Intravenous immunoglobulin therapy enhances suppressive regulatory T cells and decreases innate lymphoid cells in children with immune thrombocytopenia.

BACKGROUND: This study aimed to investigate the relationship between CD4+ regulatory T cells (Tregs) and innate lymphoid cells (ILCs) in children with primary immune thrombocytopenia (ITP) undergoing high-dose intravenous immunoglobulin (IVIG) therapy. METHODS: We enrolled a cohort of 30 children with newly diagnosed ITP and 30 healthy controls and collected blood samples for levels of Tregs, ILCs, relevant cytokines, and Treg suppression assay at the diagnosis, two days, four weeks, and one year (only platelet count) after high-dose IVIG treatment. IVIG partial responders was defined by a platelet count less than 100 × 109 /L at 12 months after IVIG treatment. RESULTS: Children with newly diagnosed ITP exhibited elevated levels of ILC1, ILC2, ILC3, Th17, myeloid dendritic cells (DCs), plasmacytoid DCs, and serum IFN-γ and IL-17A levels, accompanied by a decrease in IL-10-producing Tregs. High-dose IVIG therapy reversed these aberrations. Platelet counts positively correlated with Tregs (rho = 0.72) and negatively correlated with both ILC1 (rho = -0.49) and ILC3 (rho = -0.60) (P < 0.05). Significantly lower Tregs and higher ILC1, ILC3, DCs, and serum IL-17A levels were noted in the partial responders (n = 8) versus responders (n = 22; P < 0.05). We found that Tregs suppressed proliferation of ILCs and CD4+ T cells in CD25-depleted peripheral PBMCs and enhanced the apoptosis of CD4+ CD45RO+ T cells in vitro following IVIG therapy. CONCLUSIONS: Effective high-dose IVIG therapy for children with newly diagnosed ITP appears to result in the induction of Tregs, which suppresses ILC proliferation in vitro and is associated with platelet response.

Pomegranate extract inhibits migration and invasion of oral cancer cells by downregulating matrix metalloproteinase-2/9 and epithelial-mesenchymal transition.

Discovering drug candidates for the modulation of metastasis is of great importance in inhibiting oral cancer malignancy. Although most pomegranate extract applications aim at the antiproliferation of cancer cells, its antimetastatic effects remain unclear, especially for oral cancer cells. The aim of this study is to evaluate the change of two main metastasis characters, migration and invasion of oral cancer cells. Further, we want to explore the molecular mechanisms of action of pomegranate extract (POMx) at low cytotoxic concentration. We found that POMx ranged from 0 to 50 µg/mL showing low cytotoxicity to oral cancer cells. In the case of oral cancer HSC-3 and Ca9-22 cells, POMx inhibits wound healing migration, transwell migration, and matrix gel invasion. Mechanistically, POMx downregulates matrix metalloproteinase (MMP)-2 and MMP-9 activities and expressions as well as epithelial-mesenchymal transition (EMT) signaling. POMx upregulates extracellular signal-regulated kinases 1/2 (ERK1/2), but not c-Jun N-terminal kinase (JNK) and p38 expression. Addition of ERK1/2 inhibitor (PD98059) significantly recovered the POMx-suppressed transwell migration and MMP-2/-9 activities in HSC-3 cells. Taken together, these findings suggest to further test low cytotoxic concentrations of POMx as a potential antimetastatic therapy against oral cancer cells.

Diverse effects of parenteral arginine on systemic and local oxidant-antioxidant homeostasis and nitrosative stress in rats with subacute peritonitis.

BACKGROUND: The beneficial effects of arginine on oxidative stress have been previously reported; however, excess production of nitric oxide, an arginine metabolite, may cause hemodynamic instability and inflammatory response. Previous studies have demonstrated that parenteral arginine levels at 2%-4% of total calories may alleviate inflammation and enhance immunity, whereas greater than 6% of total calories may have adverse effects in rats with subacute peritonitis. Herein, we investigated the effects of parenteral arginine dose on lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and antioxidant enzyme activities in the plasma and organs. MATERIALS AND METHODS: Male Wistar rats with cecal puncture-induced subacute peritonitis were infused with parenteral nutrition solutions containing 1.61% (CP group), 2.85% (LA group), 4.08% (MA group), and 6.54% (HA group) of total calories as arginine for 7 d. Healthy, orally fed rats (NC group) were used as references. RESULTS: Subacute peritonitis significantly elevated the levels of nitrate, nitrite and TBARS in the plasma and decreased glutathione peroxidase activity in the kidneys. These changes were significantly reversed in the MA and HA groups. The MA and HA groups had significantly increased nitrotyrosine levels in the plasma. The LA, MA, and HA groups had significantly increased glutathione peroxidase activity in the plasma, cytochrome P450 levels in the liver, and nitrotyrosine levels in the heart and had significantly decreased TBARS levels in the kidneys compared with the CP group. CONCLUSIONS: Our results suggest that parenteral arginine at a dose less than 4% of total calories may attenuate lipid peroxidation and increase antioxidant enzyme activities without leading to nitrosative stress in subacute peritonitis.

Effectiveness of corticosteroids and epinephrine use in neonates for the first extubation attempt: A retrospective study.

BACKGROUND: This study aimed to analyze the use of corticosteroids and epinephrine in neonates for the first extubation attempt and compared clinical characteristics of infants with successful and failed extubation events. METHODS: This was a retrospective cohort study conducted at a single level III neonatal intensive care unit in Taiwan. The study included 215 infants born between 2020 and 2021 who had been intubated for more than 48 h before their first extubation attempt. We compared perinatal and peri-extubation characteristics and outcomes between the two groups. Successful extubation was defined as freedom from invasive ventilatory support 72 h after extubation. The relationship between corticosteroids, local epinephrine, and successful extubation was determined using multivariate logistic regression analysis. RESULTS: In the univariate analysis, the failed extubation group received a significantly higher proportion of intravenous dexamethasone (p = 0.006) than the successful extubation group. Furthermore, the failed extubation group had a longer duration of nebulized epinephrine (p = 0.034) and more episodes of local application of epinephrine to the superior larynx (p = 0.003) than the successful extubation group. Multivariate analysis revealed that the absence of lung atelectasis, tachycardia 72 h after extubation, and lower post-extubation PCO2 were the key factors associated with successful extubation. CONCLUSIONS: There were trends toward systemic dexamethasone, local application of epinephrine to the superior larynx, and longer duration of nebulized epinephrine in the reintubation group. However, corticosteroid or local epinephrine use was not significantly associated with successful extubation. Lung atelectasis, elevated levels of carbon dioxide, and tachycardia were identified as risk factors for extubation failure.

Neurodevelopment Outcomes in Very-Low-Birth-Weight Infants with Metabolic Bone Disease at 2 Years of Age.

Metabolic bone disease (MBD) predominantly affects preterm infants, particularly very-low-birth-weight (VLBW) infants weighing <1500 g. However, there are limited reports on MBD and neurodevelopmental outcomes. This study aimed to analyze the risk factors for MBD and understand its impact on neurodevelopmental outcomes at 2 years of corrected age. Overall, 749 VLBW infants weighing <1350 g at birth were enrolled. Exclusion criteria were major congenital abnormalities, chromosomal abnormalities, and loss of follow-up on the Bayley Scales of Infant Development, Third Edition (BSID-III) test at 24 months of corrected age. Infants were retrospectively assessed by a trained case manager using the BSID-III test at 6, 12, and 24 months old. Infants were categorized as with or without MBD according to radiographic signs. Of those enrolled, 97 VLBW infants were diagnosed with MBD, compared to 362 VLBW infants without MBD. The proportion of infants that completed three follow-ups was 86%. At the assessment at 2 years of age, infants with MBD had lower and more significant differences in motor, language, and cognitive composites. MBD is associated with poor neurodevelopmental outcomes in cognitive, motor, and language composites for VLBW infants at 24 months of corrected age.

Combination treatment of parenteral arginine and nitric oxide inhibitor N(G)-nitro-L-arginine methyl ester in rats with peritonitis.

PURPOSE: It has been shown that parenteral arginine may facilitate ureagenesis and improve leukocytic and splenocytic immunity and that the infusion of nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) may facilitate the production of arginine-associated amino acids in rats with subacute peritonitis. Herein, we investigated the effects of the combined treatment of parenteral arginine and L-NAME on arginine metabolism and inflammatory response. METHODS AND MATERIALS: Male Wistar rats underwent cecal puncture for induction of subacute peritonitis and were infused with conventional parenteral nutrition (arginine 0.95 g/kg/d) or parenteral nutrition supplemented with arginine (1.88 g/kg/d), L-NAME (25 mg/kg/d), or arginine plus L-NAME. Sham-operated and nonperitonitic rats with oral feeding (R group) or conventional parenteral nutrition (TPN group) were also included. RESULTS: After 7 d of parenteral feeding, the L-NAME treatment significantly attenuated the peritonitis-induced reduction in body weight gain (1-way ANOVA, P < 0.05) and had a significant impact on decreasing body water percentage and on increasing body fat percentage and serum insulin concentrations (2-way ANOVA, P < 0.05). Parenteral arginine had a significant impact on increasing plasma arginine and ornithine and on decreasing serum glutamate oxaloacetate transaminase and plasma nitrite/nitrate in peritonitic rats. In addition, plasma interleukin-6 was significantly decreased by arginine and/or L-NAME treatment, and plasma prostaglandin E2 was significantly decreased by arginine plus L-NAME treatment. CONCLUSION: These results suggest that the combination treatment of parenteral arginine and L-NAME may improve liver function and alleviate inflammatory response in rats with subacute peritonitis; however, it seems that parenteral arginine treatment is more beneficial than L-NAME.

Reducing Medication Errors in Children's Hospitals.

OBJECTIVES: Knowledge of the prevalence and characteristics of medication errors in pediatric and neonatal patients is limited. This study aimed to evaluate the incidence and medication error characteristics in a pediatric hospital over 5 years and to determine whether serial error prevention programs to optimize a computerized physician order entry (CPOE) system reduce error incidence. METHODS: We retrospectively reviewed medication errors documented between January 2015 and December 2019. RESULTS: A total of 2,591,596 prescriptions were checked, and 255 errors were identified. Wrong dose prescriptions constituted the most common errors (56.9%). Medications with the highest rate of errors were antibiotics/antiviral drugs (36.9%). Oral route medications comprised the highest portion (60.8%), followed by intravenous ones (28.6%). The most common stage for medication errors was physician ordering (93.3%). Junior residents were responsible for most errors (45.9%). Most errors occurred in the pediatric ward (53.7%). In total, 221 (86.7%) errors were near misses. Only 4 errors (1.6%) were considered significant and required active monitoring or intervention. Type of error, stage of error, staff composition, and severity level of errors were significantly related to the number of errors in different years. There was a statistically significant decrease in errors per 100,000 prescriptions across different years after optimizing the CPOE system. CONCLUSIONS: The incidence of medication errors decreased with extensive use of the CPOE system. Continuous application of the CPOE optimization program can effectively reduce medication errors. Further incorporation of pediatric-specific decision-making and support tools and error prevention measures into CPOE systems is needed.

Long-term enteral arginine supplementation in rats with intestinal ischemia and reperfusion.

BACKGROUND: The effects of short-term enteral arginine supplementation on intestinal ischemia-reperfusion (IR) injury have been widely studied, especially the ischemic preconditioning supplementation. The aim of this study was to investigate the effects of long-term intra-duodenal supplementation of arginine on intestinal morphology, arginine-associated amino acid metabolism, and inflammatory responses in rats with intestinal IR. MATERIALS AND METHODS: Male Wistar rats with or without three hours of ileal ischemia underwent duodenal cannulation for continuous infusion of formula with 2% arginine or commercial protein powder for 7 d. The serological examinations, plasma amino acid and cytokine profiles, and intestinal morphology were assessed. RESULTS: Intestinal IR injury had significant impacts on the decreases in circulating red blood cells, hemoglobin, ileum mass, and villus height and crypt depth of the distal jejunum. In addition, arginine supplementation decreased serum cholesterol and increased plasma arginine concentrations. In rats with intestinal IR injury, arginine supplementation significantly decreased serum nitric oxide, plasma citrulline and ornithine, and the mucosal protein content of the ileum. CONCLUSIONS: These results suggest that long-term intra-duodenal arginine administration may not have observable benefits on intestinal morphology or inflammatory response in rats with intestinal ischemia and reperfusion injury. Therefore, the necessity of long-term arginine supplementation for patients with intestinal ischemia and reperfusion injury remains questionable and requires further investigation.

Survival of Hydrops Fetalis with and without Fetal Intervention.

OBJECTIVES: To investigate the survival rate of hydrops fetalis after fetal interventions and neonatal intensive care. METHODS: We reviewed the medical records of patients diagnosed with hydrops fetalis from January 2009 to December 2019 at Changhua Christian Children's Hospital. All cases had abnormal fluid accumulation in at least two body compartments during pre- and postnatal examination. The primary outcome measure was the mortality rate. We also collected information regarding disease etiology, duration of hospital stay, Apgar score, gestational age at birth, initial hydrops fetalis diagnosis, fetal intervention, first albumin and pH levels, and maternal history. RESULTS: Of the 42 cases enrolled, 30 survived and 12 died; the mortality rate was 28.6%. Furthermore, 22 cases received fetal intervention, while 20 cases did not; there was no significant difference in their survival rates (75% and 68%, respectively). Survival rate was associated with gestational age at birth, initial diagnosis time, birthweight, Apgar score, initial albumin and pH levels, and gestational hypertension. Only one case was immune-mediated. Among the nonimmune-mediated cases, the three most common etiologies were lymphatic dysplasia (12/42), idiopathic disorders (10/42), and cardiovascular disorders (5/42). CONCLUSIONS: Overall, hydrops fetalis was diagnosed early, and fetal intervention was performed in a timely manner. Preterm births were more frequent, and birthweight was lower in the cases that underwent fetal intervention than in those that did not, but there was no significant between-group difference in mortality. The initial diagnosis time, gestational age at birth, birthweight, Apgar score, and first albumin and pH levels were independently associated with mortality.

Relationship between Maternal Fever and Neonatal Sepsis: A Retrospective Study at a Medical Center.

Various risk factors are associated with neonatal sepsis; however, its relationship to maternal postpartum fever is unknown. This study aimed to determine the relationship between maternal postpartum fever and neonatal sepsis. Full-term and late preterm stable infants born from January 2019 to June 2021 and whose mothers developed intra- or post-partum fever were included in the study. After the newborns were transferred to the nursery, laboratory assessments were performed. Based on clinical conditions and data, the newborns were divided into unlikely sepsis and probable/proven sepsis groups. Maternal fever onset, duration, and maximum body temperature were recorded. We included 1059 newborns whose mothers developed fever intra-partum (n = 192), post-partum (n = 844), and intra- and post-partum (n = 23). The newborns were grouped into those with unlikely sepsis (n = 550) and those with probable/proven sepsis (n = 509). The incidence of intrapartum fever was higher in the probable/proven sepsis group than in the unlikely sepsis group (27.9% vs. 13.3%, p < 0.001). The incidence of postpartum fever was lower in the probable/proven sepsis group than in the unlikely sepsis group (74.7% vs. 88.5%, p < 0.001). Development of maternal fever within 1.8 h postpartum and a newborn respiratory rate of >60 breaths/min were positive predictors (91.6%) for neonatal probable/proven sepsis.

Safety and reactogenicity of a liquid formulation of human rotavirus vaccine (porcine circovirus-free): A phase III, observer-blind, randomized, multi-country study.

BACKGROUND: The introduction of rotavirus vaccines in national immunization programs has decreased mortality and hospitalizations due to diarrhea. GSK's live-attenuated, human rotavirus vaccine (HRV) is a 2-dose vaccine for oral administration. Following the detection of porcine circovirus type 1 (PCV-1) in HRV, a PCV-free (no detection of PCV-1 and PCV-2 according to the detection limits of tests used) HRV was developed. The immunogenicity, reactogenicity and safety of a liquid (liq) PCV-free HRV were assessed in two prior studies. The present study aimed to generate additional reactogenicity and safety data. METHODS: This phase III, observer-blind, randomized, controlled multi-country study enrolled healthy 6-12-week-old infants. Infants were randomized to receive 2 doses of either the liq PCV-free HRV (N = 677) or the lyophilized (lyo) HRV (N = 674) 1-2 months apart. Solicited adverse events (AEs) were recorded for 8 days after each dose, unsolicited AEs for 31 days and serious AEs (SAEs) from dose 1 until the end of the 6-month safety follow-up. RESULTS: The occurrence of solicited general AEs was comparable between the liq PCV-free HRV and the lyo HRV groups, with irritability/fussiness being the most frequently reported (74.9% [95% confidence interval: 71.4-78.1] and 72.1% [68.6-75.5]). Unsolicited AEs were reported for 29.7% (26.3-33.3) and 30.6% (27.1-34.2) of infants in the liq PCV-free HRV and the lyo HRV group. A total of 39 and 38 infants reported at least one SAE, respectively. The most common SAEs were upper respiratory tract (0.7% and 0.9%) and urinary tract infections (0.9% and 0.6%). One SAE (constipation) in the liq PCV-free HRV group was considered as potentially causally related to vaccination by the investigator. No deaths were reported. CONCLUSIONS: The study showed that the reactogenicity and safety profiles of the liq PCV-free HRV and the lyo HRV are similar. CLINICALTRIALS: gov identifier: NCT0395474.

Dose effects of chronically infused nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester on anabolic response and arginine metabolism in rats with subacute peritonitis.

Nitric oxide synthase (NOS) inhibitors alleviate the adverse effects of nitric oxide (NO) overproduction that occurs during peritonitis, a clinical condition that is accompanied by arginine deficiency. However, the variations in the disease severity and the dosage, route, and period of NOS inhibitor administration are debatable. Therefore, we investigated the dose effects of chronically infused NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on the anabolism, inflammatory responses, and arginine metabolism in parenterally fed rats with cecal puncture-induced subacute peritonitis. Male Wistar rats were divided into 4 groups and were administered total parenteral nutrition solutions with 0, 5 (low dose), 25 (medium dose), or 50 (high dose) mg·kg(-1)·d(-1) of L-NAME for 7 d. Sham-operated rats administered total parenteral nutrition solution and normal healthy rats fed chow diet were also included. Our results showed that parenteral infusion significantly decreased body weight gain and plasma citrulline concentrations. In rats with subacute peritonitis, the parenteral infusion-induced increases in circulating white blood cells and NO were significantly decreased, whereas the decrease in serum albumin levels was significantly increased. Rats with subacute peritonitis that were administered chronic infusion of L-NAME had a significantly reduced nitrogen balance. In addition, rats administered the medium dose of L-NAME had significantly increased plasma arginine, ornithine, glutamate, and proline. In conclusion, chronic infusion of NOS inhibitors may not alter systemic NO homeostasis and inflammatory response but may facilitate the production of arginine-associated amino acids and nitrogen excretion in cases of subacute peritonitis.

Neurodevelopment of preterm infants with glucose and sodium abnormalities.

BACKGROUND: Blood glucose and serum sodium abnormalities in very low birth weight infants may cause increased morbidity and mortality, but data regarding the long-term outcomes are limited. This study aimed to investigate the association between the peak and nadir blood glucose and serum sodium levels and neurodevelopmental outcomes in very low birth weight infants. METHODS: A single-center retrospective medical record of 284 infants with birth weight<1500 g born between February 1, 2011 and January 31, 2015 was reviewed. We analyzed the correlation between peak and nadir blood glucose and serum sodium levels during hospitalization and Bayley Scales of Infant and Toddler Development, third edition at 6, 12, and 24 months of corrected age. RESULTS: A total of 284 very low birth weight premature infants were eligible, and 223, 208, and 188 patients were assessed at 6, 12, and 24 months of corrected age, respectively. Multiple linear regression analysis with generalized estimating equations showed that the BSID-III cognitive scores were significantly lower in the peak serum sodium group when sodium was ≧150 mmol/L (95% confidence interval -11.681 to -0.822) than when sodium did not exceed 150 mmol/L. CONCLUSION: A peak serum sodium of ≧150 mmol/L is associated with poor cognitive outcomes in very low birth weight infants. Further studies are necessary to determine if this association is causal or an expression of disease severity.

Parenteral nutrition with fish oil-based lipid emulsion reduces the risk of cholestasis in preterm infants.

OBJECTIVE: Preterm infants receive long-term parenteral nutrition (PN) for gastrointestinal immaturity. This study aimed to determine if mixed lipid emulsions containing fish oil decrease the incidence of PN-associated cholestasis by reducing oxidative stress and providing an anti-inflammatory effect. METHODS: This retrospective cohort study enrolled 399 very low birth weight premature infants (gestational age ≤32 weeks) between January 2009 and November 2017 at a single neonatal intensive care unit. Preterm infants received total PN with either mixed lipid emulsion including fish oil (SMOFlipid®, n = 195) or soybean oil-based lipid emulsion (Lipovenoes®, n = 204) for at least 7 days. We compared the outcomes of PN-associated cholestasis, comorbidities, and mortality between the groups. RESULTS: The incidence of PN-associated cholestasis was significantly lower in the SMOFlipid group than in the Lipovenoes group. The duration to full feeding days was significantly shorter in the SMOFlipid group compared with the Lipovenoes group. Relevant complications, such as severe retinopathy of prematurity and bronchopulmonary dysplasia, were also significantly reduced in the SMOFlipid group compared with the Lipovenoes group. CONCLUSION: In premature infants, PN with fish oil-based lipid emulsions is associated with a lower incidence of PN-associated cholestasis compared with soybean oil-based lipid emulsions.

Heat Shock Protein-70 Levels Are Associated With a State of Oxidative Damage in the Development of Bronchopulmonary Dysplasia.

Background: Heat shock protein-70 (Hsp-70) exhibits cytoprotective effects against oxidative stress-induced airway injury. This study aimed to examine Hsp-70 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) from tracheal aspirates (TA) in very low-birth weight (VLBW) preterm infants to predict the development of bronchopulmonary dysplasia (BPD). Methods: This birth cohort study enrolled 109 VLBW preterm infants, including 32 infants who developed BPD. Hsp-70 and 8-OHdG concentrations from TA were measured by immunoassay. The apoptosis of TA epithelial cells obtained on Day 28 after birth was measured using annexin-V staining assay. Results: Hsp-70 and 8-OHdG levels in TA fluid were persistently increased from Day 1 to Day 28 of life in the BPD group. Multiple linear regression analysis demonstrated that BPD was significantly associated with gestational age, respiratory distress syndrome, and TA Hsp-70 and 8-OHdG levels on post-natal Day 28. The TA Hsp-70 level positively correlated with TA 8-OHdG level on the Day 1 (r = 0.47) and Day 28 of life (r = 0.68). Incubation of recombinant Hsp-70 with primary epithelial cells derived from TA of patients decreased hydrogen peroxide-induced epithelial cell death. Conclusions: Hsp-70 levels are associated with a state of oxidative injury in the development of BPD.

Implementation of nutrition practice improves growth velocity and weight gain in premature infants ≤ 1250 grams.

BACKGROUND: The concept of parental nutritional care for premature infants has been applied and advanced over the past decade. This study compared the clinical outcomes before and after nutrition practice (NP) implementation and evaluated the effects of implementation on growth velocity and weight gain in premature infants. METHODS: Descriptive data of premature infants (gestational age < 30 weeks; body weight ≤ 1250 g) born 4 years before and after NP implementation were retrospectively reviewed in a neonatal intensive care unit at a hospital in Taiwan. Nutrient intake, growth velocity, weight gain, and nutrition-related biochemical markers were compared at weeks 1, 2, and 4 after delivery. RESULTS: A total of 77 premature infants were enrolled before NP implementation (non-NP group), whereas 89 were enrolled after implementation (NP group). The non-NP group consumed less fat and energy in week 1, and less protein, fat, and energy in weeks 2 and 4 compared with the NP group. Growth velocity was slower in the non-NP group. Fat intake was significantly positively correlated with body weight at week 4 in the non-NP group. However, protein and fat intake were significantly associated with body weight at week 1, fat and energy intakes were significantly associated with body weight at week 2, and fat intake was significantly associated with body weight at week 4 in the NP group. CONCLUSION: These findings indicate that the NP implemented in this study is relatively safe and can improve growth velocity and body weight gain in premature infants.

Effects of fish oil-containing lipid emulsions on retinopathy of prematurity in very low birth weight infants.

BACKGROUND: The aim of the study was to assess the impact of different types of parenteral emulsions on retinopathy of prematurity (ROP) in very low birth weight (VLBW, birth body weight < 1500 g) infants by comparing fish oil-containing and soy-based parenteral emulsions. METHODS: Data of preterm infants with body weights below 1500 gm at birth and receiving total parenteral nutrition (TPN) for a minimum of 7 days during the period between January 2009 and November 2017 were analyzed in this retrospective study. We compared clinical outcomes in two epochs using different lipid emulsions: epoch 1 (soybean-based lipid emulsions, January 2009-February 2014) versus epoch 2 (fish oil-containing lipid emulsions, January 2015-November 2017). The primary outcomes measured were the incidence of ROP and the number of ROP cases requiring bevacizumab therapy. RESULTS: A total of 396 infants were enrolled in this study (203 in epoch 1 and 193 in epoch 2). A lower incidence of any stage ROP (24.1 vs. 11.4%, p < 0.001) and lower requirement of bevacizumab therapy (12.8 vs. 5.2%, p = 0.001) were observed in epoch 2. Gestational age, glutamic-pyruvic transaminase, total bilirubin, and alkaline phosphatase levels, and type of lipid emulsion in TPN were associated with higher ROP incidence. Multivariate logistic regression analysis revealed that parenteral nutrition in the form of lipid emulsions containing fish oil was associated with a lower risk of development of ROP [Odds Ratio: 0.178, 95% confidence interval (CI): 0.095-0.330, p < 0.001]. CONCLUSIONS: Compared with soybean-based lipid solutions, the use of fish oil-containing lipid solutions may be associated with a lower incidence of ROP and decreased need for bevacizumab treatment in preterm infants.

Early or late surgical ligation of medical refractory patent ductus arteriosus in premature infants.

Optimal time to surgical ligation of patent ductus arteriosus (PDA) in very-low-birth-weight (< 1500 g) premature infants remains an area of controversy. We compared the outcomes of early or late ligation of medical refractory PDA in very-low-birth-weight premature infants. Fifty-six infants underwent surgical closure of PDA after failure of or having contraindications to medical treatment. Thirteen infants were in the early ligation (< or = 14 days) and 43 in the late ligation (> 14 days) groups. Basic clinical features, major morbidity of prematurity and mortality were compared. Clinical features and major outcomes were similar. The early ligation group had earlier onset of symptomatic PDA (5.7 +/- 1.6 days vs. 8.1 +/- 3.6 days, p = 0.024), and fewer days of total parenteral nutrition (TPN) (39.6 +/- 13.9 days vs. 60.4 +/- 31.4 days, p = 0.025) and ventilator use (11.1 +/- 6.7 days vs. 18.6 +/- 10.5 days, p = 0.019). Early ligation of medical refractory PDA in very-low-birth-weight premature infants improves enteral feeding tolerance and reduces TPN and ventilator use, but long-term benefits need further investigation.

Intravenous fish oil containing lipid emulsion attenuates inflammatory cytokines and the development of bronchopulmonary dysplasia in very premature infants: A double-blind, randomized controlled trial.

BACKGROUND & AIMS: Preterm infants have lower levels of long-chain polyunsaturated fatty acids (LCPUFAs). Supplementing very premature infants with intravenous lipid emulsions that fish oil, which is rich in n-3 LC-PUFAs, may decrease bronchopulmonary dysplasia (BPD) by modulating inflammation and neonatal immune function. METHODS: Sixty very low birth weight (VLBW) premature infants requiring ventilator support were randomized in a double-blind manner to 2 groups and received total parenteral nutrition with fish oil containing LE (intervention group, n = 30) or soybean oil containing LE (control group, n = 30) for 7 days. Blood samples and bronchoalveolar lavage fluid (BALF) were obtained for assay on day 1 and 7 days after LE. The primary outcome was to compare the levels of interleukin (IL)-1ß and IL-6 in serum and BALF. Secondary outcomes were to compare mortality and co-morbidities. RESULTS: The levels of IL-1ß and IL-6 in serum and BALF were significantly lower in the intervention group at day 8 (p < 0.05). The incidence of BPD in the intervention group compared to the control group was 13.3% versus 36.7% (p = 0.04; odds ratio [OR], 0.36; 95% confidence interval [CI], 0.21-0.86). The duration of ventilator support and oxygen use was significantly less in the intervention group than in the control group (p < 0.05). The level of alanine aminotransferase was significantly lower in the intervention group on day 8 (p = 0.031). CONCLUSIONS: In very premature infants, early administration of fish oil containing LE significantly decreased IL-1ß and IL-6 levels in serum and BALF and was associated with shorter duration of ventilator support and less bronchopulmonary dysplasia (BPD). TRIAL REGISTRATION NUMBER: ISRCTN 11427103.

Correlates of Elevated Interleukin-6 and 8-Hydroxy-2'-Deoxyguanosine Levels in Tracheal Aspirates from Very Low Birth Weight Infants Who Develop Bronchopulmonary Dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains the most common complication of very low birth weight (VLBW) preterm infants, and inflammatory regulation plays a role in the development of the BPD. Interleukin-6 (IL-6) has an important role in airway inflammation and therefore can be used as a marker of airway injury. The study aimed to compare the changes between IL-6 and oxidative stress marker with 8-hydroxy-2'-deoxyguanosine (8-OHdG) from serum and tracheal aspiration (TA) in VLBW preterm infants following development of BPD. METHODS: This birth cohort study enrolled 80 VLBW preterm infants, including 26 who developed BPD. All infants completed the study and survived at 36 weeks postmenstrual age. IL-6 and 8-OHdG concentrations from serum and TA on Day 1 and Day 28 after birth were measured using immunoassay. RESULTS: IL-6 and 8-OHdG in serum and TA were higher in the BPD group than in the non-BPD group on the 1st day after birth (p < 0.05). The IL-6 and 8-OHdG levels in TA fluid were persistently increased on the 28th day of life in the BPD group (p < 0.05). The TA IL-6 was positively correlated with 8-OHdG levels on the 1st day (r = 0.64, p < 0.05) and 28th day of life (r = 0.76, p < 0.05). Based on receiver operating characteristic curves as a predictor of BPD development, TA IL-6 (cutoff, 456.8 pg/mg) had 81.5% sensitivity and 77.8% specificity, whereas TA 8-OHdG (cutoff, 4.4 ng/mg) had a sensitivity of 81.5% and a specificity of 64.4%. CONCLUSION: Persistent inflammation with oxidative DNA damage in the respiratory tract may be a crucial mechanism in BPD.