Critical illness‑related corticosteroid insufficiency in children: A single center, prospective, cohort study

Background: Although guidelines for diagnosis and management of critical illness‑related corticosteroid insufficiency (CIRCI) in adults are developed, there is a paucity of data on CIRCI in children. Objective: To study the incidence, risk factors, mechanism, and associations of CIRCI in children using adrenocorticotropic hormone (ACTH) stimulation test. Materials and Methods: Single‑center prospective cohort study was conducted in eight bedded pediatric intensive care unit of teaching hospital over a period of 1 year. Serum total cortisol concentration was measured in 110 critically ill children before and after stimulation with 250 μg ACTH. CIRCI was defined by post‑ACTH increment in serum cortisol ≤9 μg/dl. Children with and without CIRCI were compared. Results: Incidence of CIRCI was 38.2%. Children with CIRCI had higher median age (34 vs. 18 months), higher pediatric risk of mortality score (17.79±2.60 vs. 16.37±3.68), and significantly higher basal cortisol levels (27.37±11.64 vs. 22.02±7.26) (p=0.004) than those without CIRCI. There was a significantly higher (p=0.000) requirement of catecholamines (2.71±0.457 vs. 2.00±0.792) and higher additional fluid boluses (15.79±4.7 vs. 10.65±4.60) in children with CIRCI. However, duration of catecholamine use was not significantly different between two groups. The presence of CIRCI was not found to be an independent risk factor for mortality. For each additional use of catecholamine, the risk of CIRCI increased to 5.6 times; and for each extra fluid bolus, the risk increased to 1.2 times. Conclusion: CIRCI occurs in a wide spectrum of diseases in critically ill children associated with increased need for catecholamine and fluids. CIRCI is likely to be multifactorial in etiology and associated with high basal cortisol levels

LKB1 Destabilizes Microtubules in Myoblasts and Contributes to Myoblast Differentiation

Background: Skeletal muscle myoblast differentiation and fusion into multinucleate myotubes is associated with dramatic cytoskeletal changes. We find that microtubules in differentiated myotubes are highly stabilized, but premature microtubule stabilization blocks differentiation. Factors responsible for microtubule destabilization in myoblasts have not been identified. Findings: We find that a transient decrease in microtubule stabilization early during myoblast differentiation precedes the ultimate microtubule stabilization seen in differentiated myotubes. We report a role for the serine-threonine kinase LKB1 in both microtubule destabilization and myoblast differentiation. LKB1 overexpression reduced microtubule elongation in a Nocodazole washout assay, and LKB1 RNAi increased it, showing LKB1 destabilizes microtubule assembly in myoblasts. LKB1 levels and activity increased during myoblast differentiation, along with activation of the known LKB1 substrates AMPactivated protein kinase (AMPK) and microtubule affinity regulating kinases (MARKs). LKB1 overexpression accelerated differentiation, whereas RNAi impaired it. Conclusions: Reduced microtubule stability precedes myoblast differentiation and the associated ultimate microtubule stabilization seen in myotubes. LKB1 plays a positive role in microtubule destabilization in myoblasts and in myoblast differentiation. This work suggests a model by which LKB1-induced microtubule destabilization facilitates the cytoskeleta