Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

What is the impact of intraperitoneal surfactant administration against postoperative intraabdominal adhesion formation? an experimental study.

Background/Aim: Surfactant is a surface-active substance that, in addition to its detergent effect, also has effects that reduce inflammation and fibrosis. Because of these effects, it was aimed herein to investigate the effect of intraperitoneal surfactant application on preventing postoperative peritoneal adhesion formation in a uterine horn adhesion model. Materials and methods: Twenty-one Wistar albino rats were randomly divided into 3 groups (G1-G3), as follows: G1 (n = 7): control group. The abdomen was opened and then closed; G2 (n = 7): adhesion group. The abdomen was opened. Then, a 2-cm linear incision was made over the right uterine horn, 2 mL of isotonic saline was administered intraperitoneally, and the abdomen was closed; and G3 (n = 7): treatment group. The abdomen was opened, a 2-cm linear incision was made over the right uterine horn, 2 mL (70 mg/kg) of surfactant was administered intraperitoneally, and the abdomen was closed. After 15 days, the rats were euthanized, the abdomens were reopened, and adhesion scoring was performed. After the right uterine horns were removed and fixed with 10% formalin, appropriate sections were taken from the traumatized tissue, stained with Masson's trichrome, and fibrosis and inflammation scoring were performed. Results: The adhesion area and intensity were significantly higher in G2 than in G1 and G3 (p = 0.001) and were similar in G1 and G3 (p = 0.165). While fibrosis and inflammation were significantly higher in G2 than in G1 and G3 (p = 0.001), there was no difference between G1 and G3 (p = 0.5). Conclusion: Intraperitoneal surfactant administration at a dose of 70 mg/kg was found to be effective in preventing intraabdominal adhesion formation in a rat uterine horn model.

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)

Droplets generated from toilets during urination as a possible vehicle of carbapenem-resistant Klebsiella pneumoniae.

BACKGROUND: In the health care setting, infection control actions are fundamental for containing the dissemination of multidrug-resistant bacteria (MDR). Carbapenemase-producing Enterobacterales (CPE), especially Klebsiella pneumoniae (CR-KP), can spread among patients, although the dynamics of transmission are not fully known. Since CR-KP is present in wastewater and microorganisms are not completely removed from the toilet bowl by flushing, the risk of transmission in settings where toilets are shared should be addressed. We investigated whether urinating generates droplets that can be a vehicle for bacteria and explored the use of an innovative foam to control and eliminate this phenomenon. METHODS: To study droplet formation during urination, we set up an experiment in which different geometrical configurations of toilets could be reproduced and customized. To demonstrate that droplets can mobilize bacteria from the toilet bowl, a standard ceramic toilet was contaminated with a KPC-producing Klebsiella pneumoniae ST101 isolate. Then, we reproduced urination and attached culture dishes to the bottom of the toilet lid for bacterial colony recovery with and without foam. RESULTS: Rebound droplets invariably formed, irrespective of the geometrical configuration of the toilet. In microbiological experiments, we demonstrated that bacteria are always mobilized from the toilet bowl (mean value: 0.11 ± 0.05 CFU/cm2) and showed that a specific foam layer can completely suppress mobilization. CONCLUSIONS: Our study demonstrated that droplets generated from toilets during urination can be a hidden source of CR-KP transmission in settings where toilets are shared among colonized and noncolonized patients.

A self-assembled amphiphilic polysaccharide-based co-delivery system for egg white derived peptides and curcumin with oral bioavailability enhancement.

Egg white derived peptides (EWDP) and curcumin are well known for diverse biological activities, but the combinational usage of the two natural nutraceuticals is extremely limited by their low oral bioavailability and distinctly different polarities. Therefore, this study aimed to exploit a facile self-assembled amphiphilic system for oral co-delivery of hydrophilic egg white derived peptides (EWDP) and hydrophobic curcumin. The hydrophobic curcumin was first loaded into the hydrophobic cavity of ß-cyclodextrin (ß-CD) as a core. Then, the hydrophilic EWDP was absorbed into the region between the core and the N-[(2-hydroxy-3-trimethyl ammonium) propyl] chitosan (HTCC) shell to form the amphiphilic nanoparticles (NPs) via layer-by-layer self-assembly. The resulting NPs showed ideal oral applicability with excellent colloidal properties and encapsulation capacity for EWDP and curcumin at pH 2.0-7.0. X-ray Photoelectron Spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results indicated that hydrogen bonding and hydrophobic interaction were the main driving force for the formation of amphiphilic NPs. Upon combination with HTCC, EWDP (both shell material and core nutraceuticals) could facilitate curcumin loading into the deeper ß-CD cavity site with admirable solubility improvement. Moreover, EWDP and curcumin after co-delivery exhibited superior bioavailability (especially for bioactivity and cellular absorption) than the simple mixture and conventional curcumin inclusion complex. Overall, these findings are enlightening for the rational peptide based oral co-delivery system formulations for a broader range of hydrophilic and hydrophobic nutraceuticals (initially synergistic or not) in the food and related health-promoting fields.

Sequential administration of PEG-Span 80 niosome enhances anti-tumor effect of doxorubicin-containing PEG liposome.

To improve the anti-tumor effect of polyethylene glycol-modified liposome containing doxorubicin (DOX-PEG liposome), the effect of sequential administration of PEG-Span 80 niosome was investigated for Colon-26 cancer cells (C26)-bearing mice. The concept of the current study is as follows: Since both particulates would be accumulated in the tumor tissue due to the enhanced permeability and retention (EPR) effect, PEG-Span 80 niosome, mainly composed of synthetic surfactant (Span 80), would interact with DOX-PEG liposome and be a trigger to induce the release of DOX from the liposome within the tumor tissue, leading to the improvement of anti-tumor effect of DOX-PEG liposome. To find out an adequate liposome for this strategy, several PEG liposomes with different compositions were examined in terms of drug release enhancement and it was found that PEG-Span80 niosome could significantly enhance the release of calcein and DOX from a PEG liposome composed of 90% hydrogenated soybean phosphatidylcholine (HSPC) and 10% cholesterol. The sequential administration of PEG-Span 80 niosome at 24 or 48 h after dosing of DOX-PEG liposome provided a higher anti-tumor effect than the single dose of DOX-PEG liposome in the C26-bearing mice. Particularly, the 24 h-later dosing of PEG-Span 80 niosome has been found to be more effective than the 48 h-later dosing. It was also confirmed that the coexistence of PEG-Span 80 niosome with DOX-PEG liposome in 50% serum or in 50% supernatant of tumor tissue homogenate significantly increased DOX release from PEG liposome, suggesting that DOX release from DOX-PEG liposome within tumor tissue would be enhanced via the interaction with PEG-Span 80 niosome. This strategy would lead to the safer and more inexpensive chemotherapy, since it could make it possible to provide the better anti-tumor effect by utilizing the lower dose of DOX.

Low-dose repeated exposure to chemical surfactant impairs corneal epithelium: When personal cleaning products entering the eye.

Studies have reported that the incidence of ocular discomfort in people who often wear makeup is higher than that in the normal population. The incidence of ocular discomfort of these people may be also related to the daily ocular exposure to chemical surfactants during cleaning. The objectives of this study were to explore morphological and pathological changes in the murine ocular surface after low-dose repeated exposure to disodium cocoamphodiacetate (DC), a kind of chemical surfactant widely used in personal cleaning products, and to investigate the possible mechanisms. DC was administered in low dose (0.1%) to the ocular surface of C56BL/6 once daily for two weeks. We found that there were an increase of sodium fluorescein staining on the cornea, a significant thinning of corneal epithelial thickness, and increased TUNEL-positive cells in corneal epithelium in vivo. DC treatment also modulated the distribution of K14+ and P63+ epithelia from the limbal to the center on the cornea. In cultured murine corneal epithelial progenitor cell line (TKE2), DC treatment induced cell detachment and decreased the activation of Ak strain transforming protein (AKT), and extracellular signal-regulated kinase (ERK). And DC increased TUNEL-positive cells in vitro with increased expression of cleaved Caspase3 and B-cell lymphoma-2 associated X protein (Bax). Our results indicated that repeated low-dose DC exposure on ocular surface caused significant impairment on the structure and viability of the corneal epithelium by inhibiting epithelial proliferation and inducing apoptosis. It provides the foundations to understand the harmful effects of cleaning products daily exposure on the ocular surface.

Multifunctional nanoplatforms co-delivering combinatorial dual-drug for eliminating cancer multidrug resistance.

Clinically, the primary cause of chemotherapy failure belongs to the occurrence of cancer multidrug resistance (MDR), which directly leads to the recurrence and metastasis of cancer along with high mortality. More and more attention has been paid to multifunctional nanoplatform-based dual-therapeutic combination to eliminate resistant cancers. In addition to helping both cargoes improve hydrophobicity and pharmacokinetic properties, increase bioavailability, release on demand and enhance therapeutic efficacy with low toxic effects, these smart co-delivery nanocarriers can even overcome drug resistance. Here, this review will not only present different types of co-delivery nanocarriers, but also summarize targeted and stimuli-responsive combination nanomedicines. Furthermore, we will focus on the recent progress in the co-delivery of dual-drug using such intelligent nanocarriers for surmounting cancer MDR. Whereas it remains to be seriously considered that there are some knotty issues in the fight against MDR of cancers via using co-delivery nanoplatforms, including limited intratumoral retention, the possible changes of combinatorial ratio under complex biological environments, drug release sequence from the nanocarriers, and subsequent free-drug resistance after detachment from the nanocarriers. It is hoped that, with the advantage of continuously developing nanomaterials, two personalized therapeutic agents in combination can be better exploited to achieve the goal of cooperatively combating cancer MDR, thus advancing the time to clinical transformation.

Surfactant therapy via thin catheter in preterm infants with or at risk of respiratory distress syndrome.

BACKGROUND: Non-invasive respiratory support is increasingly used for the management of respiratory dysfunction in preterm infants. This approach runs the risk of under-treating those with respiratory distress syndrome (RDS), for whom surfactant administration is of paramount importance. Several techniques of minimally invasive surfactant therapy have been described. This review focuses on surfactant administration to spontaneously breathing infants via a thin catheter briefly inserted into the trachea. OBJECTIVES: Primary objectives In non-intubated preterm infants with established RDS or at risk of developing RDS to compare surfactant administration via thin catheter with: 1. intubation and surfactant administration through an endotracheal tube (ETT); or 2. continuation of non-invasive respiratory support without surfactant administration or intubation. Secondary objective 1. To compare different methods of surfactant administration via thin catheter Planned subgroup analyses included gestational age, timing of intervention, and use of sedating pre-medication during the intervention. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 30 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. SELECTION CRITERIA: We included randomised trials comparing surfactant administration via thin catheter (S-TC) with (1) surfactant administration through an ETT (S-ETT), or (2) continuation of non-invasive respiratory support without surfactant administration or intubation. We also included trials comparing different methods/strategies of surfactant administration via thin catheter. We included preterm infants (at < 37 weeks' gestation) with or at risk of RDS. DATA COLLECTION AND ANALYSIS: Review authors independently assessed study quality and risk of bias and extracted data. Authors of all studies were contacted regarding study design and/or missing or unpublished data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 16 studies (18 publications; 2164 neonates) in this review. These studies compared surfactant administration via thin catheter with surfactant administration through an ETT with early extubation (Intubate, Surfactant, Extubate technique - InSurE) (12 studies) or with delayed extubation (2 studies), or with continuation of continuous positive airway pressure (CPAP) and rescue surfactant administration at pre-specified criteria (1 study), or compared different strategies of surfactant administration via thin catheter (1 study). Two trials reported neurosensory outcomes of of surviving participants at two years of age. Eight studies were of moderate certainty with low risk of bias, and eight studies were of lower certainty with unclear risk of bias. S-TC versus S-ETT in preterm infants with or at risk of RDS Meta-analyses of 14 studies in which S-TC was compared with S-ETT as a control demonstrated a significant decrease in risk of the composite outcome of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.48 to 0.73; risk difference (RD) -0.11, 95% CI -0.15 to -0.07; number needed to treat for an additional beneficial outcome (NNTB) 9, 95% CI 7 to 16; 10 studies; 1324 infants; moderate-certainty evidence); the need for intubation within 72 hours (RR 0.63, 95% CI 0.54 to 0.74; RD -0.14, 95% CI -0.18 to -0.09; NNTB 8, 95% CI; 6 to 12; 12 studies, 1422 infants; moderate-certainty evidence); severe intraventricular haemorrhage (RR 0.63, 95% CI 0.42 to 0.96; RD -0.04, 95% CI -0.08 to -0.00; NNTB 22, 95% CI 12 to 193; 5 studies, 857 infants; low-certainty evidence); death during first hospitalisation (RR 0.63, 95% CI 0.47 to 0.84; RD -0.02, 95% CI -0.10 to 0.06; NNTB 20, 95% CI 12 to 58; 11 studies, 1424 infants; low-certainty evidence); and BPD among survivors (RR 0.57, 95% CI 0.45 to 0.74; RD -0.08, 95% CI -0.11 to -0.04; NNTB 13, 95% CI 9 to 24; 11 studies, 1567 infants; moderate-certainty evidence). There was no significant difference in risk of air leak requiring drainage (RR 0.58, 95% CI 0.33 to 1.02; RD -0.03, 95% CI -0.05 to 0.00; 6 studies, 1036 infants; low-certainty evidence). None of the studies reported on the outcome of death or survival with neurosensory disability. Only one trial compared surfactant delivery via thin catheter with continuation of CPAP, and one trial compared different strategies of surfactant delivery via thin catheter, precluding meta-analysis. AUTHORS' CONCLUSIONS: Administration of surfactant via thin catheter compared with administration via an ETT is associated with reduced risk of death or BPD, less intubation in the first 72 hours, and reduced incidence of major complications and in-hospital mortality. This procedure had a similar rate of adverse effects as surfactant administration through an ETT. Data suggest that treatment with surfactant via thin catheter may be preferable to surfactant therapy by ETT. Further well-designed studies of adequate size and power, as well as ongoing studies, will help confirm and refine these findings, clarify whether surfactant therapy via thin tracheal catheter provides benefits over continuation of non-invasive respiratory support without surfactant, address uncertainties within important subgroups, and clarify the role of sedation.

The effects of poloxamer and sodium alginate mixture (Guardix-SG®) on range of motion after axillary lymph node dissection: A single-center, prospective, randomized, double-blind pilot study.

PURPOSE: Restricted shoulder mobility is a major upper extremity dysfunction associated with lower quality of life and disability after breast cancer surgery. We hypothesized that a poloxamer and sodium alginate mixture (Guardix-SG®) applied after axillary lymph node dissection (ALND) would significantly improve shoulder range of motion (ROM) in patients with breast cancer. METHODS: We conducted a double-blind, randomized, prospective study to evaluate the clinical efficacy and safety of Guardix-SG® for the prevention of upper extremity dysfunction after ALND. The primary outcome measure was shoulder ROM at baseline (T0) and 3 (T1), 6 (T2), and 12 months (T3) after surgery. Secondary outcome measures were the Disabilities of the Arm, Shoulder, and Hand score(DASH), pain associated with movement, which was assessed using a numeric rating scale, and lymphedema assessed using body composition analyzer. RESULTS: A total of 83 women with breast cancer were randomly assigned to either the Guardix-SG® group or the control group. In the Guardix-SG® group (n = 37), Guardix-SG® was applied to the axillary region after ALND. In the control group (n = 46), ALND was performed without using Guardix-SG®. Comparing ROM for shoulder flexion before surgery (178.2°) and 12 months after surgery (172.3°), that was restored 12 months after surgery in the Guardix-SG® group, and there was no statistically significant difference between that at before surgery and 12 months after surgery (p = 0.182). No adverse effect was observed in either group. CONCLUSIONS: The results of this study have shown that Guardix-SG® help improve shoulder ROM without causing adverse effects in patients who underwent breast cancer surgery. However, there was no statistically significant difference from the control group. A further large-scale study is needed to obtain a more conclusive conclusion. TRIAL REGISTRATION: CRISKCT0003386; https://cris.nih.go.kr (20181207).

Core-crosslinked nanomicelles based on crosslinkable prodrug and surfactants for reduction responsive delivery of camptothecin and improved anticancer efficacy.

As an important DNA topoisomerase I inhibitor in oncotherapy, camptothecin (CPT) with traditional formulation only shows a limited clinical application mainly because of its poor solubility. In this study, a novel redox responsive nanoscaled delivery system was developed to overcome the inherent defect of CPT. Firstly, a CPT prodrug (CPT-LA) and two crosslinkable surfactants (SO-LA and MPEG-LA) was synthesized, all of which contained the same lipoic acid (LA) structure. In the preparation, highly core-crosslinked structure was formed by adding a thiol crosslinker, which can induce LA ring opening polymerization and disulfide crosslinking. The resulting CPT-LA core-crosslinked nanomicelles (CPT-LA CNM) were formulated with a highly crosslinked core and a PEG hydrophilic shell. Dynamic light scattering (DLS) characterization indicated that CPT-LA CNM possessed a narrow size distribution (184.6 ± 3.6 nm) and negatively charged zeta potential (-3.5 ± 1.2 mV). The storage and physiological stabilities showed that the size distribution of CPT-LA CNM was relatively stable in both conditions which were neutral PBS at 4 °C (1 week period) and PBS containing 10% serum at 37 °C (24 h period). Moreover, the effective CPT release behavior of CPT-LA CNM was confirmed in the reducing circumstances containing dithiothreitol (DTT). Under confocal laser scanning microscopy (CLSM), CPT-LA CNM demonstrated a rapid cellular uptake behavior against cancer cells when compared to CPT suspension. Finally, the enhanced anticancer efficacy of CPT-LA CNM was also detected by in vitro cytotoxicity and cell apoptosis assay. In summary, the core-crosslinked CPT-LA CNM could be a promising CPT delivery system because of high stability, effectively controlled release as well as improved anticancer activity.

Bovine or Porcine: Does the Type of Surfactant Matter?

BACKGROUND: Hyaline membrane disease contributes majorly to preterm mortality, particularly in the developing world. There are two animal-derived surfactants available in South Africa: poractant-alfa (120 mg/1.5 ml) and beractant (100 mg/4 ml). At equivalent doses, studies have shown no difference in mortality or morbidity, although there are limited data from the developing world. Both surfactants have been available for use at Groote Schuur Hospital in Cape Town but due to policy change, poractant-alfa was no longer available from November 2014. Due to weight-based dosing charts, infants who were given poractant-alfa received 20% higher dosages of phospholipid. METHODS: A before-and-after policy change non-experimental study was performed including infants from 2013 to 2015. Infants weighing <1500 g were recruited by identifying them from the surfactant register and further data were obtained from patient records. Data fields included infant weight, gestation, respiratory support and outcomes. RESULTS: Two hundred and eight infants were included. One hundred and eight received beractant and 100 received poractant-alfa. The mean birth weight was 1031 g and gestational age 28.8 weeks. Seventy-nine percent of the infants received surfactant via the INSURE (intubation, surfactant and extubation) method. The combined outcome for death or bronchopulmonary dysplasia was 35.3% in the beractant group and 36% in the poractant-alfa group (p = 0.902). All secondary outcomes including neonatal morbidities, oxygen at 28 days or length of ventilation were not statistically significant. CONCLUSION: There were no significant differences in outcomes between the two groups of infants who received different surfactants at the dosages used in our unit. This is one of the few studies of this type performed in a low- and middle-income countries.

Less invasive surfactant administration: best practices and unanswered questions.

PURPOSE OF REVIEW: The purpose of this review is to describe current concepts in the field of Less Invasive Surfactant Administration (LISA). The use of continuous positive airway pressure (CPAP) has become standard for the treatment of premature infants with respiratory problems throughout the world. However, if CPAP fails, technologies like LISA are needed that can combine surfactant delivery and spontaneous breathing with the support of noninvasive modes of ventilation. RECENT FINDINGS: LISA with thin catheters has been in use in Germany for more than 15 years. In the last 5 years, there was substantial interest in this method around the world. Randomized studies and recent metaanalyses indicate that the LISA technique helps to avoid mechanical ventilation especially in emerging respiratory distress syndrome (RDS). LISA is also associated with improved outcomes of preterm infants, specifically in the prevention of bronchopulmonary dysplasia (BPD) and intracranial hemorrhage (ICH). By now, a variety of different LISA catheters, devices and techniques have been described. However, most of the technologies are still connected with the unpleasant experience of laryngoscopy for the affected infants, so that the search for even less invasive techniques, for example, surfactant application by nebulization, goes on. SUMMARY: Maintenance of spontaneous breathing with support by the LISA technique holds big promise in the care of preterm infants. Patient comfort and lower complication rates are strong arguments to further investigate and promote the LISA approach. Open questions include exact indications for different patient groups, the usefulness of devices/catheters that have recently been built for the LISA technique and -- perhaps most urgently -- the issue of analgesia/sedation during the procedure. Studies on long-term outcome after LISA are under way.

Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE).

BACKGROUND: Initial trials of lung-targeted budesonide (0.25 mg/kg) in surfactant to prevent bronchopulmonary dysplasia (BPD) in premature infants have shown benefit; however, the optimal safe dose is unknown. METHODS: Dose-escalation study of budesonide (0.025, 0.05, 0.10 mg/kg) in calfactatant in extremely low gestational age neonates (ELGANs) requiring intubation at 3-14 days. Tracheal aspirate (TA) cytokines, blood budesonide concentrations, and untargeted blood metabolomics were measured. Outcomes were compared with matched infants receiving surfactant in the Trial Of Late SURFactant (TOLSURF). RESULTS: Twenty-four infants with mean gestational age 25.0 weeks and 743 g birth weight requiring mechanical ventilation were enrolled at mean age 6 days. Budesonide was detected in the blood of all infants with a half-life of 3.4 h. Of 11 infants with elevated TA cytokine levels at baseline, treatment was associated with sustained decrease (mean 65%) at all three dosing levels. There were time- and dose-dependent decreases in blood cortisol concentrations and changes in total blood metabolites. Respiratory outcomes did not differ from the historic controls. CONCLUSIONS: Budesonide/surfactant had no clinical respiratory benefit at any dosing levels for intubated ELGANs. One-tenth the dose used in previous trials had minimal systemic metabolic effects and appeared effective for lung-targeted anti-inflammatory action.

Nano-vesicles based on phospholipid-like amphiphilic polyphosphazenes to orally deliver ovalbumin antigen for evoking anti-tumor immune response.

Aimed at evoking an adequate anti-tumor immune response via oral administration route, this study constructed functionally and structurally mimicking-bacteria-membrane (MBM) nano-vesicle (RGD-PEOP) to orally deliver ovalbumin (OVA) antigen. In terms of simulating bacterial membrane structure, we creatively designed this nano-vesicle to have phospholipid-like octadecylphosphoethanolamine groups in vesicle membrane to improve OVA loading by means of specific interactions including salt bridge and hydrogen bond interaction. For simulating bacterial membrane function, the RGD peptide was modified onto the nano-vesicle surface, and the resulting vector displayed a good transport ability with a 3.4-fold higher than free OVA. In vitro and in vivo assay showed that the expression of co-stimulatory molecules and MHC class II complexes was significantly enhanced by MBM nano-vesicle. IFN-γ and IL-4 levels also increased several folds in the MBM nano-vesicle group. Consequently, MBM nano-vesicle achieved the highest in vivo inhibition rate of 69% against E.G7-OVA tumors among all the oral groups. These results suggest that this MBM nano-vesicle may be a promising vector to orally deliver OVA antigen for cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Developing an effective non-bacterial carrier for oral cancer immunotherapy remains challenging. This work constructed a mimicking-bacteria-membrane nano-vesicle based on phospholipid-like amphiphilic polyphosphazenes for oral delivery of ovalbumin antigen. With the considerable capability to load ovalbumin antigen and target M cells, the nano-vesicle produced remarkable tumor suppression in vivo by evoking anti-tumor immune response.

Study on phase transition and contrast-enhanced imaging of ultrasound-responsive nanodroplets with polymer shells.

Ultrasound-responsive nanodroplets show great potential in ultrasound diagnosis and targeted tumour therapy due to their unique phase transition properties. However, the mechanism underlying the phase transition and the properties of contrast-enhanced imaging have not been well elucidated, which impedes the development and application of nanodroplets in clinic. Herein, the phase transition of polymeric nanodroplets with a core of perfluoronpentane (PFP) was studied through the measurement of particle size and in vitro/in vivo contrast-enhanced imaging, and imaging performance was further evaluated by introducing intensity analysis of acoustic signals. The average particle size of nanodroplets increased and became polydispersed when heated at 37 °C, which may result from vaporization of a portion of nanodroplets. For imaging in vitro, no acoustic signals were observed at 25 °C when the mechanical index (MI) varied from 0.08 to 1.0. At 37 °C, acoustic signals were observed for MI ≥ 0.4, and the intensity was stronger for higher MIs. For imaging in mice livers, the nanodroplets showed similar contrast enhancement behaviours with SonoVue® at low MI (0.08), which produced strong acoustic signals immediately and were cleared within 10 min. The acoustic signals at high MI (1.0) were weaker but lasted more than 1 h. These results indicated that the phase transition of polymeric nanodroplets could be induced by diagnostic ultrasound, and contrast-enhanced imaging is closely related to particle size, temperature and MI. This study provides a better understanding of phase transition and contrast-enhanced imaging for ultrasound-responsive nanodroplets with polymer shells.

A Review of Sclerosing Foam Stability in the Treatment of Varicose Veins.

BACKGROUND: Varicose veins are common clinical entities. Foam sclerotherapy is a minimally invasive and simple procedure; however, the side effects, efficacy, and stability of sclerosing foam are not ideal. OBJECTIVE: To summarize the current studies on sclerosing foam stability and promote foam sclerotherapy development. MATERIALS AND METHODS: We reviewed the literature before June 2018 and included only representatives studies on sclerosing foam stability. We summarized the foam half-life time (FHT) of polidocanol (POL) under 17 preparation conditions and the FHT of sodium tetradecyl sulfate under 21 preparation conditions. The preparation conditions included various combinations of temperature, liquid-gas ratio, preparation method, etc. RESULTS: The FHT of POL varied between 40 and 4,000 seconds under different conditions. The FHT of sodium tetradecyl sulfate varied from 25.7 to 390 seconds. The higher the drug concentration, the lower the temperature required to increase foam stability. The addition of surfactant greatly increased foam stability. For different gas compositions, the FHT sequence was as follows: CO2 < CO2 + O2 < O2 < air. CONCLUSION: Foam stability can be improved by changing the preparation conditions; therefore, the role of surfactants and predictive methods for FHT are worth investigating further.

Combination of bisacodyl suppository and 1 L polyethylene glycol plus ascorbic acid is a non-inferior and comfortable regimen compared to 2 L polyethylene glycol plus ascorbic acid.

BACKGROUND AND AIM: Appropriate bowel cleansing before colonoscopy is an important factor in increasing the detection rate of lesions. Low-volume polyethylene glycol (PEG) plus ascorbic acid (PEG-Asc) reduces the dosage of bowel preparation agent, but still presents discomfort to patients. The primary aim of the present study was to compare the efficacy of bowel cleansing between 2 L PEG-Asc (control) and 1 L PEG-Asc with bisacodyl suppository (suppository) groups, and the secondary aim was to investigate complications and tolerability between the two groups. METHODS: This was a single-center prospective randomized controlled study. We identified 168 patients scheduled for colonoscopy between August 2017 and January 2018 and randomly assigned them to the control or to the suppository groups. Efficacy of bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS), and side-effects were surveyed using questionnaires. RESULTS: No significant difference was detected in baseline characteristics including insertion and withdrawal times, and adenoma detection rates between the two groups. Total BBPS score was 7.93 ± 1.06 and 7.74 ± 1.02 in the control and suppository groups, respectively (P = 0.22). Incidence of abdominal pain and nausea was not statistically different, whereas that of sleep disturbance and anal discomfort was higher in the control group. (P = 0.00). CONCLUSIONS: One liter PEG-Asc with bisacodyl suppository resulted in an equivalent bowel-cleansing outcome with reduced patient discomfort compared to 2 L PEG-Asc. Therefore, PEG-Asc with bisacodyl suppository represents a potential alternative and increases patient compliance with bowel preparation.