Effects on hemodynamics and gas exchange of omega-3 fatty acid-enriched lipid emulsion in acute respiratory distress syndrome (ARDS): a prospective,randomized, double-blind,parallel group study

Introduction  

We investigated the effects on hemodynamics and gas exchange of a lipid emulsion enriched with omega-3 fatty acids in patients with ARDS.     

Alveolar epithelial barrier in patients with acute respiratory distress syndrome (ARDS)

The clearance of alveolar fluid depends on the anatomic and physiologic integrity of alveolar epithelial barrier. The vectorial transport of sodium begins at the apical surface in the type II cell through amiloride-sensitive sodium channel. Sodium is pumping by Na, K-ATPasa from the basolateral surface of type II cell to the interstice. Water passes through specialized channels in the type I cell membrane by the osmotic gradient created by sodium. The activity of the sodium transporters is regulated actively by genetics and depends on molecular processes that involve the hormonal stimulation. The damage to the epithelial membrane produces an increased of the permeability of great molecules, which favors generation of edema in the alveolar space, delay in the resolution and incapacity to regenerate epithelium. More clinic trials are required to demonstrate the paper of the transport of chloride and to clarify the true function of the specialized water channels in the regulation of the alveolar fluid clearance.     

重症监护病房中急性呼吸窘迫综合征的预后危险因素探讨

目的 探讨重症监护病房(ICU)中急性呼吸窘迫综合征(ARDS)的死亡率以及预后危险因素.方法 根据从2009年1月～2011年1月入住某院重症监护病房(ICU)中的急性呼吸窘迫综合征(ARDS)的230例患者,采用1992年欧美ARDS联席会议提议通过的ARDS诊断标准,对患者进行持续24h的治疗时间,并进行临床观察.结果 2009年1月～2011年1月入住的重症监护病房(ICU)中的急性呼吸窘迫综合征(ARDS)的230例患者,其中肺源性患者85例,肺外源性患者145例.在此治疗期间,采用APACHEII评分标准对死亡率进行调整,调整2年时间内死亡率没有明显变化(P=0.85),并且根据多方面因素的资料研究分析,ARDS死亡因素有很多,包括患者年龄、基础病理、多功能器官功能障碍妨碍住院时间的治疗,其中导致死亡率最高的因素就是脓毒性休克和心功能衰竭,死于呼吸衰竭的患者其实很少.结论 急性呼吸窘迫综合征(ARDS)是近两年来该院接收最常见的患者之一,也是死亡率比较高的急重病,脓毒性休克和心功能衰竭都是导致ARDS死亡率增高的主要原因.     

Mechanical ventilation in acute respiratory distress syndrome (ARDS): lung protecting strategies for improved alveolar recruitment

For patients with acute respiratory distress syndrome (ARDS) the most important objective of mechanical ventilation is opening and keeping open the alveoli to achieve adequate oxygenation, without further damaging the lungs or negatively affecting the circulation. Alveolar recruitment is achieved by making use of positive end-expiratory pressure (PEEP). The best PEEP level is that with which the largest improvement in oxygen transport and lung compliance is achieved, without a decrease in the stroke volume of the left ventricle. In addition to the usual volume-controlled ventilation with PEEP, pressure-limited ventilation is also possible. In this a preselected pressure is never exceeded, whereas a maximum inspiratory airflow at the start of inspiration provides more opportunity for gaseous exchange. The oxygenation can possibly be further improved by increasing the inspiration-expiration ratio. As a result of the reduced expiratory period the alveoli which tend to collapse at the end of a normal expiration are kept open. Mechanical ventilation with a lower tidal volume decreases mortality. Ventilation in a prone position increases the end-expiratory lung volume and reduces the intrapulmonary shunt and the regional differences in the degree of ventilation. These factors possibly contribute to preventing ventilation-induced lung damage. Administration of natural surfactant during the ventilation of patients with ARDS seems to be a highly promising strategy; the clinical effectiveness still needs to be demonstrated.     

Intake of 25-hydroxyvitamin D3 reduces duration and severity of upper respiratory tract infection: A randomized,double-blind,placebo-controlled,parallel group comparison study

Objectives

This study aimed to assess the effect of 25-hydroxyvitamin D3 (25OHD) which is a hydroxide of vitamin D3 ingestion on upper respiratory tract infection (URTI).

Design and Setting

A prospective, randomized, double-blind, placebo-controlled study was performed from December 2015 to September 2016 in the Nihonbashi Egawa Clinic, Kei Medical Office TOC Building Medical Clinic, and Medical Corporation Kaiseikai Kita-Shinyokohama Medical Clinic, in Japan.

Participants

Four hundred twenty eight participants aged 45-74 years were screened by their serum 25-hydoroxyvitamin D concentration.

Intervention

The participants were randomized to either 25OHD (10 μg/day) or placebo capsule, daily, for 16 consecutive weeks.

Measurements

The primary outcome measure was the incidence proportion of URTI, and the secondary outcome measures were the physical severity score, the quality-of-life (QOL) score, the duration of URTI, and the incidence proportion of new URTI events every four weeks. Data were collected using cold diary Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) during the intervention.

Results

Of 428 participants screened, 252 with serum 25-hydroxyvitamn D levels were deficient or insufficient (75 nmol/L or less) were enrolled in this study. Of these, 105 placebo and 110 25OHD group subjects completed the study. For the incidence proportion of URTI, no effect of 25OHD intake was observed. On the other hand, the duration of URTI was shorter in the 25OHD (P = 0.061) compared to placebo. For the incidence proportion of URTI every four weeks, the incidence of new URTI was decreased in both groups over the time of intake. However, when the 25OHD and the placebo were compared, a decrease in the incidence proportion of URTI was seen earlier in the 25OHD. When the total physical severity score and the total QOL score during the study were assessed, they both were significantly improved in the 25OHD compared to placebo.

Conclusions

The intake of 25OHD may reduce the duration of URTI, the physical severity, and the QOL when suffering from URTI.

     

A prospective, randomized clinical trial on perioperative feeding with an arginine-, omega-3 fatty acid-, and RNA-enriched enteral diet: effect on host response and nutritional status

BACKGROUND: The use of immune-enhancing enteral diets in the postoperative period has given contrasting results. The purpose of this prospective, randomized, double-blinded clinical study was to evaluate the effect of immunonutrition given perioperatively on cytokine release and nutritional parameters. METHODS: Patients with cancer of the stomach or colo-rectum were eligible. Subjects consumed 1 L/d of either a control enteral formula (n = 25; control group) or a formula supplemented with arginine, omega-3 fatty acids, and RNA (n = 25; verum group) for 1 week before surgery. Both formulas were given by mouth. Six hours after the operation, jejunal infusion with the same diets was started and maintained for 7 days. Blood was drawn at different time points to assess albumin, prealbumin (PA), transferrin, cholinesterase activity, retinol binding protein (RBP), interleukin-2 receptors alpha (IL-2Ralpha), IL-6, and IL-1 soluble receptors (IL-1RII). The composite score of delayed hypersensitivity response (DHR) to skin test also was determined (the higher the score, the lower the immune response). RESULTS: During the 7 days of presurgical feeding, none of the above parameters changed in either group. Eight days after operation, in the control group, the concentration of PA and RBP was lower than in the verum group (0.18 vs 0.26 g/L for PA and 30.5 vs 38.7 mg/L for RBP; p < .05). IL-2Ralpha concentration was 507 pg/mL in the verum group vs 238 pg/mL in the control group (p < .001), whereas IL-6 and IL-1RII were higher in the control group than in the verum group (104 vs 49 and 328 vs 183 pg/mL, respectively; p < .01). The DHR score was 0.68 in the control group vs 0.42 in the verum group (p < .05). CONCLUSIONS: Perioperative feeding with a supplemented enteral diet modulates cytokine production and enhances cell-mediated immunity and the synthesis of short half-life proteins.     

A 3-month double-blind randomised study comparing an olive oil- with a soyabean oil-based intravenous lipid emulsion in home parenteral nutrition patients

Intravenous lipid emulsions (ILE) have demonstrated advantages including prevention of essential fatty acid (EFA) deficiency; however, too much EFA can down regulate fatty acid elongation leading to an imbalance of nutritional compounds in plasma and cell membranes. An olive oil-based ILE containing long-chain triacylglycerols (LCT) with a low content (20 %) of PUFA was administered for home parenteral nutrition (HPN) and compared with a conventional soyabean oil-based ILE (PUFA content, 60 %). Thirteen patients (26-92 years) with stable intestinal failure were randomised after a 1-month run-in period with a medium-chain triacylglycerols-LCT-based ILE, to receive 3 months of HPN with either olive oil- (n 6) or soyabean oil-based (n 7) ILE. The nutritional impact and safety of HPN, oral intakes and absorption rates, phospholipid fatty acids in plasma and lymphocyte cell membrane were assessed. The only clinical event reported was one case of pneumonia (soya group). In both groups, 20 : 3n-9:20 : 4n-6 ratios remained within normal ranges (0.03-0.07). There was a significant increase of gamma-linolenic acid (gamma-LA) in plasma and lymphocyte cell membrane (P=0.02) and of oleic acid in plasma (P<0.01) in the olive compared with the soya group. A significant correlation was found between gamma-LA (day 90 - day 0) in plasma and PUFA parenteral intakes (P=0.02), but neither with fat intakes nor with fat absorption rates. In conclusion, plasma and lymphocyte EFA pattern remained in normal ranges without EFA deficiency with both lipid emulsions, despite a lower content of n-3 and n-6 series with the olive oil-based ILE.     

Effect of an omega-3 fatty acid containing lipid emulsion alone and in combination with 5-fluorouracil (5-FU) on growth of the colon cancer cell line Caco-2

Summary. Background: In this study we examined the effects of a fish oil-based lipid emulsion (FO) rich in omega-3 fatty acids, which is used in humans as a component of parenteral nutrition, on the growth of the colon cancer cell line Caco-2. Aim of the study: The aim of the present study was to investigate whether the FO influences growth and chemosensitivity of the colon cancer cell line Caco-2. FO was tested alone and in combination with the anticancer drug 5-fluorouracil (5-FU). Methods: Cell numbers were determined with crystal violet staining, cell cycle distribution was assessed using a flow cytometer and apoptosis was visualized by staining nuclei with diamino-phenylindole hydrochloride. Results: FO inhibited growth of Caco-2 cells in a time and dose dependent manner. FO treatment evoked apoptosis as confirmed by cell morphology. Cell cycle analysis identified an accumulation of cells in the G₂/M phase after incubation with FO. The combined treatment of the cells with FO and 5-FU resulted in a significant enhancement of the growth inhibition seen after exposure to either substance alone. Treatment of the cells with 5-FU specifically blocked the cell cycle in the S phase. The combined treatment of 5-FU with FO showed a further increase in the accumulation of cells in the S phase. Conclusions: In conclusion, FO has a potent antiproliferative effect on Caco-2 cells, at least in part, due to a decrease in the progression of the cell cycle and the induction of apoptosis. The combination of FO with 5-FU results in an additive growth inhibitory effect.     

Effects of 2 lipid emulsions (LCT versus MCT/LCT) on the fatty acid composition of plasma phospholipid: a double-blind randomized trial

BACKGROUND: Fatty acids from the diet or from IV fat emulsions are incorporated into the plasma and cell membrane phospholipids and act as substrates in the synthesis of eicosanoids. This study reports the effect of 2 parenteral lipid emulsions in plasma phospholipids fatty acids. METHODS: A total of 83 patients aged 18 to 75 years were randomized to receive long-chain triglycerides (LCT) or 50/50 mix of long- and medium-chain triglyceride emulsion (LCT/MCT). Blood samples were collected at baseline and at weekly intervals for 28 days. Plasma phospholipid fatty acids were measured by gas chromatography. RESULTS: Patients receiving LCT versus MCT/LCT emulsion have an increase in 18:2n6 and a decrease in 20:4n6 and 22:4n6 after 7, 14, and 21 days of treatment with parenteral nutrition. Phospholipid fatty acids at 15 days of treatment with parenteral nutrition with LCT versus MCT/LCT for 18:2n6 were 17.30% versus 22,90% (p < .05), for 20:4n6 10.44% versus 8.38% (p < .05), and for 22:4n6 0.51% versus 0.40% (p < .05). The 20:4n6 percentage inversely correlated with the percentage of 18:2n6 on days 7, 14, and 21: regression coefficients: -7.40 (p < .001), -7.39 (p < .001), and 5.70 (p < .001), respectively. CONCLUSIONS: Parenteral lipid emulsions modify fatty acid profiles in plasma phospholipids. MCT/LCT emulsions produce in phospholipids a fatty-acid profile that is closer to normality than that achieved with LCT emulsions. These changes in phospholipid fatty acids are suggestive of an inhibition of A-5-desaturase in patients who received LCT emulsions.     

Effects of omega-3 fatty acids on the frequency,severity, and duration of migraine attacks: A systematic review and meta-analysis of randomized controlled trials

The present systematic review with meta-analysis of randomized controlled trials (RCTs) aimed to analyze the effectiveness of omega-3 fatty acids on the frequency, severity, and duration of migraine. This systematic review was performed by searching several databases for controlled clinical trials. Of the 13 trials, five, two, and three RCTs met the eligibility criteria to evaluate the efficacy of omega-3 on the frequency, duration, and severity of migraine attacks, respectively. The Jadad scale was used to evaluate the risk of bias analysis. Overall estimates of the intervention effect were obtained from random-effect meta-analysis. The studies’ heterogeneity was evaluated using the chi-squared test (χ²) (Cochran’s test (Q test)) and I² Index. Potential sources of heterogeneity among the trials were investigated by meta-regression analyses. The results showed that omega-3 intake had no effect on frequency (WMD?=??0.20; 95%CI ?0.67, 0.27; P?=?0.401, and I²?=?4.6%; P?=?0.380) and severity (SMD?=??0.59; 95%CI??1.85, 0.66; P?=?0.35, and I²?=?88.8%; P?=?0.000) of migraine but had a reduction effect on the duration of migraine attacks (WMD?=??3.44; 95%CI ?5.70, ?1.19; P?=?0.003, and I²?=?0.0%; P?=?0.926). In conclusion, omega-3 intake leads to a significant reduction of approximately 3.44 hours in the duration of migraine. Further randomized controlled trials of high methodological quality with adequate sample sizes are required to confirm the results of the meta-analyses.     

A priori dietary omega-3 lipid supplementation results in local pancreatic macrophage and pulmonary inflammatory response attenuation in a model of experimental acute edematous pancreatitis (AEP)

BACKGROUND: Acute pancreatitis is often complicated by multiorgan dysfunction, which is postulated to occur in part by macrophage infiltration into the pancreas. Eicosapentaenoic acid (EPA), an omega-3 fatty acid, is the principal biologic component of fish oil and has clinically and experimentally been demonstrated to be anti-inflammatory. We hypothesized that dietary EPA supplementation before the induction of pancreatitis would attenuate both M-mediated local pancreatic and systemic pulmonary inflammatory response in an in vivo model of acute edematous pancreatitis (AEP). METHODS: Male Sprague-Dawley (SD) rats were pretreated 2 times per day with oral gavage with EPA (omega-3 fatty acid; 5 mg/kg/dose) or omega-6 fatty acid control (5 mg/kg/dose) or saline (equal volume) for 2 weeks. AEP was induced in omega-3, omega-6, and saline pretreated rats by 5 hourly subcutaneous (SC) injections of cerulein. Pancreas, lung, and serum were harvested 3 hours after the last cerulein injection. Severity of pancreatitis was confirmed by serum amylase and by histopathologic score. Pancreatic macrophage infiltration was assessed by confocal fluorescent microscopy, and pulmonary leukocyte respiratory burst (LRB) analysis was performed on mononuclear cells obtained from bronchioalveolar lavage (BAL). RESULTS: All animals demonstrated acute pancreatitis through hyperamylasemia and histopathologic examination. Confocal analysis demonstrated significantly lower macrophage infiltration, and BAL analysis by flow cytometry demonstrated significantly lower (p < .05) LRB in the omega-3-treated group compared with the omega-6 and the saline pancreatitis group. CONCLUSIONS: Attenuation of both pancreatic MPhi inflammatory response and pulmonary leukocyte respiratory burst in AEP by EPA supports further investigation into the potential role for EPA dietary supplementation in the progression of pancreatitis-associated sequelae.     

Immunogenicity and safety of a cell culture-derived inactivated trivalent influenza vaccine (NBP607): A randomized,double-blind,multi-center,phase 3 clinical trial

BackgroundCell culture-derived influenza vaccines (CCIVs) have several important advantages over egg-based influenza vaccines, including shorter production time, better preservation of wild-type virus antigenicity and large-scale production capacity.MethodsA randomized, double-blind, phase 3 trial was undertaken to evaluate the immunogenicity and safety of a novel cell culture-derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals, Seongnam, Korea) compared to the control vaccine (Agrippal^®S1, Novartis Vaccines and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older (Clinical trial Number—NCT02344134). Immunogenicity was determined at pre-vaccination, 1 month and 6 month post-vaccination by the hemagglutination inhibition assay. Solicited and unsolicited adverse events were assessed after vaccination.ResultsA total of 1156 healthy subjects were recruited. NBP607 met all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at 21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy the seroconversion criteria for influenza B irrespective of age. Although the geometric mean titer for each influenza subtype declined gradually, seroprotection rate still remained ≥80% for all subtypes up to six month after NBP607 administration. NBP607 recipients met the seroprotection criteria for all three influenza subtypes up to 6 month post-vaccination. There was no significant difference in the occurrence of adverse events between the NBP607 and control groups.ConclusionNBP607, a novel CCIV, showed excellent immunogenicity that lasted ≥6 months after vaccination and had tolerable safety profiles. In particular, NBP607 was more immunogenic against influenza B compared to the control, an egg-based subunit vaccine.     

A randomized,double-blind,controlled clinical trial to evaluate the safety and immunogenicity of an intranasally administered trivalent inactivated influenza vaccine with adjuvant LTh(αK): A phase I study

Background

A nasal influenza vaccine has been available only in a live attenuated form, which limits the range of recipients to immune-competent individuals. The present study evaluated a newly developed intranasal inactivated influenza vaccine with a novel adjuvant, heat-labile enterotoxin (LT) derived from E. coli (LTh(αK)).