Glutathione Supplementation Prevents Neonatal Parenteral Nutrition-Induced Short- and Long-Term Epigenetic and Transcriptional Disruptions of Hepatic H2O2 Metabolism in Guinea Pigs.

The parenteral nutrition (PN) received by premature newborns is contaminated with peroxides that induce global DNA hypermethylation via oxidative stress. Exposure to peroxides could be an important factor in the induction of chronic diseases such as those observed in adults who were born preterm. As endogenous H2O2 is a major regulator of glucose-lipid metabolism, our hypothesis was that early exposure to PN induces permanent epigenetic changes in H2O2 metabolism. Three-day-old guinea pigs were fed orally (ON), PN or glutathione-enriched PN (PN+GSSG). GSSG promotes endogenous peroxide detoxification. After 4 days, half the animals were sacrificed, and the other half were fed ON until 16 weeks of age. The liver was harvested. DNA methylation and mRNA levels were determined for the SOD2, GPx1, GCLC, GSase, Nrf2 and Keap1 genes. PN induced GPx1 hypermethylation and decreased GPx1, GCLC and GSase mRNA. These findings were not observed in PN+GSSG. PN+GSSG induced Nrf2 hypomethylation and increased Nrf2 and SOD2 mRNA. These observations were independent of age. In conclusion, in neonatal guinea pigs, PN induces epigenetic changes, affecting the expression of H2O2 metabolism genes. These changes persist for at least 15 weeks after PN. This disruption may signify a permanent reduction in the capacity to detoxify peroxides.

[Severe small bowel involvement and chronic intestinal pseudo-obstruction in systemic sclerosis (scleroderma): Pathophysiological, diagnostic and therapeutic basis, including parenteral nutrition]. / Atteinte sévère de l'intestin grêle et pseudo-obstruction intestinale chronique au cours de la sclérodermie systémique : bases physiopathologiques, diagnostiques et thérapeutiques, dont la nutrition parentérale.

Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively.

Treatment-related problems in neonates receiving parenteral nutrition: risk factors and implications for practice.

OBJECTIVES: Parenteral nutrition (PN) can be associated with several treatment-related problems (TRPs) and complications in neonatal settings. Thus, understanding the extent and type of these problems and related factors is pivotal to prevent negative consequences of these preparations. Thus, the aim of this study is to assess factors affecting TRPs in neonatal patients receiving PN. METHODS: This was a retrospective chart review of neonates receiving PN in NICU and other wards. We collected their demographics, and laboratory workup. TRPs related to PN preparations as well as their pharmacotherapy were the primary outcomes. RESULTS: Medical charts of 96 neonate were reviewed. The most encountered TRPs related to patients' pharmacotherapy were the lack of frequent monitoring (34.2%) and low dose (17.5%). For PN-related TPRs, a mismatch between patients' nutritional needs and PN composition was observed in third of the patients. Statistically significant positive correlations between number of medications during hospital stay and number of reported TRPs [(r = 0.275, p < 0.01) and (r = 0.532, p < 0.001)] were observed. CONCLUSION: In neonates who receive parenteral nutrition (PN), TRPs are often observed. These problems primarily arise from issues in patients' pharmacotherapy, namely monitoring and dosing. Identifying the risk factors for these TRPs emphasizes the full and effective integration of clinical pharmacists into the healthcare team, which can serve as a potential preventive strategy to lower the occurrence of TRPs.

A medium-chain fatty acid analogue prevents hepatosteatosis and decreases inflammatory lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis.

BACKGROUND: Parenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis. METHODS: Two in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro. RESULTS: In the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both ß- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake. CONCLUSIONS: SEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both ß- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis.

Parenteral Nutrition in the Pediatric Oncologic Population: Are There Any Sex Differences?

Gender-based medicine is attracting increasing interest every day, but studies on pediatric populations are still limited. In this setting, sex differences among patients undergoing total parenteral nutrition (TPN) have not been previously reported. This study investigated the presence of sex differences in parenteral nutrition composition and outcomes among a cohort of pediatric patients admitted at the Oncohematology and Bone Marrow Transplant Unit of the Institute for Maternal and Child Health "Burlo Garofolo" of Trieste, Italy. For all 145 recruited patients (87 males, 58 females), the following data were collected: age, sex, volume and duration of TPN, macro- and micronutrient composition of TPN bags, electrolytic or blood gases imbalance, glycolipid alterations, liver damage during TPN, and the incidence of sepsis and thrombosis. The analysis showed that females required higher daily phosphate intake (p = 0.054) and essential amino acid supplementation (p = 0.07), while males had a higher incidence of hypertriglyceridemia (p < 0.05) and cholestasis. A higher incidence of sepsis was found in the non-transplanted male population (p < 0.05). No significant differences were appreciable in other analyzed variables. This study aims to create a basis for future gender-based nutritional recommendations in the pediatric field.

Metabolic impact of high lipid low dextrose parenteral nutrition.

BACKGROUND: Parenteral nutrition (PN) containing 100% soybean oil lipids and high amounts of dextrose may lead to liver dysfunction and hyperglycemia. Mixed lipids have less pro-inflammatory components, so higher doses may be given to decrease the amount of dextrose provided. The purpose of this study is to provide a descriptive analysis of patients who received PN with high mixed lipid and low dextrose content versus PN with lower 100% soybean oil lipid and high dextrose content. METHODS: We retrospectively reviewed 62 patients aged ≥18 years receiving PN ≥ 7 days from 2016 to 2021 in an acute care hospital. Participants were divided into two groups: high lipid low dextrose (HLLD) containing a four-oil lipid (>30% kcal or ≥1 g/kg) vs adequate lipid high dextrose (ALHD) containing a 100% soybean oil lipid (<30% kcal or <1 g/kg SO-ILE). RESULTS: Patients in the HLLD group (n = 31) had 64.1% lower incidence of blood glucose levels >180 mg/dL, decreased insulin requirements, 52.7% lower alkaline phosphatase levels, 40.6% higher prealbumin levels, and 42.6% lower c-reactive protein levels while maintaining similar calorie targets compared to the ALHD group (n = 31). CONCLUSION: Changing from 100% soybean oil to a mixed lipid in PN is helpful to reduce soybean oil intake. However, it is also important to increase the mixed lipid dose to decrease the amount of dextrose provided. PNs containing higher amounts of mixed lipids (40-45% kcal) with lower amounts of dextrose (20-30% kcal) may have clinical benefits that warrant further exploration.

In vitro comparison of the effectiveness of various antimicrobial locks with taurolidine in the treatment and prevention of catheter-related bloodstream infections in patients receiving parenteral nutrition.

OBJECTIVES: To evaluate the effectiveness of various taurolidine solutions in the prevention and treatment of catheter-related bloodstream infections (CRBSIs) caused by the entire spectrum of microbes in patients receiving parenteral nutrition in a shorter period of time. METHODS: The in vitro method was used to test for eradication of biofilm. Different locks were used: TauroSept (2%), TauroLock (1.35%), TauroLock half concentration, and 3.5% taurolidine and tested on Staphylococcus (S.) epidermidis, S. aureus, S. hominis, methicillin-resistant S. aureus (MRSA), Pseudomonas (P.) aeruginosa (PSAE), multidrug-resistant P. aeruginosa (MR PSAE), vancomycin-resistant enterococci, Klebsiella pneumoniae producing carbapenemase (KPC), Klebsiella pneumoniae producing extended-spectrum beta-lactamase (KLPN ESBL), Candida (C.) albicans, and C. glabrata. Broviac catheters were incubated for growth of each organism and then incubated in lock solutions. Colony forming units (CFUs) were then counted after 30 min, 60 min, and 120 min of incubation. RESULTS: A statistically significant decrease in CFUs was observed after 30 min of taurolidine exposure for S. hominis, PSAE, KLPN ESBL, KLPN KPC, C. albicans, and C. glabrata; after 60 min of exposure for S. epidermidis, PSAE, MR PSAE, KLPN ESBL, KPC, C. albicans, and C. glabrata; and after 120 min of exposure for S. epidermidis, S. hominis, S. aureus, PSAE, MR PSAE, KLPN ESBL, KPC, C. albicans, C. glabrata. CONCLUSIONS: The application of taurolidine is effective in the treatment of CRBSIs. Taurolidine proved to be more effective against Gram-negative microorganisms during a 30-min exposure. Using 0.675% taurolidine is still effective. To achieve the required antimicrobial effect, the catheter must be sanitized for at least 2 h.

An Overview of Short-Bowel Syndrome in Pediatric Patients: Focus on Clinical Management and Prevention of Complications.

Short-bowel syndrome (SBS) in pediatric age is defined as a malabsorptive state, resulting from congenital malformations, significant small intestine surgical resection or disease-associated loss of absorption. SBS is the leading cause of intestinal failure in children and the underlying cause in 50% of patients on home parental nutrition. It is a life-altering and life-threatening disease due to the inability of the residual intestinal function to maintain nutritional homeostasis of protein, fluid, electrolyte or micronutrient without parenteral or enteral supplementation. The use of parenteral nutrition (PN) has improved medical care in SBS, decreasing mortality and improving the overall prognosis. However, the long-term use of PN is associated with the incidence of many complications, including liver disease and catheter-associated malfunction and bloodstream infections (CRBSIs). This manuscript is a narrative review of the current available evidence on the management of SBS in the pediatric population, focusing on prognostic factors and outcome. The literature review showed that in recent years, the standardization of management has demonstrated to improve the quality of life in these complex patients. Moreover, the development of knowledge in clinical practice has led to a reduction in mortality and morbidity. Diagnostic and therapeutic decisions should be made by a multidisciplinary team that includes neonatologists, pediatric surgeons, gastroenterologists, pediatricians, nutritionists and nurses. A significant improvement in prognosis can occur through the careful monitoring of nutritional status, avoiding dependence on PN and favoring an early introduction of enteral nutrition, and through the prevention, diagnosis and aggressive treatment of CRSBIs and SIBO. Multicenter initiatives, such as research consortium or data registries, are mandatory in order to personalize the management of these patients, improve their quality of life and reduce the cost of care.

Twin Premature Infants With Riboflavin and Biotin Deficiency Presenting With Refractory Lactic Acidosis, Rash, and Multiorgan Failure During Prolonged Parenteral Nutrition.

We are reporting monochorionic, diamniotic twin premature infants born at 25 weeks and 6 days gestation with riboflavin (vitamin B2) and biotin (vitamin B7) deficiency, while on prolonged total parenteral nutrition (TPN) during vitamin shortage. They presented initially with skin rash, lactic acidosis, and thrombocytopenia. Both twins progressed to severe respiratory failure, severe lactic acidosis, with refractory vasodilatory shock, pancytopenia, ischemic bowel injury, acute kidney injury, liver injury, and capillary leak syndrome leading to death of twin A. The surviving twin B was diagnosed with riboflavin and biotin deficiency that presented with abnormal metabolic work up suggestive of maple syrup urine disease, glutaric acidemia type 2, and X-linked adrenoleukodystrophy. Twin B was started on riboflavin and biotin supplementation at 41 days of life, with rapid improvement in clinical findings and laboratory abnormalities within days of starting biotin and riboflavin supplementation. He was discharged home in stable condition at 49 weeks of postmenstrual age.

Proinflammatory mediators in lipid emulsions and parenteral nutrition-associated liver disease: Review of leading factors.

Lipid injectable emulsions have been in clinical use for over 60 years. The first product launched was Intralipid, which consisted of an emulsion of soybean oil in water for intravenous administration. It was a key source of essential fatty acids and an alternative source of energy for patients with gastrointestinal dysfunction requiring long-term parenteral nutrition. With clinical experience, a condition known as parenteral nutrition-associated liver disease (PNALD), or intestinal failure-associated liver disease (IFALD), was observed, with a focus on carbohydrate and fat energy. Modifying the daily doses and infusion rates had some salutary effects, but PNALD persisted. Subsequently, on closer inspection of the fatty acids profile and phytosterol concentrations, degradation products arising from chemical and physical stability issues of the available lipid injectable emulsions were implicated. Recently, the US Food and Drug Administration convened an online workshop entitled "The Role of Phytosterols in PNALD/IFALD," with an emphasis on (1) the multifactorial pathophysiology of PNALD/IFALD, (2) risk associated with phytosterols, and (3) regulatory history. The scope of this review includes the multifactorial pathophysiology of PNALD/IFALD as it relates to the pharmaceutical aspects of the various lipid injectable emulsions on the market, with respect to potential proinflammatory components, as well as physical and chemical stability issues that may also affect products' safe intravenous administration to patients.

Evolution of parenteral nutrition practices in a comprehensive cancer center: Comparative audits.

INTRODUCTION: Malnutrition affects 20% to 70% of oncology patients depending on the patient's age, type and stage of cancer. Two audits were carried out in 2016 and 2019 to evaluate the practice of Parenteral Nutrition (PN). METHODS: Records of adult medical inpatients who received PN between January 1, 2018 and April 30, 2019 were retrospectively analysed. Twenty criteria were defined. We conducted a statistical analysis to compare the two audit data. RESULTS: Between January 1, 2018 and April 30, 2019, 86 hospitalizations with a PN prescription were analysed. Of the 69 patients, 66% were female, the mean and median age was 60 years. These were most often medical oncology patients in palliative care. Gynecological and digestive tumors were the two main tumor localization. Bowel obstruction and palliative care management were the two main reasons for hospitalization. Nutritional assessment, amount of energy prescribed, monitoring, and duration of PN remain with poor results. CONCLUSION: Our study seems to show improvements in the relevance of PN indications, the prescription, and monitoring in patients due to the computerization of prescription and training of professionals. PN remains often prescribed in exclusive palliative situations. We need to continue our improvements, particularly for the initial clinical and biological assessment, and the monitoring. It requires a referral team to improve management of patients treated with PN.

Pharmacological and nutritional therapy of children and adults with chronic intestinal pseudo-obstruction.

INTRODUCTION: Chronic intestinal pseudoobstruction (CIPO) is a rare, heterogenous, and severe form of gastrointestinal dysmotility. AREAS COVERED: Pertinent literature on pediatric and adult CIPO management has been assessed via PubMed, Scopus, and EMBASE from inception to June 2022. Prokinetics, aimed at restoring intestinal propulsion (e.g. orthopramides and substituted benzamides, acetyl cholinesterase inhibitors, serotonergic agents, and others), have been poorly tested and the available data showed only partial efficacy. Moreover, some prokinetic agents (e.g. orthopramides and substituted benzamides) can cause major side effects. CIPO-related small intestinal bacterial overgrowth requires treatment preferably via poorly absorbable antibiotics to avoid bacterial resistance. Apart from opioids, which worsen gut motility, analgesics should be considered to manage visceral pain, which might dominate the clinical manifestations. Nutritional support, via modified oral feeding, enteral, or parenteral nutrition, is key to halting CIPO-related malnutrition. EXPERT OPINION: There have been significant roadblocks preventing the development of CIPO treatment. Nonetheless, the considerable advancement in neurogastroenterology and pharmacological agents cast hopes to test the actual efficacy of new prokinetics via well-designed clinical trials. Adequate dietary strategies and supplementation remain of crucial importance. Taken together, novel pharmacological and nutritional options are expected to provide adequate treatments forthese patients.

[Guideline for clinical application of parenteral and enteral nutrition in adults patients in China (2023 edition)].

Malnutrition refers to the state of energy or nutrient deficiency caused by insufficient intake or utilization, which is the main factor leading to adverse clinical outcomes. In order to further standardize the nutritional support treatment process, nearly 100 experts in related fields were organized by the Chinese Society of Parenteral and Enteral Nutrition (CSPEN) to elaborate on the following topics based on the existing evidence-based medical evidence: nutritional screening and assessment; diagnosis and monitoring of malnutrition; diagnosis and treatment process, energy targets and health economic benefits of nutritional support therapy; indication, starting time, infusion mode and formula selection of enteral nutrition (EN) and parenteral nutrition (PN); monitoring of tolerance of nutritional support treatment, prevention and management of complications, etc. Finally, 37 questions and 60 recommendations were put forward to provide reference for clinical standard application of parenteral and enteral nutrition.

An observational study of the effects of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on postoperative complications in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease. Most patients with CD require surgery but exhibit an elevated incidence of postoperative complications. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are considered beneficial for nutrition, anti-inflammation, immunity, and intestinal microflora balance in humans. This study assessed the effects of ω-3 PUFA-supplemented parenteral nutrition (PN) on postoperative complications in CD patients. METHODS: Overall, 186 CD patients undergoing bowel resection were recruited for this study. The patient data were collected from a prospectively maintained database. After surgery, 83 patients received ω-3 PUFA-supplemented PN, and 103 did not. The postoperative complications were compared between the groups. Complication risk factors were identified by univariate and multivariate analyses. RESULTS: Patients who received ω-3 PUFA-supplemented PN after surgery had lower C-reactive protein (CRP) levels on postoperative day 3 (57.2±5.3 vs. 43.5±3.9 mg/L, P=0.047) and shorter postoperative hospital stays (12.1±1.1 vs. 9.3±0.6 days, P=0.041) than those who did not. The ω-3 PUFA group exhibited significantly fewer overall complications (40.8% vs. 24.1%, P=0.016) and major complications (23.3% vs. 9.6%, P=0.014) than the control group. Postoperative complications were associated with infliximab, ω-3 PUFAs, CRP levels, operative time, and laparoscopic surgery. The multivariate regression revealed that preoperative infliximab use was a positive risk factor and postoperative ω-3 PUFA-supplemented PN was a negative risk factor for postoperative complications. CONCLUSIONS: ω-3 PUFA-supplemented PN reduced post-surgery inflammatory response of CD patients, which in turn decreased the postoperative complications and accelerated recovery.

Prevalence of thyroid dysfunction in neonates receiving parenteral nutrition in the intensive care unit.

OBJECTIVE: The use of parenteral nutrition (PN) formulations that do not contain iodine can contribute to the deficiency of this mineral, potentially leading to hypothyroidism and, ultimately, neurocognitive impairments. This study aimed to evaluate TSH alterations in newborns receiving PN. METHODS: Retrospective study of neonatal intensive care unit patients receiving PN for > 15 days. Nutritional, anthropometric, and biochemical variables (TSH, T4, CRP) were analyzed. Hypothyroidism was defined by TSH > 10 mU/L. RESULTS: Two hundred newborns were evaluated [156 (78%) preterm, 31±5 weeks of gestational age, 112 (56%) with very or extremely low birth weight]. The median (IQR) hospital stay was 68 (42-110) days, PN duration was 31 (21-47) days, and 188 (94%) patients also received enteral nutrition. Overall, 143 (71.5%) newborns underwent at least one TSH measurement. The prevalence of hypothyroidism was 10.5%. The Median PN duration in this group was 51 (34-109) days. Among those with hypothyroidism, 10 received Lugol's solution and six levothyroxine. Thirteen patients received prophylactic Lugol's solution with a median PN duration of 63 (48-197) days. TSH levels correlated positively with PN duration (r = 0.19, p = .02). CONCLUSIONS: The present data suggest that changes in TSH and T4 levels are present in neonates receiving PN for > 15 days, suggesting this population may be at risk for developing hypothyroidism. Therefore, the authors suggest that TSH and T4 measurements should be included as routine in neonatal patients receiving PN for > 15 days if PN formulations are not supplemented with iodine, and that iodine supplementation be provided as necessary.

Comparison of catheter-related bloodstream infection rates in pediatric patients receiving parenteral nutrition with soybean oil-based intravenous fat emulsion versus a mixed oil fat emulsion.

STUDY OBJECTIVE: To compare rates of catheter-related bloodstream infections (CR-BSI) in pediatric patients who received parenteral nutrition (PN) with either soybean oil-based intravenous fat emulsion (SO-IFE) or mixed oil-IFE (MO-IFE). We hypothesized that the use of MO-IFE would be independently associated with reduced infection rates compared with SO-IFE. DESIGN: Retrospective cohort study. SETTING: Tertiary referral children's hospital and its associated gastrointestinal rehabilitation clinic (01 January, 2015-31 July, 2019). PATIENTS: Days of IFE exposure were counted for patients aged <18 years on IFE initiated during the review period, who had a central venous catheter (CVC) placed for PN administration, received IFE at least three times weekly, and for at least 7 days. MEASUREMENTS: The primary outcome included total and categorical CR-BSI rates expressed as the average with standard error (SE) number of infections per 1000 fat emulsion days. The following categories were specified: Candida albicans, non-albicans Candida spp., coagulase-negative Staphylococcus (CoNS), Enterobacterales, methicillin-resistant S. aureus, methicillin-susceptible S. aureus, and Pseudomonadales. Average infection rate comparisons were quantified as incidence rate ratios (IRR) using generalized linear mixed modeling with a Poisson distribution. MAIN RESULTS: Seven hundred and forty-three SO-IFE and 450 MO-IFE exposures were reviewed from 1131 patients, totaling 37,599 and 19,796 days of therapy, respectively. From those found significantly different, the average rate of infections with CoNS was 3.58 (SE 0.5)/1000 days of SO-IFE and 1.39 (SE 0.45)/1000 days of MO-IFE (IRR [95% confidence interval, CI]: 0.27 [0.16-0.46]; p < 0.01). Total average rates of infection were 7.33 (SE 0.76)/1000 days of SO-IFE and 4.52 (SE 0.75)/1000 days of MO-IFE (IRR [95% CI]: 0.60 [0.44-0.81]; p < 0.01). Other factors associated with higher infection rates include female gender, neonatal age, and inpatient-only IFE exposure. CONCLUSIONS: Receipt of MO-IFE was associated with lower rates of CoNS and total CR-BSIs compared with SO-IFE in pediatric patients. These findings could have major implications on IFE selection for pediatric patients receiving PN.

Early hypophosphatemia in critically ill children and the effect of parenteral nutrition: A secondary analysis of the PEPaNIC RCT.

BACKGROUND & AIMS: Hypophosphatemia during critical illness has been associated with adverse outcome. The reintroduction of enteral or parenteral nutrition, leading to refeeding hypophosphatemia (RFH), has been presented as potential risk factor. We investigated the occurrence of early RFH, its association with clinical outcome, and the impact of early parenteral nutrition (PN) on the development of early RFH in pediatric critical illness. METHODS: This is a secondary analysis of the PEPaNIC randomized controlled trial (N = 1440), which showed that withholding supplemental parenteral nutrition (PN) for 1 week (late-PN) in the pediatric intensive care unit (PICU) accelerated recovery and reduced new infections compared to early-PN (<24 h). Patients with renal replacement therapy or unavailable phosphate concentrations were excluded from this analysis. Early RFH was defined as serum/plasma phosphate <0.65 mmol/L and a drop of >0.16 mmol/L within 3 days of admission to the PICU. The association between baseline characteristics and early RFH, and the association of early RFH with clinical outcome were investigated using logistic and linear regression models, both uncorrected and corrected for possible confounders. To examine the impact of nutritional intake on phosphate concentrations, structural nested mean models with propensity score and censoring models were used. RESULTS: A total of 1247 patients were eligible (618 early-PN, 629 late-PN). Early RFH occurred in 40 patients (3%) in total, significantly more in the early-PN group (n = 31, within-group occurrence 5%) than in the late-PN-group (n = 9, within-group occurrence 1%, p < 0.001). Patients who were older (OR 1.14 (95% CI 1.08; 1.21) per year added, p < 0.001) and who had a higher Pediatric Risk of Mortality (PIM3) score had a higher risk of developing early RFH (OR 1.36 (95% CI 1.15; 1.59) per unit added, p < 0.001), whereas patients in the late-PN group had a lower risk of early RFH (OR 0.24 (95% CI 0.10; 0.49), p < 0.001). Early RFH was significantly associated with a 56% longer PICU stay (p = 0.003) and 42% longer hospital stay (p = 0.007), but not with new infections (OR 2.01 (95% CI 0.90; 4.30), p = 0.08) or length of mechanical ventilatory support (OR 1.05 (95% CI -3.92; 6.03), p = 0.68), when adjusted for possible confounders. Increase of parenteral nutrition intake (in % kcal of predicted resting energy expenditure) decreased phosphate concentrations (c = -0.002 (95% CI -0.002; -0.001). CONCLUSIONS: Early RFH occurred in 3% of critically ill children. Patients randomized to late-PN had a lower chance of developing early RFH, which may be explained by the more gradual build-up of nutrition. As early RFH might impact recovery, it is important to closely monitor phosphate concentrations in patients, especially of those at risk for early RFH.

Hospital change to mixed lipid emulsion from soybean oil-based lipid emulsion for parenteral nutrition in hospitalized and critically ill adults improves outcomes: a pre-post-comparative study.

INTRODUCTION: Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes. METHODS: We conducted a single-center retrospective cohort study among adult patients (> 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort. RESULTS: We identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95-0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87-0.93, p < 0.0001), as well as a shorter ICU LOS (IRR 0.90, 95% CI 0.82-0.99, p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (- 1.6, 95% CI - 2.8 to - 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26-0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients. CONCLUSION: 4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients.

Oral, enteral and parenteral nutritional therapies in scleroderma: A systematic review.

BACKGROUND & AIMS: Scleroderma is a multi-system disease that causes hardening of connective tissue. The gastrointestinal (GI) tract is affected in 90% of patients, which may cause nutritional decline. Due to the rarity of the disease, current nutritional guidelines in scleroderma are extrapolated from evidence in other chronic diseases. This systematic review examines the effects of oral nutrition supplements (ONS), enteral nutrition (EN) and parenteral nutrition (PN) on both clinical and nutritional outcomes of scleroderma patients. METHOD: Three separate systematic searches for scleroderma and ONS, EN, and PN were performed. The searches were conducted using EMBASE, PubMed and Web of Science databases. RESULTS: A total of 9 studies (ONS: 2, EN: 1 and PN: 6) met the inclusion and exclusion criteria and were included in the review. All patients had scleroderma and were malnourished or at risk of malnutrition [weighted average age: 53 years, Body Mass Index (BMI): 19 kg/m2]. Artificial nutrition support was shown to be an effective therapy for preventing nutritional decline and reversing malnutrition but had no impact on disease progression. Mean BMI increased with home parenteral nutrition (HPN) and EN, from 15 kg/m2 to 21.0 kg/m2. Weight was maintained with ONS, and sarcopenia decreased. Only HPN positively impacted quality of life and GI symptoms, with complication rates similar to patients with other indications. CONCLUSION: Scleroderma patients should be routinely screened for malnutrition. Malnutrition is treated in a stepwise manner, starting with ONS, then EN and finally PN, based on GI sufficiency and tolerance of the patient. HPN is an effective therapy for patients with advanced disease and intestinal failure. However, larger, long-term, prospective studies for each nutritional therapy are required to make firm conclusions.

The Role of Manganese in Very Low Birth Weight Infants.

OBJECTIVES: High manganese (Mn) levels during fetal growth or prolonged parenteral nutrition (PN) may have adverse effects on neurodevelopment. We aim to report on Mn levels and their short-term impact on clinical course in very low birth weight infants. METHODS: An observational study including newborns with a gestational age (GA) ≤32 weeks and/or ≤1500 g of birth weight (BW). Newborns received intravenous supplementation of Mn at 1 µg/kg/day (Peditrace ® ) in PN and continued with fortified breast milk. Mothers answered surveys about dietary and other habits and blood levels of Mn in newborns were analyzed at days 1, 15, and 30 of life. Associations of Mn levels with mothers' and newborns' data were evaluated and adjusted for multiple comparisons. RESULTS: One hundred and sixty premature infants were recruited. Median blood Mn levels at birth were 43.0 and 24.5 µg/L at day 30. No important association with mothers' data was found. Median [interquartile range (IQR)] duration of PN was 8 days (7-14). A prolonged PN and late oral feeding showed a nonsignificant association with lower blood Mn levels at day 30 ( P = 0.010, P threshold 0.003). Mn levels at day 15 and 30 were associated with increasing GA ( P < 0.001). Low Mn was not a significant predictor of adverse outcomes such as retinopathy of prematurity, bronchopulmonary dysplasia, or respiratory distress syndrome after adjusting for potential confounders and multiple testing. CONCLUSIONS: Mn showed lower levels with decreasing GA and prolonged PN. Using a low Mn PN solution may not raise blood Mn levels in premature infants.