Milrinone in persistent pulmonary hypertension of newborn: a scoping review.

Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition in newborns admitted to the neonatal intensive care units (NICUs). PPHN has still a high mortality and morbidity. Inhaled nitric oxide (iNO) is the first line vasodilator therapy for PPHN in high income countries. In low-to-middle income countries (LMICs), availability of iNO remains scarce and expensive. The purpose of this scoping review was to evaluate the current existing literature for milrinone therapy in PPHN and to identify the knowledge gaps in milrinone use in infants with PPHN. The available evidence for milrinone remains limited both as monotherapy and as an adjuvant to iNO. The studies were heterogeneous, conducted in different settings, with different populations and more importantly the endpoints of these trials were short-term outcomes such as changes in oxygenation and blood pressure. Large prospective studies investigating long-term outcomes, mortality, and the need for Extracorporeal membrane oxygenation (ECMO) are warranted. Randomized controlled trials with milrinone as monotherapy are needed in LMICs where iNO availability remains limited. IMPACT: Milrinone has a potential role in the management of PPHN both as an adjuvant to iNO as well as a monotherapy. This scoping review identified the problems existing in the published literature on milrinone and the barriers to generalization of these results. Multi-centre randomized controlled trials on milrinone, especially involving centers from low- and middle-income countries are needed, where it can be evaluated as first-line pulmonary vasodilator therapy.

Left heart hypoplasia operated using double pulmonary arterial banding with double arterial duct stenting: A case report.

Hypoplastic left heart syndrome is a heterogeneous group of congenital cardiac malformations which associates hypoplastic/aplastic left ventricle, mitral and aortic valve, hypoplastic/atresia and severe aortic artery coarctation, and represents a medical-surgical emergency. We present a case of a newborn hospitalised in three clinics (two clinics from Timisoara and one from Vienna), and operated for hypoplastic left heart syndrome, without aortic coarctation, using a mixed technique cardiovascular repair surgery. The initial therapeutic conduct included maintaining the permeability of the arterial canal with prostaglandin E1. At the Vienna General Hospital, at the age of 17 days, bilateral banding of the pulmonary artery was performed and, at the age of 20 days, during the cardiac catheterisation, the Rashkind procedure (balloon atrial septostomy) was performed, with two stents being implanted in the arterial canal. Postoperative complications were postcardiotomy syndrome, pneumonia with Enterococcus faecalis and Stenotrophomonas maltophilia, sepsis with methicillin-resistant Staphylococcus aureus, coagulopathy, mixed anaemia, and metabolic acidosis. The patient died 1 month after the intervention due to cardiorespiratory arrest, bilateral congestive heart failure, left heart hypoplasia with shunt through the arterial canal and pulmonary artery banding, multiorgan failure, and severe secondary haemorrhagic disease. In conclusion, the initial cardiac surgical reconstruction consisted of a mixed technique, and anticoagulant medical treatment with heparin, antibiotics (bacterial endocarditis prophylaxis to be performed throughout life); postintervention hypoxic and infectious complications resulted in multiorgan failure and death.

CHARGE syndrome associated with de novo (I1460Rfs*15) frameshift mutation of CHD7 gene in a patient with arteria lusoria and horseshoe kidney.

CHARGE syndrome is an autosomal dominant condition caused by mutations in the chromodomain helicase DNA binding protein 7 (CHD7) gene. The present study reported on the case of a 16-month-old female with plurimalformative syndrome, whose etiology was identified by clinical whole-exome sequencing (WES) analysis. Clinical and follow-up assessments identified multiple craniofacial dysmorphisms, congenital defects and functional symptoms, including dysphagia and Marcus Gunn jaw winking synkinesis. Trio-WES analysis was performed for the patient and their parents and the presence of CHARGE syndrome was further indicated using single-molecule real-time sequencing. A de novo pathogenic variant, c.4379_4380del (p.Ile1460Argfs*15), was identified in exon 19 of the CHD7 gene, which resulted in a premature translational stop signal. Trio-WES analysis was used for further investigation, indicating that neither of the patient's parents had the mutation and confirming its de novo nature. To the best of our knowledge, the case of the present study was the first reported case of CHARGE syndrome in Romania with congenital defects including an aberrant right subclavian artery and a horseshoe kidney. CHARGE syndrome was diagnosed in the patient based on the pathogenic mutation in the CHD7 gene. To the best of our knowledge, the present case report is the first to suggest that the CHD7 gene variant is associated with CHARGE syndrome.