Gastroschisis Outcomes: Presence of Histologic Chorioamnionitis and the Impact on Time to Full Enteral Feeds and Length of Hospital Stay.

OBJECTIVE: Despite improvements in our ability for early diagnosis and providing supportive care for infants with gastroschisis, it continues to be associated with long length of stay and morbidity. Intestinal dysfunction secondary to chronic inflammatory insult to exposed bowel is well known; however, little research has been done on the impact of acute inflammation in the perinatal period on intestinal function. This study's aim was to investigate the impact of acute chorioamnionitis on the time to achieve full enteral feeds and length of hospital stay. STUDY DESIGN: Retrospective chart review of 60 mothers and their infants born with gastroschisis at a Level IV NICU from November 2011 to June 2020 was performed. Infants were divided into two groups based on the presence of histologic chorioamnionitis, and outcomes were compared. The primary outcome was delayed full enteral feeds (full enteral feeds after 28 days of life). The secondary outcomes were differences in their time to achieve full enteral feeds and time to hospital discharge, and prolonged length of hospital stay (discharge after 30 days of life). Univariate and multivariate logistic regression analyses were performed to assess the association between the dependent and the predictor variables. RESULT: Of the 60 infants enrolled, 23 (38%) had evidence of histologic chorioamnionitis. The median gestational age was 37 weeks. Fifty-four (90%) infants achieved full enteral feeds, with a median time of 24 days. Median length of hospital stay was 31 days. The presence of histologic chorioamnionitis was not associated with delayed full enteral feeds (odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.14-4.23; p = 0.80) or prolonged length of hospital stay (OR = 0.45; 95% CI = 0.1-0.23; p = 0.32) in the adjusted analysis. CONCLUSION: Acute placental inflammation during the perinatal period does not impact the infant's time to achieve full feeds or prolong their hospital stay. Larger studies are needed to confirm these findings. KEY POINTS: · Chronic inflammatory injury to exposed bowel in utero is well known in fetuses with gastroschisis.. · Acute inflammatory injury during perinatal period may impact enteral feeding outcomes.. · No impact of acute placental inflammation on time to full enteral feeds..

Thoracoscopic Neonatal Congenital Diaphragmatic Hernia Repair: How We Do It.

Background: Congenital diaphragmatic hernia (CDH) is a relatively common congenital anomaly, typically requiring repair in the neonatal period. Approaches to surgical repair of a CDH are varied. A small defect may be repaired primarily while a large defect often requires a patch repair. Minimally invasive and open techniques have been reported to have varying benefits and outcomes. Materials and Methods: The authors describe their technique of CDH repair and present a review of the literature. Results: In a stabilized neonate with a small-to-moderate CDH defect, a thoracoscopic primary repair with biological mesh underlay (or a patch repair if needed to reduce tension) represents our approach of choice to treat this pathology. However, attention to specific technical details is required to minimize incidence of recurrence. Conclusions: The data favor a minimally invasive approach to CDH repair in the appropriate patients.

The International Pediatric Endosurgery Group Evidence-Based Guideline on Minimal Access Approaches to the Operative Management of Inguinal Hernia in Children.

Introduction: Minimally invasive surgery (MIS) for inguinal hernia repair (IHR) in children has been reported for more than two decades. The International Pediatric Endosurgery Group (IPEG) Evidence-Based Review Committee chose MIS IHR as the inaugural topic for review and presentation at the 2016 IPEG annual meeting. Materials and Methods: English language articles published between January 1, 2009, and December 31, 2015, were reviewed and included in this evidence-based review after searching PubMed, Cochrane Reviews, ClinicalTrials.gov, Google Scholar, and EMBASE. Results: Level 1a and 1b evidence supports the recommendations that operative time for bilateral IHRs should be considered shorter and postoperative complications rates should be considered lower in MIS repair over open. Recurrence rates are similar between the two methods (level 1a and 1b evidence). No level 1 evidence exists to support one MIS technique over another or that operating on a detected contralateral patent processus vaginalis during laparoscopy makes any difference in long-term outcome to the patient. Conclusions: The advantages of lower postoperative complications and shorter operative times have been found in studies of surgeons experienced in MIS repair and differences were small. The evidence in this review supports that MIS repair is a safe, effective method of IHR with proper training and mentorship.

Hemodialysis and peritoneal dialysis access related outcomes in the pediatric and adolescent population.

BACKGROUND: There is paucity of comparative data on the objective performance of arteriovenous fistulas (AVF), grafts (AVG), hemodialysis (HD) catheter and peritoneal dialysis (PD) catheter in the pediatric population. METHODS: A retrospective analysis of all patients <21 years in the United States Renal Database System who had an AVF, AVG, HD catheter or PD catheter placed for dialysis access between 1/2007 and 12/2014 was performed. Multivariable cox regression was used to evaluate mortality, patency (primary, primary-assisted and secondary), maturation and catheter survival. RESULTS: The 11,575 patients studied comprised of 9445 (82%) HD, 1435 (12%) PD, 528 (4.6%) HD to PD and 167 (1.4%) PD to HD patients. The HD subcohort comprised of 1296 (13.7%) AVF initiates, 199 (2.1%) AVG initiates, 1347 (14.3%) AVF converts after initial HD catheter use, 292 (3.1%) AVG converts and 6311 (67%) patients who persistently utilized HD catheters. There was no difference between PD and HD in patients 0-5 (aHR: 1.36; 95% CI: 0.89-2.07; P = 0.15) and 6-12 years (aHR: 1.05; 95% CI: 0.72-1.52; P = 0.8). However, PD was associated with 73% and 76% increase in mortality relative to HD among patients in the 13-17 (aHR: 1.73; 95% CI: 1.35-2.21; P < 0.001) and 18-20 (aHR: 1.76; 95% CI: 1.38-2.24; P < 0.001) age categories. AVG was associated with 78% increase in mortality compared to AVF (aHR: 1.78; 95% CI: 1.41-2.25; P < 0.001). Persistent use of HD catheters was associated with 29% increase in mortality (aHR: 1.29; 95% CI: 1.07-1.57; P = 0.009) compared to initiation and persistent use of AVF. Conversion from HD catheter to AVF was associated with 66% decrease in mortality compared to persistent HD catheter use (aHR: 0.34; 95% CI: 0.28-0.40; P < 0.001). Primary, primary assisted and secondary patency were higher for AVF compared to AVG. CONCLUSION: There was no difference in risk adjusted mortality between HD and PD in children less than 13 years. PD is associated with higher mortality compared to HD in adolescents. Initiation of HD with AVF is associated with better patency and patient survival relative to AVG and persistent use of HD catheters in pediatric patients irrespective of transplant potential. Conversion from HD catheter to AVF or AVG in patients who inevitably initiate HD with a catheter is associated with better survival compared to persistent HD catheter use. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: Level II.

Urologic trauma from vaginal dilation for congenital vaginal stenosis: A newly-described and challenging complication.

Vaginal dilation is first line therapy for vaginal agenesis. No major urologic complications have even been described. We present the management and successful outcome of immediate repair for urethral trauma in a patient with history of congenital anomalies managed with vaginal dilation. Proper exposure is difficult, but urologic repair can be achieved with or without concomitant vaginal repair.

Lipocalin-type prostaglandin D2 synthase (L-PGDS) modulates beneficial metabolic effects of vertical sleeve gastrectomy.

BACKGROUND: Vertical sleeve gastrectomy (VSG) ameliorates metabolic complications in obese and diabetic patients through unknown mechanisms. OBJECTIVE: The objective of this study was to investigate the role of lipocalin-type prostaglandin D2 synthase (L-PGDS) in glucose regulation in response to VSG using L-PGDS knock-out (KO), knock-in (KI), and C57BL/6 (wild type) mice. SETTING: Winthrop University Hospital Research Institute. METHODS: Animals were divided into 6 groups: L-PGDS KO sham/VSG (n = 5), L-PGDS KI sham/VSG (n = 5), and C57BL/6 (wild type) sham/VSG (n = 5). Related parameters were measured in fasting animals after 10 weeks. RESULTS: Our intraperitoneal glucose tolerance tests and homeostatic model assessment insulin resistance results showed significant glycemic improvement 10 weeks post-VSG in both C57BL/6 and KI groups compared with the sham group. In contrast, the KO group developed glucose intolerance and insulin resistance similar to or greater than the sham group 10 weeks post-VSG. Interestingly, weight gain was insignificant 10 weeks post-VSG in all the groups and even trended higher in the KO group compared with sham. Peptide YY levels in the KO group post-VSG were slightly increased but significantly less than other groups. Similarly, the KO group showed significantly less leptin sensitivity in response to VSG compared with the KI group. Total cholesterol level remained unchanged in all groups irrespective of sham or surgery but interestingly, the KO group had significantly higher cholesterol levels. In parallel, adipocyte size was also found to be significantly increased in the KO group post-VSG compared with the sham group. CONCLUSION: Our findings propose that L-PGDS plays an important role in the beneficial metabolic effects observed after VSG.

Roux-en-Y gastric bypass attenuates the progression of cardiometabolic complications in obese diabetic rats via alteration in gastrointestinal hormones.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes (T2DM) and obesity through alteration in gastrointestinal (GI) hormones. OBJECTIVE: The objective of this study was to investigate the effect of RYGB on GI hormones and cardiometabolic parameters in Zucker diabetic fatty (ZDF) rodents. SETTING: Winthrop University Hospital, Research and Academic Center METHODS: Animals were divided into 3 groups, pair-fed (n = 4), ad lib (n = 4), and RYGB (n = 5). This study was carried out for 4 weeks and all related parameters were measured pre- and postsurgery in fasted obese diabetic Zucker rodents. RESULTS: Postoperatively, RYGB significantly decreased fasting blood glucose by 32% compared with ad lib. Plasma insulin and leptin levels were also found to be significantly decreased, by 66% and 38%, respectively, after surgery. Moreover, both glucose-dependent insulinotropic polypeptide (GIP) and peptide tyrosine-tyrosine (PYY) were significantly increased after RYGB-by 300% and 51%, respectively. Glucagon-like peptide-1 (GLP-1) levels were also increased, but the increase was not statistically significant. Total cholesterol levels of the RYGB group remained unchanged for 4 weeks. However, total cholesterol in the ad lib and pair-fed groups increased by 25% and 34%, respectively, compared with initial levels. The cholesterol/high-density lipoprotein (HDL) ratio was decreased in the RYGB group by 14% and 30% compared with the ad lib and pair-fed group, respectively. The RYGB group had a significant decrease in aortic wall thickness of 25% compared with the ad lib and pair-fed groups. Similarly, the RYGB group had a 20-unit (mm Hg) decrease in systolic blood pressure compared with the presurgical value. CONCLUSION: RYGB has beneficial cardiometabolic effects through alterations in GI hormones in a severely obese and diabetic rodent model.

Diet-induced obesity associated with steatosis, oxidative stress, and inflammation in liver.

BACKGROUND: Obesity induces steatosis and increases oxidative stress, as well as chronic inflammation in the liver. The balance between lipogenesis and lipolysis is disrupted in obese animals. At a cellular level, the changes in metabolic sensors and energy regulators are poorly understood. We hypothesized that diet-induced steatosis increases oxidative stress, inflammation, and changes the metabolic regulators to promote energy storage in mice. The setting was a university-affiliated basic science research laboratory. METHODS: Four-week-old C57BL mice were fed a high-fat diet (n = 8) or regular chow (n = 8) for 7 weeks. The liver sections were stained for fat content and immunofluorescence. Liver homogenates were used for protein analysis by immunoblotting and mRNA analysis by reverse transcriptase-polymerase chain reaction. The gels were quantified using densitometry P ≤ .05 was considered significant. RESULTS: The high-fat diet upregulated protein kinase-C atypical isoforms ζ and λ and decreased glucose tolerance and the interaction of insulin receptor substrate 2 with phosphoinositide kinase-3. The high-fat diet increased the transcriptional factors liver X receptor (4321 ± 98 versus 2981 ± 80) and carbohydrate response element-binding protein (5132 ± 135 versus 3076 ± 91), the lipogenesis genes fatty acid binding protein 5, stearoyl-co-enzyme A desaturase-1, and acetyl-co-enzyme A carboxylase protein, and fatty acid synthesis. The high-fat diet decreased 5'-adenosine monophosphate-activated protein kinase (2561 ± 78 versus 1765 ± 65), glucokinase-3ß (2.214 ± 34 versus 3356 ± 86), and SIRT1 (2015 ± 76 versus 3567 ± 104) and increased tumor necrosis factor-α (3415 ± 112 versus 2042 ± 65), nuclear factor kappa B (5123 ± 201 versus 2562 ± 103), cyclooxygenase-2 (4230 ± 113 versus 2473 ± 98), nicotinamide-adenine dinucleotide phosphate oxidase (3501 ± 106 versus 1600 ± 69) and reactive oxygen species production (all P < .001, obese mice versus lean mice). CONCLUSION: A high-fat diet impairs glucose tolerance and hepatic insulin signaling, upregulates transcriptional and translational activities that promote lipogenesis, cytokine production, proinflammatory signaling, and oxidative stress, and downregulates lipolysis. Understanding the complex cellular signals triggered by obesity might have profound clinical implications.

Roux-en-Y gastric bypass alters tumor necrosis factor-α but not adiponectin signaling in immediate postoperative period in obese rats.

BACKGROUND: Adiponectin has anti-inflammatory properties and is increased with weight loss. Tumor necrosis factor (TNF)-α is a pro-inflammatory cytokine that negatively regulates adiponectin. Previously, we have demonstrated that Roux-en-Y gastric bypass (RYGB) induces weight loss and improves steatosis in obese rats. We hypothesized that RYGB would alter the interplay of TNF-α and adiponectin signaling in the postoperative period. METHODS: Obese Sprague-Dawley male rats that had undergone RYGB (n = 5) or sham (n = 4) were euthanatized at 9 weeks postoperatively. The adiponectin levels from serial serum samples were measured by enzyme-linked immunosorbent assay. Adiponectin, adiponectin receptor 2, and TNF-α mRNA from adipose and liver samples were quantified by reverse transcriptase-polymerase chain reaction. Data are presented as mean ± standard deviation; using a t test, P <.05 was significant. RESULTS: RYGB did not change the serum adiponectin, adipose tissue adiponectin mRNA, or hepatic adiponectin receptor 2 levels compared with the levels in the sham-operated rats (P >.05). However, the TNF-α mRNA levels had decreased in the adipose tissue (P >.05) but remained unchanged in the liver compared with the sham controls (P >.05). CONCLUSION: Surgically-induced weight loss in a rat model of RYGB did not increase adiponectin signaling in the immediate postoperative period but was associated with decreased pro-inflammatory signaling in the adipose tissue. During this period, pro-inflammatory signaling might play a more important role than adiponectin. Additional studies with longer follow-up are necessary to determine whether adiponectin plays a role in weight loss and improvement of steatosis after RYGB.

Does LKB1 mediate activation of hepatic AMP-protein kinase (AMPK) and sirtuin1 (SIRT1) after Roux-en-Y gastric bypass in obese rats?

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) improves steatosis and reduces liver triglycerides in obese rats. Sirtuin1 (SIRT1) and AMP-activated protein kinase (AMPK) are key metabolic regulators that reduce lipogenesis and increase fatty acid oxidation. LKB1 phosphorylates AMPK and may activate SIRT1. We hypothesize that RYGB in obese rats is associated with an upregulation of the LKB1-AMPK-SIRT1 signaling pathway. METHODS: Obese Sprague-Dawley male rats underwent RYGB or sham. Liver tissue was obtained at 9 weeks postoperatively. Protein levels of SIRT1, LKB1, p-LKB1, AMPKalpha, p-AMPKalpha, and p-protein kinase C-zeta (PKC-zeta ) were determined. Protein associations of LKB1 with each of SIRT1, AMPKalpha, and PKC-zeta were determined by coimmunoprecipitation.Data are mean +/- SD; for t test, p<0.05 was significant. RESULTS: RYGB increased protein levels of hepatic AMPKalpha, p-AMPKalpha, and SIRT1 (all p<0.001 vs. sham); p-LKB1 but not LKB1 increased after RYGB (p<0.001 vs. sham). Physical interactions of LKB1-AMPK and LKB1-SIRT1 increased after RYGB (p<0.001 vs. sham). Although PKC-zeta mRNA and p-PKC-zeta did not change, interactions between LKB1 and PKC-zeta increased after RYGB (p<0.001 vs. sham). CONCLUSION: RYGB increases hepatic levels of SIRT1, AMPK, and p-AMPK as well as increasing interactions of LKB1 with AMPK or SIRT1. p-PKC-zeta may play an intermediary role in the interaction between AMPK and SIRT. These findings demonstrate key signaling changes in powerful metabolic regulators that may account for the resolution of steatosis after RYGB.

Involvement of adiponectin-SIRT1-AMPK signaling in the protective action of rosiglitazone against alcoholic fatty liver in mice.

The development of alcoholic fatty liver is associated with reduced adipocyte-derived adiponectin levels, decreased hepatic adiponectin receptors, and deranged hepatic adiponectin signaling in animals. Peroxisomal proliferator-activated receptor-gamma (PPAR-gamma) plays a key role in the regulation of adiponectin in adipose tissue. The aim of the present study was to test the ability of rosiglitazone, a known PPAR-gamma agonist, to reverse the inhibitory effects of ethanol on adiponectin expression and its hepatic signaling, and to attenuate alcoholic liver steatosis in mice. Mice were fed modified Lieber-DeCarli ethanol-containing liquid diets for 4 wk or pair-fed control diets. Four groups of mice were given a dose of either 3 or 10 mg.kg body wt(-1).day(-1) of rosiglitazone with or without ethanol in their diets for the last 2 wk of the feeding study. Coadministration of rosiglitazone and ethanol increased the expression and circulating levels of adiponectin and enhanced the expression of hepatic adiponectin receptors (AdipoRs) in mice. These increases correlated closely with the activation of a hepatic sirtuin 1 (SIRT1)-AMP-activated kinase (AMPK) signaling system. In concordance with stimulated SIRT1-AMPK signaling, rosiglitazone administration enhanced expression of fatty acid oxidation enzymes, normalized lipin 1 expression, and blocked elevated expression of genes encoding lipogenic enzymes which, in turn, led to increased fatty acid oxidation, reduced lipogenesis, and alleviation of steatosis in the livers of ethanol-fed mice. Enhanced hepatic adiponectin-SIRT1-AMPK signaling contributes, at least in part, to the protective action of rosiglitazone against alcoholic fatty liver in mice.

Downregulation of adiponectin/AdipoR2 is associated with steatohepatitis in obese mice.

BACKGROUND: Recent evidence suggests that obesity is associated with hypo-adiponectinmia and chronic inflammation. Adiponectin regulates fat storage, energy expenditure, and inflammation. We propose that high fat diet induces steatohepatitis, reduces serum adiponectin, and liver adiponectin receptors. METHODS: A 4-week-old C57BL male mice were fed high fat diet (n = 8) or regular chow (control; n = 6) for 7 weeks. Body weight, liver weight, and serum adiponectin were measured. Liver sections were stained with hematoxylin and eosin and oil red for fat content. Liver homogenates were used for protein (immunoblotting) and mRNA (reverse transcription PCR) of Toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, sterol regulatory element-binding proteins (SREBP)-1c, and adiponectin receptors (AdipoR1/AdipoR2) in addition to nuclear phorsphorylated p65NF-kappaB. Gels were quantified using densitometry; t test was used, and p < 0.05 was significant. RESULTS: High fat diet increased body (50%) and liver weight (33%), as well as hepatocyte fat content and ballooning. Mice fed high fat diet exhibited reduced serum adiponectin and liver AdipoR2. High fat diet increased hepatic levels of SREBP-1c, TLR4, TNF-alpha, and IL-6 protein and mRNA and increased activation of p65NF-kappaB. CONCLUSIONS: Diet-induced liver steatosis is associated with increased lipogensis, upregulation of pro-inflammatory cytokines, and transcription factors as well as downregulation of AdipoR2. Reduction in serum adiponectin suggests that adiponectin signaling may be the crosslink between high fat diet, hepatic inflammation, and nonalcoholic fatty liver disease.

Deletion of toll-like receptor-4 downregulates protein kinase C-zeta and attenuates liver injury in experimental pancreatitis.

BACKGROUND: Toll-like receptor-4 (TLR4) and protein kinase C-zeta (PKC-zeta) play a role in macrophage activation. We hypothesized that deletion of TLR4 downregulates PKC-zeta and attenuates liver cell apoptosis in experimental pancreatitis. METHODS: Acute pancreatitis was induced by choline-deficient ethionine diet in C57/BL6 (TLR4+/+ and TLR4-/-) mice. RESULTS: During pancreatitis, staining for TLR4 and PKC-zeta, which colocalized in Kupffer cells but not in hepatocytes, increased in TLR4+/+ mice and decreased in TLR4-/- mice. In TLR4+/+ mice, pancreatitis increased TLR4 protein and mRNA and PKC-zeta protein and activity, nuclear factor (NF)-kappaB, ERK1/2, caspase-3 cleavage, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining; all P < .01 versus controls. In TLR4-/- mice with pancreatitis, PKC-zeta mRNA and activity were reduced, ERK1/2 and caspase-3 did not increase, and NF-kappaB and TUNEL (mostly in hepatocytes) increased mildly (all P < .01 vs control). PKC-zeta did not interact directly with NF-kappaB; however, during pancreatitis, coimmunoprecipitation of PKC-zeta with ERK1/2 was increased in TLR4+/+ mice and was attenuated in TLR4-/- mice (all P < .01 vs control), indicating that PKC-zeta interacts with ERK1/2. CONCLUSION: Acute pancreatitis upregulates TLR4, PKC-zeta, NF-kappaB, and ERK1/2, and increases apoptosis in mice livers. PKC-zeta induces nuclear translocation of NF-kappaB via ERK1/2-dependent mechanisms. Deletion of TLR4 downregulates PKC-zeta, NF-kappaB, and ERK1/2, and attenuates pancreatitis-induced liver cell apoptosis.