Severe Lymphatic Disorder and Multifocal Atrial Tachycardia Treated with Trametinib in a Patient with Noonan Syndrome and SOS1 Mutation.

Noonan syndrome (NS) is a multisystemic disorder caused by germline mutations in the Ras/MAPK cascade, causing a broad spectrum of phenotypical abnormalities, including abnormal facies, developmental delay, bleeding diathesis, congenital heart disease (mainly pulmonary stenosis and hypertrophic cardiomyopathy), lymphatic disorders, and uro-genital abnormalities. Multifocal atrial tachycardia has been associated with NS, where it may occur independently of hypertrophic cardiomyopathy. Trametinib, a highly selective MEK1/2 inhibitor currently approved for the treatment of cancer, has been shown to reverse left ventricular hypertrophy in two RIT1-mutated newborns with NS and severe hypertrophic cardiomyopathy. Severe lymphatic abnormalities may contribute to decreased pulmonary compliance in NS, and pulmonary lymphangiectasias should be included in the differential diagnosis of a newborn requiring prolonged oxygen administration. Herein we report the case of a pre-term newborn who was admitted to our unit for the occurrence of severe respiratory distress and subentrant MAT treated with trametinib.

Reducing post-extubation failure rates in very preterm infants: is BiPAP better than CPAP?

BACKGROUND AND AIM: Continuous positive airway pressure (CPAP) is currently used in neonates after mechanical ventilation though it may occasionally be associated with air leaks syndromes or it may fail to support the baby. The pressure difference offered by bilevel continuous positive distending pressure (BiPAP) respect to CPAP may be an advantage to the spontaneously breathing patient. In this study, we compared the efficacy of CPAP and BiPAP in the firstweek post-extubation in a series of very preterm infants. METHODS: Inborn neonates less than 30 weeks of gestational age who were intubated shortly after birth from January 2011 to December 2017 were enrolled in a retrospective study. The attending clinician assessed the patients for non-invasive respiratory support readiness and allocated them to CPAP (PEEP 4-6 cmH2O) or BiPAP (PEEP 4-5 cmH2O, rate 10-40; Thigh 0.7-1.2; upper-pressure level 8-10 cmH2O). Both techniques were compared for preventing extubation failure within 7 days from extubation as defined per local protocol (primary outcome). Secondary outcomes were: definitive failure of extubation, pneumothorax during non-invasive respiratory support, periventricular leukomalacia, bronchopulmonary dysplasia, sepsis, patent ductus arteriosus and retinopathy of prematurity at discharge. RESULTS: We enrolled 134 neonates; the CPAP group included 89 babies while 45 received BiPAP. Patients did not differ for their general characteristics (EG, antenatal steroids, incidence of SGA, maternal hypertension, surfactant replacement therapy). Short term extubation failure was significantly higher in the former group (23/89 in CPAP vs 5/45 in BiPAP; p = .005). No infant developed air leak syndrome. Secondary outcomes were comparable between groups. Multivariate analysis showed that on the whole population the extubation failure was correlated to the insurgence of late-onset sepsis. CONCLUSION: BiPAP safely reduced early extubation failure compared to CPAP in our cohort of very preterm neonates within 7 days from extubation.

Are IgM-enriched immunoglobulins an effective adjuvant in septic VLBW infants?

AIM: To investigate the effectiveness of IgM-enriched immunoglobulins (IgM-eIVIG) in reducing short-term mortality of neonates with proven late-onset sepsis. METHODS: All VLBW infants from January 2008 to December 2012 with positive blood culture beyond 72 hours of life were enrolled in a retrospective cohort study. Newborns born after June 2010 were treated with IgM-eIVIG, 250 mg/kg/day iv for three days in addition to standard antibiotic regimen and compared to an historical cohort born before June 2010, receiving antimicrobial regimen alone. Short-term mortality (i.e. death within 7 and 21 days from treatment) was the primary outcome. Secondary outcomes were: total mortality, intraventricular hemorrhage, necrotizing enterocolitis, periventricular leukomalacia, bronchopulmonary dysplasia at discharge. RESULTS: 79 neonates (40 cases) were enrolled. No difference in birth weight, gestational age or SNAP II score (disease severity score) were found. Significantly reduced short-term mortality was found in treated infants (22% vs 46%; p = 0.005) considering all microbial aetiologies and the subgroup affected by Candida spp. Secondary outcomes were not different between groups. CONCLUSION: This hypothesis-generator study shows that IgM-eIVIG is an effective adjuvant therapy in VLBW infants with proven sepsis. Randomized controlled trials are warranted to confirm this pilot observation.