Less invasive surfactant administration versus intubation-surfactant-extubation in the treatment of neonatal respiratory distress syndrome: a systematic review and meta-analyses

Abstract Objectives To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax, bronchopulmonary dysplasia (BPD), need for mechanical ventilation (MV), regional cerebral oxygen saturation (rSO2), peri‑intraventricular hemorrhage (PIVH) and mortality. Methods A systematic search in PubMed, Embase, Lilacs, CINAHL, SciELO databases, Brazilian Registry of Randomized Clinical Trials (ReBEC), Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. RCTs evaluating the effects of the LISA technique versus INSURE in preterm infants with gestational age < 36 weeks and that had as outcomes evaluation of the rates of pneumothorax, BPD, need for MV, rSO2, PIVH, and mortality were included in the meta-analysis. Random effects and hazard ratio models were used to combine all study results. Inter-study heterogeneity was assessed using Cochrane Q statistics and Higgin's I2 statistics. Results Sixteen RCTs published between 2012 and 2020 met the inclusion criteria, a total of 1,944 preterms. Eleven studies showed a shorter duration of MV and CPAP in the LISA group than in INSURE group. Two studies evaluated rSO2 and suggested that LISA and INSURE transiently affect brain autoregulation during surfactant administration. INSURE group had a higher risk for MV in the first 72 h of life, pneumothorax, PIVH and mortality in comparison to the LISA group. Conclusion This systematic review and meta-analyses provided evidence for the benefits of the LISA technique in the treatment of RDS, decreasing CPAP time, need for MV, BPD, pneumothorax, PIVH, and mortality when compared to INSURE.

Molecular docking and cytotoxicity interactions of naringenin and its nano-structured lipid carriers in ER? positive breast cancer

Phytoestrogens are known to have beneficial properties in various carcinomas. They exhibit its efficacy at cellular levels. Naringenin a flavonoidal phytoestrogen is been explored for its antioxidant, cardio protective and cytotoxic function. The low absorbtion and poor bioavailability of naringenin makes it less efficient in targeting tumours at cellular levels. Due to the structural similarity of naringenin with estradiol and considering the affinity of naringenin with estrogen receptor, this study explores the interactions of naringenin on important signaling proteins involved in ER positive breast cancer through molecular docking studies and the prepared naringenin solid lipid nano particles were characterized and studied for its preventive potential against breast cancer cell lines. The lipidoid form of phytoestrogen shows promising cytotoxic potential compared with naringenin.

The effects of quality improvement program on the incidence of bronchopulmonary dysplasia in very preterm infants / 中国新生儿科杂志

Objective:To evaluate the effects of quality improvement (QI) program on the incidence of bronchopulmonary dysplasia (BPD) in very preterm infants (VPIs) [gestational age (GA)<32 weeks].Methods:From July to December 2017,VPIs admitted to the Department of Neonatology of Yancheng Maternity and Child Health Care Hospital were retrospectively enrolled and were assigned into pre-quality improvement program group (Pre-QI group).From July to December 2018, VPIs were assigned into post-quality improvement program group (Post-QI group). QI program included delayed umbilical cord clamping (DCC), early postnatal nasal continuous positive airway pressure ventilation (nCPAP) and minimally invasive pulmonary surfactant therapy (MIST). The clinical data and prognostic indicators of the two groups of VPIs and their mothers were compared. Independent sample t-test or continuity-adjusted Chi-square test (or Fisher's exact test) and Logistic regression were used for statistical analysis. Results:A total of 204 VPIs were enrolled, including 96 cases in Pre-QI group and 108 cases in Post-QI group. 1 min Apgar score and hematocrit on admission to the neonatal intensive care unit (NICU) in the Post-QI group were significantly higher than the Pre-QI group( P<0.05). The incidence of delivery room resuscitation, endotracheal intubation at birth and endotracheal intubation in NICU in the Post-QI group were significantly lower than the Pre-QI group( P<0.05). The application of pulmonary surfactant and mechanical ventilation, the incidence of neonatal respiratory distress syndrome and BPD in the Post-QI group were lower than the Pre-QI group ( P<0.05). After adjusting for confounding factors, Logistic regression analysis showed that DCC ( aOR=0.261,95% CI 0.091~0.718, P=0.023), nCPAP ( aOR=0.284,95% CI 0.123~0.667, P=0.015), MIST ( aOR=0.276,95% CI 0.114~0.627, P=0.011) were protective factors of BPD, and MV ( aOR=2.023,95% CI 1.048~3.918, P=0.036) was risk factor of BPD. Conclusions:The QI program consisting of DCC, early nCPAP and MIST for VPIs can reduce the incidence of BPD.

Dynamic changes and clinical value of serum angiopoietin-2 and surfactant protein D in pediatric acute respiratory distress syndrome / 中国小儿急救医学

Objective:To study the relationship between the dynamic changes of angiopoietin-2 (Ang-2) and surfactant protein D (SP-D) in pediatric acute respiratory distress syndrome (pARDS) and the severity and prognosis of the disease.Methods:Using nested case-control study method, 80 children with pneumonia complicated with pARDS admitted to PICU at Fujian Maternal and Child Health Hospital from June 2018 to May 2021 were selected as pARDS group, and 19 healthy children with corresponding age were selected as control group.According to the oxygenation, the children in pARDS group were divided into three subgroups: mild group (23 cases), moderate group (32 cases) and severe group (25 cases). According to the prognosis at discharge, the children in pARDS group were divided into survival group (67 cases) and death group (13 cases). Ang-2 and SP-D were detected by enzyme-linked immunosorbent assay.The levels of Ang-2 and SP-D in children with pARDS of different severity on the first day were compared; The changes of Ang-2 and SP-D levels on the 1st, 3rd and 8th day of children in survival group and death group were compared, and the receiver operating characteristic (ROC) curve was plotted to compare the predictive value of Ang-2 and SP-D for pARDS prognosis.Results:(1) The levels of Ang-2 and SP-D on the first day in pARDS group were significantly higher than those in control group( P<0.001). (2) The levels of Ang-2 and SP-D on the first day in children with pARDS of different severity levels were significantly different ( P<0.001), and the levels of Ang-2 and SP-D increased gradually with the increase of disease severity.(3) The levels of Ang-2 and SP-D in death group were significantly higher than those in survival group on the 1st, 3rd and 8th day ( P<0.05). (4) Prognostic efficacy of Ang-2 and SP-D levels in pARDS group at different time points: when the areas under the ROC curve predicted by Ang-2 on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.808, 0.981 and 0.989, respectively; the optimal cut-off values were 6 000 pg/mL, 6 971 pg/mL and 4 171 pg/mL, respectively; the sensitivity was 84.6%, 92.3% and 92.3%, respectively; and the specificity was 76.1%, 97.0% and 98.5%, respectively.The areas under the ROC curve predicted by SP-D on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.689, 0.993 and 0.983, respectively; the optimal cut-off values were 13544 pg/mL, 16003 pg/mL and 12294 pg/mL, respectively; the sensitivity was 84.6%, 100.0% and 100.0%, respectively; and the specificity was 46.3%, 98.5% and 97.0%, respectively. Conclusion:Serum Ang-2 and SP-D levels in children with pARDS increase with the aggravation of the disease.The dynamic changes of Ang-2 and SP-D in children with pARDS with different prognosis are different during the course of disease, and monitoring serum Ang-2 and SP-D during the course of disease has a certain predictive value for clinical outcome.

Meta-analysis of efficacy and safety of early intratracheal instillation budesonide combined with pulmonary surfactant in the prevention of bronchopulmonary dysplasia / 中国小儿急救医学

Objective:To evaluate the efficacy and safety of early intratracheal drops of budesonide combined with pulmonary surfactant in the prevention of bronchopulmonary dysplasia(BPD).Methods:Embase, PubMed, Cochrane Library, CNKI and Wanfang database were searched from the establishment of library construction to February 2022.Literature selection, quality assessment and data extraction were conducted according to the inclusion and exclusion criteria, and Meta-analysis was performed on the included literature using Rev Man 5.3 software.Results:Nine randomised controlled studies were included in this study, with a total of 884 children, including 433 in the experimental group and 451 in the control group.The results showed that there was a statistically significant difference in the incidence of BPD between the two groups[ OR=0.40, 95% CI(0.29, 0.53), P<0.001], and there was no statistically significant difference in the morbidity between the two groups[ OR=0.65, 95% CI(0.34, 1.22), P=0.18]. The risks of retinopathy of prematurity[ OR=0.42, 95% CI(0.54, 1.28), P=0.40], patent ductus arteriosus[ OR=0.79, 95% CI(0.57, 1.10), P=0.17], intracranial hemorrhage[ OR=1.09, 95% CI(0.77, 1.53), P=0.63], necrotizing enterocolitis[ OR=0.89, 95% CI(0.55, 1.44), P=0.64], and neonatal septicemia[ OR=0.73, 95% CI(0.49, 1.08), P=0.11] occurred in the experimental group had no statistically significant differences compared to the control group (all P>0.05). Conclusion:Early postnatal intratracheal drops of budesonide combined with pulmonary surfactant can significantly reduce the incidence of BPD, and has no significant effect on mortality or short-term complications.

Clinical and follow-up study of premature infants with neonatal respiratory distress syndrome managed by the less invasive surfactant administration / 中华实用儿科临床杂志

Objective:To explore the clinical therapeutic effect and follow-up prognosis of preterm infants with neonatal respiratory distress syndrome (NRDS) managed by less invasive surfactant administration (LISA) and traditional intubation-surfactant-extubation (INSURE) of pulmonary surfactant (PS).Methods:Data during hospitalization and follow-up period of 187 NRDS preterm infants (gestational age 24 weeks to 31 + 6 weeks, and birth weight <1 500 g) admitted to the Department of Neonatology, the Women and Children′s Hospital of Chongqing Medical University from March 2019 to February 2021 were retrospectively analyzed.NRDS preterm infants who were injected with PS by LISA were included in the LISA group (144 cases), and those who were injected with PS by INSURE were included in the INSURE group (43 cases). The propensity score matching method was used to correct the confounding factors between groups, and the covariate equilibrium samples between groups were obtained (39 cases in each group). Clinical treatment effect and prognosis of physical development, hearing and vision development, nervous system development, respiratory system diseases and other conditions of the two groups of children were compared using the t test, Chi- square test and other statistical analysis methods as appropriate. Results:(1)Compared with that of the INSURE group, the incidence of BPD [12 cases (33.3%) vs.23 cases (63.9%), χ2=6.727, P=0.009] and ROP [13 cases (36.1%) vs.26 cases (72.2%), χ2=9.455, P=0.002] in the LISA group were significantly lower.The incidence of mild BPD [8 cases (22.2%) vs.16 cases (44.4%), χ2=4.000, P=0.046] and stage Ⅰ-Ⅱ ROP [11 cases (30.6%) vs.22 cases (61.1%), χ2=6.769, P=0.009] in the LISA group was significantly lower than that of the INSURE group.There was no significant difference in the incidence of moderate and severe BPD and stageⅢ ROP and above between groups (all P>0.05). (2)There were no statistical differences in the repeated use of PS, mechanical ventilation rate within 72 h, pneumothorax/pulmonary hemorrhage, grade Ⅲ-Ⅳ periventricula-rintraventricular hemorrhage, stage Ⅱ-Ⅲ neonatal necrotizing enterocolitis, sepsis, abnormal amplitude integrated electroencephalogram, mortality in 36 weeks of corrected gestational age, total oxygen inhalation duration and hospitalization duration between the two groups (all P>0.05). (3)Follow-up within 1 year of corrected age after discharge.There were no significant differences in extrauterine body mass, body length and head circumference development, visual development, hearing development, Neonatal Behavioral Neurological Assessment score at corrected gestational age of 40 weeks, Bayley Scales of Infants Development score at corrected gestational age of 6 months and age of 1 year, pneumonia and re-hospitalization due to respiratory diseases between groups (all P>0.05). Conclusions:PS administration with LISA technology can reduce the incidence of mild BPD and stage Ⅰ-Ⅱ ROP in premature infants with NRDS who had the gestational age of 24-31 + 6 weeks and birth weight<1 500 g, without increasing the risk of other complications.The long-term prognosis of them treated with PS administration with LISA and INSURE is similar.

Clinical research of less invasive surfactant administration combined with nasal intermittent positive pressure ventilation in preterm infants with respiratory distress syndrome / 中华急诊医学杂志

Objective:To evaluate the efficacy and safety of less invasive surfactant administration (LISA) combined with nasal intermittent positive pressure ventilation (NIPPV) in the treatment of infants with respiratory distress syndrome (RDS).Methods:A prospective study was conducted on preterm infants of gestational age ≤34 weeks with RDS who were admitted to the Neonatal Intensive Care Unit of Xuzhou Central Hospital from October 2019 to November 2021. The infants were randomly assigned into the LISA+NIPPV group and the intubation-surfactant-extubation (INSURE) +nasal continuous positive airway pressure (NCPAP) group. In the LISA+NIPPV group, with the support of NIPPV, a Lisa tube was inserted through the vocal cords under direct vision with direct laryngoscope, and then pulmonary surfactant (PS) was infused into the lung. In the INSURE+NCPAP group, the patients were endotracheally intubated and infused with PS into the lung through endotracheal tube, then extubated and continued to receive NCPAP therapy (INSURE). The blood gas analysis at 1 h and 6 h after PS infusion, the adverse reactions during injection, clinical efficacy, bronchopulmonary dysplasia (BPD) and other related complications were compared between the two groups.Results:A total of 112 preterm infants with RDS were enrolled, including 58 in the LISA+NIPPV group and 54 in the INSURE+NCPAP group. The blood oxygen partial pressure (PaO 2) and PaO 2/FiO 2 (P/F) in the LISA+NIPPV group were significantly higher than those in the INSURE+NCPAP group at 1 h and 6 h after PS infusion, while carbon dioxide partial pressure (PaCO 2) were significantly lower than that in the INSURE+NCPAP group, and the differences were statistically significant (all P<0.05). The rate of tracheal intubation within 72 h (15.5% vs. 33.3%), the duration of non-invasive ventilation [ (7.5 ± 4.3) d vs.(9.9 ± 5.5) d ], total oxygen inhaling [ (10.5 ± 3.5) d vs.(13.3 ± 4.1) d ], failure rate of machine withdrawal (8.6% vs. 31.0% ), the times of apnea [7.0 (3.0-21.0) times vs. 15.0 (4.0-28.0) times ] and re-administration of PS (17.2% vs. 33.3%) in the LISA+NIPPV group were significantly lower than those in the INSURE+NCPAP group, and the differences were statistically significant ( P<0.05). The incidence of regurgitation in the LISA+NIPPV group was lower than that in the INSURE+NCPAP group (13.8% vs. 35.2%), and the difference was statistically significant ( P<0.05). There was no significant difference in the time needed for intubation between the two groups ( P>0.05). The occurrence of BPD in the LISA+NIPPV group was significantly lower than that in the INSURE+NCPAP group (10.3% vs. 25.9%), and there was no significant difference in other related complication between the two groups (all P>0.05). Conclusions:LISA combined with NIPPV in the treatment of preterm infants with RDS can effectively improve oxygenation, reduce carbon dioxide retention, reduce the mechanical ventilation rate, shorten the duration of noninvasive mechanical ventilation, and reduce the incidence of BPD.

Progress on methodology of pulmonary surfactant replacement therapy in neonates / 国际儿科学杂志

Pulmonary surfactant(PS)is a kind of phospholipid-protein complex, whose main function is to reduce the surface tension of alveoli.Exogenous PS replacement therapy has been widely used in the clinical treatment of respiratory distress syndrome(RDS)and other diseases.The clinical application methods include preventive or rescue treatment, invasive or minimally invasive treatment, intubation-surfactant-extubation(INSURE)technology and atomization treatment, etc.Nowadays, INSURE technology has been widely accepted in clinical application, and new non-invasive drug administration methods such as thin catheter, laryngeal mask airway and atomization are being studied or adopted.In this article, the progress of methodological research on clinical application of PS in newborns in recent years is reviewed.

The role of surfactant associated protein-A in silicosis / 中国职业医学

Objective: To investigate the role of surfactant associated protein-A (SP-A) in the development and progression of silicosis, and its mechanism. Methods: Homozygous and heterozygous mice of SP-A knockout of specific pathogen free (SPF) grade were selected for mating, and mice with SP-A-/- genotype were selected for subsequent experiments. SP-A wild-type (SP-A+/+) and SP-A-/- mice were divided into SP-A+/+ control group, SP-A-/- control group, SP-A+/+ silicosis group and SP-A-/- silicosis group with six mice in each group by random number table method. Mice in both silicosis groups were given 20.0 μL 250 g/L silica suspension by tracheal exposure, and mice in both control groups were injected with 0.9% sodium chloride solution at the same volume. On the 28th day after modeling, mice were sacrificed. Lung tissues were used for lung histopathology examination. The apoptosis of alveolar type Ⅱ epithelial cells of mice was detected by TUNEL method. The mRNA expression of B-lymphoblastoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase (Caspase)-3 and Caspase-9 in lung tissues of mice was detected by quantitative real-time polymerase chain reaction. Results: The histopathological result of mice showed that thickened alveolar septum, scattered silicon nodule and collagen fiber formation were observed in the mice lungs of SP-A+/+ silicosis group, and a large number of inflammatory cells were observed in silicosis nodule, after exposure to silica dust. SP-A-/- silicosis group resulted in a more severe pulmonary inflammation and interstitial fibrosis compared to SP-A+/+ silicosis group. The apoptosis of alveolar type Ⅱ epithelial cells and the mRNA relative expression levels of Bax, Caspase-3 and Caspase-9 in lung tissues of mice in each silicosis groups were increased compared with their control groups (all P<0.05). The above four indexes of mice in SP-A-/- silicosis group were higher than those in SP-A+/+ silicosis group (all P<0.05). There was no significant difference in the expression of Bcl-2 mRNA in lung tissues of these four groups (P>0.05). Conclusion: Knockout of SP-A can aggravate inflammation and pulmonary fibrosis in silicosis model mice, and promote apoptosis of alveolar type Ⅱ epithelial cells. The mechanism may be related to the Bcl-2/Bax/Caspase-3 signaling pathway which affects the apoptosis of mitochondrial pathway.

Fisiología respiratoria: fisiología del surfactante pulmonar / Physiology of pulmonary surfactant

El proceso de respiración y el intercambio gaseoso requiere la interacción de variadas fuerzas en los distintos tejidos y órganos involucrados. La tensión superficial a nivel alveolar provocaría colapso de dichas estructuras de no ser por las características del surfactante que lo recubre. Revisaremos en este articulo la fisiología involucrada en su estructura física, producción y efectos pulmonares.

The process of breathing and gas exchange requires the interaction of various forces in the different tissues and organs involved. The surface tension at the alveolus would cause collapse of these structures without of the surfactant that covers it. We will review in this article the physiology involved in its physical structure, production, and pulmonary effects.

Administración de surfactante mediante técnica mínimamente invasiva en neonatos / Administration of Surfactants by Minimally Invasive Technique in Neonates

Introducción: La administración de surfactante pulmonar tradicionalmente se realiza mediante un tubo endotraqueal, pero desde hace años existen técnicas menos invasivas como la administración mediante másscara laríngea, aerosolización y cateterización traqueal. Objetivos: Demostrar la evolución de tres neonatos que recibieron surfactante pulmonar mediante una cateterización traqueal y describir la técnica empleada para su administración. Presentación de casos: Se atendieron tres recién nacidos de muy bajo peso al nacer, que ingresaron en la unidad de cuidados intensivos neonatales del Hospital General Docente Iván Portuondo, San Antonio de los Baños, con síndrome de dificultad respiratoria del prematuro. Todos se trataron con surfactante pulmonar exógeno, Surfacen®, el cual se administró mediante cateterización traqueal empleando un catéter umbilical. Se trata de una técnica mínimamente invasiva que se realizó sin dificultades y siempre en el primer intento. Los tres pacientes mostraron mejoría clínica, gasométrica y radiográfica con esta forma de administración y solo uno de ellos tuvo una complicación durante el proceder, que no constituyó una limitante para su realización. Este método permitió mantener una ventilación no invasiva, y fue innecesaria la intubación endotraqueal en los neonatos. Los profesionales encargados de la ejecución de esta técnica recibieron entrenamiento previo. Conclusiones: La administración mínimamente invasiva de surfactante pulmonar resultó un método eficaz con el que se consiguió la resolución total del cuadro de dificultad respiratoria en los neonatos. El procedimiento empleado permitió una administración rápida y segura del Surfacen®(AU)

Introduction: Pulmonary surfactant administration is traditionally performed by endotracheal tube, but for years there have been less invasive techniques such as administration by laryngeal mask, aerosolization and tracheal catheterization. Objectives: To demonstrate the evolution of three neonates who received pulmonary surfactant via tracheal catheterization and to describe the technique used for its administration. Case presentation: Three very low birth weight newborns were attended and admitted to the neonatal intensive care unit of Iván Portuondo General Teaching Hospital, at San Antonio de los Baños municipality, with preterm respiratory distress syndrome. All were treated with exogenous pulmonary surfactant, Surfacen®, which was administered by tracheal catheterization using an umbilical catheter. This is a minimally invasive technique that was performed without difficulty and always on the first attempt. The three patients showed clinical, gasometric and radiographic improvement with this form of administration and only one of them had a complication during the procedure, which did not constitute a limitation for its performance. This method allowed maintaining non-invasive ventilation, and endotracheal intubation was unnecessary in neonates. The professionals in charge of performing this technique received previous training. Conclusions: Minimally invasive administration of pulmonary surfactant was an effective method that achieved total resolution of respiratory distress in neonates. The procedure used allowed rapid and safe administration of Surfacen®(AU)

Comparison of the effectiveness of two pulmonary surfactant administration methods among premature infants with respiratory distress syndrome / 预防医学

Objective@#To compare the effectiveness of less invasive surfactant administration (LISA) and intubate surfactant extubation (INSURE) on respiratory distress syndrome (RDS) among premature infant, so as to provide insights into improving treatment effects and reducing complications of RDS among premature infants.@*Methods@#A total of 71 premature infants with RDS in Anhui Provincial Maternity and Child Health Hospital were randomly assigned into the LISA and INSURE group, and pulmonary surfactant (PS) administration was carried out by LISA and INSURE with basic support therapy and respiratory support therapy. The general information, arterial blood gas analysis before and after treatment, respiratory support time and incidence of complications were collected and compared between the two groups.@*Results@#There were 31 cases in the LISA group, with a gestational age of (29.81±0.99) weeks and 22 male cases, and 40 cases in the INSURE group, with a gestational age of (30.02±1.13) weeks and 26 male cases. There were no significant differences in basic characteristics (including gestational age, birth weight, gender, etc.) between the two groups (all P>0.05). After administration, the level of PaO2 was lower in the LISA group than in the INSURE group [(78.35±6.55) mmHg vs. (87.68±8.21) mmHg, P<0.05], the level of PaCO2 was higher in the LISA group than in the INSURE group [(43.03±6.34) mmHg vs. (38.68±9.69) mmHg, P<0.05], and the incidence of bronchopulmonary dysplasia was lower in the LISA group than in the INSURE group (48.39% vs. 72.50%, P<0.05). Linear regression analysis showed that with the duration of LISA administration increase (2-7 min), the minimum heart rate of premature infants increased linearly (β=13, P<0.05). @*Conclusions@#Compared with INSURE, LISA administration could slowly improve ventilation oxygenation, reduce hyperventilation and incidence of bronchopulmonary dysplasia among premature infants with RDS. The incidence of slow heart rate may be reduced by appropriately prolonging the administration duration.

Surveys on management of neonatal respiratory distress syndrome in ten hospitals in Northwest China in 2016 and 2021 / 中华围产医学杂志

Objective:To analyze the status of neonatal respiratory distress syndrome (RDS) management in 10 hospitals in Northwest China over the past five years and to investigate the strategies for improving the prevention and treatment of RDS.Methods:This retrospective study involved premature infants with RDS who were admitted to the neonatal intensive care units (NICU) of 10 hospitals (six in Shaanxi Province, three in Gansu Province, and one in Xinjiang Uygur Autonomous Region) of the Northwest China Neonatal Collaborative Group within 3 d after birth from January 1 to December 31, 2016, and from January 1 to December 31, 2021. Basic information, perinatal condition, treatment approaches, complications, and prognosis of the patients were compared. T-test, rank sum, and Chi-square tests were used for statistical analysis. Result:(1) This study enrolled 322 premature infants with RDS in 2016 and 349 in 2021. Premature infants at the gestational age of 30 to 33 weeks were mainly affected, and the majority were male [64.3% (207/322) and 57.3% (200/349)]. The average maternal age in 2021 was older than that in 2016 [(30.6±4.8) years vs (28.6±5.4) years, t=24.02, P<0.001], and the proportion of women at advanced maternal age was also higher in 2021 [19.2% (67/349) vs 12.4% (40/322), χ2=4.18, P<0.05]. (2) The proportions of pregnancies conceived with assisted reproductive technologies [11.7% (41/349) vs 1.9% (6/322), χ2=25.12], underwent routine prenatal examinations [58.5% (204/349) vs 30.4% (98/322), χ2=53.33], exposed to steroids [62.2% (217/349) vs 28.6% (92/322), χ2=82.58] and delivered by cesarean section or elective cesarean section [73.6% (257/349) vs 51.6% (166/322), χ2=35.06; 24.1% (84/349) vs 6.5% (21/322), χ2=39.07], as well as the ratio of cesarean scar pregnancy [7.4% (26/349) vs 3.4% (11/322), χ2=5.23] were all higher in 2021 than those in 2016 (all P<0.05). Moreover, the incidence of fetal distress [30.1% (105/349) vs 20.2% (65/322), χ2=8.68], gestational hypertension [24.6% (86/349) vs 13.0% (42/322), χ2=14.59], premature rupture of membranes [16.0% (56/349) vs 10.2% (33/322), χ2=4.89], meconium-stained amniotic fluid [12.6% (44/349) vs 5.6% (18/322), χ2=9.83], placental abruption [10.3% (36/349) vs 5.3% (17/322), χ2=5.84], gestational diabetes mellitus [10.3% (36/349) vs 1.6%(5/322), χ2=22.41], chorioamnionitis [4.6%(16/349) vs 0.9% (3/322), χ2=8.12], thyroid dysfunction [4.3% (15/349) vs 0.6% (2/322), χ2=7.88] and heart disease [4.3% (15/349) vs 0.3% (1/322), χ2=9.17] were higher in 2021 than in 2016 (all P<0.05). (3) In 2021, the rate of pulmonary surfactant (PS) usage, the dosage of porcine PS, and the proportion of bovine PS usage were all significantly higher than those in 2016 [73.6% (257/349) vs 67.1% (216/322), χ2=11.62; (178.5±38.0) mg/kg vs (165.2±42.8) mg/kg, t=7.85; 47.9% (123/257) vs 19.4% (42/216), χ2=41.72; all P<0.01]. No significant difference in the incidence of intubation-surfactant-extubation (INSURE), early PS administration (≤2 h after birth), or the arterial blood gas values before and after PS treatment was found between the cases enrolled in 2021 and 2016. The duration of antibiotic treatment [7.0 d (5.0-14.0 d) vs 5.0 d (1.0-8.0 d), Z=7.55] and assisted ventilation [144 h (81-264 h) vs 73 h (47-134 h), Z=8.20] and the median hospital stay [24 d(14-42 d) vs 16 d (10-25 d), Z=6.74] were significantly longer in 2021 than in 2016 (all P<0.01). More patients required nasal intermittent positive pressure ventilation [29.6% (100/338) vs 1.0% (3/306), χ2=97.81] and conventional ventilation [42.6% (144/338) vs 30.1% (92/306), χ2=10.87] in 2021 as compared with those five years ago (both P<0.01). (4) In 2021, the incidence of patent ductus arteriosus [15.5% (54/349) vs 6.2% (20/322), χ2=63.40], bronchopulmonary dysplasia [9.2% (32/349) vs 2.8% (9/322), χ2=12.88], persistent pulmonary hypertension [5.4% (19/349) vs 0.6% (2/322), χ2=12.85], periventricular leukomalacia [4.3% (15/349) vs 1.2% (4/322), χ2=7.52] and pneumothorax [3.4% (12/349) vs 0.3% (1/322), χ2=9.68] increased as compared with those in 2016 (all P<0.05), while the incidence of nosocomial infection decreased significantly [7.4% (26/349) vs 19.6% (63/322), χ2=21.37, P<0.001]. (5) The cure rate of premature infants with RDS was 70.8% (247/349) in 2021, which was significantly higher than that in 2016 [56.2% (181/322), χ2=15.37, P<0.001]. Moreover, the rate of withdrawing treatment and the total mortality rate was lower in 2021 than in 2016 [7.7% (27/349) vs 14.3% (46/322), χ2=7.41; in-hospital: 1.4% (5/349) vs 5.6% (18/322), χ2=8.74; out of hospital: 8.3% (29/349) vs 13.7% (44/322), χ2=4.96; all P<0.05]. Conclusions:The clinical management of RDS in premature infants in the involved hospitals has been improved. However, there is room for improvement in prenatal examinations.

Outcome of Early Versus Late Surfactant Therapy in Preterm Neonates with Respiratory Distress Syndrome at a Tertiary Care Centre

Background: Respiratory distress syndrome (RDS) or hyaline membrane disease (HMD), has been recognized as the most common co-morbidity of prematurity. Prematurity and RDS largely contribute to early neonatal morbidity and mortality. With adequate antenatal steroid and early continuous positive airway pressure, early surfactant therapy improve survival outcome.Material & Methods:Prospective interventional study included newborns with prematurity 28-36 weeks(GA) with clinical Respiratory distress syndrome and birth weight(BW)>650 gm. All subjects were preferably provided early surfactant therapy (within 2hours after birth). Surfactant (survanta) was delivered by INSURE technique (Intubate- Surfactant administration- Extubate) and only those who required further respiratory support were ventilated. Records on birth weight, gestational age, timing of therapy (early/late), sepsis, complications, and survival/death outcome were collected and data was analyzed using SSPS version 20 software.Results:Out of 76 neonates (42 male, 34 female), 46 received early surfactant therapy and 30 obtained it late; Although mortality was observed with both early(36.66%) and late therapy(63.33%), there was significantly higher survival with early therapy. higher mortality occurred in lower Birth weight(LBW) /Gestational age (GA) subgroups. Culture positive sepsis was found in 52.6% with higher association with late therapy . Hypotension was most common complication with late intervention , whereas there was no difference for pulmonary haemorrhage or apnea.Conclusion:Early surfactant administration improved survival with minimal complications in RDS except for extremely premature/LBW babies.

Antifungal potential of biosurfactants produced by strains of Bacillus spp. (Bacillales: Bacillaceae) selected by molecular screening / Potencial antifúngico de biosulfactantes producidos por cepas de Bacillus spp. (Bacillales: Bacillaceae) seleccionadas por tamizaje molecular

Introduction: Bacillus species are used as biological controllers for phytopathogenic fungi, and the mechanisms to produce controllers include biosynthesis of lipopeptide biosurfactants with antifungal activity. Objective: To evaluate the antifungal potential of the biosurfactants produced by Bacillus strains, selected by molecular screening, on Fusarium oxysporum. Methods: We selected four molecular markers, related to the biosynthesis of surfactin, fengicin, and lichenysin (srfA, spf, fenB, LichAA) in nine Bacillus strains. We used two mineral media with several culture conditions, for biosurfactant production, and a well diffusion test for antifungal potential. Results: Only the biosurfactant produced by UFAB25 inhibits the mycelial growth of F. oxysporum (44 % ± 13): this biosurfactant was positive for srfA, spf, and fenB genes involved in the synthesis of surfactin and fengicine. Antifungal activity depends on culture conditions and the strain. Conclusions: Genetic markers are useful to detect strains with antifungal potential, facilitating the selection of bio-controllers. The biosurfactant profile is influenced by the strain and by culture conditions.

Introducción: Especies de Bacillus han sido empleadas como controladores biológicos contra hongos fitopatógenos. Entre los mecanismos utilizados se destaca la biosíntesis de biosurfactantes lipopeptídicos con actividad antifúngica. Objetivo: Evaluar el potencial antifúngico de los biosurfactantes producidos por cepas Bacillus nativas, previamente seleccionadas mediante tamizaje molecular, sobre Fusarium oxysporum. Métodos: Se utilizaron cuatro marcadores moleculares, relacionados con la biosíntesis de surfactina, fengicina y liquenisina (srfA, spf, fenB, LichAA) sobre nueve cepas de Bacillus. Se utilizaron dos medios minerales con diferentes condiciones de cultivo para la producción del biosurfactante. Se evaluó el potencial antifúngico de los biosurfactantes mediante la prueba de difusión en pozos. Resultados: Se determinó que solo el biosurfactante producido por UFAB25 actúa como inhibidor del crecimiento micelial de Fusarium oxysporum (43.6 % ± 13), esta cepa es positiva para los genes srfA, spf y fenB, involucrados en la síntesis de surfactina y fengicina. La actividad antifúngica depende de las condiciones de cultivo y la cepa. Conclusiones: Los marcadores genéticos ayudan a detectar cepas con potencial antifúngico, facilitando la selección de biocontroladores. El perfil del biosurfactante está influenciado no solo por la cepa, sino también por las condiciones del cultivo.

Effect of temperature and chain length of added primary amines on the sphere to rod transition of aqueous ionic micelles

The importance of micelles as templates for nanomaterials is growing day by day. This resulted in an increasing interest for micelles in different sizes and shapes. Addition of n-amines to micellar solutions was found to bring change in the shape of the micelles from sphere to rod in aqueous ionic micellar solutions. The change in shape is qualitatively obtained from sudden change in the slope of pH versus amine concentration plots because the degree or protonation of n-alkylamines depends on the shape of micelles. In the present investigation, pH is measured at different temperatures to elucidate the influence of addition of n-amines on sphere-to-rod transition in aqueous micellar solutions. The surfactants employed in the present investigation are cetyltrimethyl ammonium bromide (CTAB), cetylpyridinium chloride (CPC), and sodium dodecyl sulphate (SDS).As the amine concentration is increased, the pH increases linearly at certain amine concentration and the slope of the resulting straight line changes on further addition of amine. It is noticed that increasing temperature requires more amine for structural transition of aqueous ionic micelles. It is also observed that the effectiveness of added amines leading to shape transition from sphere to rod is in the order of C8NH2>C7NH2> C6NH2.

Seguridad del tratamiento con surfactante pulmonar en el síndrome de dificultad respiratoria aguda en niños / Safety of pulmonary surfactant therapy in acute respiratory distress syndrome in children

RESUMEN Introducción: Los surfactantes pulmonares junto a otras medidas terapéuticas constituyen un tratamiento de elección en diversas afecciones respiratorias. Objetivo: Demostrar la seguridad del tratamiento con Surfacen® en el síndrome de dificultad respiratoria aguda en niños. Materiales y Métodos: Ensayo clínico fase III multicéntrico, abierto, controlado y aleatorizado con dos grupos de tratamiento. El Grupo A recibió tratamiento convencional de oxigenación y ventilación mecánica combinado con Surfacen® en dosis de 100 mg cada ocho horas durante tres días. El Grupo B recibió tratamiento convencional. Se incluyeron niños entre los 28 días de nacido hasta 18 años de edad, de cualquier sexo, con diagnóstico de síndrome de dificultad respiratoria aguda. Se identificó y cuantificó la aparición de eventos adversos, intensidad, actitud seguida ante su aparición, resultado, relación de causalidad y mortalidad al día 28. Resultados: Se incluyeron 42 niños: 20 en el grupo A y 22 en el grupo B. En el grupo A se reportaron 23 eventos adversos en nueve pacientes y en el grupo B, 97 eventos adversos en 18 pacientes. La hipertensión arterial fue el evento adverso más frecuente. En el grupo A, 73,9% de los eventos adversos se manifestaron con intensidad severa, 86,9 % se mantuvo sin cambios frente al medicamento, 73,9 % tuvo causalidad remota respecto al surfactante. La mortalidad al día 28 fue de 41,5 %; en el grupo A, 20 % y en el grupo B, 62%. Conclusiones: Surfacen® fue bien tolerado y seguro al notificarse un número reducido de eventos adversos relacionados con su administración.

ABSTRACT Introduction: Pulmonary surfactants, together with other therapeutic measures, constitute a treatment of choice for various respiratory conditions. Objective: To demonstrate the safety of the treatment with Surfacen® in acute respiratory distress syndrome in children. Material and Methods: A multicenter, open, controlled, randomized Phase III clinical trial with two treatment groups. Group A received conventional oxygen therapy and mechanical ventilation combined with Surfacen® at a dosage of 100 mg every eight hours for three days. Group B received conventional treatment. Children 28 days of life to 18 years of age, of either sex, with the diagnosis of acute respiratory distress syndrome were included. The occurrence of adverse events, intensity, attitude followed after the appearance, outcome, and relationship between causality and mortality at day 28 were identified and quantified. Results: A total of 42 children were included: twenty children in group A and twenty-two ones in group B. In group A, 23 adverse events were reported in nine patients, while 97 adverse events were reported in 18 patients from group B. Hypertension was the most frequent adverse event. In group A, 73.9 % of adverse events of severe intensity were reported, 86.9 % remained unchanged after the administration of the drug, and 73.9 % had a remote causality with respect to the surfactant. Mortality at day 28 was 41.5 %; 20 % in group A, and 62 % in group B. Conclusions: Surfacen® was safe and well tolerated since a small number of adverse events related to its administration were reported.

The clinical efficacy of minimally invasive pulmonary surfactant therapy technology in the treatment of neonatal respiratory distress syndrome and the high-risk factors for failure / 中国医师进修杂志

Objective:To discuss the clinical efficacy of minimally invasive pulmonary surfactant (PS) therapy technology (MIST) in the treatment of neonatal respiratory distress syndrome (NRDS) and analyze the high-risk factors for failure.Methods:A total of 91 NRDS infants treated in the Affiliated Hospital of Jining Medical College from July 2017 to July 2019 were selected as the research objects, and 46 cases were performed minimally MIST (MIST group), 45 cases performed intubate-surfactant-extubate to continuous positive airway pressure (INSURE group), the infants were given 70-100 mg/kg porcine pulmonary phospholipid injection through vascular catheter or endotracheal intubation, respectively. The clinical efficacy of the two groups was compared and the risk factors for failure in the treatment of NRDS by PS were analyzed.Results:The total operating time in the MIST group was longer than that in the INSURE group: (90.06 ± 14.38) min vs. (62.57 ± 11.44) min, there was statistical difference ( P<0.05). The duration of non-invasive auxiliary ventilation, total oxygen uptake time and length of hospitalization time in two groups had no significant differences ( P>0.05). The incidence of bronchopulmonary dysplasia in the MIST group was lower than that in the INSURE group :10.87%(5/46) vs. 31.11%(14/45), there was statistical difference ( χ2 = 5.64, P<0.05). Univariate analysis showed that the male, cesarean section, birth weight <1 500 g, maternal gestational diabetes, arterial partial blood oxygen pressure (PaO 2) <59 mmHg (1 mmHg = 0.133 kPa) before the application of PS, and PaO 2/inhaled oxygen concentration (FiO 2) <185 mmHg and arterial partial pressure of carbon dioxide>55 mmHg were high risk factors for failure ( P<0.05). Conclusions:Although the operation of MIST is difficult, it is safe and feasible. In clinical work, various risk factors should be comprehensively analyzed to select an appropriate early respiratory support model for NRDS children.

Less invasive surfactant administration combined with bi-level positive airway pressure in preterm infants with respiratory distress syndrome : a clinical research / 中国新生儿科杂志

Objective:To study the efficacy and safety of less invasive surfactant administration (LISA) combined with bi-level positive airway pressure (BiPAP) ventilation in premature infants with respiratory distress syndrome (RDS).Methods:Premature infants with RDS at gestational age of 26~32 weeks in the NICU of our hospital from January 2020 to October 2021 were enrolled in this randomized controlled trial. They were randomly assigned to the LISA+BiPAP group or the intubation-surfactant-extubation (INSURE) + nasal continuous positive airway pressure (NCPAP) group, and given the corresponding treatment according to the group. The blood gas analysis at 1 h and 6 h after intratracheal instillation of pulmonary surfactant (PS), medication, noninvasive respiratory support time, total oxygen use time, weaning failure rate and endotracheal intubation rate within 72 h after PS administration were compared between the two groups, as well as the incidence of bronchopulmonary dysplasia (BPD).Results:A total of 86 preterm infants with RDS were enrolled in the study, including 44 in the LISA+BiPAP group and 42 in the INSURE+NCPAP group. Arterial partial pressure of oxygen in the LISA+BiPAP group at 1 h and 6 h after intratracheal instillation of PS were higher than those in the INSURE+NCPAP group, while PaCO 2 and oxygenation index (OI) were lower than those in the INSURE+NCPAP group, and the differences were statistically significant (all P<0.05). The duration of noninvasive respiratory support time [(12.2±8.7) d vs. (16.0 ±7.6) d], total oxygen use time [(16.6 ±8.3) d vs. (20.3±7.4) d], length of hospitalization[(22.6±10.3) d vs. (27.1±12.6) d], weaning failure rate [(11.4% (5/44) vs. 31.0% (13/42)], endotracheal intubation rate within 72 h after PS administration [11.4% (5/44) vs. 28.6% (12/42)], and re-administration of PS [18.2% (8/44) vs. 38.1% (16/42)] in the LISA+BiPAP group were lower than those in the INSURE+NCPAP group, and the differences were statistically significant ( P<0.05). The time needed for intubation and the incidence of regurgitation in the LISA+BiPAP group were lower than those in the INSURE+NCPAP group, and the differences were statistically significant ( P<0.05). The incidence of BPD in the LISA+BiPAP group was lower than those in the INSURE+NCPAP group [11.4% (5/44) vs. 31.0% (13/42)] ( P<0.05), the difference was also statistically significant ( P<0.05). There was no significant difference in the incidence of other complications between the two groups ( P>0.05). Conclusions:LISA combined with BiPAP can effectively improve oxygenation, reduce the mechanical ventilation rate, shorten the duration of non-invasive respiratory support, and reduce the incidence of BPD in the treatment of premature infants with RDS at the gestational age of 26~32 weeks.

Efficacy analysis of nasal intermittent positive pressure ventilation and minimally invasive surfactant therapy in very preterm infants with respiratory distress syndrome / 中国新生儿科杂志

Objective:To study the efficacy of nasal intermittent positive pressure ventilation (NIPPV) and minimally invasive surfactant therapy (MIST) in very preterm infants with respiratory distress syndrome (RDS).Methods:From January to December 2020, very preterm infants (gestation age ≤30 weeks) with RDS born and treated in our hospital were randomly assigned into NIPPV group and nasal continuous positive airway pressure (NCPAP) group. Both groups were treated with MIST technique. The following items were compared between the two groups:adverse reactions during MIST, partial pressure of carbon dioxide (PaCO 2) at 2 h after MIST, the incidences of intubation within 72 h, two or more doses of pulmonary surfactant (PS), frequent apnea, other complications and the parameters of respiratory support treatment. Results:A total of 62 cases were included, with 32 in the NIPPV group and 30 in the NCPAP group. Compared with the NCPAP group, the NIPPV group had lower incidences of bradycardia (6.3% vs. 30.0%), decreased oxygen saturation (12.5% vs. 40.0%) and apnea (6.3% vs. 30.0%) during MIST ( P<0.05). No significant difference existed in the incidence of regurgitation ( P>0.05). PaCO 2 at 2 h after MIST [40.1(38.2,43.8)mmHg vs. 48.3(44.1,50.0)mmHg], the incidences of intubation within 72 h (6.3% vs. 30.0%), two or more doses of PS (6.3% vs. 30.0%)and frequent apnea (6.3% vs. 30.0%) in NIPPV group were lower than NCPAP group ( P<0.05). No significant differences existed between the two groups on the following items: the durations of invasive ventilation, non-invasive ventilation, oxygen therapy, the incidences of bronchopulmonary dysplasia, intraventricular hemorrhage (≥Ⅲ), periventricular leukomalacia, retinopathy of prematurity (≥Ⅱ), necrotizing enterocolitis (≥Ⅱb), nasal injury, air leak and death ( P>0.05). Conclusions:Combining NIPPV and MIST can reduce the incidence of adverse reactions during PS administration without increasing respiratory support duration and common complications in preterm infants. It is recommended for clinical use.