analysis for assessing the diagnostic accuracy of the SHRE cutoff associated with CV events was estimated using hierarchical summary receiver operating characteristic analysis. RESULTS: We included 8 studies with 47 188 participants and a median follow­up of 19.3 years. Exaggerated SHRE was found in patients with composite events (CV mortality and coronary artery disease; hazard ratio [HR], 1.363; 95% CI, 1.135-1.604; P <0.001), in those with coronary artery events (HR, 1.532; 95% CI, 1.240-1.893; P <0.001), and in those with CV mortality (HR, 1.286; 95% CI, 1.075-1.539; P =0.006), as compared with individuals with normal response. An exercise systolic blood pressure of 196 mm Hg predicted CV events with a sensitivity of 62% (54%-69%) and specificity of 75% (60%-86%), with a positive likelihood ratio of less than 3 and a strong correlation (r = -0.71). CONCLUSIONS: Our study supports the clinical relevance of exaggerated SHRE as a predictor of composite and individual CV clinical outcome. These findings should be considered as thought­provoking evidence for better stratification and, consequently, for optimal management of this high­risk population.

Complete revascularization for patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease: a meta-analysis of randomized trials.

INTRODUCTION: Despite the recent findings in randomized clinical trials (RCTs) with limited sample sizes and the updates in clinical guidelines, the current available data for the complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) at the time of primary percutaneous coronary intervention (PCI) are still contradictory. AIM: The aim of this meta-analysis of the existing RCTs was to assess the efficacy of the CR versus revascularization of infarct-related artery (IRA) only during primary PCI in patients with STEMI and multivessel disease (MVD). PATIENTS AND METHODS: We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases aiming to find RCTs for patients with STEMI and MVD which compared CR with IRA-only. Random effect risk ratios (RRs) were calculated for efficacy and safety outcomes. RESULTS: Ten RCTs with 3291 patients were included. The median follow-up duration was 17.5 months. Major adverse cardiac events (RR=0.57; 0.43-0.76; P<0.0001), cardiac mortality (RR=0.52; 0.31-0.87; P=0.014), and repeat revascularization (RR=0.50; 0.30-0.84; P=0.009) were lower in CR compared with IRA-only strategies. However, there was no significant difference in the risk of all-cause mortality, recurrent nonfatal myocardial infarction, stroke, major bleeding events, and contrast-induced nephropathy. CONCLUSION: For patients with STEMI and MVD undergoing primary PCI, the current evidence suggests that the risk of major adverse cardiac events, repeat revascularization, and cardiac death is reduced by CR. However, the risk for all-cause mortality and PCI-related complications is not different from the isolated culprit lesion-only treatment. Although these findings support the cardiac mortality and safety benefit of CR in stable STEMI, further large trials are required to provide better guidance for optimum management of such patients.

Does Dexamethasone Helps in Meningococcal Sepsis?

PURPOSE: Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. METHODS: In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. RESULTS: Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. CONCLUSION: The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease.

Coarctation repair normalizes left ventricular function and aorto-septal angle in neonates.

BACKGROUND AND AIMS: Patients with coarctation of the aorta (CoA) have increased left ventricular (LV) afterload that has been shown to impact the LV and ascending aortic function. We aimed to examine the effect of coarctation on LV function and aorto-septal angle (AoSA) before and after surgical repair. METHODS: We retrospectively studied 21 patients with surgically repaired CoA at a median age of 9 (2-53) days at three time points: (1) just before intervention, (2) at short-term follow-up, and (3) at medium-term follow-up after intervention. AoSA was measured from the parasternal long axis view, at three time points during the cardiac cycle: (1) end diastole, (2) beginning of systole, and (3) at peak ejection in the descending aorta. In addition to conventional LV structure and function, global longitudinal strain, and strain rate were measured using STE technique and Tomtec software. Three groups of age matched healthy children served as controls at each time point. RESULTS: AoSA was significantly wider before intervention, in particular at peak ejection in the descending aorta (144° ± 6.4° vs. 136° ± 4.1°; P < .0001), and correlated with CoA pressure gradient. After intervention, AoSA normalized and significantly correlated with the increase of LV cavity function and overall LV deformation parameters. CONCLUSIONS: AoSA is abnormally wide in neonates with CoA and is associated with severity of obstruction, LV dysfunction and compromised LV global deformation.

Congenital Nephrotic Syndrome - Finish Type.

INTRODUCTION: Identification of the NPHS1 gene, which encodes nephrin, was followed by many studies demonstrating its mutation as a frequent cause of congenital nephrotic syndrome (CNS). While this gene is found in 98% of Finnish children with this syndrome, non-Finnish cases have lower level of incidence ranging from 39 to 80%. CASE REPORT: This report describes the clinical presentation of a two-week-old neonate who presented with periorbital and lower extremities edema, abdominal distention, heavy proteinuria, serum hypoproteinemia and failure to thrive. Genetic analysis revealed NHPS1 gene mutation leading to CNS-Finnish type diagnosis. CONCLUSION: Through this case we want to create awareness about diagnosis and treatment challenges in developing countries for rare congenital diseases.

Persistent reduced myocardial deformation in neonates after CoA repair.

INTRODUCTION: Surgical repair of coarctation of the aorta (CoA) is a safe procedure in children, however the condition is known for its potential recurrence and other related complications. The available evidence shows abnormal intrinsic properties of the aorta in CoA, thus suggesting additional effect, even after CoA repair, on left ventricular (LV) function. Accordingly, we sought to obtain a better understanding of LV myocardial mechanics in very early-corrected CoA using two-dimensional STE. METHODS AND RESULTS: We retrospectively studied 21 patients with corrected CoA at a median age of 9 (2-53) days at three time points: 1) just before intervention, 2) at short-term follow-up and 3) at medium-term follow-up after intervention and compared them with normal values. Speckle tracking analysis was conducted via vendor independent software, Tomtec. After intervention, LV function significantly improved (from -12.8±3.9 to -16.7±1.7; p<0.001), however normal values were not reached even at medium term follow-up (-18.3±1.7 vs. -20±1.6; p=0.002). Medium term longitudinal strain correlated with pre intervention EF (r=0.58, p=0.006). Moreover, medium term subnormal values were more frequently associated with bicuspid aortic valve (33.3% vs. 66.6%; p<0.05). CONCLUSION: LV myocardial function in neonates with CoA can be feasibly evaluated and followed up by speckle tracking echocardiography. LV subendocardial dysfunction however, remains in early infancy coarctation long after repair. Long-term follow-up through adulthood using myocardial deformation measurements should shed light on the natural history and consequences of this anomaly.

Hashimoto Thyroiditis and Nephrocalcinosis in a Child with Down Syndrome.

INTRODUCTION: Hypothyroidism has been reported to affect renal function and structure. However, the association of hypothyroidism with distal renal tubular acidosis (dRTA) is rarely reported in children. CASE PRESENTATION: We present a 6-year-boy with Down syndrome admitted in our department due to vomiting, weakness, polyuria, polydipsia, irritability and weight loss in the last few weeks. Investigations revealed features of hypokalemia, metabolic acidosis and alkaline urine consistent with dTRA. Abdominal ultrasound found nephrocalcinosis. In addition, Antithyroid peroxidase antibodies were positive, suggesting an autoimmune background for the pathogenesis of the tubular dysfunction. Treatment for dRTA and hypothyroidism was started and symptomatic improve was noticed. CONCLUSION: dRTA should be excluded in children with autoimmune disorders who develop weakness, polyuria, polydipsia or growth failure. Early diagnosis would reduce long-term complications.

Comparison of drug-eluting balloon versus drug-eluting stent treatment of drug-eluting stent in-stent restenosis: A meta-analysis of available evidence.

BACKGROUND: In-stent restenosis (ISR) remains an important concern despite the recent advances in the drug-eluting stent (DES) technology. The introduction of drug-eluting balloons (DEB) offers a good solution to such problem. OBJECTIVES: We performed a meta-analysis to assess the clinical efficiency and safety of DEB compared with DES in patients with DES-ISR. METHODS: A systematic search was conducted and all randomized and observational studies which compared DEB with DES in patients with DES-ISR were included. The primary outcome measure-major adverse cardiovascular events (MACE)-as well as individual events as target lesion revascularization (TLR), stent thrombosis (ST), myocardial infarction (MI), cardiac death (CD) and all-cause mortality, were analyzed. RESULTS: Three randomized and 4 observational studies were included with a total of 2052 patients. MACE (relative risk [RR]=1.00, 95% confidence interval (CI) 0.68 to 1.46, P=0.99), TLR (RR=1.15 [CI 0.79 to 1.68], P=0.44), ST (RR=0.37[0.10 to 1.34], P=0.13), MI (RR=0.97 [0.49 to 1.91], P=0.93) and CD (RR=0.73 [0.22 to 2.45], P=0.61) were not different between patients treated with DEB and with DES. However, all-cause mortality was lower in patients treated with DEB (RR=0.45 [0.23 to 0.87, P=0.019) and in particular when compared to only first generation DES (RR 0.33 [0.15-0.74], P=0.007). There was no statistical evidence for publication bias. CONCLUSIONS: The results of this meta-analysis showed that DEB and DES have similar efficacy and safety for the treatment of DES-ISR.

Normal ranges of left ventricular strain in children: a meta-analysis.

AIMS: The definition of normal values of two-dimensional speckle-tracking echocardiography derived left ventricular (LV) deformation parameters, is of critical importance for the routine application of this modality in children. The objectives of this study were to perform a meta-analysis of normal ranges for longitudinal, circumferential and radial strain/strain rate values and to identify confounders that may contribute to differences in reported measures. METHODS AND RESULTS: A systematic search was conducted. Studies describing normal healthy subjects and observational studies that used control groups as a comparison were included. Data were combined using a random-effect model. Effects of demographic, clinical and equipment variables were assessed through meta-regression. The search identified 1,192 subjects form 28 articles. Longitudinal strain (LS) normal mean values varied from -12.9 to -26.5 (mean, -20.5; 95% CI, -20.0 to -21.0). Normal mean values of circumferential strain (CS) varied from -10.5 to -27.0 (mean, -22.06; 95% CI, -21.5 to -22.5). Radial strain (RS) normal mean values varied from 24.9 to 62.1 (mean, 45.4; 95% CI, 43.0 to 47.8). Meta-regression showed LV end diastolic diameter as a significant determinant of variation for LS. Longitudinal systolic strain rate (LSRs) was significantly determined by the age and RS by the type of vendor used. CONCLUSION: Variations among different normal ranges were dependent on the vendor used, LV end-diastolic diameter and age. Vendor-independent software for analyzing myocardial deformation in children, using images from different vendors would be the ideal solution for strain measurements or else using the same system for patient's follow up.

Left ventricular response to pressure afterload in children: aortic stenosis and coarctation: a systematic review of the current evidence.

Congenital aortic stenosis (CAS) and Coarctation of Aorta (CoA) represent two forms of pressure afterload that affect the left ventricle (LV), hence require regular echocardiographic monitoring. Subclinical dysfunction of the LV exists even in asymptomatic patients with preserved left ventricular ejection fraction (EF), implying low sensitivity of EF in predicting optimum time for intervention. In this article we review patterns of LV myocardial deformation before and after correction of CAS and CoA in infants, children and adolescents, showing their important role in monitoring the course of LV dysfunction. A systematic search using PubMed was performed and suitable studies are presented on a narrative form. Normal EF and/or fractional shortening (FS), with subclinical myocardial dysfunction are reported in all studies before intervention. The short-term results, after intervention, were related to the type of procedure, with no improvement or further deterioration related to surgery but immediate improvement after balloon intervention. Long term follow-up showed further improvement but still subnormal function. Thus correction of CAS and CoA before irreversible LV dysfunction is vital, and requires longitudinal studies in order to identify the most accurate parameter for function prognostication. Until then, conventional echocardiographic parameters together with myocardial velocities and deformation parameters should continue to provide follow-up reproducible measures of ventricular function.