Oleaginous Microbial Lipids' Potential in the Prevention and Treatment of Neurological Disorders.

The products of oleaginous microbes, primarily lipids, have gained tremendous attention for their health benefits in food-based applications as supplements. However, this emerging biotechnology also offers a neuroprotective treatment/management potential for various diseases that are seldom discussed. Essential fatty acids, such as DHA, are known to make up the majority of brain phospholipid membranes and are integral to cognitive function, which forms an important defense against Alzheimer's disease. Omega-3 polyunsaturated fatty acids have also been shown to reduce recurrent epilepsy seizures and have been used in brain cancer therapies. The ratio of omega-3 to omega-6 PUFAs is essential in maintaining physiological function. Furthermore, lipids have also been employed as an effective vehicle to deliver drugs for the treatment of diseases. Lipid nanoparticle technology, used in pharmaceuticals and cosmeceuticals, has recently emerged as a biocompatible, biodegradable, low-toxicity, and high-stability means for drug delivery to address the drawbacks associated with traditional medicine delivery methods. This review aims to highlight the dual benefit that lipids offer in maintaining good health for disease prevention and in the treatment of neurological diseases.

Tafazzin mediates tamoxifen resistance by regulating cellular phospholipid composition in ER-positive breast cancer.

Tamoxifen is the frontline therapeutic agent for the estrogen receptor-positive (ER + ) subtype of breast cancer patients, which accounts for 70-80% of total breast cancer incidents. However, clinical resistance to tamoxifen has become increasingly common, highlighting the need to identify the underlying cellular mechanisms. In our study, we employed a genome-scale CRISPR-Cas9 loss-of-function screen and validation experiments to discover that Tafazzin (TAZ), a mitochondrial transacylase, is crucial for maintaining the cellular sensitivity of ER+ breast cancer cells to tamoxifen and other chemotherapies. Mechanistically, we found that cardiolipin, whose synthesis and maturation rely on TAZ, is required to maintain cellular sensitivity to tamoxifen. Loss of metabolic enzymatic activity of TAZ causes ERα downregulation and therapy resistance. Interestingly, we observed that TAZ deficiency also led to the upregulation of lysophosphatidylcholine (LPC), which in turn suppressed ERα expression and nuclear localization, thereby contributing to tamoxifen resistance. LPC is further metabolized to lysophosphatidic acid (LPA), a bioactive molecule that supports cell survival. Thus, our findings suggest that the depletion of TAZ promotes tamoxifen resistance through an LPC-LPA phospholipid synthesis axis, and targeting this lipid metabolic pathway could restore cell susceptibility to tamoxifen treatment.

Co-encapsulation of fisetin and cisplatin into liposomes: Stability considerations and in vivo efficacy on lung cancer animal model.

Lung cancer is a highly vascularized tumor for which a combination between an antitumor agent, cisplatin, and an antiangiogenic molecule, fisetin, appears a promising therapeutic approach. In order to deliver both chemotherapies within the tumor, to enhance fisetin solubility and decrease cisplatin toxicity, an encapsulation of both drugs into liposomes was developed. Purification and freeze-drying protocols were optimized to improve both the encapsulation and liposome storage. The cytotoxicity of the encapsulated chemotherapies was evaluated on Lewis lung carcinoma (3LL) cell lines. The antitumor effect of the combination was evaluated in vivo on an ectopic mouse model of Lewis Lung carcinoma. The results showed that fisetin and cisplatin co-loaded liposomes were successfully prepared. Freeze-drying allowed a 30 days storage limiting the release of both drugs. The combination index between liposomal fisetin and liposomal cisplatin on 3LL cell line after 24 h of exposure showed a clear synergism: CI = 0.7 for the co loaded liposomes and CI = 0.9 for the mixture of cisplatin loaded and fisetin loaded liposomes. The co-encapsulating formulation showed in vivo efficacy against an ectopic murine model of Lewis Lung carcinoma with a probable reduction in the toxicity of cisplatin through co-encapsulation with fisetin.

Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and leads to the poorest patient outcomes despite surgery and chemotherapy treatment. Exploring new molecular mechanisms of TNBC that could lead to the development of novel molecular targets are critically important for improving therapeutic options for treating TNBC. METHODS: We sought to identify novel therapeutic targets in TNBC by combining genomic and functional studies with lipidomic analysis, which included mechanistic studies to elucidate the pathways that tie lipid profile to critical cancer cell properties. Our studies were performed in a large panel of human breast cancer cell lines and patient samples. RESULTS: Comprehensive lipid profiling revealed that phospholipid metabolism is reprogrammed in TNBC cells. We discovered that patatin-like phospholipase domain-containing lipase 8 (PNPLA8) is overexpressed in TNBC cell lines and tissues from breast cancer patients. Silencing of PNPLA8 disrupted phospholipid metabolic reprogramming in TNBC, particularly affecting the levels of phosphatidylglycerol (PG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and glycerophosphocholine (GPC). We showed that PNPLA8 is essential in regulating cell viability, migration and antioxidation in TNBC cells and promoted arachidonic acid and eicosanoid production, which in turn activated PI3K/Akt/Gsk3ß and MAPK signaling. CONCLUSIONS: Our study highlights PNPLA8 as key regulator of phospholipid metabolic reprogramming and malignant phenotypes in TNBC, which could be further developed as a novel molecular treatment target.

Protease-Activated Receptor-2 and Phospholipid Metabolism Analysis in Hyperuricemia-Induced Renal Injury.

Interstitial inflammation is an important mechanism of pathological damage in renal injury caused by hyperuricemia. Protease-activated receptor-2 (PAR2) is a class of targets that act upstream of the PI3K/AKT/NF-κB pathway and is involved in various inflammatory diseases. We induced a hyperuricemia model in rats by adenine and ethambutol gavage in an in vivo experiment. We demonstrated that PAR2 and PI3K/AKT/NF-κB pathway expression were significantly upregulated in renal tissues, with massive inflammatory cell infiltration in the renal interstitium and renal tissue injury. Treating hyperuricemic rats with AZ3451, a selective metabotropic antagonist of PAR2, we demonstrated that PAR2 antagonism inhibited the PI3K/AKT/NF-κB pathway and attenuated tubular dilation and tubulointerstitial inflammatory cell infiltration. The phospholipid metabolism profiles provided a perfect separation between the normal and hyperuricemic rats. In addition, we also found that AZ3451 can affect phospholipid metabolism. Our work suggests that PAR2 may mediate hyperuricemia-mediated renal injury by activating the PI3K/AKT/NF-κB pathway. The PAR2 antagonist AZ3451 may be a promising therapeutic strategy for hyperuricemia-induced inflammatory responses.

Engineered Liposomes in Interventional Theranostics of Solid Tumors.

Engineered liposomal nanoparticles have unique characteristics as cargo carriers in cancer care and therapeutics. Liposomal theranostics have shown significant progress in preclinical and clinical cancer models in the past few years. Liposomal hybrid systems have not only been approved by the FDA but have also reached the market level. Nanosized liposomes are clinically proven systems for delivering multiple therapeutic as well as imaging agents to the target sites in (i) cancer theranostics of solid tumors, (ii) image-guided therapeutics, and (iii) combination therapeutic applications. The choice of diagnostics and therapeutics can intervene in the theranostics property of the engineered system. However, integrating imaging and therapeutics probes within lipid self-assembly "liposome" may compromise their overall theranostics performance. On the other hand, liposomal systems suffer from their fragile nature, site-selective tumor targeting, specific biodistribution and premature leakage of loaded cargo molecules before reaching the target site. Various engineering approaches, viz., grafting, conjugation, encapsulations, etc., have been investigated to overcome the aforementioned issues. It has been studied that surface-engineered liposomes demonstrate better tumor selectivity and improved therapeutic activity and retention in cells/or solid tumors. It should be noted that several other parameters like reproducibility, stability, smooth circulation, toxicity of vital organs, patient compliance, etc. must be addressed before using liposomal theranostics agents in solid tumors or clinical models. Herein, we have reviewed the importance and challenges of liposomal medicines in targeted cancer theranostics with their preclinical and clinical progress and a translational overview.

Exosome-Based Smart Drug Delivery Tool for Cancer Theranostics.

Exosomes are the phospholipid-membrane-bound subpopulation of extracellular vesicles derived from the plasma membrane. The main activity of exosomes is cellular communication. In cancer, exosomes play an important rolefrom two distinct perspectives, one related to carcinogenesis and the other as theragnostic and drug delivery tools. The outer phospholipid membrane of Exosome improves drug targeting efficiency. . Some of the vital features of exosomes such as biocompatibility, low toxicity, and low immunogenicity make it a more exciting drug delivery system. Exosome-based drug delivery is a new innovative approach to cancer treatment. Exosome-associated biomarker analysis heralded a new era of cancer diagnostics in a more specific way. This Review focuses on exosome biogenesis, sources, isolation, interrelationship with cancer and exosome-related cancer biomarkers, drug loading methods, exosome-based biomolecule delivery, advances and limitations of exosome-based drug delivery, and exosome-based drug delivery in clinical settings studies. The exosome-based understanding of cancer will change the diagnostic and therapeutic approach in the future.

Efficacy of synthetic surfactant (CHF5633) bolus and/or lavage in meconium-induced lung injury in ventilated newborn rabbits.

BACKGROUND: The pathogenesis of neonatal meconium aspiration syndrome (MAS) involves meconium-induced lung inflammation and surfactant inactivation. Bronchoalveolar lavage (BAL) with diluted surfactant facilitates the removal of meconium. CHF5633, one of the most promising synthetic surfactants, is effective in neonatal respiratory distress syndrome. Here we investigated its efficacy via BAL in an experimental MAS model. METHODS: Experimental MAS was induced at birth in near-term newborn rabbits by intratracheal instillation of reconstituted human meconium. First, undiluted CHF5633 was compared with a porcine-derived surfactant (Poractant alfa) via intratracheal bolus (200 mg/kg). Second, the efficacy of BAL with diluted CHF5633 (5 mg/mL, 20 ml/kg) alone, or followed by undiluted boluses (100 or 300 mg/kg), was investigated. RESULTS: Meconium instillation caused severe lung injury, reduced endogenous surfactant pool, and poor survival. CHF5633 had similar benefits in improving survival and alleviating lung injury as Poractant alfa. CHF5633 BAL plus higher boluses exerted better effects than BAL or bolus alone in lung injury alleviation by reversing phospholipid pools and mitigating proinflammatory cytokine mRNA expression, without fluid retention and function deterioration. CONCLUSIONS: CHF5633 improved survival and alleviated meconium-induced lung injury, the same as Poractant alfa. CHF5633 BAL plus boluses was the optimal modality, which warrants further clinical investigation. IMPACT: To explore the efficacy of a synthetic surfactant, CHF5633, in neonatal lung protection comparing with Poractant alfa in a near-term newborn rabbit model with meconium-induced lung injury. Similar effects on improving survival and alleviating lung injury were found between CHF5633 and Poractant alfa. Optimal therapeutic effects were identified from the diluted CHF5633 bronchoalveolar lavage followed by its undiluted bolus instillation compared to the lavage or bolus alone regimens. Animals with CHF5633 lavage plus bolus regimen exerted neither substantial lung fluid retention nor lung mechanics deterioration but a trend of higher pulmonary surfactant-associated phospholipid pools.

Induction of immunogenic cell death in murine colon cancer cells by ferrocene-containing redox phospholipid polymers.

Immunogenic cell death (ICD), activated by damage-associated molecular patterns (DAMPs), is an apoptotic cell death process that elicits antitumor immunity. Although anticancer drugs that can induce ICD are promising for cancer treatment, the design strategy for ICD inducers remains unclear. In this study, we demonstrated the cell-penetrating redox phospholipid polymer poly(2-methacryloyloxyethyl phosphorylcholine-co-vinyl ferrocene) (pMFc) inducing ICD in murine colon cancer CT26 cells. pMFc produced oxidative stress by extracting electrons from CT26 cells and induced the release of DAMPs, such as calreticulin, adenosine triphosphate, and high-mobility group box 1. Moreover, the injection of pMFc-treated CT26 cells inhibited tumor formation in subsequently challenged CT26 cells, indicating that pMFc elicited antitumor immunity through ICD. Using in vivo therapy, intratumoral injections of pMFc induced complete tumor regression in 20% (1/5) of mice. These results suggested that the redox phospholipid polymer provides a new option for ICD-inducing anticancer polymers.

Poractant alfa versus bovine lipid extract surfactant: prospective comparative effectiveness study.

OBJECTIVE: To compare short term respiratory outcomes in preterm infants treated with bovine lipid extract surfactant or poractant alfa. STUDY DESIGN: Prospective comparative effectiveness cohort study of infants <32 weeks' gestational age requiring surfactant in thirteen centers. Each center provided bovine lipid extract surfactant for a set period of time in the year 2019 and then changed to poractant alfa for the remainder of the year. The primary outcome was total duration of respiratory support. RESULT: 968 infants were included. 494 received bovine lipid extract surfactant and 474 received poractant alfa. No difference was observed in the total duration of respiratory support (mechanical ventilation or non-invasive) (median 38 vs 40.5 days), need to re-dose surfactant, bronchopulmonary dysplasia, survival to discharge, or length of admission. CONCLUSION: In this pragmatic study, we did not identify any difference in short term outcomes between the groups based on the type of surfactant received.

Phospholipids in small extracellular vesicles: emerging regulators of neurodegenerative diseases and cancer.

Small extracellular vesicles (sEVs) are generated by almost all cell types. They have a bilayer membrane structure that is similar to cell membranes. Thus, the phospholipids contained in sEVs are the main components of cell membranes and function as structural support elements. However, as in-depth research on sEV membrane components is conducted, some phospholipids have been found to participate in cellular biological processes and function as targets for cell-cell communication. Currently, sEVs are being developed as part of drug delivery systems and diagnostic factors for various diseases, especially neurodegenerative diseases and cancer. An understanding of the physiological and pathological roles of sEV phospholipids in cellular processes is essential for their future medical application. In this review, the authors discuss phospholipid components in sEVs of different origins and summarize the roles of phospholipids in sEV biogenesis. The authors further collect the current knowledge on the functional roles of sEV phospholipids in cell-cell communication and bioactivities as signals regulating neurodegenerative diseases and cancer and the possibility of using sEV phospholipids as biomarkers or in drug delivery systems for cancer diagnosis and treatment. Knowledge of sEV phospholipids is important to help us identify directions for future studies.

Physiologically Active Molecules and Functional Properties of Soybeans in Human Health-A Current Perspective.

In addition to providing nutrients, food can help prevent and treat certain diseases. In particular, research on soy products has increased dramatically following their emergence as functional foods capable of improving blood circulation and intestinal regulation. In addition to their nutritional value, soybeans contain specific phytochemical substances that promote health and are a source of dietary fiber, phospholipids, isoflavones (e.g., genistein and daidzein), phenolic acids, saponins, and phytic acid, while serving as a trypsin inhibitor. These individual substances have demonstrated effectiveness in preventing chronic diseases, such as arteriosclerosis, cardiac diseases, diabetes, and senile dementia, as well as in treating cancer and suppressing osteoporosis. Furthermore, soybean can affect fibrinolytic activity, control blood pressure, and improve lipid metabolism, while eliciting antimutagenic, anticarcinogenic, and antibacterial effects. In this review, rather than to improve on the established studies on the reported nutritional qualities of soybeans, we intend to examine the physiological activities of soybeans that have recently been studied and confirm their potential as a high-functional, well-being food.

The Potential for Phospholipids in the Treatment of Airway Inflammation: An Unexplored Solution.

Asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) are major inflammatory respiratory diseases. Current mainstay therapy for asthma, and chronic obstructive pulmonary disease are corticosteroids, which have well-established side effect profiles. Phospholipids (PLs) are ubiquitous, diverse compounds with varying functions such as their structural role in the cell membrane, energy storage, and cell signaling. Recent advances in understanding PLs role as inflammatory mediators in the body as well as their widespread long-standing use as carrier molecules in drug delivery demonstrate the potential application of PLs in modulating inflammatory conditions. This review briefly explains the main mechanisms of inflammation in chronic respiratory diseases, current anti-inflammatory treatments and areas of unmet need. The structural features, roles of endogenous and exogenous phospholipids, including their use as pharmaceutical excipients, are reviewed. Current research on the immunomodulatory properties of PLs and their potential application in inflammatory diseases is the major section of this review. Considering the roles of PLs as inflammatory mediators and their safety profile established in pharmaceutical formulations, these small molecules demonstrate great potential as candidates in respiratory inflammation. Future studies need to focus on the immunomodulatory properties and the underlying mechanisms of PLs in respiratory inflammatory diseases.

PLACK syndrome is potentially treatable with intralipids.

We describe an 11-year-old girl with PLACK Syndrome (peeling skin, leukonychia, acral punctate keratosis, cheilitis, and knuckle pads), who was found to have a novel homozygous variant in CAST, the pathogenicity of which was confirmed using blood-derived RNA. There is no established treatment for PLACK syndrome. However, we demonstrate for the first time that this condition is associated with low levels of vitamin A and essential fatty acids, which prompted us to consider a potential treatment strategy. Indeed, we initiated this patient on intravenous lipid infusion (Vitalipid®; an emulsion of fat-soluble vitamins and lipofundin-MCT/LCT 20%) and the response was dramatic. Following the fourth monthly course of treatment, pruritis disappeared and the skin lesions showed remarkable objective improvement. PLACK syndrome is a very rare genodermatosis and only six families have been described to date with pathogenic CAST variants. This is the first report of an objective response to a therapeutic agent, which suggests that PLACK is a potentially treatable condition. The remarkable response we report and the relative safety of the intervention should prompt healthcare providers who care for PLACK syndrome patients to explore this as a potential treatment strategy in future studies.

Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial.

OBJECTIVE: To compare efficacy and safety of a new synthetic surfactant, CHF5633, enriched with surfactant proteins, SP-B and SP-C peptide analogues, with porcine surfactant, poractant alfa, for the treatment of respiratory distress syndrome in infants born preterm. STUDY DESIGN: Neonates born preterm on respiratory support requiring fraction of inspired oxygen (FiO2) ≥0.30 from 240/7 to 266/7 weeks and FiO2 ≥0.35 from 270/7 to 296/7 weeks of gestation to maintain 88%-95% oxygen saturation were randomized to receive 200 mg/kg of CHF5633 or poractant alfa. If necessary, redosing was given at 100 mg/kg. Efficacy end points were oxygen requirement (FiO2, respiratory severity score [FiO2 × mean airway pressure]) in the first 24 hours, 7 and 28 days, discharge home, and/or 36 weeks of postmenstrual age; mortality and bronchopulmonary dysplasia at 28 days and 36 weeks of PMA. Adverse events and immunogenicity were monitored for safety. RESULTS: Of the 123 randomized neonates, 113 were treated (56 and 57 in CHF5633 and poractant alfa groups, respectively). In both arms, FiO2 and respiratory severity score decreased from baseline at all time points (P < .001) with no statistically significant differences between groups. Rescue surfactant use (19 [33.9%] vs 17 [29.8%]), bronchopulmonary dysplasia (31 [55.4%] and 32 [56.1%]), and mortality at day 28 (4 [7.1%] and 3 [5.3%]) were similar in the CHF5633 and poractant alfa groups, respectively. In 2 (3.4%) and 1 (1.7%) neonates, adverse drug reactions were reported in CHF5633 and poractant alfa groups, respectively. No immunogenicity was detected. CONCLUSIONS: Treatment with CHF5633 showed similar efficacy and safety as poractant alfa in neonates born preterm with moderate-to-severe respiratory distress syndrome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02452476.

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.

Preconditioning rats with three lipid emulsions prior to acute lung injury affects cytokine production and cell apoptosis in the lung and liver.

BACKGROUND: Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. We sought to study whether preconditioning with representative of lipid emulsions for one week could benefit rats from ALI. METHODS: Using a lipopolysaccharide (LPS)-induced ALI rat model and techniques such as polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: PGE2 production in the serum was highest in the LPS group, followed with Intralipid group, and the PGE2 level of these two groups was significantly (P < 0.05) higher than the rest. Intralipid conditioning caused significantly less production of LTB4 than the LPS, Clinoleic, or Omegaven group. In contrast to Intralipid, rats pretreated with Clinoleic or Omegaven significantly decreased their production of inflammatory mediators (IL-1 ß, IL-6 and TNF-α), had less apoptosis in the lung tissues, and Omegaven greatly improved liver function upon lipopolysaccharide (LPS) challenge. CONCLUSIONS: In an ALI setting, preconditioning with Omegaven or Clinoleic was better than Intralipid in decreasing the intensity of the cytokine storm and apoptosis caused by LPS challenge, and Omegaven in addition had the potential to improve liver function. The results from the present study set a basis for further investigation of the molecular mechanisms of ALI, including the up- and downstream pathways of proinflammatory factor production, in search of (small) molecules intervening with the pathogenesis of ALI in order to translate relevant research findings into clinical benefit for patients with ALI. The use of Omegaven or Clinoleic, particularly in patients with ALI, is still characterized by uncertainty due to a lack of relevant studies. Future investigations must specifically focus on the route of administration and mode of application (enteral vs. parenteral/bolus vs. continuous), determining an optimal dose of Omegaven or Clinoleic, and the defining the best timepoint(s) for administration. Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. The effect of lipid emulsion via parenteral nutrition on liver function was first time evaluated in rats in an ALI setting. The comparison of three forms of lipid emulsion in a rat model of acute lung injury was first time studied. The fish oil-based lipid emulsion decrease in PGE 2 and increase in LTB 4 was first time reported.

Effect of two different early rescue surfactant treatments on mortality in preterm infants with respiratory distress syndrome.

INTRODUCTION: Although current evidence suggests that initial dose of 200 mg/kg poractant alfa reduces mortality in the treatment of respiratory distress syndrome (RDS), these data were obtained in a highly heterogeneous group of patients and neither of them addressed mortality as primary outcome. OBJECTIVE: The aim of this study was to investigate the effects of poractant alfa and beractant on mortality when administered as early rescue surfactant therapy in very preterm infants. METHODS: We retrospectively evaluated preterm infants followed in our unit between May 2017 and November 2018 whose gestational age (GA) was ≤28 weeks and received surfactant within the first 2 hours of life. Morbidities and mortality rates were compared between infants who received initial doses of 200 mg/kg poractant alfa and 100 mg/kg beractant. RESULTS: Data from 200 infants who met the inclusion criteria were analyzed. There were 112 patients in the poractant alfa group and 88 patients in beractant group. Mean gestational age in these groups was 26 ± 2 and 25.8 ± 1.8 weeks (P = 0.45) and mean birth weight was 812 ± 243 and 840 ± 208 g (P = 0.39), respectively. The poractant alfa and beractant groups had similar rates of overall mortality (53.5% vs 56.8%), mortality in first 7 days (30.5% vs 25.8%), and beyond day 7 (16.4% vs 13.3%) (P > 0.05). There were no differences in the incidence of preterm morbidities among the two groups. CONCLUSION: We were unable to demonstrate the superiority of poractant in terms of mortality in very preterm infants with RDS. These findings need to be supported by multicenter, randomized controlled trials.

A Comparison of Smoflipid® and Intralipid® in the Early Management of Infants with Intestinal Failure.

PURPOSE: Cholestasis is problematic for infants with intestinal failure (IF). The soy-based lipid Intralipid® (IL) has been implicated. An alternative, Smoflipid® (SMOF), is increasingly used. However, its role in cholestasis prevention is unclear. This study compares the incidence and degree of cholestasis between infants with IF receiving SMOF or IL. METHODS: Infants with IF receiving SMOF or IL during the first 8 weeks of parenteral nutrition (PN) support between 2014 and 2017 were reviewed. Clinical characteristics, cholestasis incidence (conjugated bilirubin (Cbili) >2 mg/dL for >2 weeks), and nutritional parameters were compared using Welch's t-test. RESULTS: 91% (21/23) of IL and 76% (16/21) of SMOF babies became cholestatic (p = 0.18). There was no significant difference in median peak Cbili, but SMOF babies normalized more quickly (p = 0.04). Median z-scores for weight were similar throughout the study. SMOF patients getting full PN had a lower incidence of cholestasis compared to IL patients (78% vs. 92%, p = 0.057), but those with cholestasis had similar peak Cbili, time to resolution, and growth. CONCLUSION: Early use of Smoflipid® did not reduce the incidence of cholestasis compared to Intralipid® in infants with IF, but hyperbilirubinemia did resolve more quickly. SMOF may be most beneficial for infants tolerating no enteral nutrition. LEVEL OF EVIDENCE: Level III Retrospective Comparative Treatment Study. TYPE OF STUDY: Retrospective Review.