PRIM1 deficiency causes a distinctive primordial dwarfism syndrome.

DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated in human disease, and here we report PRIM1 encoding the catalytic subunit of DNA primase as a novel disease gene. Using a variant classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased interorigin distances, replication stress, and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients' extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation.

[Trends in the management of respiratory distress syndrome in very preterm infants transferred to the Clinical Center of the University of Debrecen]. / A respirációs distressz szindróma kezelésének trendjei a Debreceni Egyetem Klinikai Központjába szállított igen éretlen koraszülöttekben.

INTRODUCTION: Although in utero transport is recommended in the case of threatening preterm delivery, it is not always possible. Management during postnatal transport may influence neonatal outcomes. OBJECTIVE: The aim of this study was to investigate the trends in patient characteristics, respiratory management and outcomes in very preterm infants requiring postnatal transfer between 2008 and 2021. METHOD: We conducted a retrospective study. Data were collected from both written and electronic medical records. Trends were assessed using joinpoint regression analysis and summarized as annual percentage changes (APC). RESULTS: A total of 177 infants were included. The number of transfers per year showed non-significant increase over time (APC = 6.8%, p = 0.087). The proportion of time above 60 minutes for care provided by the transport team at the referral site significantly increased (APC = 7.4%, p = 0.016). Between 2008 and 2010, the use of mechanical ventilation during transports increased (APC = 36.4%, p = 0.578), then it showed a decreasing trend during the rest of the study period (APC = -7.2%, p = 0.068). The use of oxygen concentrations above 40% significantly decreased (APC = -9.5%, p = 0.043). The proportion of surfactant doses less than 150 mg/kg showed a decreasing trend (APC = -7.65%, p = 0.162), while doses above 180 mg/kg significantly increased over time (APC = 8.5%, p = 0.031). Neonatal long-term outcome indicators showed improving trends. DISCUSSION: We observed relevant trends toward non-invasive approaches and improving outcomes. CONCLUSION: Our study can facilitate the ongoing change of approach to care during postnatal transport, promote the development of relevant protocols and guidelines, which together can improve the outcome of preterm infants born outside tertiary care centers. Orv Hetil. 2023; 164(15): 571-576.

Comparison of flexible nasogastric tube and semi-rigid catheter during less invasive surfactant administration.

BACKGROUND: Various flexible and semi-rigid catheter techniques have been reported for surfactant delivery during less invasive surfactant administration (LISA) in preterm infants. Data on the effect of catheter selection on procedural success rates and adverse events are limited. Our objective was to compare the rates of success and adverse events of LISA performed with nasogastric tube and semi-rigid catheter. METHODS: This was a post-hoc analysis of data from a quality improvement project. LISA was performed according to the standardized local protocol. Baseline characteristics, data on performance of LISA, degree of difficulty in laryngoscopy and vital parameters after the initiation of LISA were collected and outcomes were compared between groups. RESULTS: Fifty-six infants were included (21 with nasogastric tube, and 35 with semi-rigid catheter). Procedure success rate (defined as a single LISA attempt resulting in intratracheal administration of the planned dose of surfactant), incidence of adverse events, heart rate and oxygen saturation values and outcomes did not differ significantly between the two groups. When using a nasogastric tube for LISA, a significantly higher fraction of inspired oxygen was needed in the 3rd (0.62 vs. 0.48, P=0.024), 4th (0.61 vs. 0.37, P<0.001) and 5th minute (0.48 vs. 0.37, P=0.001) to maintain normal oxygen saturations. CONCLUSIONS: Use of the semi-rigid catheter was associated with better oxygenation during and shortly after the procedure. Our results may help neonatal units to develop local guidelines.

Incidence, predictors of success and outcome of LISA in very preterm infants.

OBJECTIVES: The aim of this study was to examine the success rate of less invasive surfactant administration (LISA), to identify early predictive factors for the outcome of LISA, and to compare neonatal outcomes between the LISA failure group and the group of infants who were successfully treated with LISA. DESIGN: A retrospective cohort study. PATIENTS: Infants born at less than 33 weeks of gestation (n = 158) and treated with LISA for respiratory distress syndrome. RESULTS: LISA was successful in 86 cases (54.4%); 72 preterm infants (45.6%) needed additional surfactant therapy and/or mechanical ventilation in the first 72 h (LISA failure). In a multivariate logistic regression analysis, six independent predictors of LISA success were identified: core temperature at the time of admission (adjusted odds ratio (OR): 3.56), dose of poractant alfa (<200 mg/kg; adjusted OR: 0.254), elevated C-reactive protein (>10 mg/L) at 24 h of life (adjusted OR: 0.28), highest respiratory severity score (RSS) during the first hour of life or at the time of LISA (adjusted OR: 0.463), maternal age (adjusted OR: 0.923), and birth weight (adjusted OR: 1.003). The receiver operating curve created by using the identified factors indicates good predictive power with an area under the curve of 0.85. LISA failure was associated with a substantially higher risk of complications. CONCLUSION: LISA success can be predicted by variables available before the intervention. Failure of LISA is relatively frequent event in very preterm infants and is associated with adverse outcomes. Prevention of hypothermia during early stabilization and appropriate dosing of surfactant may increase LISA success rates and improve patient outcome.