Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Factores pronósticos de mortalidad a 30 días en neumonía por SARS-CoV-2 / Prognostic Factors for 30-day Mortality in SARS-CoV-2 Pneumonia

Introducción: SARS-CoV-2 ha causado millones de muertes a nivel global desde su primer caso reportado en China. En Guatemala existen pocos estudios que describan los factores pronósticos. Nuestro objetivo fue determinar los factores asociados de mortalidad a 30 días en pacientes con neumonía (Nm) por SARS-CoV-2 y construir un modelo predictor. Material y Métodos: Estudio retrospectivo en 144 sujetos en el Hospital Roosevelt de marzo a diciembre 2020 con criterios de Nm por SARS-CoV-2. Se revisó el expediente médico para datos clínicos y de laboratorio desde ingreso hasta alta hospitalaria o muerte. Resultados: Se evaluaron 105 hombres y 39 mujeres con media de edad 53 años. El 47% tenía comorbilidades como diabetes mellitus 2 e hipertensión arterial sistémica. Promedio de días de hospitalización: 13. Cuadros leves a moderados de Síndrome de Distrés Respiratorio Agudo (SDRA): 92%. Se indicó ventilación mecánica invasiva (VMI) a 46 pacientes. La mortalidad general fue 35%. Factores asociados a mortalidad a 30 días: edad ≥50 años, inicio de síntomas ≥7 días, SDRA severo, radio NL >4,4, recibir VMI, alteración en LDH y procalcitonina. Nuestro modelo mostró que los mejores predictores de mortalidad eran alteración en procalcitonina (OR: 4,45), recibir VMI (OR: 112) y días de estancia hospitalaria (OR: 1,12) con precisión de 91,5% y área bajo la curva de 94,4%. Conclusiones: Los factores pronósticos de mortalidad en pacientes guatemaltecos con Nm por SARS-CoV-2 son múltiples e incluyen rasgos demográficos, clínicos y serológicos; identificarlos y contar con un modelo pronóstico ayudará a brindar atención médica de precisión.

Introduction: SARS-CoV-2 has caused millions of deaths globally since its first case was reported in China. In Guatemala, few studies describe prognostic factors. Our objective was to determine the factors associated with 30 day mortality in patients with Pneumonia (Nm) due to SARS-CoV-2 and to build a predictor model. Material and Methods: Retrospective study in 144 subjects at Roosevelt Hospital from March to December 2020 with Nm criteria for SARS-CoV-2. The medical record was rviewed, obtaining clinical and laboratory data from admission to hospital discharge or death. Results: 105 men and 39 women with an average age of 53 years were evaluated. 47% had comorbidities, with type 2 diabetes mellitus and systemic arterial hypertension being common. The average number of days of hospitalization was 13. 92% had mild to moderate acute respiratory distress syndrome (ARDS). Invasive mechanical ventila-tion (IMV) was indicated for 46 patients. Overall mortality was 35%. The factors asso-ciated with 30-day mortality were age ≥50 years, the onset of symptoms ≥7 days, severe ARDS, N/L ratio >4.4, receiving IMV, alterations in LDH, and procalcitonin. Our model showed that the best predictors of mortality were altered procalcitonin (OR: 4.45), receiving IMV (OR: 112), and days of hospital stay (OR: 1.12) with precision of 91.5% and area under the curve of 94.4%. Conclusions: The prognostic factors of mortality in Guatemalan patients with Nm due to SARS-CoV-2 are multiple and include demographic, clinical and serological features; identifying them and having a prognostic model will help provide precision medical care.

Changes in Lung Function Among Infants Born Extremely Preterm over a 20-Year Period in the Post-Surfactant Era: A Retrospective Study.

Lung function was assessed at 8 years in 308 infants born extremely preterm between 1994 and 2013. Although lung function of those infants born at 22 through 25 weeks remained unchanged, those who were born at 26-27 weeks showed a significant improvement over the past 2 decades.

Surfactant administration methods for premature newborns: LISA vs. INSURE comparative analysis.

INTRODUCTION: Respiratory Distress Syndrome (RDS) is the most common respiratory disorder among premature infants. The use of surfactant has significantly reduced respiratory complications and mortality. There are two conventional methods for administering surfactant: Intubate-Surfactant-Extubate (INSURE) and Less Invasive Surfactant Administration (LISA). This study aims to compare the effects of surfactant administration using these two methods on the treatment outcomes of premature newborns. MATERIALS AND METHODS: In this retrospective cohort study, we included 100 premature newborns with RDS and spontaneous breathing who were admitted to the Neonatal Intensive Care Unit of Besat Hospital in Sanandaj city in 2021. Exclusion criteria comprised congenital anomalies and the needing for intubation for resuscitation at birth. The outcomes of epmericaly trated with two methods were compared: the LISA (50 neonates) and the INSURE (50 neonates). Our interesting outcomes were needing for mechanical ventilation, duration of ventilation, pneumothorax, pulmonary hemorrhage, severe retinopathy, CPAP duration, and bronchopulmonary dysplasia. Finally, we entered the data into STATA-14 statistical software and analyzed it using chi-square and t-tests. RESULTS: In this study, 69% of the neonates were boys. The LISA group exhibited significantly lower rates of need for mechanical ventilation (P = 0.003) and ventilation duration (P < 0.001) compared to the INSURE group. Conversely, there were no significant differences between the two groups (P > 0.05) in terms of pneumothorax, pulmonary hemorrhage, severe retinopathy, CPAP duration, and bronchopulmonary dysplasia rates. CONCLUSION: The results of this study suggest that the LISA method is a safe and non-invasive approach for surfactant administration. Notably, it resulted in a reduced need for mechanical ventilation and decreased ventilation duration compared to the INSURE method.

Congenital glottic stenosis as a clinical manifestation of FREM1-associated disorders in a neonate with respiratory distress and aphonia.

A female infant born at 38 weeks and 2 days via induced vaginal delivery was admitted to the neonatal intensive care unit for respiratory distress soon after birth. Noted to have aphonia on examination, the patient underwent direct laryngoscopy and was diagnosed with an anterior glottic web and subglottic stenosis. The patient underwent a genetic workup including whole exome sequencing which resulted in a diagnosis of a FREM1-associated disorder. Congenital glottic webs and subglottic stenoses have not been previously described as clinical manifestations of FREM1-associated disorders.

Comparison of neurally adjusted ventilatory assist and synchronized intermittent mandatory ventilation in preterm infants after patent ductus arteriosus ligation: a retrospective study.

OBJECTIVE: This study aimed to compare the efficacy of neurally adjusted ventilatory assist (NAVA) to synchronized intermittent mandatory ventilation (SIMV) in preterm infants requiring mechanical ventilation after patent ductus arteriosus (PDA) ligation. METHODS: A retrospective analysis was conducted on intubated preterm infants who underwent PDA ligation at our hospital from July 2021 to January 2023. Infants were divided into NAVA or SIMV groups based on the ventilation mode after surgery. RESULTS: Fifty preterm infants were included. During treatment, peak inspiratory pressure (PIP) and mean airway pressure (MAP) were lower with NAVA compared to SIMV (PIP: 19.1 ± 2.9 vs. 22.4 ± 3.6 cmH2O, P < 0.001; MAP: 9.1 ± 1.8 vs. 10.9 ± 2.7 cmH2O, P = 0.002). PaO2 and PaO2/FiO2 were higher with NAVA (PaO2: 94.0 ± 11.7 vs. 84.8 ± 15.8 mmHg, P = 0.031; PaO2/FiO2: 267 [220-322] vs. 232 [186-290] mmHg, P = 0.025). Less sedation was required with NAVA (midazolam: 1.5 ± 0.5 vs. 1.1 ± 0.3 µg/kg/min, P < 0.001). CONCLUSION: Compared to SIMV, early use of NAVA post PDA ligation in preterm infants was associated with decreased PIP and MAP. Early NAVA was also associated with reduced sedation needs and improved oxygenation. However, further studies are warranted to quantify the benefits of NAVA ventilation.

Fungal microbiota in newborn infants with and without respiratory distress syndrome.

BACKGROUND: Pneumocytis jirovecii infection in preterm newborns has recently been associated with neonatal respiratory distress syndrome and bronchopulmonary dysplasia. Changes in the bacterial microbiota of the airways have also been described in infants with bronchopulmonary dysplasia. However, until now there has been no information on the airway mycobiota in newborns. The purpose of this study was to describe the airway mycobiota in term and preterm newborns and its possible association with respiratory distress syndrome. METHODS: Twenty-six matched preterm newborns with and without respiratory distress syndrome were studied, as well as 13 term babies. The identification of the fungal microbiota was carried out using molecular procedures in aspirated nasal samples at birth. RESULTS: The ascomycota phylum was identified in 89.7% of newborns, while the basidiomycota phylum was found in 33.3%. Cladosporium was the predominant genus in both term and preterm infants 38.4% vs. 73% without statistical differences. Candida sake and Pneumocystis jirovecii were only found in preterm infants, suggesting a potential relationship with the risk of prematurity. CONCLUSIONS: This is the first report to describe the fungal microbiota of the airways in term and preterm infants with and without respiratory distress syndrome. Although no differences have been observed, the number of cases analyzed could be small to obtain conclusive results, and more studies are needed to understand the role of the fungal microbiota of the airways in neonatal respiratory pathology.

Non-invasive versus invasive respiratory support in preterm infants.

Respiratory insufficiency is almost ubiquitous in infants born preterm, with its incidence increasing with lower gestational age. A wide range of respiratory support management strategies are available for these infants, separable into non-invasive and invasive forms of respiratory support. Here we review the history and evolution of respiratory care for the preterm infant and then examine evidence that has emerged to support a non-invasive approach to respiratory management where able. Continuous positive airway pressure (CPAP) is the non-invasive respiratory support mode currently with the most evidence for benefit. CPAP can be delivered safely and effectively and can commence in the delivery room. Particularly in early life, time spent on non-invasive respiratory support, avoiding intubation and mechanical ventilation, affords benefit for the preterm infant by virtue of a lessening of lung injury and hence a reduction in incidence of bronchopulmonary dysplasia. In recent years, enthusiasm for application of non-invasive support has been further bolstered by new techniques for administration of exogenous surfactant. Methods of less invasive surfactant delivery, in particular with a thin catheter, have allowed neonatologists to administer surfactant without resort to endotracheal intubation. The benefits of this approach appear to be sustained, even in those infants subsequently requiring mechanical ventilation. This cements the notion that any reduction in exposure to mechanical ventilation leads to alleviation of injury to the vulnerable preterm lung, with a long-lasting effect. Despite the clear advantages of non-invasive respiratory support, there will continue to be a role for intubation and mechanical ventilation in some preterm infants, particularly for those born <25 weeks' gestation. It is currently unclear what role early non-invasive support has in this special population, with more studies required.

The impact of combined administration of surfactant and intratracheal budesonide compared to surfactant alone on bronchopulmonary dysplasia (BPD) and mortality rate in preterm infants with respiratory distress syndrome: a single-blind randomized clinical trial.

BACKGROUND: Respiratory distress syndrome (RDS) is one of the most important and common disorders among premature infants. OBJECTIVE: This study aimed to compare the effect of the combination of surfactant and budesonide with surfactant alone on Bronchopulmonary dysplasia (BPD) and mortality rate among premature infants with RDS. METHOD: An outcome assessor-blind randomized clinical trial was conducted on 134 premature infants with RDS who were born in Ayatollah Mousavi Hospital, Zanjan, Iran in 2021. The covariate adaptive randomization method was utilized to allocate participants into two groups (surfactant alone and a combination of surfactant and budesonide). The primary outcomes were BPD and Mortality rate from admission to hospital discharge. The data in this study were analyzed using SPSS software version 18. RESULTS: Overall the comparison of mortality rate and BPD between the two groups did not show a significant difference(p > 0.05). The subgroup results showed that administering surfactant with budesonide to infants under 30 weeks of age significantly reduced the number of deaths compared to using surfactant alone (5 vs. 17). Similar positive effects were observed for the occurrence of Pulmonary Hemorrhage, the need for a second dose of surfactant, oxygen index, mean blood pressure and mean arterial pressure (MAP) in infants under 34 weeks of age compared to more than 34 weeks (p < 0.05). CONCLUSION: These findings suggest that the combination therapy of surfactant and budesonide may be beneficial, particularly in preterm infants with less than 34 weeks gestational age and 1500 birth weight. However, further studies with larger sample sizes and longer follow-up periods are needed to confirm these results and assess long-term outcomes. TRIAL REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials website under the code IRCT20201222049802N1. https://en.irct.ir/user/trial/48117/view . REGISTRATION DATE: 28/02/2021. PUBLIC REPOSITORY: DATA SET: This research data set link is displayed on the Zanjan-Iran Medical Sciences website: https://repository.zums.ac.ir/cgi/users/login? target=https%3 A%2 F/repository.zums.ac.ir/id/eprint .

Vaginal Progesterone to Prevent Spontaneous Preterm Birth in Women With a Sonographic Short Cervix: The Story of the PREGNANT Trial.

The PREGNANT trial was a randomized, placebo-controlled, multicenter trial designed to determine the efficacy and safety of vaginal progesterone (VP) to reduce the risk of birth < 33 weeks and of neonatal complications in women with a sonographic short cervix (10 to 20 mm) in the mid-trimester (19 to 23 6/7 wk). Patients allocated to receive VP had a 45% lower rate of preterm birth (8.9% vs 16.1%; relative risk = 0.55; 95% CI: 0.33-0.92). Neonates born to mothers allocated to VP had a 60% reduction in the rate of respiratory distress syndrome. This article reviews the background, design, execution, interpretation, and impact of the PREGNANT Trial.

Impacto de la edad, las comorbilidades y las complicaciones en pacientes con COVID-19 con síndrome de dificultad respiratoria aguda en la ventilación mecánica invasiva. Estudio multicéntrico observacional / Impact of Age, Comorbidities and Complications in COVID-19 Patients with Acute Respiratory Distress Syndrome on Invasive Mechanical Ventilation. An Observational Multicenter Study

Objetivos: Millones de pacientes con COVID-19 fueron internados en terapia intensiva en el mundo, la mitad desarrollaron síndrome de dificultad respiratoria aguda (SDRA) y recibieron ventilación mecánica invasiva (VMI), con una mortalidad del 50%. Analiza-mos cómo edad, comorbilidades y complicaciones, en pacientes con COVID-19 y SDRA que recibieron VMI, se asociaron con el riesgo de morir durante su hospitalización.Métodos: Estudio de cohorte observacional, retrospectivo y multicéntrico realizado en 5 hospitales (tres privados y dos públicos universitarios) de Argentina y Chile, durante el segundo semestre de 2020.Se incluyeron pacientes >18 años con infección por SARS-CoV-2 confirmada RT-PCR, que desarrollaron SDRA y fueron asistidos con VMI durante >48 horas, durante el se-gundo semestre de 2020. Se analizaron los antecedentes, las comorbilidades más fre-cuentes (obesidad, diabetes e hipertensión), y las complicaciones shock, insuficiencia renal aguda (IRA) y neumonía asociada a la ventilación mecánica (NAV), por un lado, y las alteraciones de parámetros clínicos y de laboratorio registrados.Resultados: El 69% era varón. La incidencia de comorbilidades difirió para los diferentes grupos de edad. La mortalidad aumentó significativamente con la edad (p<0,00001). Las comorbilidades, hipertensión y diabetes, y las complicaciones de IRA y shock se asociaron significativamente con la mortalidad. En el análisis multivariado, sólo la edad mayor de 60 años, la IRA y el shock permanecieron asociados con la mortalidad. Conclusiones: El SDRA en COVID-19 es más común entre los mayores. Solo la edad >60 años, el shock y la IRA se asociaron a la mortalidad en el análisis multivariado.

Objectives: Millions of patients with COVID-19 were admitted to intensive care world-wide, half developed acute respiratory distress syndrome (ARDS) and received invasive mechanical ventilation (IMV), with a mortality of 50%. We analyzed how age, comor-bidities and complications in patients with COVID-19 and ARDS who received IMV were associated with the risk of dying during their hospitalization.Methods: Observational, retrospective and multicenter cohort study carried out in 5 hospitals (three private and two public university hospitals) in Argentina and Chile, during the second half of 2020.Patients >18 years of age with SARS-CoV-2 infection confirmed by RT-PCR, who devel-oped ARDS and were assisted with IMV for >48 hours, during the second half of 2020, were included. History, the most frequent comorbidities (obesity, diabetes and hyper-tension) and the complications of shock, acute renal failure (AKI) and pneumonia as-sociated with mechanical ventilation (VAP), on the one hand, and the alterations of re-corded clinical and laboratory parameters, were analyzed.Results: 69% were men. The incidence of comorbidities differed for different age groups. Mortality increased significantly with age (p<0.00001). Comorbidities, hyper-tension and diabetes, and complications of ARF and shock were significantly associat-ed with mortality. In the multivariate analysis, only age over 60 years, ARF and shock remained associated with mortality.Conclusions: ARDS in COVID-19 is more common among the elderly. Only age >60 years, shock and ARF were associated with mortality in the multivariate analysis

Descripción de las intervenciones broncoscópicas en estenosis traqueales posterior a infección por COVID-19 / Description of Bronchoscopic Interventions in Post-COVID Tracheal Stenosis

Introducción: La infección por SARS-CoV-2 puede presentar síndrome de distrés res-piratorio agudo con requerimiento de ventilación mecánica prolongada y retraso en la realización de traqueostomía. Esto trae como consecuencia un incremento en casos de estenosis traqueal y la necesidad de métodos menos invasivos para su abordaje. Métodos: Estudio descriptivo de corte transversal, desde marzo 2020 hasta diciem-bre 2021 en el Hospital Universitario Nacional de Colombia, en adultos con estenosis traqueal postintubación asociado SARS-CoV-2. Se realizó análisis univariado entre los grupos con infección o no por SARS-CoV-2 como control, y reintervención, grado de estenosis, uso de inyección intramucosa con dexametasona intratraqueal o múltiples estenosis como desenlaces de importancia. Se usó test exacto de Fisher, t Student y Man-Whitney según la naturaleza de variables. Se consideró p estadísticamente significativo menor a 0.05.Resultados: Se identificaron 26 pacientes, 20 tenían COVID-19 y 6 no. Se encontraron diferencias en edad (p=0,002), epilepsia (p=0,007) y estenosis múltiple (p= 0,04). En 85% de los casos se utilizó láser blue más dilatación con balón pulmonar, en 35% inyección intramucosa con dexametasona intratraqueal y reintervención en 35%, sin diferencias significativas entre grupos. Conclusiones: Se observó un incremento tres veces mayor de pacientes con estenosis múltiple en el grupo de infección por COVID-19, así mismo se encontró que el método más utilizado en este grupo para la recanalización fue el uso de láser blue más dilatación con balón pulmonar y la innovación en el uso de inyección intramucosa.

Introduction: SARS-CoV-2 infection can lead to acute respiratory distress syndrome with a prolonged need for mechanical ventilation and delayed tracheostomy, resulting in an increase in cases of tracheal stenosis and the necessity for less invasive approaches.Methods: A descriptive cross-sectional study was conducted from March 2020 to December 2021 at the Hospital Universitario Nacional de Colombia, focusing on adults with post-intubation tracheal stenosis associated with SARS-CoV-2. Univariate analysis was performed between groups with or without SARS-CoV-2 infection as a control, considering reintervention, degree of stenosis, use of intratracheal steroids, or multiple stenoses as important outcomes. Fisher's exact test, Student's t-test, and Mann-Whit-ney test were employed based on the nature of variables. A p-value less than 0.05 was considered statistically significant.Results: A total of 26 patients were included, with 20 having COVID-19 and 6 without. Significant differences were found in age (p=0.002), epilepsy (p=0.007), and multiple stenosis (p=0.04). In 85% of cases, laser blue plus balloon pulmonary dilation was used, intratracheal dexamethasone in 35%, and reintervention in 35%, with no significant differences between groups.Conclusions: A threefold increase in subglottic stenosis was observed during the SARS-CoV-2 pandemic, with more instances of multiple stenosis and predominantly the use of laser blue plus balloon pulmonary dilation as a successful recanalization technique. There was a higher use of intratracheal dexamethasone in this group compared to oth-er pathologies causing tracheal stenosis.

Mechanical ventilation in special populations.

Optimal respiratory support can only be achieved if the ventilator strategy utilized for each individual patient at any given point in the evolution of their disease process is tailored to the underlying pathophysiology. The critically ill newborn infant requires individualized patient care when it comes to mechanical ventilation. This can only occur if the clinician has a good understanding of the different pathophysiologies of a variety of conditions that can lead to respiratory failure. In this chapter we describe the key pathophysiological features of bronchopulmonary dysplasia, meconium aspiration syndrome and lung hypoplasia syndromes with emphasis on congenital diaphragmatic hernia. We review available evidence to guide management an provide specific recommendations for pathophysiologically-based mechanical ventilation support.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants.

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

Measurement of lung oxygenation by near-infrared spectroscopy in preterm infants with bronchopulmonary dysplasia.

INTRODUCTION: It has recently been reported that it is possible to monitor lung oxygenation (rSO2L) by near-infrared spectroscopy (NIRS) in preterm infants with respiratory distress syndrome (RDS). Thus, our aim was to assess the possibility of monitoring rSO2L in infants with evolving and established bronchopulmonary dysplasia (BPD) and to evaluate if rSO2L correlates with BPD severity and other oxygenation indices. METHODS: We studied 40 preterm infants with gestational age ≤30 weeks at risk for BPD. Patients were continuously studied for 2 h by NIRS at 28 ± 7 days of life and 36 weeks ± 7 days of postmenstrual age. RESULTS: rSO2L was similar at the first and second NIRS recordings (71.8 ± 7.2 vs. 71.4 ± 4.2%) in the overall population, but it was higher in infants with mild than in those with moderate-to-severe BPD at both the first (73.3 ± 3.1 vs. 71.2 ± 3.2%, p = .042) and second (72.3 ± 2.8 vs. 70.5 ± 2.8, p = .049) NIRS recording. A rSO2L cutoff value of 71.6% in the first recording was associated with a risk for moderate-to-severe BPD with a sensitivity of 66% and a specificity of 60%. Linear regression analysis demonstrated a significant positive relationship between rSO2L and SpO2/FiO2 ratio (p = .013) and a/APO2 (p = .004). CONCLUSIONS: Monitoring of rSO2L by NIRS in preterm infants with evolving and established BPD is feasible and safe. rSO2L was found to be higher in infants with mild BPD, and predicts the risk for developing moderate-to-severe BPD and correlates with other indices of oxygenation.

The contribution and therapeutic implications of IGHMBP2 mutations on IGHMBP2 biochemical activity and ABT1 association.

Mutations within immunoglobulin mu DNA binding protein (IGHMBP2), an RNA-DNA helicase, result in SMA with respiratory distress type I (SMARD1) and Charcot Marie Tooth type 2S (CMT2S). The underlying biochemical mechanism of IGHMBP2 is unknown as well as the functional significance of IGHMBP2 mutations in disease severity. Here we report the biochemical mechanisms of IGHMBP2 disease-causing mutations D565N and H924Y, and their potential impact on therapeutic strategies. The IGHMBP2-D565N mutation has been identified in SMARD1 patients, while the IGHMBP2-H924Y mutation has been identified in CMT2S patients. For the first time, we demonstrate a correlation between the altered IGHMBP2 biochemical activity associated with the D565N and H924Y mutations and disease severity and pathology in patients and our Ighmbp2 mouse models. We show that IGHMBP2 mutations that alter the association with activator of basal transcription (ABT1) impact the ATPase and helicase activities of IGHMBP2 and the association with the 47S pre-rRNA 5' external transcribed spacer. We demonstrate that the D565N mutation impairs IGHMBP2 ATPase and helicase activities consistent with disease pathology. The H924Y mutation alters IGHMBP2 activity to a lesser extent while maintaining association with ABT1. In the context of the compound heterozygous patient, we demonstrate that the total biochemical activity associated with IGHMBP2-D565N and IGHMBP2-H924Y proteins is improved over IGHMBP2-D565N alone. Importantly, we demonstrate that the efficacy of therapeutic applications may vary based on the underlying IGHMBP2 mutations and the relative biochemical activity of the mutant IGHMBP2 protein.

Laryngeal mask airway surfactant administration for prevention of morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome.

BACKGROUND: Laryngeal mask airway surfactant administration (S-LMA) has the potential benefit of surfactant administration whilst avoiding endotracheal intubation and ventilation, ventilator-induced lung injury and bronchopulmonary dysplasia (BPD). OBJECTIVES: To evaluate the benefits and harms of S-LMA either as prophylaxis or treatment (rescue) compared to placebo, no treatment, or intratracheal surfactant administration via an endotracheal tube (ETT) with the intent to rapidly extubate (InSurE) or extubate at standard criteria (S-ETT) or via other less-invasive surfactant administration (LISA) methods on morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome (RDS). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and three trial registries in December 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster- or quasi-RCTs of S-LMA compared to placebo, no treatment, or other routes of administration (nebulised, pharyngeal instillation of surfactant before the first breath, thin endotracheal catheter surfactant administration or intratracheal surfactant instillation) on morbidity and mortality in preterm infants at risk of RDS. We considered published, unpublished and ongoing trials. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included eight trials (seven new to this update) recruiting 510 newborns. Five trials (333 infants) compared S-LMA with surfactant administration via ETT with InSurE. One trial (48 infants) compared S-LMA with surfactant administration via ETT with S-ETT, and two trials (129 infants) compared S-LMA with no surfactant administration. We found no studies comparing S-LMA with LISA techniques or prophylactic or early S-LMA. S-LMA versus surfactant administration via InSurE S-LMA may have little or no effect on the composite outcome of death or BPD at 36 weeks' postmenstrual age (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.27 to 8.34, I 2 = not applicable (NA) as 1 study had 0 events; risk difference (RD) 0.02, 95% CI -0.07 to 0.10; I 2 = 0%; 2 studies, 110 infants; low-certainty evidence). There may be a reduction in the need for mechanical ventilation at any time (RR 0.53, 95% CI 0.36 to 0.78; I 2 = 27%; RD -0.14, 95% CI -0.22 to -0.06, I 2 = 89%; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 5 to 17; 5 studies, 333 infants; low-certainty evidence). However, this was limited to four studies (236 infants) using analgesia or sedation for the InSurE group. There was little or no difference for air leak during first hospitalisation (RR 1.39, 95% CI 0.65 to 2.98; I 2 = 0%; 5 studies, 333 infants (based on 3 studies as 2 studies had 0 events); low-certainty evidence); BPD among survivors to 36 weeks' PMA (RR 1.28, 95% CI 0.47 to 3.52; I 2 = 0%; 4 studies, 264 infants (based on 3 studies as 1 study had 0 events); low-certainty evidence); or death (all causes) during the first hospitalisation (RR 0.28, 95% CI 0.01 to 6.60; I 2 = NA as 2 studies had 0 events; 3 studies, 203 infants; low-certainty evidence). Neurosensory disability was not reported. Intraventricular haemorrhage ( IVH) grades III and IV were reported among the study groups (1 study, 50 infants). S-LMA versus surfactant administration via S-ETT No study reported death or BPD at 36 weeks' PMA. S-LMA may reduce the use of mechanical ventilation at any time compared with S-ETT (RR 0.47, 95% CI 0.31 to 0.71; RD -0.54, 95% CI -0.74 to -0.34; NNTB 2, 95% CI 2 to 3; 1 study, 48 infants; low-certainty evidence). We are very uncertain whether S-LMA compared with S-ETT reduces air leak during first hospitalisation (RR 2.56, 95% CI 0.11 to 59.75), IVH grade III or IV (RR 2.56, 95% CI 0.11 to 59.75) and death (all causes) during the first hospitalisation (RR 0.17, 95% CI 0.01 to 3.37) (1 study, 48 infants; very low-certainty evidence). No study reported BPD to 36 weeks' PMA or neurosensory disability. S-LMA versus no surfactant administration Rescue surfactant could be used in both groups. There may be little or no difference in death or BPD at 36 weeks (RR 1.65, 95% CI 0.85 to 3.22; I 2 = 58%; RD 0.08, 95% CI -0.03 to 0.19; I 2 = 0%; 2 studies, 129 infants; low-certainty evidence). There was probably a reduction in the need for mechanical ventilation at any time with S-LMA compared with nasal continuous positive airway pressure without surfactant (RR 0.57, 95% CI 0.38 to 0.85; I 2 = 0%; RD -0.24, 95% CI -0.40 to -0.08; I 2 = 0%; NNTB 4, 95% CI 3 to 13; 2 studies, 129 infants; moderate-certainty evidence). There was little or no difference in air leak during first hospitalisation (RR 0.65, 95% CI 0.23 to 1.88; I 2 = 0%; 2 studies, 129 infants; low-certainty evidence) or BPD to 36 weeks' PMA (RR 1.65, 95% CI 0.85 to 3.22; I 2 = 58%; 2 studies, 129 infants; low-certainty evidence). There were no events in either group for death during the first hospitalisation (1 study, 103 infants) or IVH grade III and IV (1 study, 103 infants). No study reported neurosensory disability. AUTHORS' CONCLUSIONS: In preterm infants less than 36 weeks' PMA, rescue S-LMA may have little or no effect on the composite outcome of death or BPD at 36 weeks' PMA. However, it may reduce the need for mechanical ventilation at any time. This benefit is limited to trials reporting the use of analgesia or sedation in the InSurE and S-ETT groups. There is low- to very-low certainty evidence for no or little difference in neonatal morbidities and mortality. Long-term outcomes are largely unreported. In preterm infants less than 32 weeks' PMA or less than 1500 g, there are insufficient data to support or refute the use of S-LMA in clinical practice. Adequately powered trials are required to determine the effect of S-LMA for prevention or early treatment of RDS in extremely preterm infants. S-LMA use should be limited to clinical trials in this group of infants.

[Establishment and efficiency test of a clinical prediction model of bronchopulmonary dysplasia associated pulmonary hypertension in very premature infants].

Objective: To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants. Methods: This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1st, 2015 to December 31st, 2021 of the Seventh Medical Center of the People's Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children's Hospital from January 1 st, 2020 to December 31st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks' corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model's discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results: A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95%CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions: A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

Heated and humidified high flow therapy (HHHFT) in extreme and very preterm neonates with respiratory distress syndrome (RDS): a retrospective cohort from a tertiary care setting in Pakistan.

OBJECTIVE: To determine the role of heated humidified high flow therapy (HHHFT) as primary respiratory support in spontaneously breathing moderate-late, very and extreme preterm neonates with respiratory distress syndrome (RDS) at a tertiary care hospital from a developing country. DESIGN: Retrospective cohort study. SETTING: Neonatal intensive care unit of Indus Hospital and Health Network, Karachi, Pakistan. PATIENTS: All preterm neonates with RDS and who received HHHFT as primary respiratory support were included retrospectively, while neonates with orofacial anomalies, congenital heart and lung diseases other than RDS, abdominal wall defects, encephalopathy, congenital pneumonia and received continuous positive airway pressure or invasive ventilation were excluded. INTERVENTIONS: HHHFT as primary respiratory support for RDS. MAIN OUTCOME MEASURES: Effectiveness, duration, failure rate and complications of HHHFT as a primary respiratory support in moderate-late, very and extremely preterm neonates were evaluated. RESULTS: The cohort included 138 neonates during a period of 12 months. The median gestational age was 32 weeks, and the median birth weight was 1607 g. Grade 1-2 RDS was seen in 97%, surfactant instillation was done in 10.8% and HHHFT was provided in all the neonates as primary respiratory support. The total duration of HHHFT support was <1 week in 94% of neonates. Bronchopulmonary dysplasia and pneumothorax until discharge or death were observed in one neonate, haemodynamically significant Patent Ductus Artriosus (HsPDA) in two neonates and intraventricular haemorrhage Grade ≥2 in five neonates, while only one neonate died. CONCLUSION: This study appears to show that HHHFT is a simple, safe, efficient and cheap mode of primary respiratory support that can be given to spontaneously breathing moderate-late, very and extremely preterm neonates with RDS, especially in low- or middle-income countries.