Intraduodenal fecal microbiota transplantation ameliorates gut atrophy and cholestasis in a novel parenteral nutrition piglet model.

Total parenteral nutrition (TPN) provides lifesaving nutritional support intravenously; however, it is associated with significant side effects. Given gut microbial alterations noted with TPN, we hypothesized that transferring fecal microbiota from healthy controls would restore gut-systemic signaling in TPN and mitigate injury. Using our novel ambulatory model (US Patent: US 63/136,165), 31 piglets were randomly allocated to enteral nutrition (EN), TPN only, TPN + antibiotics (TPN-A), or TPN + intraduodenal fecal microbiota transplant (TPN + FMT) for 14 days. Gut, liver, and serum were assessed through histology, biochemistry, and qPCR. Stool samples underwent 16 s rRNA sequencing. Permutational multivariate analysis of variance, Jaccard, and Bray-Curtis metrics were performed. Significant bilirubin elevation in TPN and TPN-A versus EN (P < 0.0001) was prevented with FMT. IFN-G, TNF-α, IL-ß, IL-8, and lipopolysaccharide (LPS) were significantly higher in TPN (P = 0.009, P = 0.001, P = 0.043, P = 0.011, P < 0.0001), with preservation upon FMT. Significant gut atrophy by villous-to-crypt ratio in TPN (P < 0.0001) and TPN-A (P = 0.0001) versus EN was prevented by FMT (P = 0.426 vs. EN). Microbiota profiles using principal coordinate analysis demonstrated significant FMT and EN overlap, with the largest separation in TPN-A followed by TPN, driven primarily by Firmicutes and Fusobacteria. TPN-altered gut barrier was preserved upon FMT; upregulated cholesterol 7 α-hydroxylase and bile salt export pump in TPN and TPN-A and downregulated fibroblast growth factor receptor 4, EGF, farnesoid X receptor, and Takeda G Protein-coupled Receptor 5 (TGR5) versus EN was prevented by FMT. This study provides novel evidence of prevention of gut atrophy, liver injury, and microbial dysbiosis with intraduodenal FMT, challenging current paradigms into TPN injury mechanisms and underscores the importance of gut microbes as prime targets for therapeutics and drug discovery.NEW & NOTEWORTHY Intraduodenal fecal microbiota transplantation presents a novel strategy to mitigate complications associated with total parenteral nutrition (TPN), highlighting gut microbiota as a prime target for therapeutic and diagnostic approaches. These results from a highly translatable model provide hope for TPN side effect mitigation for thousands of chronically TPN-dependent patients.

A randomized translational study on protein- and glucose metabolism in skeletal muscles evaluated by gene-ontology, following preoperative oral carbohydrate loading compared to overnight peripheral parenteral nutrition (PPN) before major cancer surgery.

BACKGROUND: Effects of preoperative drinks on muscle metabolism are unclear despite general recommendations. The aim of the present study was therefore to compare metabolic effects of a preoperative oral nutrition drink, recommended by protocols for enhanced recovery after surgery (ERAS), compared to overnight preoperative peripheral total parenteral nutrition (PPN) on skeletal muscle metabolism in patients aimed at major gastrointestinal cancer surgery. METHODS: Patients were randomized, based on diagnosis and clinical characteristics, to receive either a commercial carbohydrate-rich nutrition drink (Drink); or overnight (12 h) peripheral parenteral nutrition (PPN) as study regimens; compared to isotone Ringer-acetate as Control regimen. Arterial blood- and abdominal muscle tissue specimens were collected at start of surgery. Blood chemistry included substrate- and hormone concentrations. Muscle mRNA transcript analyses were performed by microarray and evaluated for changes in gene activities by Gene Ontology algorithms. RESULTS: Patient groups were comparable in all measured preoperative assessments. The Nutrition Drink had significant metabolic alterations on muscle glucose metabolism (p < 0.05), without any significant effects on amino acid- and protein metabolism. PPN showed similar significant effects on glucose metabolism as Drinks (p < 0.05), but indicated also major positive effects on amino acid- (p < 0.001) and protein anabolism (p < 0.05), particularly by inhibition of muscle protein degradation, related to both ubiquitination of proteins and autophagy/lysosome pathways (p < 0.05). CONCLUSION: Conventional overnight preoperative PPN seems effective to induce and support improved muscle protein metabolism in patients aimed at major cancer surgery while preoperative oral carbohydrate loading, according to ERAS-protocols, was ineffective to improve skeletal muscle catabolism and should therefore not be recommended before major cancer surgery. Trial registration Clinical trials.gov: NCT05080816, Registered June 10th 2021- Retrospectively registered. https://clinicaltrials.gov/study/NCT05080816.

Targeted metabolomics unravels altered phenylalanine levels in piglets receiving total parenteral nutrition.

Parenteral nutrition, received by many patients with intestinal failure, can induce hepatobiliary complications, which is termed as parenteral nutrition-associated liver disease (PNALD). The spectrum of PNALD ranges from cholestasis and steatosis to fibrosis and cirrhosis. Although many factors contribute to the pathogenesis of PNALD, the underlying mechanisms remain unclear. In this study, we performed targeted metabolomics to characterize the metabolomic profile in neonatal piglets receiving total parenteral nutrition (TPN) or enteral nutrition (EN) for 1 or 2 weeks. Overall, the metabolomic signature of TPN groups differed from EN groups at both time points. Among the 20 acylcarnitines identified, a majority of them were significantly reduced in TPN groups. KEGG pathway analysis showed that phenylalanine metabolism-associated pathways were dysregulated accompanied by more progressive liver steatosis associated with TPN. Next, we evaluated phenylalanine catabolism and its association with fatty acid oxidation in piglets and rats with PNALD. We showed that the hepatic expression of phenylalanine-degrading enzyme phenylalanine hydroxylase (PAH) was reduced and systemic phenylalanine levels were increased in both animal models of PNALD. Moreover, carnitine palmitoyltransferase 1A, a central regulator of fatty acid oxidation, was downregulated and its expression was negatively correlated with phenylalanine levels in TPN-fed animals. To explore the effects of phenylalanine accumulation on lipid metabolism, we treated HepG2 cells with phenylalanine co-cultured with sodium palmitate or soybean oil emulsion to induce lipid accumulation. We found that phenylalanine treatment exacerbated lipid accumulation by inhibiting fatty acid oxidation without affecting fatty acid synthesis. In summary, our findings establish a pathogenic role of increased phenylalanine levels in driving liver steatosis, linking dysregulation of phenylalanine catabolism with lipid accumulation in the context of PNALD.

Management of Traumatic Duodenal Injury: Is There a Role for Early Parenteral Nutrition?

INTRODUCTION: Traumatic duodenal injuries are complex in nature and pose major challenges to trauma surgeons. These injuries are associated with high mortality rates ranging from 18% to 30% and require prompt, comprehensive care. Traumatic injury induces a hypercatabolic state that mobilizes body energy stores, leading to muscle wasting, delayed healing, and potential multi-organ failure. Nutritional support is vital in keeping up with the metabolic demands of traumatically injured patients. However, exactly when and how nutrition should be provided for traumatic duodenal injuries is unclear. We hypothesize that patients who sustain high-grade duodenal injuries (grades III-V) will be unable to tolerate enteral nutrition (EN) and may benefit from early initiation of total parenteral nutrition (TPN). METHODS: In this retrospective chart review study, we queried the trauma registry for patients admitted between January 2018 and December 2022 with duodenal injury. Individuals under the age of 18 and individuals who were pregnant were excluded. Twenty-eight patients met the inclusion/exclusion criteria. The primary endpoint was median number of days from initial injury to supplemental nutrition. We also evaluated the route used to achieve adequate nutrition based on duodenal injury grade (I-V), mortality based on duodenal injury grade, morbidity based on route of nutrition supplementation (hospital length of stay [LOS], intensive care unit LOS, and ventilator days), and complications based on route of nutrition supplementation. RESULTS: Of the 28 patients analyzed, 11 received EN, 10 received TPN (6 of which survived to transition to EN), and 7 died within 3 d of admission and did not receive any form of nutrition. The median number of days post-trauma to toleration of enteral feeding (defined as by mouth or tube feeding that meet total caloric needs based on nutritionist recommendations) was 4 d for those who did tolerate and maintained tolerance of enteral feeding, compared to 7.5 d post-trauma to initiate total parenteral feeding (P = 0.061). Injury grades I and II tolerated EN within a median of 6 d, whereas injury grades III and IV showed inability to tolerate EN until after a median of 22 d or longer (P = 0.02). Mortality increased as injury grade increased. Patients who received TPN were more likely to develop abscesses than those receiving EN (80% vs 27%, P = 0.03) but not more likely to develop a duodenal leak (P = 0.31). Patients who received TPN had longer hospital LOS (35.5 d vs 9 d, P = 0.008), longer intensive care unit LOS (17 d vs 4 d, P = 0.005), and increased ventilator days (9 d vs 1 d, P = 0.005) when compared to patients who received EN. CONCLUSIONS: Individuals with higher grade duodenal injuries showed inability to tolerate EN until after a median of 22 d, and therefore, consideration should be given to initiating TPN early to mitigate the catabolic effects of malnutrition. Further studies need to be done with a larger number of patients to evaluate the effects of malnutrition in these patients.

Impact of total parenteral nutrition v. exclusive enteral nutrition on postoperative adverse outcomes in patients with penetrating Crohn's disease undergoing surgical resection: a retrospective cohort study.

Achieving optimal nutritional status in patients with penetrating Crohn's disease is crucial in preparing for surgical resection. However, there is a dearth of literature comparing the efficacy of total parenteral nutrition (TPN) v. exclusive enteral nutrition (EEN) in optimising postoperative outcomes. Hence, we conducted a case-matched study to assess the impact of preoperative EEN v. TPN on the incidence of postoperative adverse outcomes, encompassing overall postoperative morbidity and stoma formation, among penetrating Crohn's disease patients undergoing bowel surgery. From 1 December 2012 to 1 December 2021, a retrospective study was conducted at a tertiary centre to enrol consecutive patients with penetrating Crohn's disease who underwent surgical resection. Propensity score matching was utilised to compare the incidence of postoperative adverse outcomes. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with adverse outcomes. The study included 510 patients meeting the criteria. Among them, 101 patients in the TPN group showed significant improvements in laboratory indicators at the time of surgery compared with pre-optimisation levels. After matching, TPN increased the occurrence of postoperative adverse outcomes (92·2 % v. 64·1 %, P = 0·001) when compared with the EEN group. In the multivariate analysis, TPN showed a significantly higher OR for adverse outcomes than EEN (OR = 4·241; 95 % CI 1·567-11·478; P = 0·004). The study revealed that penetrating Crohn's disease patients who were able to fulfil their nutritional requirements through EEN exhibited superior nutritional and surgical outcomes in comparison with those who received TPN.

A novel nutritional approach to infants and children with congenital diarrhea due to homozygous DGAT1 mutations.

OBJECTIVES: Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride synthesis. DGAT1 is expressed in human enterocytes and is essential for fat absorption. Homozygous DGAT1 deficiency often presents with severe diarrhea and protein-losing enteropathy (PLE) in the 1st weeks of life. Because severe restriction of fat intake controls diarrhea and decreases PLE, total parenteral nutrition (TPN) was the initial standard therapy in infants and children. We present tertiary center experience managing infants and children with DGAT1 deficiency resulting in the development of a nutritional approach that minimizes the use of TPN. METHODS: From 2014 to 2020, 12 infants with DGAT1 deficiency were treated. Stool output, growth, and development, as well as essential fatty acid status, were monitored. This retrospective experience formed the basis for treatment recommendations, which include an ultralow fat formula with intermittent peripheral intravenous lipid infusions during the 1st year of life. RESULTS: All patients with prolonged intestinal fat exposure had PLE, which resolved when treated with the nutrition protocol. Essential fatty acid status as measured by triene:tetraene ratios normalized in all treated patients. Over time, early genetic diagnosis and prompt initiation of an ultralow fat diet with peripheral intravenous lipid infusions replaced the need for TPN. CONCLUSIONS: Children with DGAT1 deficiency respond to dietary restriction of lipids. Management with a novel nutritional approach provides effective treatment for infants with DGAT1 deficiency, treats diarrhea and PLE, promotes growth and development, avoids TPN dependency, and decreases the potential for essential fatty acid deficiency.

Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures.

Parenteral nutrition (PN) is typically administered to individuals with gastrointestinal dysfunction, a contraindication for enteral feeding, and a need for nutritional therapy. When PN is the only energy source in patients, it is defined as total parenteral nutrition (TPN). TPN is a life-saving approach for different patient populations, both in infants and adults. However, despite numerous benefits, TPN can cause adverse effects, including metabolic disorders and liver injury. TPN-associated liver injury, known as intestinal failure-associated liver disease (IFALD), represents a significant problem affecting up to 90% of individuals receiving TPN. IFALD pathogenesis is complex, depending on the TPN components as well as on the patient's medical conditions. Despite numerous animal studies and clinical observations, the molecular mechanisms driving IFALD remain largely unknown. The present study was set up to elucidate the mechanisms underlying IFALD. For this purpose, human liver spheroid co-cultures were treated with a TPN mixture, followed by RNA sequencing analysis. Subsequently, following exposure to TPN and its single nutritional components, several key events of liver injury, including mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, apoptosis, and lipid accumulation (steatosis), were studied using various techniques. It was found that prolonged exposure to TPN substantially changes the transcriptome profile of liver spheroids and affects multiple metabolic and signaling pathways contributing to liver injury. Moreover, TPN and its main components, especially lipid emulsion, induce changes in all key events measured and trigger steatosis.

Continuous versus intermittent bolus infusion of calcium in preterm infants receiving total parenteral nutrition: a randomized blind clinical trial.

BACKGROUND: Premature neonates need adequate nutritional support to provide sufficient essential nutrients for optimal growth. Calcium (Ca) is one of the important nutrients in parental nutrition support of premature infants. This study aimed to compare the effect of continuous and intermittent bolus infusion of Ca on the incidence of metabolic bone disease (MBD) in preterm infants. METHODS: This randomized double-blind clinical trial was conducted on ninety preterm infants in the NICU of Al-Zahra Hospital in Tabriz, Iran. The preterm infants were randomly allocated to either a continuous infusion group (received 4-5 ml/kg/day of Ca gluconate 10% by PN solution in a 24-h period) or an intermittent bolus administration group (received 1-2 ml/kg/day Ca gluconate 10% three to four times per day). Serial serum levels of Ca, phosphorous, alkaline phosphatase (ALP), vitamin D and parathyroid hormone (PTH) were assessed on the 7th day, 30th day and 45th day of life. RESULTS: A total of 78 infants completed the study. The serum ALP level on the 45th day after birth was 753.28 ± 304.59 IU/L and 988.2 ± 341.3 IU/L in the continuous infusion and intermittent bolus administration groups, respectively (P < 0.05). MBD in preterm infants with ALP levels above 900 IU/L on the 45th day of life was significantly lower in the continuous infusion group than in the intermittent bolus administration group (p < 0.05). The mean serum levels of calcium, phosphorus, vitamin D and PTH in 45-day-old infants were not significantly different between the two groups. CONCLUSION: The MBD in preterm infants who received continuous infusion of Ca was lower than that in preterm infants who received intermittent bolus administration of Ca. TRIAL REGISTRATION: The Iranian Registry of Clinical Trials ( http://www.irct.ir ) with the identification No. IRCT20210913052466N1.

Risk factors associated with anemia of prematurity requiring red blood cell transfusion in very low birth weight infants: a retrospective study.

BACKGROUND: Anemia of prematurity (AOP) is prevalent among very low birth weight infants (VLBWIs). Red blood cell (RBC) transfusions, while necessary for managing AOP, have been linked to adverse neonatal outcomes. METHODS: This retrospective study analyzed the medical records of 98 VLBWIs (24-31 weeks gestation) admitted to the Chungbuk National University Hospital neonatal intensive care unit. Infants were categorized based on RBC transfusion status and birth weight (< 1000 g and 1000-1499 g). Clinical outcomes between the groups were compared. RESULTS: Of the 98 infants, 35 (35.7%) received RBC transfusions. The RBC transfusion group exhibited significantly higher incidence of bronchopulmonary dysplasia ([Formula: see text]moderate), prolonged invasive mechanical ventilation, intraventricular hemorrhage (grades 1-2), extended time to full enteral feeding, and extended total parenteral nutrition (TPN) compared to the non-RBC transfusion group. Birth weight was inversely correlated with the number of RBC transfusions (p = 0.004). The duration of invasive mechanical ventilation and TPN administration were positively associated with the number of RBC transfusions (p < 0.001 and p = 0.025, respectively). CONCLUSIONS: The RBC transfusion group experienced more comorbidities than the non-transfusion group. Birth weight, duration of invasive ventilation, and duration of TPN were associated with the number of RBC transfusions. Strategies to reduce the duration of invasive ventilation and early discontinuation of TPN may mitigate the need for RBC transfusions in AOP.

Altered hepatic and intestinal homeostasis in a neonatal murine model of short-term total parenteral nutrition and antibiotics.

Parenteral nutrition (PN) prevents starvation and supports metabolic requirements intravenously when patients are unable to be fed enterally. Clinically, infants are frequently provided PN in intensive care settings along with exposure to antibiotics (ABX) to minimize infection during care. Unfortunately, neonates experience extremely high rates of hepatic complications. Adult rodent and piglet models of PN are well-established but neonatal models capable of leveraging the considerable transgenic potential of the mouse remain underdeveloped. Utilizing our newly established neonatal murine PN mouse model, we administered ABX or controlled drinking water to timed pregnant dams to disrupt the maternal microbiome. We randomized mouse pups to PN or sham surgery controls +/- ABX exposure. ABX or short-term PN decreased liver and brain organ weights, intestinal length, and mucosal architecture (vs. controls). PN significantly elevated evidence of hepatic proinflammatory markers, neutrophils and macrophage counts, bacterial colony-forming units, and evidence of cholestasis risk, which was blocked by ABX. However, ABX uniquely elevated metabolic regulatory genes resulting in accumulation of hepatocyte lipids, triglycerides, and elevated tauro-chenoxycholic acid (TCDCA) in serum. Within the gut, PN elevated the relative abundance of Akkermansia, Enterococcus, and Suterella with decreased Anaerostipes and Lactobacillus compared with controls, whereas ABX enriched Proteobacteria. We conclude that short-term PN elevates hepatic inflammatory stress and risk of cholestasis in early life. Although concurrent ABX exposure protects against hepatic immune activation during PN, the dual exposure modulates metabolism and may contribute toward early steatosis phenotype, sometimes observed in infants unable to wean from PN.NEW & NOTEWORTHY This study successfully established a translationally relevant, murine neonatal parenteral nutrition (PN) model. Short-term PN is sufficient to induce hepatitis-associated cholestasis in a neonatal murine model that can be used to understand disease in early life. The administration of antibiotics during PN protects animals from bacterial translocation and proinflammatory responses but induces unique metabolic shifts that may predispose the liver toward early steatosis.

Potential negative effect of total parenteral nutrition on the human circadian clock.

When patients cannot eat on their own, total parenteral nutrition (TPN) is a clinically beneficial method of maintaining nutrition. However, many animal studies have demonstrated that circadian rhythms are strongly affected by feeding time, raising the concern that continuous TPN around the clock may have an unexpected negative impact on the circadian clock of patients. To investigate this concern, we compared clock gene expression of aged subjects with or without TPN using hair follicle cells and found that while none of the non-TPN subjects showed any obvious defects in circadian rhythms of peripheral clock gene expression, a portion of aged subjects receiving continuous TPN showed abnormal circadian rhythms in peripheral clocks. Continuous TPN around the clock may therefore potentially perturb peripheral circadian rhythms, giving rise to the proposal that TPN needs to be administered with consideration to time factors.

Case Studies of Intradialytic Total Parenteral Nutrition in Nocturnal Home Hemodialysis.

The standard use of intradialytic parenteral nutrition has yielded heterogeneous clinical results. Confounders include patient selection, limited dialysis sessional duration, and frequency. Nocturnal home hemodialysis provides an intensive form of kidney replacement therapy (5 sessions per week and 8 hours per treatment). We present a series of 4 nocturnal home hemodialysis patients who required intradialytic total parenteral nutrition (IDTPN) as their primary source of caloric intake. We describe the context, effectiveness, and complications of IDTPN in these patients. Our patients received a range of 1200 to 1590 kCal (including 60 to 70 g of amino acids) with each IDTPN session for up to 27 months. As the availability of home hemodialysis continues to grow, the role of supplemental or primary IDTPN will require further research for this vulnerable patient population.

Intestinal Transplant Immunology and Intestinal Graft Rejection: From Basic Mechanisms to Potential Biomarkers.

Intestinal transplantation (ITx) remains a lifesaving option for patients suffering from irreversible intestinal failure and complications from total parenteral nutrition. Since its inception, it became obvious that intestinal grafts are highly immunogenic, due to their high lymphoid load, the abundance in epithelial cells and constant exposure to external antigens and microbiota. This combination of factors and several redundant effector pathways makes ITx immunobiology unique. To this complex immunologic situation, which leads to the highest rate of rejection among solid organs (>40%), there is added the lack of reliable non-invasive biomarkers, which would allow for frequent, convenient and reliable rejection surveillance. Numerous assays, of which several were previously used in inflammatory bowel disease, have been tested after ITx, but none have shown sufficient sensibility and/or specificity to be used alone for diagnosing acute rejection. Herein, we review and integrate the mechanistic aspects of graft rejection with the current knowledge of ITx immunobiology and summarize the quest for a noninvasive biomarker of rejection.

Evaluating the efficacy of a programme to educate nurses on CLABSI linked to total parenteral nutrition administration.

BACKGROUND: There is a major need to improve the knowledge and practice of critical care nurses in India regarding central line-associated bloodstream infection (CLABSI), which is a serious potential complication of total parenteral nutrition (TPN). OBJECTIVES: To develop and validate a skills competency programme; assess knowledge and practice of critical care nurses regarding prevention of CLABSI due to TPN administration; evaluate the effectiveness of the programme; find correlation between knowledge and practice scores. DESIGN: Quasi-experimental: non-equivalent pre-test post-test design. SETTINGS: Two hospitals in Meerut, India. PARTICIPANTS: 80 nurses (40 in the control group in one hospital, 40 in the experimental group in another hospital). Inclusion criteria: staff nurses from critical care units only, who were present at the time of data collection and willing to participate. Exclusion criteria: staff nurses with <6 months' work experience. METHOD: Knowledge was assessed using a structured knowledge questionnaire and interpretation scoring. To assess practice, the OSCE (objective structured clinical examination) method was used with four stations and interpretation scoring. The skills-competency programme was delivered to the experimental group only. The post test was conducted with both groups. RESULTS: The post-test knowledge and practice scores in the control group were: mean=12.55; SD=2.57 and mean=21.82; SD= 5.13 respectively. In the experimental group, the post-test knowledge and practice scores were: mean=23.75; SD=1.75 and mean=38.9; SD=2.02 respectively. The unpaired t-test in post-test knowledge between the control and experimental groups was t=22.78, with P=0.0001 at df 39, 0.05 level of significance, 95% CI; for post-test practice the results were, t=19.59, with P=0.0001 at df 39, 0.05 level of significance, 95% CI. Correlation between post-test knowledge and the practice score was r=0.7 (P<0.05), 95% CI. CONCLUSION: There was a significant difference in post-test knowledge and practice scores, therefore, the skills competency programme was effective. It also highlighted areas that institutions should focus on for effective training and professional development programmes.

Nutrition in acute pancreatitis: when, what and how.

PURPOSE OF REVIEW: This review intends to discuss recently available evidence in three topics related to nutrition in patients with acute pancreatitis, namely timing of refeeding, type of nutritional therapy and its route of administration. RECENT FINDINGS: Recent lines of research confirm that early oral feeding leads to shorter length of stay, fewer complications and lower costs in patients with acute pancreatitis. Moreover, early (<48 h) enteral nutrition led to decreased hospital mortality in patients with mild and severe acute pancreatitis; thus, in case of intolerance to oral feeding or severe disease, nutritional therapy should be offered within 24-72 h. Furthermore, enteral nutrition should be preferred against parenteral nutrition, as it is related to shorter length of stay and less complications, while initial data bring to light the potential role of the soluble dietary fibre polydextrose as an agent that could lead to faster achievement of energy goal with concomitant lower rates of feeding intolerance. Finally, enteral nutrition can be administered through gastric or jejunal feeding, depending on digestive tolerance, whereas latest data also address the safety of percutaneous gastrostomy with a jejunal extension for enteral nutrition administration. However, more data about its real benefit are warranted. SUMMARY: Accumulating evidence confirms the importance of early oral refeeding or early administration of enteral nutrition as vital parts of the armamentarium for the management of patients with acute pancreatitis.

Direct hyperbilirubinemia and cholestasis in trisomy 13 and 18.

Trisomy 13 and 18 are common chromosomal abnormalities that affect multiple organ systems. There is a paucity of published data, however, on the hepatic complications seen in these patient populations. One of the most common pathologic hepatobiliary issues seen in the newborn period is direct hyperbilirubinemia (DH). Thus, this study sought to estimate the incidence and evaluate possible etiologies of DH in neonates with trisomy 13 or 18. This retrospective cohort study included all infants admitted to our two neonatal intensive care units between 2012 and 2020 with the diagnosis of trisomy 13 or 18. DH is most commonly diagnosed as a direct bilirubin >1 mg/dl but a cutoff of >2 mg/dl is more specific for cholestasis, so both cutoffs were evaluated. Continuous data were compared using Fisher's exact test and categorical variables by the Mann-Whitney U test. Thirty-five patients met inclusion: 13 with trisomy 13 and 22 with trisomy 18. DH of >2 mg/dl was seen in seven (53.8%) patients with trisomy 13 and five (22.7%) with trisomy 18. Using a cutoff of >1 mg/dl, the rate of trisomy 13 was unchanged, but the rate in trisomy 18 increased to 9/22 (40.9%). There was a trend toward more DH in trisomy 13 patients (p = 0.079) versus trisomy 18 and higher rates in infants who received total parenteral nutrition (TPN) (50.0 vs. 13.3%, p = 0.026). The presence of cardiac or ultrasound-defined hepatobiliary abnormalities was not correlated with DH. Due to the high rates of DH in hospitalized neonates with trisomy 13 and 18, we recommend screening newborns with trisomy 13 or 18 for DH starting in the first week of life and continuing at least weekly until 4 weeks of life or until completion of TPN, whichever comes later. Future studies should further evaluate possible etiologies of DH in this population.

Research priorities in pediatric parenteral nutrition: a consensus and perspective from ESPGHAN/ESPEN/ESPR/CSPEN.

Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this. IMPACT: The recent ESPGHAN/ESPEN/ESPR/CSPEN guidelines for pediatric parenteral nutrition provided updated guidance for providing parenteral nutrition to infants and children, including recommendations for practice. However, in several areas there was a lack of evidence to guide practice, or research questions that remained unanswered. This paper summarizes the key priorities for research in pediatric parenteral nutrition, and ranks them in order of importance according to expert opinion.

Lipid Compositions of Total Parenteral Nutrition Affect Gut Peyer's Patches and Morphology in Mice.

INTRODUCTION: Although parenteral nutrition (PN) is the only option for providing adequate nutrition to patients who cannot tolerate oral ingestion, it severely impairs intestinal barrier function in terms of morphology and immunity. While addition of either soybean oil (SO) or fish oil (FO) to PN partially reverses these defects, the effects of the oil composition (FO/SO ratio) on morphology and gut-associated lymphoid tissues (GALT) have yet to be elucidated. We focused on the effects of the FO/SO ratio in PN on the number of lymphocytes in Peyer's patches, immunoglobulin A levels, and intestinal structures. METHODS: Male ICR mice (n = 61) were randomized into five groups; oral nutrition (Chow, n = 14) and four groups receiving PN without oral nutrition. PN solutions contained fat emulsions with the following FO:SO ratios: 0:1 (SO, n = 12), 1:11.5 (11.5FSO, n = 17),1:2 (1:2FSO, n = 13) and 1:0 (FO, n = 5). All mice underwent jugular vein catheter insertion. The PN groups were given isocaloric and isonitrogenous nutritional support with 20% of total calories from fat emulsions with equivalent fat delivery in 11.9 g/kg/d. After 5 d of each feeding, Peyer's patches lymphocytes were isolated from the small intestine, counted and analyzed with flowcytometry for determination of their phenotypes (αßTCR+, γδTCR+, CD4+, CD8+ and B cells). Villus height and crypt depth of the jejunum and ileum were evaluated with hematoxylin-eosin staining. Immunoglobulin A levels in the intestinal washings were also determined. RESULTS: Numbers of total lymphocytes and B lymphocytes in PP were increased in the 1:2 FSO-PN but neither in the 1:11.5 FSO nor the FO group, as compared to the SO group. There were no marked differences among the groups in numbers neither of total T cells nor in any of T cell phenotypes determined. The 1:2 FSO group showed significantly greater villus height and crypt depth than the SO group. IgA levels did not differ significantly among the four PN groups. CONCLUSIONS: The PN with 1:2 FSO (FO:SO = 1:2) maintained lymphocyte numbers in PP and intestinal villus morphology at levels nearly the same as those obtained with chow feeding. An appropriate ratio of FO to SO in PN is expected to prevent immunological impairment and morphological atrophy of the gut associated with lack of oral nutrition.

The outcome and complications of total parenteral nutrition in pediatric hematopoietic stem cell transplantation.

BACKGROUND: Nutritional support posthematopoietic stem cell transplantation (HSCT) with total parenteral nutrition (TPN) or nasogastric tube feeding (NGT) in pediatric patients is associated with benefits and risks. METHODS: We retrospectively reviewed the indication of TPN use in our pediatric HSCT patients and its impact on survival and possible related complications. RESULTS: A total of 228 HSCTs were performed during the study period. TPN was used in 144 patients (63.2%) for a median of 14 days, while 8.8% had NGT feeding and 28% were able to tolerate oral feeding. Severe mucositis was seen in 104 TPN patients (72.2%) in comparison with 22 patients (26.2%) who were on Enteral Nutrition (EN) (p = <.001). Sinusoidal obstruction syndrome (SOS) was seen in 19 (13.2%) patients who had TPN compared to none in the patients who received EN (p = .001). The majority of patients who had SOS received myeloablative conditioning (MAC) therapy for hemoglobinopathy. Acute graft-versus-host disease (aGVHD) was seen in 24.8% of TPN patients and 9.1% of non-TPN patients (p = .01). However, there were no statistically significant differences in chronic GVHD, bacteremia, and patients' survival between both groups. CONCLUSIONS: TPN is commonly used after pediatric HSCT in cases of severe mucositis. NGT feeding was found to be the least used nutritional support method. SOS and aGVHD were associated more frequently in TPN patients compared to EN patients. This suggests the possible disadvantages of TPN and importance of SOS preventative measures in high-risk patients.

How Broad Should Gram-Negative Coverage Be for Febrile Parenteral Nutrition Dependent Short Bowel Syndrome Patients?

ABSTRACT: Broader spectrum Gram-negative antibiotics are commonly utilized empirically for central line-associated bloodstream infections (CLABSI) in febrile short bowel syndrome (SBS) patients receiving home parenteral nutrition compared to those used empirically for inpatient-acquired CLABSI. This analysis reports 57 CLABSI in 22 patients with SBS admitted from the community and 78 inpatient-acquired CLABSI in 76 patients over a 5-year period. Proportional Gram-negative CLABSI was similar between the SBS and inpatient-acquired cohorts (43.8% vs42.3%, respectively, P  = 0.78). 1.8% and 10.3% (P = 0.125) of Gram-negative CLABSI were non-susceptible to ceftriaxone and 0% and 3.8% (P = 0.52) were non-susceptible to ceftazidime in the SBS and inpatient-acquired cohorts, respectively. In the SBS cohort, home ethanol lock therapy and prior culture results impacted Gramnegative pathogen distribution. Broader empiric Gram-negative coverage for CLABSI among SBS patients compared to inpatients is unnecessary. Third-generation cephalosporins represent appropriate empiric Gramnegative agents for febrile SBS patients presenting from the community to our institution.