Congenital aflatoxicosis, mal-detoxification genomics & ontogeny trigger immune-mediated Kotb disease biliary atresia variant: SANRA compliant review.

Biliary atresia (BA) is the most common indication for pediatric liver transplantation. We describe The BA variant: Kotb disease. Liver tissue in the Kotb disease BA is massively damaged by congenital aflatoxicosis resulting in inflammation, adhesions, fibrosis, bile duct proliferation, scarring, cholestasis, focal syncytial giant cell transformation, and typical immune response involving infiltration by CD4+, CD8+, CD68+, CD14+, neutrophil infiltration, neutrophil elastase spill, heavy loads of aflatoxin B1, accelerated cirrhosis, disruption of p53 and GSTPi, and have null glutathione S transferase M1 (GSTM1). All their mothers are heterozygous for GSTM1. This inability to detoxify aflatoxicosis results in progressive inflammatory adhesions and obliterative cholangiopathy early in life. The typical disruption of both p53 and GSTPi causes loss of fidelity of hepatic regeneration. Hence, regeneration in Kotb disease BA typically promotes accelerated cirrhosis. The immune response in Kotb disease BA is for damage control and initiation of regeneration, yet, this friendly fire incurs massive structural collateral damage. The Kotb disease BA is about actual ongoing hepatic entrapment of aflatoxins with lack of ability of safe disposal due to child detoxification-genomics disarray. The Kotb disease BA is a product of the interaction of persistent congenital aflatoxicosis, genetic lack of GSTM1 detoxification, ontogenically impaired activity of other hepatic detoxification, massive neutrophil-elastase, immune-induced damage, and disturbed regeneration. Ante-natal and neonatal screening for aflatoxicosis, avoiding cord milking, and stringent control of aflatoxicosis content of human, poultry and live-stock feeds might prove effective for prevention, prompt diagnosis and management based on our recent understanding of its patho-genomics.

Echocardiographic findings in children with chronic kidney disease.

Cardiovascular diseases (CVD) are considered major cause of morbidity and mortality among children with chronic kidney disease (CKD). This study aims to determine the incidence of CVD in children with CKD, to analyze risk factors and early predictors for late onset atherosclerosis. Thirty-five CKD children [25 on regular hemodialysis (HD) and 10 on conservative management] were evaluated clinically. Left ventricular (LV) functions and carotid artery intima-media thickness (c-IMT) were assessed using conventional echocardiography, pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI). There was decreased E/A ratio and increased E/E' ratio in 66% and 77% of patients, respectively signifying diastolic cardiac dysfunction. There was a significant correlation between increased A' value (peak late diastolic annular velocity) and both increased serum cholesterol and anemia (P = 0.009, 0.004 respectively). Serum high density lipoprotein (HDL) significantly correlated negatively with inter-ventricular septal thickness and LV end-diastolic dimensions (P = 0.05, 0.02, respectively) and positively with E' value (peak early diastolic annular velocity) (P = 0.04). Abnormal c-IMT correlated significantly with HD duration (correlation coefficient = 0.428, P = 0.01) and with both increased serum cholesterol and decreased serum HDL (P = 0.021, 0.031, respectively). Diastolic dysfunction and abnormal LV dimensions are present in patients with CKD even those on conservative management. TDI appears to be more impressive than PWD in assessing early myocardial dysfunction. Increased c-IMT and dyslipidemia are prevalent in patients with CKD and more prevalent in patients on HD.

Effect of On-Line Hemodiafiltration on P-Wave Dispersion in Children.

P-wave dispersion (PWD) (difference between the maximum and minimum P-wave duration), has been proposed as a useful predictor of paroxysmal atrial fibrillation (AF). The consequences of hemodialysis (HD) on PWD and P-wave duration have not been unequivocally documented and understood, and may be complex. We aimed in this work to demonstrate the effects of online hemodiafiltration (OL-HDF) on the risk of developing AF through assessment of PWD. Thirty-three pediatric patients (14 males and 19 females with mean age of 11.66 ± 2.93 years) on conventional HD for at least 6 months underwent echocardiography, 12-lead electrocardiogram and PWD calculation. Then they were switched to OL-HDF for another 6 months and same parameters were reassessed. Thirty sex- and aged-matched healthy children, served as controls. PWD significantly decreased upon switching to OL-HDF (P < 0.001) and fractional shortening significantly improved (P < 0.001). Mean PWD of controls (24 ± 6 ms) was significantly less than PWD before and after OL-HDF (P < 0.001 and <0.001, respectively). Online HDF significantly decreased PWD and hence also the potential of AF development, which may invite a higher consideration of this renal replacement modality in a pediatric population.