Low-plasma adiponectin and high leptin and resistin level are present at the ALL diagnosis. Adipocytokines alterations are progressively restored during therapy.

Mesenchymal stem cell (MSC) extracellular vesicles (EVs) have beneficial effects in preclinical bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) models. The optimal source, dosing, route, and duration of effects are however unknown. The objectives of this study were to (a) compare the efficacy of GMP-grade EVs obtained from Wharton’s Jelly MSCs (WJ-MSCs) and bone marrow (BM-MSCs), (b) determine the optimal dosing and route of administration, (c) evaluate its long-term effects, and (d) determine how MSC EVs alter the lung transcriptome. Newborn rats exposed to normoxia or hyperoxia (85% O2) from postnatal day (P)1-P14 were given (a) intra-tracheal (IT) BM or WJ-MSC EVs or placebo, (b) varying doses of IT WJ-MSC EVs, or (c) IT or intravenous (IV) WJ-MSC EVs on P3. Rats were evaluated at P14 or 3 months. Early administration of IT BM-MSC or WJ-MSC EVs had similar beneficial effects on lung structure and PH in hyperoxia-exposed rats. WJ-MSC EVs however had superior effects on cardiac remodeling. Low, medium, and high dose WJ-MSC EVs had similar cardiopulmonary regenerative effects. IT and IV WJ-MSC EVs similarly improved vascular density and reduced PH in hyperoxic rats. Gene-set enrichment analysis of transcripts differentially expressed in WJ-MSC EV-treated rats showed that induced transcripts were associated with angiogenesis. Long-term studies demonstrated that a single early MSC EV dose has pulmonary vascular protective effects 3 months after administration. Together, our findings have significant translational implications as it provides critical insight into the optimal source, dosing, route, mechanisms of action, and duration of effects of MSC-EVs for BPD-PH.

preterm infants with bronchopulmonary dysplasia (BpD) and pulmonary hypertension (pH) have accelerated lung aging and poor long-term outcomes. Klotho is an antiaging protein that modulates oxidative stress, angiogenesis and fibrosis. Here we test the hypothesis that decreased cord Klotho levels in preterm infants predict increased BpD-pH risk and early Klotho supplementation prevents BPD-like phenotype and PH in rodents exposed to neonatal hyperoxia. In experiment 1, Klotho levels were measured in cord blood of preterm infants who were enrolled in a longitudinal cohort study. in experiment 2, using an experimental BPD-PH model, rat pups exposed to room air or hyperoxia (85% o 2) were randomly assigned to receive every other day injections of recombinant Klotho or placebo. The effect of Klotho on lung structure, PH and cardiac function was assessed. As compared to controls, preterm infants with BpD or BpD-pH had decreased cord Klotho levels. early Klotho supplementation in neonatal hyperoxia-exposed rodents preserved lung alveolar and vascular structure, attenuated PH, reduced pulmonary vascular remodeling and improved cardiac function. Together, these findings have important implications as they suggest that perinatal Klotho deficiency contributes to BPD-PH risk and strategies that preserve Klotho levels, may improve long-term cardiopulmonary outcomes in preterm infants. Bronchopulmonary dysplasia (BPD) is a multi-factorial disease which affects premature infants 1. It is characterized by alterations in lung development, vascular remodeling and lung dysfunction that range the spectrum of mild to severe and even fatal disease. Preterm infants with BPD often grow poorly 2 and in the most severe cases develop pulmonary hypertension (PH) 3 , and myocardial dysfunction 4,5. According to data from the National Institute of Child Health and Human Development, during the years 2003 to 2007, the incidence of BPD in infants less than 29 weeks gestational age was 42% 6 with an increasing trend over the past 10 years 7. Not only does BPD increase infant mortality but survivors have cardiopulmonary dysfunction extending long into adulthood 8. Various prenatal and postnatal factors contribute to the development of BPD and its sequelae. Infants with placental vascular malperfusion are at an increased risk for BPD and PH 9 while hyperoxia 10 , infection 11 and poor

Retention of a CVC was associated with an increased risk of death after adjusting for age and complexity of care at candidemia onset. Although there is likely persistence of unmeasured confounding, given the strong association between catheter retention and death, our data suggest that early CVC removal should be strongly considered.