Evaluation of cardiac fibrosis and subclinical cardiac changes in children with sickle cell disease using magnetic resonance imaging, echocardiography, and serum galectin-3.

BACKGROUND: Myocardial fibrosis has recently been proposed as one of the contributing factors to the diverse pathogenicity of cardiomyopathy in sickle cell disease. OBJECTIVE: In this study, cardiac fibrosis and subclinical cardiac changes in children with sickle cell disease were evaluated using cardiac magnetic resonance imaging (MRI), tissue Doppler echocardiography and serum galectin-3. MATERIALS AND METHODS: The study included 34 children with sickle cell disease who were compared with a similar number of healthy controls. Cardiac MRI was used to evaluate late gadolinium enhancement, native T1 mapping, extracellular volume, and T2* for estimation of iron load. Cardiac function and myocardial performance index (MPI, evaluated by tissue Doppler echocardiography) and serum galectin-3 were compared to controls. RESULTS: The mean age of the included patients was 13.3 ± 3.2 years. Myocardial iron load by T2* was normal. The mean level of extracellular volume (35.41 ± 5.02%) was significantly associated with the frequency of vaso-occlusive crises (P = 0.017) and negatively correlated with hemoglobin levels (P = 0.005). Galectin-3 levels were significantly higher among cases than controls (P = 0.00), at a cutoff value on the receiver operating characteristic curve of 6.5 ng/ml, sensitivity of 82.5% and specificity of 72.8%. The extracellular volume was significantly higher in cases, with a MPI > 0.4. CONCLUSION: Diffuse interstitial myocardial fibrosis can be detected early in children with sickle cell disease using T1 mapping and is associated with a high frequency of vaso-occlusive crisis. MPI of the left ventricle and serum galectin-3 are recommended screening tools for subclinical cardiac abnormalities.

Evaluation of cardiac function in asthmatic children by Tissue Doppler Echocardiography.

BACKGROUND: Bronchial asthma is a global health problem with rising prevalence in developing countries. Children with severe asthma can experience cor pulmonale later in life, but little is known about the cardiac changes that might be present earlier in mild or moderate severity of disease. This study aimed to evaluate biventricular function among children suffering from persistent asthma by Tissue Doppler Echocardiography (TDE). RESULTS: Thirty-five asthmatic children enrolled from Alexandria Children's Hospital between September 2021 to May 2022; they were compared to 35 healthy matched children. Chronic respiratory disease, cardiac disease, or other comorbidities were excluded. The mean age of cases was 8.87 ± 2.03 years with a male/female ratio of 54.3%:45.7%. There were 28.3% mild cases, 45.7% moderate, and 25.7% severe. Conventional echocardiographic variables of cardiac function were normal for both ventricles. The TDE indices of medial mitral annulus (S' velocity and peak E') were significantly reduced (14.55 ± 2.30 and 14.69 ± 2.30) versus controls (15.68 ± 1.96, 15.69 ± 1.76, P; 0.044, P < 0.0045) but with preserved LV function. The lateral tricuspid annulus (S' velocity and peak E') was significantly reduced (11.53 ± 3.24 and 11.56 ± 3.18) versus controls (15.71 ± 0.98, 16.02 ± 1.75, < 0.001*), while E/A and IVRT were significantly increased (1.49 ± 0.06 versus 1.70 ± 0.18 and 102.39 ± 5.37 versus 140.10 ± 34.35, respectively, P < 0.001*) with impaired RV function. Peak expiratory flow rate (PEFR) was negatively correlated with the IVRT of the tricuspid annulus (P = 0.002, r = -0.503*) and to the E'/A' (P = 0.036, r =-0.355*). All TDE variables of lateral tricuspid annulus of severe subgroups were significantly  changed versus moderate or mild subgroups. CONCLUSIONS: Tissue Doppler echocardiography is the recommended modality for early detection of biventricular cardiac dysfunction among children with different levels of asthma severity. Periodic screening is advised through the use of IVRT especially for RV.

Origanum majorana L. protects against neuroinflammation-mediated cognitive impairment: a phyto-pharmacological study.

BACKGROUND: Neuroinflammation and oxidative stress are critical players in the pathogenesis of numerous neurodegenerative diseases, such as Alzheimer's disease (AD) which is responsible for most cases of dementia in the elderly. With the lack of curative treatments, natural phenolics are potential candidates to delay the onset and progression of such age-related disorders due to their potent antioxidant and anti-inflammatory effects. This study aims at assessing the phytochemical characteristics of Origanum majorana L. (OM) hydroalcohol extract and its neuroprotective activities in a murine neuroinflammatory model. METHODS: OM phytochemical analysis was done by HPLC/PDA/ESI-MSn. Oxidative stress was induced in vitro by hydrogen peroxide and cell viability was measured using WST-1 assay. Swiss albino mice were injected intraperitoneally with OM extract at a dose of 100 mg/kg for 12 days and with 250 µg/kg LPS daily starting from day 6 to induce neuroinflammation. Cognitive functions were assessed by novel object recognition and Y-maze behavioral tests. Hematoxylin and eosin staining was used to assess the degree of neurodegeneration in the brain. Reactive astrogliosis and inflammation were assessed by immunohistochemistry using GFAP and COX-2 antibodies, respectively. RESULTS: OM is rich in phenolics, with rosmarinic acid and its derivatives being major constituents. OM extract and rosmarinic acid significantly protected microglial cells against oxidative stress-induced cell death (p < 0.001). OM protected against the LPS-induced alteration of recognition and spatial memory in mice (p < 0.001) and (p < 0.05), respectively. Mice that received OM extract prior to the induction of neuroinflammation showed comparable histology to control brains, with no overt neurodegeneration. Furthermore, OM pre-treatment decreased the immunohistochemistry profiler score of GFAP from positive to low positive and COX-2 from low positive to negative in the brain tissue, compared to the LPS group. CONCLUSION: These findings highlight the potential preventive effects of OM phenolics against neuroinflammation and pave the way toward drug discovery and development for neurodegenerative disorders.

Neuromodulatory Activity of Dietary Phenolics Derived from Corchorus olitorius L.

Dietary phenolics are known for their potent antioxidant and anti-inflammatory activities, making them promising candidates for protection against neuroinflammation and neurodegeneration. Hydroalcohol extract of Egyptian species of Corchorus olitorius L. (Co) leaves was investigated for its neuroprotective effects in a lipopolysaccharide-induced neuroinflammatory mouse model. Twenty five metabolites were characterized from the bioactive extract using high-performance liquid chromatography HPLC/PDA/HRESI/MSn , revealing 1,5-dicaffeoylquinic acid (Co11) as one of the major constituents (5.7%), which was isolated and its identity was confirmed by spectral data as first report. Co significantly protected microglia against H2 O2 -induced cytotoxicity and immunohistochemistry showed reduced expression of the astrocytic marker, glial fibrillary acidic protein, and the inflammatory marker, cyclooxygenase-2. These findings correlated with significant improvement of cognitive functions and reduction of LPS-induced neurodegeneration in Co-treated mice as revealed by histopathology. The current study shows promising effects of Co in limiting neurodegeneration and cognitive impairment caused by neuroinflammation and glial cell activation. PRACTICAL APPLICATION: Information presented here shed light on the promising effects of Corchorus olitorius (Co) for the modulation of neuroinflammatory pathways improving the neuroinflammation-related neurodegeneration and cognitive decline. This makes Co a promising candidate as a nutraceutical supplement to be used against neuroinflammation-related disorders.

Subclinical myocardial injury during vaso-occlusive crisis in pediatric sickle cell disease.

Acute painful crisis is the most frequent complication of sickle cell disease (SCD) in children. Recurrent vaso-occlusion may be associated with cardiac injury. The study aimed to assess silent myocardial injuries for sickle cell children during acute painful crisis by measuring serum level of troponin I and galectin-3. The study included 87 participates; study group (n = 44) sickle cell children presented at Jeddah hospitals in Saudi Arabia by painful crisis or acute illness as fever or cough (2017-2018). The controls were healthy children (n = 43). Demographic and history data were collected from the cases. Troponin I and galectin-3 were measured. Galectin-3 values were higher among cases with significant difference when compared to controls (7.5 ± 3.1 versus 3.2 ± 1.6, < 0.001). Galectin-3 at a cutoff > 5.1 ng/ml, the sensitivity was 88.64 and specificity was 88.37. Galectin-3 levels were higher for the pain crisis subgroup in comparison to acute illness group with significant difference (r 0.551*, p < 0.001*). Galectin-3 values were higher among troponin-positive cases with significant difference (p = 0.046) to troponin-negative cases.Conclusion: Positive results of troponin I and high levels of galectin-3 in sickle cell children during acute painful crisis were potent indicators for subclinical myocardial injury. What is Known: • The hallmark of sickle cell disease is recurrent episodes of vaso-occlusive crisis which had deleterious effects on many organs. • Cardiac changes in pediatric sickle cell disease whether structural or functional are mainly attributed to chronic anemia and or pulmonary hypertension. What is New: • The observed positive results of cardiac troponin I and high values of galectin-3 in sickle cell children during vaso-occlusive crisis are strong indicator of myocardial ischemia and ongoing cardiac fibrosis respectively. • The observed correlation between biological markers (positive troponin and high galectin-3) could be an indication of subclinical cardiac injury.

The role of diagnostic cardiac catheterization for children with congenital heart diseases: local experience.

INTRODUCTION: Despite the development of non-invasive tools of investigations for congenital heart diseases (CHDs), still the role of diagnostic cardiac catheterization (DCC) cannot be undermined. The study aimed to analyze the clinical profile of indicated CHDs cases at our center for DCC to evaluate the contribution of DCC in patients' management plans. MATERIAL AND METHODS: The study checked files of cases performed DCC between 2011 and 2012 at the pediatric catheterization unit of Alexandria University Children's Hospital by the same operator. Demographic, laboratory and hemodynamic data were collected and analyzed. RESULTS: Files of 61 children were included in the study. They were grouped into: group I (GI) (n = 25) with pulmonary hypertension (PH), and group II (GII) (n = 36) cases with obstructive pulmonary artery diseases. For the PH group, ventricular septal defect (VSD) was the most common (55%), and patients' outcome plans were based on angiography - operable subgroup GI-A: (84%) (n = 21) and non-operable (16%) GI-B: (4% inoperable, 12% recommended for sildenafil). GI-B cases were significantly older, with higher PVRI and PVRI/SVRI (3.62, 0.68, p = 0.002) compared to GI-A (0.89, 0.23, p = 0.002, respectively). For group II, tetralogy of Fallot (TOF) was predominant (60%) among the disease spectrum, and the McGoon ratio ranged from 0.7 to 3.2 (median: 1.8). Outcome for GII: 63% operable, 25% shunt, 12% stent. Only pulmonary atresia cases showed a significant difference in the unmatched plans between echocardiography and catheterization reports (χ2 = 7.438, p = 0.023). CONCLUSIONS: Diagnostic cardiac catheterization had a positive contribution for determination of the management plans for more than 84% of cases. The utility of pediatric cardiac catheterization in diagnosis should be adjusted according to the local needs of every cardiac center.