Dual-task performance and brain morphologic characteristics in Parkinson's disease.

Introduction Parkinson's disease (PD) reduces an individual's capacity for automaticity which limits their ability to perform two tasks simultaneously, negatively impacting daily function. Understanding the neural correlates of dual-tasks (DT) may pave the way for targeted therapies. To better understand automaticity in PD, we aimed to explore whether individuals with differing DT performances possessed differences in brain morphologic characteristics. Methods Data were obtained from 34 individuals with PD and 47 healthy older adults including: 1) demographics (age, sex), 2) disease severity (Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn & Yahr, levodopa equivalent daily dose (LEDD)), 3) cognition (Montreal Cognitive Assessment), 4) Levodopa Equivalent Daily Dose, 5) single task- and DT- performance during a DT-Timed-Up-and-Go test utilizing a serial-subtraction task, and 6) Cortical thicknesses and subcortical volumes obtained from volumetric MRI. Participants were categorized as low or high DT performers if their combined DT-effect was greater than the previously determined mean value for healthy older adults (µ=74.2). Nonparametric testing using Quade's ANCOVA was conducted to compare cortical thicknesses and brain volumes between the highDT and lowDT groups while controlling for covariates: age, sex, MDS-UPDRS part III, LEDD, and intracranial volume. Secondarily, similar comparisons were made between the healthy older adult group the highDT and lowDT groups. Lastly, a hierarchical linear regression model was conducted regressing combined DT-effect on covariates (block one) and cortical thicknesses (block 2) in stepwise fashion. Results The highDT group had thicker cortices than the lowDT group in the right primary somatosensory (p=0.001), bilateral primary motor (p=<0.001, left; p=0.002, right), bilateral supplementary motor area (p=0.001, left; p<0.001, right), and mean of the bilateral hemispheres (p=0.001, left; p<0.001, right). Of note, left primary cortex thickness (p=0.002), left prefrontal cortex thickness (p<0.001), and right supplementary motor area thickness (p=0.003) differed when adding a healthy comparison group. Additionally, the regression analysis found that the left paracentral lobule thickness explained 20.8% of the variability in combined DT-effect (p=0.011) beyond the influence of covariates. Conclusions These results suggest regions underlying dual-task performance; specifically, a convergence of neural control relying sensorimotor integration, motor planning, and motor activation to achieve higher levels of DT performance for individuals with PD.

Radial Artery Access for Peripheral Vascular Interventions: A Review of the Literature.

BACKGROUND: Percutaneous radial artery access for lower extremity arterial interventions has increased in popularity in recent years. The purpose of this review is to summarize available data regarding its safety and efficacy. METHODS: Studies related to the use of the percutaneous radial artery access for peripheral artery intervention were identified in a search of the PubMed database. Outcomes evaluated were access complications and technical success. RESULTS: Thirteen studies that evaluated patients undergoing percutaneous radial artery access with peripheral interventions were reviewed. Several studies were able to demonstrate use of up to 8Fr sheath; however, the majority was 6Fr. Reported rates of asymptomatic radial artery occlusion ranged up to 16% and reported radial artery access site complication rate ranged from 0 to 15.6%. Technical success ranged from 74 to 98.7%. CONCLUSIONS: Percutaneous radial artery access can effectively and safely be used in select patients.

Predicting wound complications following lower extremity revascularization.

OBJECTIVE: The aim of this study was to create a simple risk score to identify factors associated with wound complications after infrainguinal revascularization. METHODS: The Veterans Affairs Surgical Quality Improvement Program national data set was queried from 2005 to 2021 to identify 22,114 patients undergoing elective open revascularization for peripheral arterial disease (claudication, rest pain, tissue loss) or peripheral aneurysm. Emergency and trauma cases were excluded. The data set was divided into a two-thirds derivation set and one-third validation set to create a risk prediction model. The primary end point was wound complication (wound dehiscence, superficial/deep wound surgical site infection). Eight independent risk factors for wound complications resulted from the model and were assigned whole number integer risk scores. Summary risk scores were collapsed into categories and defined as low (0-3 points), moderate (4-7 points), high (8-11 points), and very high (>12 points). RESULTS: The wound complication rate in the derivation data set was 9.7% (n = 1428). Predictors of wound complication included age ≤73 (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.08-1.46), body mass index ≥35 kg/m2 (OR, 1.99; 95% CI, 1.68-2.36), non-Hispanic White (vs others: OR, 1.48; 95% CI, 1.30-1.69), diabetes (OR, 1.23; 95% CI, 1.10-1.37), white blood cell count >9900/mm3 (OR, 1.18; 95% CI, 1.03-1.35), absence of coronary artery disease (OR, 1.27; 95% CI, 1.03-1.35), operative time >6 hours (OR, 1.20; 95% CI, 1.05-1.37), and undergoing a femoral endarterectomy in conjunction with bypass (OR, 1.34; 95% CI, 1.14-1.57). In both the derivation and validation sets, wound complications correlated with risk category. Among the defined categories in the derivation set, wound complication rates were 4.5% for low-risk patients, 8.5% for moderate-risk patients, 13.8% for high-risk patients, and 23.8% for very high-risk patients, with similar results for the internal validation data set. Operative indication did not independently associate with wound complications. Patients with wound complications had higher rates of reoperation and graft failure. CONCLUSIONS: This risk prediction model uses easily obtainable clinical metrics that allow for informed discussion of wound complication risk for patients undergoing open infrainguinal revascularization.

Percutaneous radial artery access for peripheral vascular interventions is a safe alternative for upper extremity access.

OBJECTIVE: Percutaneous radial artery access has been increasingly used for peripheral vascular interventions (PVIs). Our goal was to characterize the practice patterns and perioperative outcomes among patients treated using PVI performed via radial artery access. METHODS: The Vascular Quality Initiative was queried from 2016 to 2020 for PVI performed via upper extremity access. Univariable and multivariable analyses were used to evaluate the periprocedure outcomes of radial artery access cases. A separate sample of brachial artery access cases was used as a comparator. RESULTS: A total of 520 radial artery access cases were identified. The mean age was 69 ± 10 years, and 41.3% were women. Most procedures were performed in the hospital outpatient setting (71.7%). The sheath size was ≤5F for 10%, 6F for 78%, and 7F for 12%. Ultrasound-guided access and protamine were used in 68.3% and 17.3% of cases, respectively. The interventions were aortoiliac (55%), femoropopliteal (55%), and infrapopliteal (9%). Stenting and atherectomy were performed in 55% and 19% of cases, respectively, and more often with 7F sheaths. Access site complications were any hematoma (4.8%), including hematomas resulting in intervention (0.8%), pseudoaneurysms (1%), and access stenosis or occlusion (0.8%). On multivariable analysis, sheath size was not associated with access site complications. Percutaneous brachial artery access (n = 1135) compared with radial access was independently associated with more overall hematomas (odds ratio, 1.73; 95% confidence interval, 1.06-2.81; P = .03). However, access type was not associated with hematomas resulting in intervention (odds ratio, 2.15; 95% confidence interval, 0.69-6.72; P = .19). CONCLUSIONS: PVIs via radial artery access exhibited a low prevalence of postprocedural access site complications and were associated with fewer minor hematoma complications compared with interventions performed using brachial artery access. Radial artery access compared with brachial artery access should be the preferred technique for PVIs.

Symptomatic Diaphragmatic Hernia after Thoracofemoral Bypass.

Despite its relative underutilization in the primary management of aortoiliac occlusive disease, thoracofemoral bypass is an attractive extra-anatomic surgical option in select patients. Thoracofemoral bypass classically entails passing a graft from the left chest into the retroperitoneal space through a small opening created in the diaphragm. While theoretically possible that this maneuver may predispose to a peri-graft diaphragmatic hernia, currently there are no cases of this complication reported in the literature, nor has its surgical repair been described. This case illustrates the rare complication of symptomatic diaphragmatic hernia following a thoracobifemoral bypass.

Perioperative Outcomes of Carotid Interventions in Octogenarians.

BACKGROUND: In octogenarians with carotid stenosis, data supporting the decision to intervene and choice of intervention with either carotid endarterectomy (CEA) or carotid artery stenting (CAS) have been conflicting. The purpose of this study was to compare the perioperative outcomes of CEA and CAS in octogenarians, and to identify patients at high risk for unfavorable outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (2011-2018) was queried for patients aged ≥80 years who underwent CAS or CEA. Propensity scores were created for the odds of undergoing CAS. Patients were matched 1:1 based on propensity score and outcomes were compared after matching. Multivariable logistic regression analyses were used to identify risk factors for unfavorable postoperative outcomes. RESULTS: In total, 15,858 and 527 patients who underwent CEA and CAS were identified. After matching, there was no difference between CEA and CAS in perioperative stroke (2.3% vs. 2.9%; P = 0.56), cardiac complications (2.3% vs. 2.3%; P = 0.99), mortality (1.1% vs. 1.7%; P = 0.44), length of stay (median [interquartile range], 2 [1-4] vs. 1 [1-4] days; P = 0.13), and 30-day readmission (11.8% vs. 11.6%; P = 0.92). On multivariable analysis, the following were predictive for postoperative stroke: urgent operation (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.68-2.69; P < 0.001), chronic obstructive pulmonary disease (COPD; OR, 1.52; 95% CI, 1.11-2.09; P = 0.009), and American Society of Anesthesiologists class > III (OR, 1.46; 95% CI, 1.15-1.86; P = 0.002). Urgent procedure (OR, 2.86; 95% CI, 2.11-3.87; P < 0.001), COPD (OR, 2.31; 95% CI, 1.61-3.32; P < 0.001), dependent functional status (OR, 2.05; 95% CI, 1.35-3.1; P < 0.001), and age ≥ 85 years (OR, 1.92; 95% CI, 1.43-2.57; P < 0.001) were predictive for 30-day mortality. CONCLUSIONS: Outcomes of CEA and CAS were similar in octogenarians. Risk factors for worse intervention outcomes were identified, which may guide risk-benefit discussions and shared decision-making.

A Diet With Docosahexaenoic and Arachidonic Acids as the Sole Source of Polyunsaturated Fatty Acids Is Sufficient to Support Visual, Cognitive, Motor, and Social Development in Mice.

Polyunsaturated fatty acids serve multiple functions in neurodevelopment and neurocognitive function. Intravenous lipid emulsions are administered to children that are dependent on parenteral nutrition to provide the essential fatty acids needed to sustain growth and development. One of these emulsions, derived from fish-oil, is particularly poor in the traditional essential fatty acids, linoleic and alpha-linolenic acids. However, it does contain adequate amounts of its main derivatives, arachidonic acid (ARA) and docosahexaenoic acid (DHA), respectively. This skewed composition has raised concern about the sole use of fish-oil based lipid emulsions in children and how its administration can be detrimental to their neurodevelopment. Using a custom-made diet that contains ARA and DHA as a sole source of polyunsaturated fatty acids, we bred and fed mice for multiple generations. Compared to adult, chow-fed mice, animals maintained on this special diet showed similar outcomes in a battery of neurocognitive tests performed under controlled conditions. Chow-fed mice did perform better in the rotarod test for ataxia and balance, although both experimental groups showed a conserved motor learning capacity. Conversely, mice fed the custom diet rich in DHA and ARA showed less neophobia than the chow-fed animals. Results from these experiments suggest that providing a diet where ARA and DHA are the sole source of polyunsaturated fatty acids is sufficient to support gross visual, cognitive, motor, and social development in mice.

Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children.

BACKGROUND: Parenteral fish-oil (FO) therapy is a safe and effective treatment for intestinal failure-associated liver disease (IFALD). Patients whose cholestasis does not resolve with FO may progress to end-stage liver disease. OBJECTIVE: We sought to identify factors associated with the failure of FO therapy in treating IFALD to guide prognostication and referral guidelines. DESIGN: Prospectively collected data for patients treated with FO at Boston Children's Hospital from 2004 to 2014 were retrospectively reviewed. Resolution of cholestasis was defined as sustained direct bilirubin (DB) <2 mg/dL, and treatment failure as liver transplantation or death while DB was >2 mg/dL as of July 2015. Demographics, laboratory values, and medical history at FO therapy initiation were compared between patients who achieved resolution of cholestasis and those who failed therapy. RESULTS: Among 182 patients treated with FO, 86% achieved resolution of cholestasis and 14% failed therapy. Patients who failed therapy had median (IQR) lower birth weight [1020 g (737, 1776 g) compared with 1608 g (815, 2438 g); P = 0.03] and were older at FO initiation [20.4 wk (9.9, 38.6 wk) compared with 11.7 wk (7.3, 21.4 wk); P = 0.02] than patients whose cholestasis resolved. Patients who failed therapy had more advanced liver disease at therapy initiation than patients whose cholestasis resolved, as evidenced by lower median (IQR) γ-glutamyltransferase [54 U/L (41, 103 U/L) compared with 112 U/L (76, 168 U/L); P < 0.001], higher DB [10.4 mg/dL (7.5, 14.1 mg/dL) compared with 4.4 mg/dL (3.1, 6.6 mg/dL); P < 0.001], and a higher pediatric end-stage liver disease (PELD) score [22 (14, 25) compared with 12 (7, 15); P < 0.001]. A PELD score of ≥15, history of gastrointestinal bleeding, age at FO initiation ≥16 wk, presence of nongastrointestinal comorbidities, and mechanical ventilation at FO initiation were independent predictors of treatment failure. CONCLUSIONS: Most infants with IFALD responded to FO therapy with resolution of cholestasis, and liver transplantation was rarely required. Early FO initiation once biochemical cholestasis is detected in parenteral nutrition-dependent patients is recommended. This trial was registered at clinicaltrials.gov as NCT00910104.

Challenging the 48-Hour Rule-Out for Central Line-Associated Bloodstream Infections in the Pediatric Intestinal Failure Population: A Retrospective Pilot Study.

INTRODUCTION: While parenteral nutrition (PN) has revolutionized the management of patients with intestinal failure (IF), central line-associated bloodstream infections (CLABSIs) remain a leading cause of mortality and morbidity in this population. The objective of this study is to characterize the presentation of CLABSIs in pediatric IF and to determine the time to positivity of blood cultures. METHODS: A retrospective cohort study of children with IF who presented to our institution for evaluation of a possible CLABSI from January 1, 2012, to December 31, 2012, was performed. RESULTS: Sixty patients with IF were identified. There were 33 cases of CLABSI in 16 patients, with a rate of 1.5 infections per 1000 catheter days. There were no significant differences in age, growth parameters, or catheter days between patients with or without CLABSI. Fever was documented in 85% of patients with CLABSI. These patients demonstrated an increased percentage of neutrophils and higher C-reactive protein levels compared with patients without CLABSI. The mean time to culture positivity was 13.2 hours, and 97% of cultures were positive within 24 hours. CONCLUSION: Our data suggest that most pediatric patients with IF who have CLABSI develop positive cultures within 24 hours, and the absence of fever and leukocytosis does not necessarily indicate the absence of infection. These findings may support clinical practice guidelines in favor of shorter hospital stay when CLABSI is suspected; however, a prospective analysis of CLABSI in this population is recommended to determine the safety and appropriate setting prior to any practice change.

The addition of medium-chain triglycerides to a purified fish oil-based diet alters inflammatory profiles in mice.

OBJECTIVE: Parenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development. MATERIALS/METHODS: Six groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCT), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment. RESULTS: All groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-α response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response. CONCLUSION: These results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation.

Elevated Alkaline Phosphatase in Infants With Parenteral Nutrition-Associated Liver Disease Reflects Bone Rather Than Liver Disease.

BACKGROUND: Elevated serum alkaline phosphatase (ALP) in infants with intestinal failure (IF) can be due to parenteral nutrition-associated liver disease (PNALD) or metabolic bone disease (MBD). The purpose of the study was to determine the utility of serum ALP in the diagnostic criteria for PNALD by measuring tissue-specific levels in infants with IF and PNALD. METHODS: A retrospective review of patient data for 15 infants diagnosed with PNALD between December 2012 and August 2013 was performed. PNALD was defined as the presence of 2 consecutive direct bilirubin (DB) levels >2 mg/dL. Fractionated serum alkaline phosphatase was measured in each patient, while the DB was >2 mg/dL. Parathyroid hormone (PTH), vitamin D3, calcium, and phosphate levels were recorded where available. RESULTS: In 15 infants with PNALD, elevation in total ALP was due to marked elevations in bone-specific ALP. The median liver-specific ALP remained within the normal range. PTH, vitamin D3, calcium, and phosphate levels were within normal limits. CONCLUSION: While elevated ALP can reflect biliary stasis, the ALP elevation observed in infants with IF and PNALD is predominantly of bone rather than hepatic origin. An elevated unfractionated ALP in infants with PNALD should therefore raise suspicion of underlying bone disease, rather than being attributed to liver disease alone.

The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy.

OBJECTIVE: To determine the natural history of cirrhosis from parenteral nutrition-associated liver disease (PNALD) after resolution of cholestasis with fish oil (FO) therapy. BACKGROUND: Historically, cirrhosis from PNALD resulted in end-stage liver disease, often requiring transplantation for survival. With FO therapy, most children now experience resolution of cholestasis and rarely progress to end-stage liver disease. However, outcomes for cirrhosis after resolution of cholestasis are unknown and patients continue to be considered for liver/multivisceral transplantation. METHODS: Prospectively collected data were reviewed for children with cirrhosis because of PNALD who had resolution of cholestasis after treatment with FO from 2004 to 2012. Outcomes evaluated included need for liver/multivisceral transplantation, mortality, and the clinical progression of liver disease. RESULTS: Fifty-one patients with cirrhosis from PNALD were identified, with 76% demonstrating resolution of cholestasis after FO therapy. The mean direct bilirubin decreased from 6.4 ± 4 mg/dL to 0.2 ± 0.1 mg/dL (P < 0.001) 12 months after resolution of cholestasis, with a mean time to resolution of 74 days. None of the patients required transplantation or died from end-stage liver disease. Pediatric End-Stage Liver Disease scores decreased from 16 ± 4.6 to -1.2 ± 4.6, 12 months after resolution of cholestasis (P < 0.001). In children who remained PN-dependent, the Pediatric End-Stage Liver Disease score remained normal throughout the follow-up period. CONCLUSIONS: Cirrhosis from PNALD may be stable rather than progressive once cholestasis resolves with FO therapy. Furthermore, these patients may not require transplantation and show no clinical evidence of liver disease progression, even when persistently PN-dependent.

Docosahexaenoic acid, G protein-coupled receptors, and melanoma: is G protein-coupled receptor 40 a potential therapeutic target?

BACKGROUND: To determine the effect of docosahexaenoic acid (DHA) on the growth of human melanoma in vitro and in vivo and to better understand the potential role of the G protein-coupled receptors (GPRs) in mediating this effect. MATERIALS AND METHODS: For in vitro studies, human melanoma and control fibroblast cells were treated with DHA and TAK-875 (selective GPR40 agonist) and a cell viability assay was performed to determine cell counts. A murine subcutaneous xenograft model of human melanoma was used to test the effect of dietary treatment with an omega-3 fatty acid (FA) rich diet compared with an omega-6 FA rich diet on the growth of human melanoma in vivo. A similar animal model was used to test the effect of oral TAK-875 on the growth of established melanoma tumors in vivo. RESULTS: DHA has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals on the omega-3 FA rich diet were 69% smaller in weight (P = 0.005) and 76% smaller in volume compared with tumors from animals on the omega-6 FA rich diet. TAK-875 has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals treated with TAK-875 were 46% smaller in weight (P = 0.07), 62% smaller in volume (P = 0.03), and grew 77% slower (P = 0.04) compared with the placebo group. CONCLUSIONS: DHA and TAK-875 have a profound and selective inhibitory effect on the growth of human melanoma both in vitro and in vivo.

Evaluation of anastomotic strength and drug safety after short-term sunitinib administration in rabbits.

BACKGROUND: Sunitinib (Sutent) is a Food and Drug Administration-approved receptor tyrosine kinase inhibitor found to reduce postoperative adhesion formation in animal models. The objective of the present study was to evaluate anastomotic healing and potential drug-related toxicities after short-term sunitinib administration in New Zealand White rabbits. MATERIALS AND METHODS: Under an approved study protocol, 40 rabbits underwent a laparotomy followed by colonic transection and anastomosis. Animals were randomly assigned to treatment with oral sunitinib (10 mg/kg/d) or placebo, received one preoperative dose followed by 10 postoperative doses, and were divided into two groups following the procedure: group I animals were euthanized on completion of drug treatment and group II animals were euthanized 30 d after completion of treatment. Prior to study completion, animals underwent an echocardiogram and laboratory test results were obtained. At necropsy, intestinal bursting strength (in mmHg) was evaluated. RESULTS: All animals survived until designated euthanasia. There was no evidence of intra-abdominal sepsis or intestinal obstruction. Sunitinib-treated animals were found to have lower intestinal anastomotic strength compared with placebo-treated animals, as measured by bursting pressure at euthanasia, and a greater percentage of bursting at the anastomosis. On echocardiography, all ejection and shortening fractions were within established normal reference values. There were no significant differences in liver enzymes between animals. There were no wound infections, dehiscence, or delayed wound healing in any animal. CONCLUSIONS: These results caution against the administration of sunitinib in cases involving intestinal anastomoses because of the elevated risk of anastomotic leak. No evidence of cardiotoxicity, hepatotoxicity, or detrimental effect on wound healing was found in any animal.

Neonatal intestinal physiology and failure.

The neonatal intestine is a complex organ that regulates the absorption of nutrients essential for growth and development. Intestinal failure results from insufficient or functionally inadequate bowel and can lead to failure of neonatal growth and development. Current literature on neonatal intestinal physiology and failure was reviewed and summarized. A homeostatic interplay of electrolytes, enzymes, and hormonal regulators is essential to achieve the physiologic balance needed for adequate intestinal performance. Physiologic consequences of intestinal failure are dependent on the length and anatomic location of the diseased or surgically resected bowel. Intestinal failure leads to disruption of normal intestinal physiology and may have long-term consequences for growth and development if inadequately treated. Parenteral nutrition remains the mainstay of treatment for neonatal intestinal failure.

Treatment of parenteral nutrition-associated liver disease: the role of lipid emulsions.

Parenteral nutrition is a life-saving therapy for infants with intestinal failure. However, long-term parenteral nutrition carries the risk of progressive liver disease. Substantial data has implicated components of parenteral soybean oil in the pathogenesis of parenteral nutrition-associated liver disease (PNALD). Elevated serum concentrations of phytosterols, an abundance of omega-6 polyunsaturated fatty acids, and a relative paucity of α-tocopherol have been associated with the risk of cholestasis and hepatic injury observed in PNALD. Currently available treatment strategies include the reduction of the dose of administered parenteral soybean oil and/or the replacement of parenteral soybean oil with alternative parenteral lipid emulsions. The purpose of this review is to provide an overview of the pathogenetic mechanisms associated with the development of PNALD and the data evaluating currently available treatment strategies.

Role of parenteral lipid emulsions in the preterm infant.

Parenteral nutrition (PN) is necessary for infants unable to receive adequate calories enterally due to prematurity, decreased bowel length, or functional intestinal disorders. While PN can be life saving, its use is associated with significant risks of sepsis from catheter-associated infections and progressive liver dysfunction from prolonged use. The preterm infant population is at highest risk for these complications due to the presence of multiple comorbidities and immaturity of the biliary system. Strong data has implicated parenteral lipids in the multifactorial pathogenesis of PN-associated liver disease (PNALD). However, lipids are essential in early infant development, particularly in the neurocognitive development of preterm infants. Substitution of the lipid source from soybean oil to fish oil has emerged as a safe and efficacious treatment of PNALD, with marked improvements in morbidity and mortality. Knowledge of the developmental needs and physiologic limitations of preterm infants is crucial to optimizing parenteral lipid administration to nurture growth, and minimize and treat associated complications. The purpose of this review is to provide an overview of lipid requirements of the preterm infant and discuss the role of parenteral lipid emulsions in the management of PNALD and other diseases of prematurity.

A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for metabolic bone disease.

BACKGROUND: Premature infants are at increased risk for metabolic bone disease, with resulting delayed bone growth, osteopenia, and rickets. METHOD: A systematic review of the best available evidence to answer a series of questions regarding neonatal patients at risk of metabolic bone disease receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. QUESTIONS: (1) What maternal risk factors predispose the neonate to metabolic bone disease? (2) What is the optimal type of feeding to promote neonatal bone health? (3) When and how should vitamin D supplements be administered? (4) Does parenteral nutrition (PN) predispose a neonate to metabolic bone disease, and if so, are there PN formulation recommendations to minimize this risk?

Provision of a soy-based intravenous lipid emulsion at 1 g/kg/d does not prevent cholestasis in neonates.

BACKGROUND: One of the most common and severe complications of long-term parenteral nutrition (PN) is PN-associated cholestasis. The soybean oil-based lipid emulsion administered with PN has been associated with cholestasis, leading to an interest in lipid reduction strategies. The purpose of this study was to determine whether the provision of a soybean oil-based lipid emulsion at 1 g/kg/d compared with 2-3 g/kg/d is associated with a reduced incidence of cholestasis. METHODS: Retrospective review of neonates admitted between 2007 and 2011 with a gastrointestinal condition necessitating ≥ 21 days of PN support. Neonates were divided into 2 groups based on the intravenous lipid emulsion dose: 1-g group (1 g/kg/d) and 2- to 3-g group (2-3 g/kg/d). The primary outcome measure was the incidence of cholestasis. RESULTS: Sixty-one patients met inclusion criteria (n = 29, 1-g group; n = 32, 2- to 3-g group). The 2 groups did not differ in any baseline characteristics other than associated comorbidities that were more common in the 2- to 3-g group. The duration of PN, the number of operative procedures and bloodstream infections, and enteral nutrition (EN) were similar between groups. The incidence of cholestasis was not different between groups (51.7%, 1-g group; 43.8%, 2- to 3-g group; P = .61), and there was no difference between groups in the time to cholestasis (32.6 ± 24.1 days, 1-g group; 27.7 ± 10.6 days, 2- to 3-g group; P = .48). Overall, 44.8% of patients with cholestasis were transitioned to full EN, and 55.2% were transitioned to a fish oil-based lipid emulsion after which the direct bilirubin normalized in all patients. CONCLUSION: Lipid reduction to 1 g/kg/d does not prevent or delay the onset of cholestasis in neonates.

The role of the ω-3 fatty acid DHA in the human life cycle.

Dietary consumption of the essential fatty acids linoleic acid (LA; ω-6) and α-linolenic acid (ALA; ω-3) is necessary for human growth and development. In the past 150 years, the average Western diet has changed dramatically such that humans today consume a much higher proportion of ω-6 fatty acids relative to ω-3 fatty acids than ever before. The importance of ω-3 fatty acids in human development has been well established in fetal and neonatal development, with brain and retinal tissues highly dependent on ω-3 fatty acids, specifically docosahexaenoic acid (DHA) for membrane fluidity and signal transduction. In childhood, ω-3s have been shown to contribute to ongoing cognitive development and may be involved in metabolic programming of bone turnover and adipogenesis. ω-3s may also play important roles in adult neurophysiology and disease prevention.