Search

Background: Pediatric rectal prolapse (RP) is a rare but burdensome disease. We sought to describe our RP patient population’s mental behavioral health disorder (MBHD) history and compare their outcomes. Methods: In a single center retrospective cohort study, all patients who underwent surgical evaluation of RP from 2016-2021 were identified and reviewed. Results: Of 56 patients identified, 30 met inclusion criteria, 16 (53.3%) had a documented MBHD. Those with MBHD were significantly older (14.4 vs 9.4 years, p=0.027), and had higher rates of constipation (15, 94% vs 19, 17%, p =0.05). They had significantly longer duration of medical management before intervention than those without MBHD (216 vs 57 days, p=0.046). Ultimately, more patients with MBHD underwent operative intervention for rectal prolapse (8, 50% vs 2, 14.2%, p =0.019). Conclusions: Pediatric patients with rectal prolapse have a high rate of MBHD and despite longer intervals of medical management, often require operative intervention.

Vaginal reconstruction with autologous buccal mucosa graft offers a promising alternative to the use of skin grafts and vascularized intestinal segments. Given the novelty of this procedure, the optimal approach to postoperative wound management remains unclear with current practices often requiring many months of vaginal stents/molds. This study aims to evaluate a newly developed negative pressure intravaginal wound vacuum placed at the conclusion of the vaginoplasty with the goals of facilitating graft take and healing.A retrospective review of patients (age 12-21 years) who underwent eight primary and secondary vaginoplasty procedures using autologous buccal mucosa coupled with intravaginal wound vacuum placement was performed.Vaginal reconstruction with fenestrated full-thickness buccal mucosa graft and intravaginal wound vacuum placement was successfully performed eight times in seven patients at a median age of 15.6 years. Four patients underwent robotic vaginal pull-through with buccal mucosa serving as an interposition graft, and four patients underwent vaginoplasty with buccal graft alone. All cases had excellent engraftment at time of wound vacuum removal on postoperative day seven and had healthy-appearing buccal mucosa at a mean follow-up of 148 days. Postoperatively, one patient developed a stricture at the anastomosis between native vagina and buccal mucosa graft, requiring a second buccal mucosa graft six months after the first operation.The use of autologous buccal mucosa graft for primary and secondary vaginal reconstruction coupled with intravaginal wound vacuum therapy offers a promising new approach. Negative pressure wound vacuum therapy may provide a more optimal wound healing environment for improved outcomes.Retrospective Study LEVELS OF EVIDENCE: Level IV.

Zonula occludens-2 (ZO-2), encoded by TJP2, is a multi-domain scaffolding protein that recruits claudin proteins to tight junctions. In MDCK cells, Tjp2 knockdown inhibits Hippo signaling pathway and activates Yap/Taz. In humans, TJP2 mutations within the region that mediates claudin binding are associated with cholestasis that is exacerbated by defects in bile acid conjugation. Similarly, liver-specific Tjp2 knockout mice are phenotypically normal but hypersensitive to bile-acid induced cholestatic disease. We sought to determine whether ZO-2 has similar protective functions in intestinal epithelia. Like humans with TJP2 mutations, intestinal epithelial-specific Tjp2-knockout in mice did not induce spontaneous gut disease. There was, however, increased epithelial proliferation, mucosal hyperplasia, and Yap/Taz activation. Nuclear activated Yap was increased 1.9±0.1-fold in Tjp2 knockout enterocytes relative to wild type. In hepatocytes, bile acid stress elicited liver disease. We therefore asked if intestinal epithelial Tjp2 knockout increased mucosal injury induced by systemic T cell activation, TLR3 activation (poly I:C injection), or irradiation. In contrast to hepatocytes lacking ZO-2, intestinal epithelial ZO-2 deletion accelerated proliferation and repair. However, unlike wildtype mice, intestinal epithelial proliferation remained increased in Tjp2 knockout mice after repair was complete and mitotic activity had returned to baseline in wildtype mice. This phenotype is intrinsic to epithelial cells, as Tjp2 knockout enteroids excessive proliferation and formed complex cysts with exuberant budding. These data indicate that ZO-2 is a critical regulator of proliferative homeostasis within the intestinal epithelium and suggest that ZO-2 loss may contribute to dysregulated growth of intestinal neoplasms. Supported by: National Institutes of Health grants R01DK61931 and R01DK068271 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Wound dehiscence of the anocutaneous anastomosis and/or reconstructed perineal body is a feared perioperative complication after posterior sagittal anorectoplasty (PSARP). Dehiscence of the perineal body can have long-term negative implications for fecal continence, sexual intimacy, obstetrical outcomes, and the need for reoperative surgery. We describe a modification to the traditional PSARP for repair of an imperforate anus with a rectovestibular, perineal, or absent fistula by sparing the perineal body, eliminating postoperative perineal body dehiscence and potentially improving long-term functional outcomes.A retrospective review of female patients with a rectovestibular, perineal, or absent fistula who underwent PSARP with sparing of the perineal body was performed.Six patients underwent PSARP with sparing of the perineal body between 2019 and 2022. There were no perioperative complications. At follow-up, all patients are having regular bowel function without difficulty and have an excellent appearance of their perineal body.PSARP for a rectovestibular, perineal, or absent fistula can be safely performed with a more limited incision to avoid disruption of the perineal body. This eliminates the need for perineal body reconstruction during the procedure, thereby preventing wound dehiscence. Given the significant long-term adverse sequelae of wound dehiscence and resultant inadequate perineal body, we believe this modification to the PSARP warrants strong consideration.

Problem Health professions education does not routinely incorporate training in innovation or creative problem solving. Although some models of innovation education within graduate medical education exist, they often require participants' full-time commitment and removal from clinical training or rely upon participants' existing expertise. There is a need for curricula that teach innovation skills that will enable trainees to identify and solve unmet clinical challenges in everyday practice. To address this gap in surgical graduate education, the authors developed the Surgical Program in Innovation (SPIN). Approach SPIN, a 6-month workshop-based curriculum, was established in 2016 in the Beth Israel Deaconess Medical Center Department of Surgery to teach surgical trainees the basics of the innovation process, focusing on surgeon-driven problem identification, product design, prototype fabrication, and initial steps in the commercialization process. Participating surgical residents and graduate students attend monthly workshops taught by medical, engineering, and medical technology (MedTech) industry faculty. Participants collaborate in teams to develop a novel device, fabricate a protype, and pitch their product to a panel of judges. Outcomes From academic years 2015-2016 to 2017-2018, 49 trainees, including 41 surgical residents, participated in SPIN. Across this period, 13 teams identified an unmet need, ideated a solution, and designed and pitched a novel device. Ten teams fabricated prototypes. The 22 SPIN participants who responded to both pre- and postcourse surveys reported significant increases in confidence in generating problem statements, computer-aided design, fabrication of a prototype, and initial commercialization steps (product pitching and business planning). Next steps Incorporating innovation education and design thinking into clinical training will prove essential in preparing future physicians to be lifelong problem finders and solvers. The authors plan to expand SPIN to additional clinical specialties, as well as to assess its impact in fostering future innovation and collaboration among program participants.

Intravenous fish oil lipid emulsions (FOLE) can prevent parenteral nutrition (PN)-induced liver injury in murine models and reverse PN-induced cholestasis in pediatric patients. However, the mechanisms by which fish oil protects the liver are incompletely characterized. Fish oil is rich in omega-3 fatty acids, which are ligands for the G-protein coupled receptor 120 (GPR120), expressed on hepatic Kupffer cells. This study tested the hypothesis that FOLE protects the liver from PN-induced injury through GPR120 signaling. Utilizing a previously described murine model of PN-induced liver injury in which mice develop steatosis in response to an oral parenteral nutrition diet, FOLE was able to preserve normal hepatic architecture in wild type mice, but not in congenic GPR120 knockout (gpr120 −/−) mice. To further characterize the requirement of intact GPR120 for FOLE-mediated hepatic protection, gene expression profiles of key regulators of fat metabolism were measured. PPARγ was identified as a gene that is up-regulated by the PN diet and normalized with the addition of FOLE in wild type, but not in gpr120 −/− mice. This was confirmed at the protein expression level. A PPARγ expression array further identified CD36 and SCD1, both down-stream effectors of PPARγ, to be up-regulated in PN-fed wild type mice yet normalized upon FOLE administration in wild type but not in gpr120 −/− mice. Together, these results suggest that FOLE protects the liver, in part, through activation of GPR120 and the downstream effectors PPARγ and CD36. Identification of key genetic determinants of FOLE-mediated hepatic protection may provide targets for small molecule-based hepatic protection strategies.

Introduction: The conduit of choice for esophageal replacement (ER) in children with complex esophageal atresia or caustic injury remains controversial.1 The most frequently used conduits ...

Background Ischemia reperfusion injury is a barrier to liver surgery and transplantation, particularly for steatotic livers. The purpose of this study was to determine if pretreatment with a single dose of intravenous fish oil decreases hepatic ischemia reperfusion injury and improves recovery of injured livers. Methods Sixty adult male C57BL/6 mice received 1 g/kg intravenous fish oil (Omegaven, Fresenius Kabi) or isovolumetric 0.9% NaCl (saline) via tail vein 1 hour before 30 minutes of 70% hepatic ischemia. Animals were killed 4, 8, or 24 hours postreperfusion, and livers were harvested for histologic analysis. Results Four hours postreperfusion, saline-treated livers demonstrated marked ischemia diffusely around the central veins, while intravenous fish oil–treated livers demonstrated only patchy necrosis with intervening normal parenchyma. Eight hours postreperfusion, all livers demonstrated pale areas of cell loss with surrounding regenerating hepatocytes. Ki67 staining confirmed 14.4/10 high-powered field (95% confidence interval, 3.2–25.6) more regenerating hepatocytes around areas of necrosis in intravenous fish oil–treated livers. Twenty-four hours postreperfusion, all livers demonstrated patchy areas of necrosis, with an 89% (95% confidence interval, 85–92) decrease in the area of necrosis in intravenous fish oil–treated livers. Conclusion Intravenous fish oil treatment prior to hepatic ischemia reperfusion injury decreased the area of hepatic necrosis and increased hepatocyte regeneration compared to saline treatment in a mouse model.

Intestinal failure-associated liver disease (IFALD) can be treated with parenteral fish oil (FO) monotherapy, but practitioners have raised concerns about a potential bleeding risk. This study aims to describe the incidence of clinically significant post-procedural bleeding (CSPPB) in children receiving FO monotherapy.A retrospective chart review was performed on patients at our institution treated with intravenous FO for IFALD. CSPPB was defined as bleeding leading to re-operation, transfer to the intensive care unit, re-admission, or death, up to one month after any invasive procedure.From 244 patients reviewed, 183 underwent ≥1 invasive procedure(s) (n = 732). Five (0.68%, 95% CI 0.22-1.59%) procedures resulted in CSPPB. FO therapy was never interrupted. No deaths due to bleeding occurred.Findings suggest that FO therapy is safe, with a CSPPB risk no greater than that reported in the general population. O3FA should not be held in preparation for procedures or in the event of bleeding.

Background: Fat emulsions are important components of parenteral nutrition (PN). Fish oil (FO) emulsions reverse cholestasis in PN-associated liver disease. There are 2 FO monographs. One is “FO; rich in omega-3 fatty acids” (NFO). The other, “omega-3 acids,” (PFO), is enriched in omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The purpose of this study is to compare the effects of 20% NFO and PFO emulsions produced in the laboratory in a murine model. Methods: Emulsions were compounded containing different oils: soybean oil (SO), NFO, and two PFOs differing in percentage of fatty acids as triglycerides (PFO66 and PFO90). Chow-fed mice received saline, one of the above emulsions, or a commercial FO (OM) intravenously (2.4 g/kg/day) for 19 days. On day 19, animals were euthanized. Livers, spleens, and lungs were procured for histologic analysis. Results: OM, SO, NFO, and PFO90 were well-tolerated clinically. PFO66 resulted in tachypnea and lethargy for ~1 minut...

Dietary strategies to alter the immune response to acute inflammation have the potential to improve outcomes in critically ill patients. A eucaloric ketogenic diet (EKD), composed predominantly of fat with very small amounts of carbohydrate, can provide adequate caloric support while minimizing spikes in blood glucose and reducing oxidative stress. The purpose of this study was to evaluate the effects of an EKD on glycemic control and the inflammatory response after acute endotoxemia in mice. Mice received either an EKD or a carbohydrate-based control diet (CD) for 4 weeks. Animals subsequently underwent either a 2-h fast (postprandial) or an overnight fast (postabsorptive), and half of the animals in each diet group were randomized to receive either intraperitoneal lipopolysaccharide (1 mg/kg) or an equivalent volume of saline. Glycemic response, insulin resistance, inflammatory cytokine levels, and the expression of key inflammatory and metabolic genes were measured. After endotoxin challenge, hypoglycemia was more frequent in mice fed a CD than an EKD in the postprandial period. This was due in part to the preservation of hepatic glycogen stores despite endotoxin exposure and prolonged fasting in mice fed an EKD. Furthermore, mice fed the CD had higher levels of IL-6 and TNF-α in the postabsorptive period, with a fivefold higher expression of hepatic NFκB compared to mice fed the EKD in both fasting periods. These results suggest that the unique metabolic state induced by an EKD can alter the response to acute inflammation in mice.

Background: Fish oil lipid emulsion (FOLE) and multidisciplinary care for infants with intestinal failure (IF) have been associated with reduced morbidity and mortality due to IF-associated liver disease (IFALD). With increased survival, a greater proportion of infants with IF are now able to remain on parenteral nutrition (PN) in the long term. The purpose of this study was to examine outcomes in children with IFALD who have required long-term PN and FOLE therapy due to chronic IF. Materials and Methods: A review of prospectively collected data was performed for children with IFALD who required at least 3 years of PN and FOLE therapy due to chronic IF. Outcomes examined include the incidence of death, transplantation, and essential fatty acid deficiency (EFAD), as well as growth parameters and the biochemical markers of liver disease. Results: Of 215 patients with IFALD treated from 2004–2015, 30 required PN and FOLE therapy for at least 3 years (median, 4.6 years). To date, no patients have died, requir...

Objectives To assess whether a 24-hour length of hospitalization and empiric antibiotic therapy to exclude central line-associated bloodstream infection (CLABSI) in children with intestinal failure is potentially as safe as 48 hours, which is the duration most commonly used but not evidence based. Study design A prospective single-institution observational cohort study was conducted among pediatric patients with intestinal failure from July 1, 2015, through June 30, 2018, to identify episodes of suspected CLABSI. The primary end point was time from blood sampling to positive blood culture. Secondary end points included presenting symptoms, laboratory test results, responses to a parent/legal guardian-completed symptom survey, length of inpatient stay, costs, and charges. Results Seventy-three patients with intestinal failure receiving nutritional support via central venous catheters enrolled; 35 were hospitalized with suspected CLABSI at least once during the study. There were 49 positive blood cultures confirming CLABSI in 128 episodes (38%). The median time from blood sampling to positive culture was 11.1 hours. The probability of a blood culture becoming positive after 24 hours was 2.3%. Elevated C-reactive protein and neutrophil predominance in white blood cell count were associated with positive blood cultures. Estimated cost savings by transitioning from a 48-hour to a 24-hour admission to rule-out CLABSI was $4639 per admission. Conclusions A 24-hour duration of empiric management to exclude CLABSI may be appropriate for patients with negative blood cultures and no clinically concerning signs. A multi-institutional study would more robustly differentiate patients safe for discharge after 24 hours from those who warrant longer empiric treatment.

BACKGROUND: A single dose of IV fish oil (FO) before hepatic ischemia reperfusion injury (HIRI) increases hepatocyte proliferation and reduces necrosis in wild type (WT) mice. It has been suggested that the GPR120 receptor on Kupffer cells mediates FO’s ability to reduce HIRI. The purpose of this study was to determine whether GPR120 is required for FO to reduce HIRI. Methods: Sixty-four (n=8/group) adult male WT (C57BL/6) and GPR120 knockout (KO) mice received IV FO (1 g/kg) or saline 1 hour prior to HIRI or sham operation. Mice were euthanized 24 hours post-operatively for analysis of hepatic histology, NFκB activity, and serum alanine transaminase (ALT) levels. RESULTS: FO pre-treated livers had less necrosis after HIRI than saline pre-treated livers in both WT (mean±SEM 25.9±7.3% less, P=0.007) and KO (36.6±7.3% less, P

Summary Background & aims Altering the lipid component in diets may affect the incidence of metabolic bone disease in patients dependent on parenteral nutrition. Consumption of polyunsaturated fatty acids (PUFA) can impact bone health by modulating calcium metabolism, prostaglandin synthesis, lipid oxidation, osteoblast formation, and osteoclastogenesis. The aim of this study was to evaluate the dietary effects of PUFA on murine bone health. Methods Three-weeks-old male (n = 30) and female (n = 30) C57BL/6J mice were randomized into one of three dietary groups. The diets differed only in fat composition: soybean oil (SOY), rich in ω-6 PUFA; docosahexaenoic acid alone (DHA), an ω-3 PUFA; and DHA with arachidonic acid, an ω-6 PUFA, at a 20:1 ratio (DHA/ARA). After 9 weeks of dietary treatment, femurs were harvested for micro-computed tomographic analysis and mechanical testing via 3-point bending. Separate mice from each group were used solely for serial blood draws for measurement of biomarkers of bone formation and resorption. Results At the microstructural level, although some parameters in cortical bone reached differences that were statistically significant in female mice, these were too small to be considered biologically relevant. Similarly, trabecular bone parameters in male mice were statistically different in some dietary groups, although the biological interpretation of such subtle changes translate into a lack of effect in favor of any of the experimental diets. No differences were noted at the mechanical level and in blood-based biomarkers of bone metabolism across dietary groups within gender. Conclusions Subtle differences were noted at the bones' microstructural level, however these are likely the result of random effects that do not translate into changes that are biologically relevant. Similarly, differences were not seen at the mechanical level, nor were they reflected in blood-based biomarkers of bone metabolism. Altogether, dietary consumption of PUFA do not seem to affect bone structure or metabolism in a healthy model of growing mice.

Background Vascular endothelial growth factor has been found to accelerate compensatory lung growth after left pneumonectomy in mice. The aim of this study was to determine the natural history and the effects of vascular endothelial growth factor on compensatory lung growth in a large animal model. Methods To determine the natural history of compensatory lung growth, female Yorkshire piglets underwent a left pneumonectomy on days of life 10–11. Tissue harvest and volume measurement of the right lung were performed at baseline ( n = 5) and on postoperative days 7 ( n = 5), 14 ( n = 4), and 21 ( n = 5). For pharmacokinetic studies, vascular endothelial growth factor was infused via a central venous catheter, with plasma vascular endothelial growth factor levels measured at various time points. To test the effect of vascular endothelial growth factor on compensatory lung growth, 26 female Yorkshire piglets underwent a left pneumonectomy followed by daily infusion of vascular endothelial growth factor at 200 µg/kg or isovolumetric 0.9% NaCl (saline control). Lungs were harvested on postoperative day 7 for volume measurement and morphometric analyses. Results Compared with baseline, right lung volume after left pneumonectomy increased by factors of 2.1 ± 0.6, 3.3 ± 0.6, and 3.6 ± 0.4 on postoperative days 7, 14, and 21, respectively. The half-life of VEGF ranged from 89 to 144 minutes. Lesser doses of vascular endothelial growth factor resulted in better tolerance, volume of distribution, and clearance. Compared with the control group, piglets treated with vascular endothelial growth factor had greater lung volume ( P P = 0.001), septal surface area ( P = 0.007) and total alveolar count ( P = 0.01). Conclusion Vascular endothelial growth factor enhanced alveolar growth in neonatal piglets after unilateral pneumonectomy.

Lipids not only are fundamental nutrients but also serve as basic structural components of cells and as multifunctional signaling molecules. Lipid metabolism pathways underlie basic processes in health and disease and are the targets of novel therapeutics. In this review, we explore the molecular control of lipid synthesis, trafficking, and storage, with a focus on clinically relevant pathways. To illustrate the clinical relevance of molecular lipid regulation, we highlight how these biochemical processes contribute to the pathogenesis of nonalcoholic fatty liver disease, a component of the metabolic syndrome and a paradigmatic example of lipid dysregulation.

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.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.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.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.

BackgroundDeficiency of vascular endothelial growth factor (VEGF) is associated with hypoplastic lung diseases, such as congenital diaphragmatic hernia. Provision of VEGF has been demonstrated to be beneficial in hyperoxia-induced bronchopulmonary dysplasia, and hence could induce lung growth and improve the outcome in hypoplastic lung diseases. We aimed to determine the effects of exogenous VEGF in a rodent model of compensatory lung growth after left pneumonectomy.MethodsEight-to-ten-week-old C57Bl6 male mice underwent left pneumonectomy, followed by daily intra-peritoneal injections of saline or VEGF (0.5 mg/kg). Lung volume measurement, pulmonary function tests, and morphometric analyses were performed on post-operative day (POD) 4 and 10. The pulmonary expression of angiogenic factors was analyzed by quantitative polymerase chain reaction and western blot.ResultsLung volume on POD 4 was higher in the VEGF-treated mice (P=0.03). On morphometric analyses, VEGF increased the parenchymal volume (P=0.001), alveolar volume (P=0.0003), and alveolar number (P

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.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) levels2 mg/dL. Fractionated serum alkaline phosphatase was measured in each patient, while the DB was2 mg/dL. Parathyroid hormone (PTH), vitamin D3, calcium, and phosphate levels were recorded where available.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.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.

Fecal incontinence is a significant source of morbidity and decreased quality of life (QOL) for many. Until recent years, few therapies beyond medical management were available for patients. Surgical treatment of fecal incontinence has evolved from colostomy and direct repair of muscle defects to interventional techniques such as nerve stimulation and bulking agents. We review the most recent surgical options for the treatment of fecal incontinence within the context of established therapies.Overlapping sphincteroplasty is an established therapy that improves continence and QOL, although results deteriorate over time. Implanted artificial bowel sphincter has a 100% complication rate and 80% are explanted over time. Sacral nerve stimulation has minimal risk and more durable long-term improvement in continence. Less invasive versions of nerve stimulation are being researched. Injectable biomaterials have shown some promise, although durability of results is not clear. Novel therapies, including muscle cell transfer and pelvic slings are currently being investigated.Surgical therapies for fecal incontinence continue to evolve and show promise in improving QOL with a lower risk profile. Effective valuation of these therapies is currently limited by heterogeneous studies, short duration of follow up, and inconsistent outcome measures.

Intestinal failure-associated liver disease (IFALD) is a risk of parenteral nutrition (PN)-dependence. Intravenous soybean oil-based parenteral fat can exacerbate the risk of IFALD while intravenous fish oil can minimize its progression, yet the mechanisms by which soybean oil harms and fish oil protects the liver are uncertain. Properties that differentiate soybean and fish oils include α-tocopherol and phytosterol content. Soybean oil is rich in phytosterols and contains little α-tocopherol. Fish oil contains abundant α-tocopherol and little phytosterols. This study tested whether α-tocopherol confers hepatoprotective properties while phytosterols confer hepatotoxicity to intravenous fat emulsions. Utilizing emulsions formulated in the laboratory, a soybean oil emulsion (SO) failed to protect from hepatosteatosis in mice administered a PN solution enterally. An emulsion of soybean oil containing α-tocopherol (SO+AT) preserved normal hepatic architecture. A fish oil emulsion (FO) and an emulsion of fish oil containing phytosterols (FO+P) protected from steatosis in this model. Expression of hepatic acetyl CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ), was increased in animals administered SO. ACC and PPARγ levels were comparable to chow-fed controls in animals receiving SO+AT, FO, and FO+P. This study suggests a hepatoprotective role for α-tocopherol in liver injury induced by the enteral administration of a parenteral nutrition solution. Phytosterols do not appear to compromise the hepatoprotective effects of fish oil.

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.

Parenteral nutrition (PN) can be life saving for infants unable to adequately absorb enteral nutrients due to intestinal failure from inadequate bowel length or function. However, long-term PN carries significant morbidity and mortality, with 30 to 60% of patients developing progressive liver dysfunction. The etiology of PN-associated liver disease (PNALD) is poorly understood, however the involvement of lipid emulsions in its pathogenesis has been clearly established, with new emphasis emerging on the role of omega-6 polyunsaturated fatty acids and omega-3 polyunsaturated fatty acids. Recent studies evaluating the use of parenteral fish oil lipid emulsions instead of soybean oil lipid emulsions have demonstrated marked improvements in cholestasis, morbidity, and mortality in patients with PNALD treated with fish oil. This review provides an overview of the role of lipid emulsions in the pathogenesis of PNALD and the proposed mechanisms by which parenteral fish oil lipid emulsions may be exerting their beneficial effects.

PURPOSE OF REVIEW Parenteral nutrition-associated liver disease (PNALD) is a major cause of morbidity and mortality in the parenteral nutrition-dependent population. Here, we review the most recent literature involving a fish oil-based lipid emulsion (FOLE) and its effects on PNALD. RECENT FINDINGS Vegetable oil-based lipid emulsions (VBLEs) contribute to PNALD. This may be due to parenteral phytosterols and/or the presence of pro-inflammatory mediators. Whereas a small reduction in the dose of VBLE does not appear to prevent PNALD, a significant reduction in the dose may reverse PNALD; however, it carries the risk of essential fatty acid deficiency. Furthermore, the impact of extreme lipid restriction on subsequent neurodevelopment is unknown. Combination lipid emulsions containing fish oil are associated with decreased bilirubin levels, though no studies compare these emulsions with the outcomes with FOLE alone. The utility of FOLE in the reversal of PNALD has been demonstrated and its administration does not lead to essential fatty acid deficiency. Furthermore, there is evidence that FOLE may prevent PNALD. CONCLUSION FOLE appears to be an efficacious treatment to reverse PNALD. However, more studies are necessary to determine if FOLE might also be beneficial in the prevention of PNALD. Future studies should additionally focus on the preterm infant population, as they represent a major population requiring parenteral nutrition support for survival.

Background Prosthetic graft infection is a major complication of peripheral vascular surgery. We investigated the experience of a single institution over 10 years with bypass grafts involving the femoral artery to determine the incidence and risk factors for prosthetic graft infection. Methods A retrospective cohort single-institution review of prosthetic bypass grafts involving the femoral artery from 2001 to 2010 evaluated patient demographics, body mass index, comorbidities, indications, location of bypass, type of prosthetic material, case urgency, and previous ipsilateral bypass or percutaneous interventions and evaluated the incidence of graft infections, amputations, and mortality. Results There were 496 prosthetic grafts identified with a graft infection rate of 3.8% (n = 19) at a mean follow-up of 27 months. Multivariable analysis showed that redo bypass (hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.2-15.0), active infection at the time of bypass (HR, 5.2; 95% CI, 1.9-14.2), female gender (HR, 4.5; 95% CI, 1.6-12.7), and diabetes mellitus (HR, 4.6; 95% CI, 1.5-14.3) were significant predictors of graft infection. Graft infection was predictive of major lower extremity amputation (HR, 9.8; 95% CI, 3.5-27.1), as was preoperative tissue loss (HR, 4.7; 95% CI, 1.8-11.9). Graft infection did not predict long-term mortality; however, chronic renal insufficiency (HR, 2.3; 95% CI, 1.6-3.4), tissue loss (HR, 1.4; 95% CI, 1.0-1.9), and active infection (HR, 2.3; 95% CI, 1.6-3.4) did. Infected grafts were removed 79% of the time. Staphylococcus epidermidis (37%) and methicillin-sensitive Staphylococcus aureus (26%) were the most common pathogens isolated. Conclusions Redo bypass, female gender, diabetes, and active infection at the time of bypass are associated with a higher risk for prosthetic graft infection and major extremity amputation but do not confer an increased risk of mortality. Autologous vein for lower extremity bypass and endovascular interventions should be considered when feasible in high-risk patients

Background Replacement of parenteral soybean oil (SO) with fish oil (FO) is an effective therapy for intestinal failure-associated liver disease (IFALD) in children. However, practitioners remain concerned about the risk of essential fatty acid deficiency (EFAD) and sometimes treat IFALD with a combination of 50% SO and 50% FO emulsions. The purpose of this study was to determine if mixing 50% SO and 50% FO emulsions would prevent hepatosteatosis in a murine model of parenteral nutrition (PN)-induced hepatosteatosis. Methods C57BL/6 mice were randomized to receive oral PN with parenteral saline, FO, SO, or a mixture of 50% FO and 50% SO for 19 days. Fatty acid analysis, histologic evaluation, Nonalcoholic Steatohepatitis Clinical Research Network (NSCRN) scores, and reverse-transcriptase polymerase chain reaction for key lipogenic genes were performed. Results The PN + saline group was the only group with EFAD, with a serum and hepatic triene/tetraene ratio of 0.53. NSCRN scores were highest in the PN + SO group (5.5; 95% confidence interval [CI], 4.9-6.1), followed by the PN + FO/SO (4.5; 95% CI, 3.5-5.5) group, with the lowest score in the PN + FO (2.0; 95% CI, 1.1-2.9) group. Acetyl CoA carboxylase α and acetyl CoA carboxylase β expression was lower in the PN + FO group than in the PN + FO/SO or PN + SO groups. Conclusions Our data demonstrate that a mixed fat emulsion of 50% SO and 50% FO is inferior to 100% FO in reducing hepatosteatosis in this model. These data suggest that use of parenteral SO with parenteral FO, in a 1:1 ratio, may still contribute to liver injury, although it is less hepatotoxic than pure SO.

Although commonly performed in adult swine, unilateral pneumonectomy in piglets requires significant modifications in the surgical approach and perioperative care because of their smaller size and limited physiological reserve.Nineteen neonatal piglets underwent a left pneumonectomy. They were allowed 5-7 d of preoperative acclimation and nutritional optimization. Preoperative weight gain and laboratory values were obtained before the time of surgery. A "ventro-cranial" approach is adopted where components of the pulmonary hilum were sequentially identified and ligated, starting from the most ventral and cranial structure, the superior pulmonary vein. The principle of gentle ventilation was followed throughout the entire operation.The median age of the piglets at the time of surgery was 12 (10-12) d. The median preoperative weight gain and albumin level were 20% (16-26%) and 2.3 (2.1-2.4) g/dL, respectively. The median operative time was 59 (50-70) min. Five of the first nine piglets died from complications, two from poor preoperative nutritional optimization (both with10% weight gain and 2 g/dL for albumin), one from an intubation complication, one from intra-operative bleeding, and one in the postoperative period from a ruptured bulla. No mortality occurred for the next 10 cases.Successful outcomes for unilateral pneumonectomy in piglets require special attention to preoperative nutritional optimization, gentle ventilation, and meticulous surgical dissection. Preoperative weight gain and albumin levels should be used to identify appropriate surgical candidates. The "ventro-cranial" approach allows for a technically straightforward completion of the procedure.

Long-term parenteral nutrition (PN) carries the risk of progressive liver disease in infants with intestinal failure. Although PN-associated liver disease (PNALD) is multifactorial in etiology, components of soybean oil lipid emulsions have been implicated in the disease's pathogenesis. Historically, infants with PNALD who were unable to wean from PN to full enteral feeding developed cirrhosis and end-stage liver disease, which require liver transplantation to survive. Over the past 2 decades, novel strategies for the management of parenteral lipids have improved morbidity and mortality from PNALD in infants with intestinal failure. Current strategies for the treatment of PNALD include restricting the dose of parenteral soybean oil lipid emulsion and/or replacing the soybean oil with a parenteral fish-oil lipid emulsion or emulsions of mixed-lipid sources. The purpose of this report is to review published data that evaluate these strategies in parenteral lipid management for the treatment and prevention of PNALD.

Fat is an important macronutrient in the human diet. For patients with intestinal failure who are unable to absorb nutrients via the enteral route, intravenous lipid emulsions play a critical role in providing an energy-dense source of calories and supplying the essential fatty acids that cannot be endogenously synthesized. Over the last 50 y, lipid emulsions have been an important component of parenteral nutrition (PN), and over the last 10-15 y many new lipid emulsions have been manufactured with the goal of improving safety and efficacy profiles and achieving physiologically optimal formulations. The purpose of this review is to provide a background on the components of lipid emulsions, their role in PN, and to discuss the lipid emulsions available for intravenous use. Finally, the role of parenteral fat emulsions in the pathogenesis and management of PN-associated liver disease in PN-dependent pediatric patients is reviewed.

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.

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.

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.

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.

The principles of surgical management of inflammatory bowel disease (IBD) continue to evolve with advances in medical therapy, surgical technique, and minimally invasive operative technology. The purpose of this review is to highlight such advances in colorectal and anorectal surgery for IBD over the last year.Treatment of ulcerative colitis and Crohn's disease remains challenging and relies on knowledge of both medical and surgical therapies. Recent data support shorter hospitalization prior to surgical intervention in patients with acute severe ulcerative colitis, laparoscopic surgical approaches when feasible, and ciprofloxacin as optimal therapy for pouchitis, when preventive therapy with probiotics is not successful.The management of IBD remains complex and highly individualized. In severe cases, a combination of immunosuppression and surgical therapies may be required. However, the associated risks of complications make judgments about optimal treatment plans challenging.

Objective The introduction of endovascular aneurysm repair has resulted in a decline in open abdominal aortic aneurysm repairs performed by vascular residents. The purpose of this study was to evaluate if a similar trend has occurred with open lower extremity revascularization procedures, with increased endovascular procedures producing a decrease in the number of open lower extremity revascularizations. Furthermore, this study evaluates the effect of endovascular procedure volume on the frequency of subtypes of open lower extremity procedures performed. Methods The total number of vascular procedures, lower extremity bypasses, and endovascular interventions from 2000 to 2010 were analyzed from case logs of vascular residents as reported by the Accreditation Council for Graduate Medical Education. Results The average number of cases performed by vascular residents has increased by 150% from 463.9 in 2000 to 1168 in 2009, due to the increased number of endovascular procedures. The average number of endovascular revascularizations has increased by 317% from 40.5 performed in 2000 to 168.9 in 2009. Femoral-popliteal bypasses have increased in frequency by 27% whereas the number of infrapopliteal bypass has remained unchanged. The largest difference is seen in femoral endarterectomies with a 234% increase from 3.2 per resident in 2001 to 10.7 per resident in 2010. Comparison of the proportion of femoral-popliteal and tibioperoneal interventions performed by angioplasty or bypass after 2007 revealed that endovascular interventions comprise 50% of procedures in the femoral-popliteal distribution, whereas 65% of infrapopliteal interventions are still performed using open techniques. Conclusions The number of procedures performed during vascular residency has dramatically increased over the last decade secondary to the increased number of endovascular procedures. The average vascular surgery resident's open operative experience has been stable over the last 10 years, despite the increasing endovascular case volume. Residents perform femoral endarterectomy with increasing frequency, perhaps representing an increasing volume of hybrid procedures. Gaps in information available for evaluating resident training remain a significant obstacle. Moving forward, revision of the current reporting system to a format that more accurately reflects resident experience would be beneficial.

Laser-induced vessel wall injury leads to rapid thrombus formation in an animal thrombosis model. The target of laser injury is the endothelium. We monitored calcium mobilization to assess activation of the laser-targeted cells. Infusion of Fluo-4 AM, a calcium-sensitive fluorochrome, into the mouse circulation resulted in dye uptake in the endothelium and circulating hematopoietic cells. Laser injury in mice treated with eptifibatide to inhibit platelet accumulation resulted in rapid calcium mobilization within the endothelium. Calcium mobilization correlated with the secretion of lysosomal-associated membrane protein 1, a marker of endothelium activation. In the absence of eptifibatide, endothelium activation preceded platelet accumu-lation. Laser activation of human umbilical vein endothelial cells loaded with Fluo-4 resulted in a rapid increase in calcium mobilization associated cell fluorescence similar to that induced by adenosine diphosphate (10μM) or thrombin (1 U/mL). Laser activation of human umbilical vein endothelial cells in the presence of corn trypsin inhibitor treated human plasma devoid of platelets and cell microparticles led to fibrin for-mation that was inhibited by an inhibitory monoclonal anti–tissue factor antibody. Thus laser injury leads to rapid endothelial cell activation. The laser activated endothelial cells can support formation of tenase and prothrombinase and may be a source of activated tissue factor as well.

To determine the prevalence and impact of subclavian steal syndrome (SSS) in patients undergoing assessment of the carotid arteries.Vertebral artery flow reversal is often found among patients undergoing imaging of the extracranial vessels; however, there are no large studies evaluating the prevalence and natural history of SSS in stratified patients.Patients presenting for duplex ultrasound of the carotid arteries underwent 2 sets of bilateral arm pressure measurements. Patients with a pressure differential (PD)20 mm Hg were examined in detail for vascular obstruction ipsilateral to the affected arm. When appropriate, computer tomographic angiography (CTA), magnetic resonance angiography, and angiography were performed. Signs and symptoms related to SSS and the types of interventions performed were recorded.In a period of 6 years, 7881 carotid duplex scans were performed, with a PD20 mm Hg in 514 (6.5%) patients and a left arm preponderance (82%). SSS was complete in 61%, partial in 23%, and absent in 16%. Symptoms were present in 38 patients with 32 experiencing symptoms of the posterior circulation, 4 of arm ischemia, and 2 of cardiac ischemia. Symptoms occurred more frequently as the arm PD increased. Of the 38 symptomatic patients, only 7 underwent an intervention (2 with subclavian-carotid bypass and 5 with percutaneous transluminal angioplasty stenting of the subclavian).SSS is a frequent finding in patients undergoing carotid duplex scanning. Patients are commonly asymptomatic and rarely require an intervention. A significantly elevated arm PD (40-50 mm Hg) is more commonly associated with symptoms, complete steal, and the need for intervention.

pancreaticoduodenectomy (CW), and the pylorus-preserving pancreaticoduodenectomy (PP).PP proponents argue that the less invasive extent of resection leads to shorter operative times and less intraoperative blood loss, whereas its detractors express concern that it predisposes patients to delayed gastric emptying (DGE), increasing length of stay. We set out to compare the outcomes of PP and CW within American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), with attention to operative times, transfusions, and length-of-stay as a surrogate for DGE.