Safety Analysis of Adverse Events of Ultrasound Contrast Agent Lumason/SonoVue in 49,100 Patients.

This study assessed the incidence of mild, moderate and severe adverse events (AEs) and examined their association with age, sex, body region examined, time to event and duration of the AE(s) in a large cohort of patients who underwent contrast-enhanced ultrasound (CEUS) with Lumason/SonoVue. In this retrospective observational study, 49,100 patients who underwent CEUS were analyzed. Forty-three (0.088%) patients experienced AEs, with 23 (0.047%) patients experiencing mild AEs, 13 (0.026%) experiencing moderate AEs and 7 (0.014%) experiencing severe AEs. No fatal event occurred. There was no age- or sex-related difference in the incidence of the AE(s) (p = 0.158 and p = 0.474). Inpatients (0.17%) more often experienced AEs than outpatients (0.06%, p = 0.003). The mean time to event for mild and moderate AEs was 14.50 ± 6.96 and 15.75 ± 10.40 min, respectively, whereas that for severe AEs was 1.89 ± 1.21 min after the injection. The remission time for mild and moderate AEs was approximately 30-40 min, and all patients with severe AEs recovered within 12 h. Twenty-one (48.8%) patients received medical treatment. In summary, Lumason/SonoVue has a good safety profile with a low incidence of AEs, most of which are mild with a short time to event and duration.

Trial of aerosolised surfactant for preterm infants with respiratory distress syndrome.

OBJECTIVE: To evaluate the safety of an aerosolised surfactant, SF-RI 1, administered via nasal continuous positive airway pressure (nCPAP) and a prototype breath synchronisation device (AeroFact), to preterm infants with respiratory distress syndrome (RDS). DESIGN: Multicentre, open-label, dose-escalation study with historical controls. SETTING: Newborn intensive care units at Mater Mothers' Hospital, Brisbane, and Royal Hospital for Women, Sydney, Australia. PATIENTS: Infants 26 weeks through 30 weeks gestation who required nCPAP 6-8 cmH2O and fraction of inspired oxygen (FiO2) <0.30 at <2 hours of age. INTERVENTIONS: In part 1, infants received a single dose of 216 mg/kg of aerosolised surfactant. In part 2, infants could receive up to four doses of aerosolised surfactant. Three historical control infants were matched for each enrolled infant. MAIN OUTCOME MEASURES: Treatment failure was defined as Respiratory Severity Score (FiO2×cmH2O nCPAP) >2.4, nCPAP >8 cmH2O, arterial carbon dioxide >65 mm Hg, pH <7.20 or three severe apnoeas within 6 hours during the first 72 hours of life. Other outcomes included tolerance of the AeroFact treatment and complications of prematurity. RESULTS: 10 infants were enrolled in part 1 and 21 in part 2 and were compared with 93 historical controls. No safety issues were identified. In part 2, 6 of 21 (29%) AeroFact-treated infants compared with 30 of 63 (48%) control infants met failure criteria. Kaplan-Meier analysis of patients in part 2 showed a trend towards decreased rate of study failure in the AeroFact-treated infants compared with historical controls (p=0.10). CONCLUSION: The AeroFact system can safely deliver aerosolised surfactant to preterm infants with RDS who are on nCPAP. TRIAL REGISTRATION NUMBER: ACTRN12617001458325.

Quantitative Analysis of Microperfusion in Contrast-Induced Nephropathy Using Contrast-Enhanced Ultrasound: An Animal Study.

OBJECTIVE: To investigate imaging biomarkers of microperfusion in contrast-induced nephropathy (CIN) using contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: The CIN model was fabricated by administering indomethacin (10 mg/kg), L-NAME (15 mg/kg), and iopamidol (10 mL/kg) to Sprague-Dawley rats. After 24 hours, CEUS was performed on CIN (n = 6) and control (n = 6) rats with sulphur hexafluoride microbubbles (SonoVue). From time-intensity curves obtained from the kidney arriving time (AT), acceleration time (AC), time to peak (TTP), and peak enhancement (PE) were measured and compared between the groups. After CEUS, the rats were sacrificed, and cell apoptosis markers were evaluated to confirm the development of CIN. RESULTS: Among CEUS parameters, AT (7.8 ± 1.6 vs. 4.2 ± 0.5 s, p = 0.002), AC (4.7 ± 1.4 vs. 2.0 ± 0.4 s, p = 0.002), and TTP (12.5 ± 2.9 vs. 6.2 ± 0.6 s, p = 0.002) were significantly prolonged in the CIN group compared to controls. PE was significantly higher in the control group than in the CIN group (17.1 ± 1.9 vs. 12.2 ± 2.0 dB, p = 0.004). In kidney tissue, mRNA and protein levels of the apoptotic makers were significantly higher in the CIN group than in the control group (p = 0.003 and p = 0.002). CONCLUSION: CEUS parameters can be used as imaging biomarkers for microperfusion in CIN. In rats with CIN, AT, AC, and TTP were significantly prolonged, while PE was significantly lower compared to controls.

Surfactant therapy for COVID-19 related ARDS: a retrospective case-control pilot study.

BACKGROUND: COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. METHODS: We performed retrospective analyses of data from patients receiving off-label use of exogenous natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. RESULTS: Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. CONCLUSIONS: Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration did not cause acute decompensation, may reduce mortality and mechanical ventilation duration in COVID-19 ARDS patients. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous sub-bronchial lavage with surfactant as treatment for patients with COVID-19 ARDS.

Souvenaid for Alzheimer's disease.

BACKGROUND: Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been designed to support the formation and function of synapses in the brain, which are thought to be strongly correlated with cognitive function. If effective, it might improve symptoms of Alzheimer's disease and also prevent the progression from prodromal Alzheimer's disease to dementia. We sought in this review to examine the evidence for this proposition. OBJECTIVES: To assess the effects of Souvenaid on incidence of dementia, cognition, functional performance, and safety in people with Alzheimer's disease. SEARCH METHODS: We searched ALOIS, i.e. the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science (ISI Web of Science), Cinahl (EBSCOhost), Lilacs (BIREME), and clinical trials registries up to 24 June 2020. We also reviewed citations of reference lists of landmark papers, reviews, and included studies for additional studies and assessed their suitability for inclusion in the review. SELECTION CRITERIA: We included randomised, placebo-controlled trials which evaluated Souvenaid in people diagnosed with mild cognitive impairment (MCI) due to AD (also termed prodromal AD) or with dementia due to AD, and with a treatment duration of at least 16 weeks. DATA COLLECTION AND ANALYSIS: Our primary outcome measures were incidence of dementia, global and specific cognitive function, functional performance, combined cognitive-functional outcomes and adverse events. We selected studies, extracted data, assessed the quality of trials and intended to conduct meta-analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We present all outcomes grouped by stage of AD. MAIN RESULTS: We included three randomised, placebo-controlled trials investigating Souvenaid in 1097 community-dwelling participants with Alzheimer's disease. One study each included participants with prodromal AD, mild AD dementia and mild-to-moderate AD dementia. We rated the risks of bias of all trials as low. One study (in prodromal AD) was funded by European grants. The other two studies were funded by the manufacturer of Souvenaid. One trial investigated the incidence of dementia in people with prodromal AD at baseline, and found little to no difference between the Souvenaid group and the placebo group after 24 months (RR 1.09, 95% CI 0.82 to 1.43; 1 trial, 311 participants; moderate quality of evidence). In prodromal AD, and in mild and mild-to-moderate Alzheimer's disease dementia, Souvenaid probably results in little or no difference in global or specific cognitive functions (moderate quality of evidence). Everyday function, or the ability to perform activities of daily living, were measured in mild and mild-to-moderate AD dementia. Neither study found evidence of a difference between the groups after 24 weeks of treatment (moderate quality of evidence). Two studies investigated combined cognitive-functional outcomes with the Clinical Dementia Rating Sum of Boxes and observed conflicting results. Souvenaid probably results in slight improvement, which is below estimates of meaningful change, in participants with prodromal Alzheimer's disease after 24 months (moderate quality of evidence), but probably has little to no effect in mild-to-moderate Alzheimer's disease dementia after 24 weeks (moderate quality of evidence). Adverse effects observed were low in all trials, and the available data were insufficient to determine any connection with Souvenaid. AUTHORS' CONCLUSIONS: Two years of treatment with Souvenaid probably does not reduce the risk of progression to dementia in people with prodromal AD. There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild-to-moderate stages of dementia. Conflicting evidence on combined cognitive-functional outcomes in prodromal AD and mild AD dementia warrants further investigation. Adverse effects of Souvenaid seem to be uncommon, but the evidence synthesised in this review does not permit us to make a definitive statement on the long-term tolerability of Souvenaid. The effects of Souvenaid in more severe AD dementia or in people with AD at risk of nutritional deficiencies remain unclear.

Transcholecystic Contrast-Enhanced Ultrasound-Guided Percutaneous Transhepatic Biliary Drainage for Central Bile Duct Protection During Thermal Tumor Ablation.

Intraductal cooling via a percutaneous transhepatic biliary drainage tube holds great promise in facilitating thermal ablation of liver tumors adjacent to the central bile ducts. However, the difficulties and complications associated with puncturing nondilated bile ducts are greater than those associated with puncturing dilated bile ducts. As reported here, percutaneous transcholecystic contrast-enhanced ultrasound was performed in 7 patients to visualize the nondilated bile ducts and guide percutaneous transhepatic biliary drainage, thus facilitating the intraductal cooling-assisted thermal ablation process. The procedures were technically successful in all 7 patients, and no major complications were recorded during the follow-up period.

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse.

The role of multiparametric ultrasound in the diagnosis of paediatric scrotal pathology.

Multiparametric ultrasound (MPUS), combining conventional techniques (greyscale and colour Doppler ultrasound), ultrasound strain elastography, and contrast-enhanced ultrasound (CEUS), has been successfully used in the assessment of adult scrotal pathology. Contrast-enhanced ultrasound can confidently establish testicular tissue vascularity even in the small-volume paediatric testis. Elastography provides further assessment of tissue stiffness, potentially adding useful diagnostic information. In children, ultrasonography is particularly advantageous, being safe, radiation-free and negating the need for sedation or general anaesthesia during the imaging evaluation. In this review article, we aim to familiarise readers with the MPUS scanning protocol used for paediatric scrotal examination and provide an overview of scrotal MPUS features, with particular focus to clinical indications where MPUS may be advantageous over conventional ultrasonography.

Adverse reactions after the use of SonoVue contrast agent: Characteristics and nursing care experience.

The aim of this study was to analyze the clinical manifestations of adverse reactions after the use of SonoVue contrast agent from a large retrospective database, and to evaluate the nursing care strategies and the efficacy of standardized procedure for adverse reactions of SonoVue (SPARS).From January 1, 2012 to December 30, 2018, 34,478 cases of contrast-enhanced ultrasonography were performed in our center. The clinical manifestations of adverse reactions after the use of SonoVue contrast agent were identified and analyzed. The nursing care strategies were evaluated and the outcomes of patients with moderate and severe adverse reactions before and after the application of SPARS were compared.Of the 34,478 cases, 40 cases (0.12%) of adverse reactions after the use of SonoVue were identified. Adverse reactions included anaphylatic shock, skin allergies, nausea or vomiting, dizziness or headache, numbness, chest distress, back pain, and local reactions of the injection site. Most of the adverse reactions were mild and self-limited. Only 3 cases of anaphylatic shock and 2 cases of severe rash underwent further treatments. The 3 patients who were managed by SPARS recovered quicker and spent less comparing with the other 2 patients who were not.SonoVue was a safe contrast agent, with few and mostly mild adverse reactions. SPARS may be an efficient way in tackling moderate to severe adverse reactions, although of which the incidence was rare.

Mechanistic insights into the aetiology of post-prandial decline in testosterone in reproductive-aged men.

Obesity is known to be associated with impaired testicular function potentially resulting in androgen deficiency and subfertility. While the underlying cause of obesity-related male hypogonadism is multi-factorial, here, we investigated the impact of dietary fat on testicular endocrine function. Ingestion of a high-fat "fast food" mixed meal, a common practice for obese men, produced a 25% fall in serum testosterone within an hour of eating, with levels remaining suppressed below fasting baseline for up to 4 hr. These changes in serum testosterone were not associated with any significant changes in serum gonadotrophins. The nadir in serum testosterone preceded the post-prandial increase in serum IL-6/IL-17 by several hours, suggesting that inflammation was unlikely the cause. Furthermore, intravenous administration of fat (Intralipid) had no impact on testosterone levels, while an identical oral dose of fat did suppress testosterone. These results suggest that fat does not directly impair Leydig cell function, but rather the passage of fat through the intestinal tract elicits a response that indirectly elicits a post-prandial fall in testosterone.

Cardiorespiratory Physiology following Minimally Invasive Surfactant Therapy in Preterm Infants.

INTRODUCTION: Surfactant replacement therapy through the endotracheal tube has been shown to improve lung compliance and reduce pulmonary pressures. Minimally invasive surfactant therapy (MIST) combines the benefits of continuous positive airway pressure (CPAP) and surfactant for spontaneously breathing preterm infants. We aimed to characterize the haemodynamic changes accompanying the first dose of MIST in preterm infants. METHODS: Poractant alfa (200 mg/kg) was administered as MIST while on CPAP support. Echocardiograms were performed before (T1) and 30 (T2) and 60 min (T3) after MIST to assess serial change. RESULTS: Twenty infants (mean gestational age 29.5 ± 2.8 weeks, median birth weight 1,102 g, IQR 840-1,940) received MIST at a median age of 16 h (IQR 3-24). FiO2 decreased significantly at 30 min (0.41 ± 0.08 to 0.27 ± 0.03, p < 0.001). Significant changes were noted at T2 for ductal parameters (decreased % time right to left shunt: 25% [15-33] to 14.5% [6-22], p = 0.013). Reduced pulmonary vascular resistance (PVR; increased pulmonary artery time velocity ratio 0.23 ± 0.05 to 0.28 ± 0.04 ms, p = 0.004) and improved longitudinal (tricuspid annular plane systolic excursion 4.5 ± 0.8 to 5.3 ± 0.9 mm, p = 0.004) and global (fractional area change 25 ± 2.3 vs. 27 ± 2%, p = 0.002) ventricular function were noted. CONCLUSIONS: This is the first study assessing cardiovascular adaptation to MIST, a procedure fast gaining acceptance in the neonatal community. Increased pulmonary blood flow is likely due to a combined effect of increased ductal flow, reduced PVR, and increased ventricular function.

Efficacy and tolerability of a fixed dose combination of cortex phospholipid liposomes and cyanocobalamin for intramuscular use in peripheral neuropathies.

Peripheral neuropathies are frequently encountered in clinical practice and are associated with a major impairment in quality of life. However, their management remains poor, and current therapies are often burdened with major side effects and can present poor efficacy on pain and functionality. Therefore, it has been suggested that the combination of two or more different drugs may improve analgesic efficacy and reduce side effects. Tricortin® 1000 is formulated with 12 mg of Brain cortex phospholipid liposomes + 1000 µg of Cyanocobalamin injectable solution (PL+CNCbl) for intramuscular use and is indicated in the treatment of poly-algo-neuropathic syndromes. This combination exerts a marked neurotrophic action by promoting the synthesis of endogenous phospholipids; moreover, the peculiar formulation optimizes the delivery of CNCbl which has analgesic and neurotrophic action. This paper discusses the pharmacotherapy of peripheral neuropathies, including low-back pain, neck pain, postherpetic neuropathy (PHN) and focuses on the fixed dose combination PL+CNCbl clinical efficacy in association with other treatments or in monotherapy.

Multi-component lipid emulsion vs soy-based lipid emulsion for very low birth weight preterm neonates: A pre-post comparative study.

OBJECTIVE: To examine the effectiveness of soybean oil-medium chain triglycerides-olive oil-fish oil lipid emulsion (SMOF-LE) on clinical outcomes of very-low-birth-weight neonates. STUDY DESIGN: We conducted a pre-post comparative study of very-low-birth-weight neonates, dividing them according to lipid emulsion received: Intralipid (soy-based; n = 680) or SMOF-LE (n = 617). Primary outcomes were mortality, chronic lung disease, severe retinopathy, infection, and necrotising enterocolitis. Secondary outcomes were cholestasis, osteopenia, time to full feeds, and time to regain birthweight. RESULTS: Baseline characteristics between groups were comparable. Primary outcomes did not differ significantly between groups, although any retinopathy was significantly lower in the SMOF-LE group. SMOF-LE group had lower odds of cholestasis, osteopenia, and lipid interruption, and reduced times to full feeds and to regain birthweight. CONCLUSIONS: Compared with Intralipid, SMOF-LE was not associated with differences in mortality and major morbidities but was associated with lower odds of any retinopathy, cholestasis, and osteopenia; and improved lipid tolerance.

Lipid emulsions for parenterally fed term and late preterm infants.

BACKGROUND: Lipid emulsions (LE) form a vital component of infant nutrition for critically ill, late preterm or term infants, particularly for those with gastrointestinal failure. Conventionally used soybean oil-based LE (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols, which may contribute to adverse effects including parenteral nutrition-associated liver disease (PNALD). OBJECTIVES: To compare the safety and efficacy of all LE for parenteral nutrition (PN) in term and late preterm infants (between 34 weeks' gestation and 36 weeks' and six days' gestation) with or without surgical conditions or PNALD within first six months of life, using all possible direct comparisons. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE (1946 to 18 June 2018), Embase (1974 to 18 June 2018), CINAHL (1982 to 18 June 2018), MIDRIS (1971 to 31 May 2018), conference proceedings, trial registries (ClinicalTrials.gov and the WHO's Trials Registry), and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled studies in term and late preterm infants, with or without surgical conditions or PNALD. DATA COLLECTION AND ANALYSIS: Data collection and analysis conformed to the methods of Cochrane Neonatal. We used the GRADE approach to assess the quality of evidence for important outcomes in addition to reporting the conventional statistical significance of results. MAIN RESULTS: The review included nine randomised studies (n = 273). LE were classified in three broad groups: 1. all fish oil-containing LE including pure fish oil (F-LE) and multisource LE (e.g. medium-chain triglycerides (MCT)-olive-fish-soybean oil-LE (MOFS-LE), MCT-fish-soy oil-LE (MFS-LE) and olive-fish-soy-LE (OFS-LE)); 2. conventional pure S-LE; 3. alternative-LE (e.g. MCT-soy-LE (MS-LE), olive-soy-LE (OS-LE) and borage oil-based LE).We considered four broad comparisons: 1. all fish oil LE versus non-fish oil LE (6 studies; n = 182); 2. fish oil LE versus another fish oil LE (0 studies); 3. alternative-LE versus S-LE (3 studies; n = 91); 4. alternative-LE versus another alternative-LE (0 studies) in term and late preterm infants (0 studies), term and late preterm infants with surgical conditions (7 studies; n = 233) and term and late preterm infants with PNALD/cholestasis (2 studies; n = 40).PNALD/cholestasis was defined as conjugated bilirubin (Cbil) 2 mg/dL or greater and resolution of PNALD/cholestasis as Cbil less than 2 mg/dL. We put no restriction on timing of PNALD detection. There was heterogeneity in definitions and time points for detecting PNALD in the included studies.We found one study each in surgical infants and in infants with cholestasis, showing no evidence of difference in incidence or resolution of PNALD/cholestasis (Cbil cut-off: 2 mg/dL) with use of fish oil-containing LE compared to S-LE.We considered an outcome allowing for any definition of PNALD (different Cbil cut-off levels). In infants with surgical conditions and no pre-existing PNALD, meta-analysis showed no difference in the incidence of PNALD/cholestasis (any definition) with use of fish oil-containing LE compared to S-LE (typical risk ratio (RR) 1.20, 95% confidence interval (CI) 0.38 to 3.76; typical risk difference (RD) 0.03, 95% CI -0.14 to 0.20; 2 studies; n = 68; low-quality evidence). In infants with PNALD/cholestasis (any definition), use of fish oil-LEs was associated with significantly less cholestasis compared to the S-LE group (typical risk ratio (RR) 0.54, 95% confidence interval (CI) 0.32 to 0.91; typical risk difference (RD) -0.39, 95% CI -0.65 to -0.12; number needed to treat for additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; 2 studies; n = 40; very low-quality evidence). This outcome had very low number of participants from two small studies with differences in study methodology and early termination in one study, which increased uncertainty about the effect estimates.One study in infants with cholestasis reported significantly better weight gain with a pure fish oil LE compared to a 10% S-LE (45 g/week, 95% CI 15.0 to 75.0; n = 16; very low-quality evidence). There were no significant differences in growth parameters in studies with surgical populations.For the secondary outcomes, in infants with cholestasis, one study (n = 24) reported significantly lower conjugated bilirubin levels but higher gamma glutamyl transferase levels with MOFS-LE (SMOFlipid) versus S-LE (Intralipid) and another study (n = 16), which was terminated early, reported significantly higher rates of rise in alanine aminotransferase (ALT) and conjugated bilirubin levels in the S-LE group compared to pure F-LE (Omegaven).In surgical infants, two studies each reported on hypertriglyceridaemia and Cbil levels with one study in each outcome showing significant benefit with use of a F-LE and the other study showing no difference between the groups. Meta-analysis was not performed for either of these outcomes as there were only two studies showing conflicting results with high heterogeneity between the studies.There was no evidence of differences in death, sepsis, alkaline phosphatase and ALT levels in infants with surgical conditions or cholestasis (very low-quality evidence).One study reported neurodevelopmental outcomes at six and 24 months in infants with surgical conditions (n = 11) with no evidence of difference with use of pure F-LE versus S-LE. Another study in infants with cholestasis (n = 16) reported no difference in head growth velocity between pure F-LE versus S-LE.GRADE quality of evidence ranged from low to very low as the included studies were small single-centre studies. Three of the six studies that contributed data to the review were terminated early for various reasons. AUTHORS' CONCLUSIONS: Based on the current review, there is insufficient data from randomised studies to determine with any certainty, the potential benefit of any LE including fish oil-containing LEs over another LE, for prevention or resolution of PNALD/cholestasis or any other outcomes in term and late preterm infants with underlying surgical conditions or cholestasis. There were no studies in infants without surgical conditions or cholestasis.Further research is required to establish role of fish oil or lipids from other sources in LEs to improve PNALD/cholestasis, and other clinical outcomes in parenterally fed term and late preterm infants.

Propofol use in children with allergies to egg, peanut, soybean or other legumes.

Propofol is the most commonly administered intravenous agent for anaesthesia in children. However, there are concerns that the emulsified preparation may not be safe in children with an allergy to egg, peanut, soybean or other legumes. We conducted a retrospective study of children with immunologically confirmed egg, peanut, soybean or legume allergy and who underwent general anaesthesia at Princess Margaret Hospital for Children between 2005 and 2015. We extracted details regarding allergy diagnosis, each anaesthetic administered and any adverse events or signs of an allergic reaction in the peri-operative period. A convenience sample of patients without any known food allergies was identified from our prospective anaesthesia research database and acted as a control group. We identified 304 food-allergic children and 649 procedures where propofol was administered. Of these, 201 (66%) had an egg allergy, 226 (74%) had a peanut allergy, 28 (9%) had a soybean allergy and 12 (4%) had a legume allergy. These were compared with 892 allergy-free patients who were exposed to propofol. In 10 (3%) allergy patients and 124 (14%) allergy-free patients, criteria for a possible allergic reaction were met. In nine of the food-allergic children and in all the controls valid non-allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a child with a previous history of intralipid allergy. We conclude that genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.

SMOFlipid Protects Preterm Neonates against Perinatal Nutrition-Associated Cholestasis.

OBJECTIVE: Intravenous lipid infusions improve both short- and long-term outcomes of premature neonates. However, prolonged infusion of lipids has been implicated in the development of parenteral nutrition-associated cholestasis (PNAC). We speculated that the multicomponent SMOFlipid would be hepatoprotective against PNAC. STUDY DESIGN: This is a retrospective review comparing the incidence and severity of direct hyperbilirubinemia in preterm infants <1,500 g who were hospitalized for a minimum of 2 weeks during a 20-month period in which all preterm infants on total parenteral nutrition (TPN) received fat as Lipofundin with the following 20-month period in which all preterm infants on TPN received SMOFlipid. RESULTS: Infants in the SMOFlipid period had a lower incidence of PNAC (6 vs. 13%; p = 0.022), lower peak direct bilirubin levels (3.2 vs. 7.1 mg/dL; p = 0.018), and a shorter length of stay (51 vs. 60 days; p = 0.019). The relative risk of developing direct hyperbilirubinemia during the Lipofundin period was 2.22 (1.1-4.3) as compared with period 1; p = 0.018; NNT-14. CONCLUSION: SMOFlipid was hepatoprotective in our population of preterm neonates <1,500 g receiving long-term TPN as compared with those receiving Lipofundin, despite similar levels of exposure to both intravenous lipid load and duration in the two groups.

Underdosing of Surfactant for Preterm Babies with Respiratory Distress Syndrome in Clinical Practice: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the initial doses of surfactant administered to preterm infants with respiratory distress syndrome. STUDY DESIGN: This is a retrospective cohort study of 206 preterm infants admitted in four level III neonatal intensive care units of acute tertiary care hospitals in Spain between 2013 and 2015. RESULTS: The mean initial dose of surfactant was 173.9 (37.3) mg/kg, and 47.5% of infants received a dose of 200 mg/kg ± 10% (180-220 mg/kg), 47% less than 180 mg/kg (-10%), and 5.4% more than 220 mg/kg (+10%). Very preterm infants (<28 weeks) received higher initial doses than more mature infants, but in all cases, the mean doses were below the recommended 200 mg/kg (by 9.2% in gestational age 23-28 weeks, by 15.9% in 29-32 weeks, and by 24.3% in >32 weeks). CONCLUSION: Administration of surfactant below the prescribed dose is a frequent error in clinical practice. Inadvertently rounding down doses seems a plausible explanation.

Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study): study protocol for a randomized, controlled, multicenter, international clinical trial.

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017.

Intralipid® may represent a new hope for patients with reproductive failures and simultaneously an over-immune endometrial activation.

PROBLEM: Continuous failures to achieve a pregnancy despite effective embryo transfers is extremely distressing for couples. In consequence, many adjuvant therapies to IVF have been proposed to achieve an "ideal" immune environment. We here focus on Intralipid® therapy (IL) reported to have immunosuppressive properties on NK cells. METHOD OF STUDY: 94 patients exhibited an immune profile of endometrial over-immune activation and an history of repeated implantation failures despite multiple embryos transfers (RIF). They received a slow perfusion of Intralipid®. We here report the live birth rate following the procedure at the next embryo transfer. To get new insight on its mechanism of action, a second immune profiling had been performed under Intralipid® before the embryo transfer. RESULTS: The live birth rate of the RIF cohort treated with Intralipid® reached 54% (51/94) at the next embryo transfer. In patients successfully pregnant under Intralipid® who benefitted of a test of sensibility before the embryo transfer, we observed a significant decrease of the three biomarkers used to diagnose the over-immune endometrial activation (CD56 cells; IL-18/TWEAK, IL-14/FN-14). CONCLUSIONS: Double blind placebo versus Intralipid® studies should be conducted. Intralipid® may be an option to explore in RIF patients who exhibit an over-immune activation of uNK cells.

Low-intensity pulsed ultrasound in combination with SonoVue induces cytotoxicity of human renal glomerular endothelial cells via repression of the ERK1/2 signaling pathway.

OBJECTIVES: Low-intensity pulsed ultrasound (LIPUS) and SonoVue have been used widely for diagnosis and therapeutic treatment. The effects of LIPUS and SonoVue on the microvascular system and underlying molecular mechanisms have not been established. METHODS: Cultured human renal glomerular endothelial cells (HRGECs) were treated with 5-min ultrasonic irradiation, 20% SonoVue or the combination of both treatments. Cell proliferation, viablity, and apoptosis were measured by MTT assay, Trypan blue exclusion assay and flow cytometry, respectively. Activation of extracellular regulated protein kinases (ERK) were examined by Western blot. RESULTS: We found that LIPUS and SonoVue alone do not induce cytotoxicity of HRGECs; however, the combination of the two treatments reduces cell proliferation and increases cell death. In addition, the combination of LIPUS and SonoVue suppressed the activation of ERK 1/2 in HRGRCs. With pretreatment of the inhibitor of ERK1/2 signaling, PD98059, LIPUS, and SonoVue does not induce additional cell death and inhibition of proliferation. CONCLUSIONS: LIPUS combined with SonoVue induces cytotoxicity of HRGECs via repression of the ERK1/2 signaling pathway.