Readmission characteristics of elective pediatric circumcisions using large-scale administrative data.

INTRODUCTION AND BACKGROUND: Elective circumcision is a common procedure, known to be safe and associated with minimal morbidity. There are few data reporting the rates of readmission and reoperation following elective circumcision. OBJECTIVE: We sought to define the rates of readmission and reoperation in the first 7 days following circumcision to accurately counsel families about the risks of this elective procedure. STUDY DESIGN: The Pediatric Health Information System (PHIS) was interrogated from 2004 to 2013 for all ambulatory, elective circumcisions (ICD-9 CM code of 640). We assessed readmission with respect to age, insurance status, race, readmission diagnosis, time to readmission, and seasonal differences (due to higher rates of all-cause hospital admissions). We performed logistical regression analysis with a dependent variable of readmission within 7 days and independent variables of age, race, month of admission, and insurance status. RESULTS: We identified 95,046 circumcisions from 2004 to 2013 performed in ambulatory surgery centers. Of those, 2906 (3.1%) of patients had an additional encounter at the same facility within 7 days. A total of 2409 (2.4%) of encounters were ER visits, and 253 (0.3%) were encounters for hospital admission or observation. One hundred and thirty-two patients (0.1%) underwent a second ambulatory procedure within the first 7 days following circumcision. Black patients (OR 1.26, p < 0.001) and patients on Medicaid (OR 1.63, p < 0.001) were more likely to seek care of any kind at the same institution within 7 days of the original circumcision operation. No difference was found with regard to time of year on logistic regression. Older age at circumcision was associated with increased likelihood of reoperation compared to children <1 year, with children 12-18 years old having an OR of 1.91 (p = 0.033). DISCUSSION: We present a descriptive study of clinical events occurring at the same tertiary children's hospital within the first 7 days following more than 95,000 elective postneonatal circumcisions. Limitations include a cohort generated from a single set of ICD-9 codes, and a follow-up of 7 days. CONCLUSION: Elective circumcision remains a safe procedure with a readmission rate of 0.3%, and a reoperative rate of 0.1%. However, a relatively high percentage of patients (3.1%) will have a secondary encounter within the first 7 days following circumcision, most of them seeking care in an ER, although not necessarily for circumcision-related reasons. These may be useful data when counseling patients.

Vitamin B12 deficiency in patients after enterocystoplasty.

INTRODUCTION: Serum B12 deficiency is a known sequlae of enterocystoplasty. The complications of B12 deficiency include megaloblastic anemia, neuropsychiatric disease, and demyelinating diseases such as peripheral neuropathy. Some studies have suggested that underlying disease states may be more important than enteric absorptive capacity in predicting acquired B12 deficiency. A 38% incidence of low or low-normal serum B12 in patients who have undergone enterocystoplasty has previously been reported, and oral B12 supplementation has been demonstrated to be an effective short-term therapy; however, the long-term results remain unclear. AIMS: This study hypothesized that oral vitamin B12 supplementation in patients with B12 deficiency following enterocystoplasty is an effective long-term treatment. Additionally, it sought to determine if underlying disease state predicts B12 deficiency following enterocystoplasty. DESIGN: Children who underwent enterocystoplasty at the present institution prior to August 2007 were reviewed. Patients with non-ileal augment, insufficient follow-up or hematologic disorders were excluded. Patients with low or low-normal B12 levels were included. Treatment consisted of daily oral therapy of 250 mcg or monthly parenteral therapy of 1000 mcg IM. Separately, the institutional database of 898 patients who underwent enterocystoplasty was searched and patients with at least one post-operative B12 level were highlighted. The indication for enterocystoplasty was classified as neuropathic or non-neuropathic. RESULTS: Twenty-three patients met inclusion criteria. The mean follow-up was 49 months (range 5-85) following initial abnormal B12 level. On the last follow-up, 4/23 (17%) patients had normal serum B12 levels. No patients reported sequelae of long-term B12 deficiency. In the secondary investigation, 113 patients met inclusion criteria. A total of 101 had neuropathic indications for enterocystoplasty, and 12 had non-neuropathic indications. At any time during follow-up, 48/101 (47.5%) neuropathic patients had low or low-normal B12 levels, and 4/12 (33.3%) non-neuropathic patients had low or low-normal B12 levels during follow-up (P = 0.54) (Figure). DISCUSSION: The initial success of oral B12 deficiency treatment following enterocystoplasty does not persist over time. This contradicts previous results with short duration follow-up. Underlying disease as the indication for enterocystoplasty did not predict B12 deficiency risk. The study was limited by the small number of patients with B12 deficiency who were started on treatment, as well as by the small number of patients with non-neuropathic indications for enterocystoplasty. CONCLUSION: The aims of the study were met. Further investigation is required to assess predictors of B12 deficiency following enterocystoplasty.

A novel colonoscopic approach for the management of a Malone antegrade continence enema channel, which cannot be catheterized in the immediate postoperative period: a case report.

Early Malone antegrade continence enema (MACE) complications are rare, but can be devastating, particularly if they involve loss of the channel. Management of these complications is not well described. We report on a patient who had her MACE channel successfully salvaged in the immediate postoperative period using a colonoscopic retrograde wire and catheter placement after failing antegrade percutaneous endoscopic management. To our knowledge, this is the first report of a novel, colonoscopic, minimally invasive technique of managing select MACE channels, which cannot be otherwise recatheterized. We also review the management of postoperative MACE complications.

A diet containing a nonfat dry milk matrix significantly alters systemic oxylipins and the endocannabinoid 2-arachidonoylglycerol (2-AG) in diet-induced obese mice.

BACKGROUND: Diets rich in dairy and/or calcium (Ca) have been associated with reductions in adiposity and inflammation, but the mechanisms underlying this remain to be fully elucidated. Oxylipins and endocannabinoids are bioactive lipids, which influence energy homeostasis, adipose function, insulin signaling, and inflammation. Our objective was to determine if these metabolites associate with metabolic and inflammatory phenotypes stemming from dietary Ca and dairy in diet induced obese mice. METHODS: In one study, C57BL6/J mice were fed high fat diets (45% energy) with varying dietary matrices for 12 weeks: soy protein and Ca adequate (0.5%; CONTROL), soy protein and high Ca (1.5%; HighCa), or nonfat-dry-milk based high Ca (NFDM). In a second study, mice were pre-fattened for 12 weeks on the CONTROL high fat diet, and then fed one of three high fat diets for an additional 8 weeks: CONTROL, HighCa, or NFDM. In both studies, adiposity and associated metabolic and inflammatory outcomes were measured and a targeted lipidomics analysis was performed on plasma collected during the post-absorptive condition. RESULTS: As reported previously, mice fed NFDM had less body fat and reduced mRNA markers of adipose inflammation (p < 0.05) than CONTROL mice despite greater cumulative energy intake. Moreover, NFDM fed mice lipid mediator profiles were distinct from CONTROL and HighCa mice. NFDM fed mice showed elevated plasma monoacylglycerols (6 - 46% increase from CONTROL), including 2-arachidonoylglycerol (2-AG), and reduced fatty acid diols (8-75% decrease from CONTROL). CONCLUSIONS: Differences in specific plasma lipid mediator profiles reflect the metabolic and inflammatory phenotypes seen in NFDM feeding.

Indomethacin treatment prevents high fat diet-induced obesity and insulin resistance but not glucose intolerance in C57BL/6J mice.

Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 ß-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet.

Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J mice.

High-protein diets induce alterations in metabolism that may prevent diet-induced obesity. However, little is known as to whether different protein sources consumed at normal levels may affect diet-induced obesity and associated co-morbidities. We fed obesity-prone male C57BL/6J mice high-fat, high-sucrose diets with protein sources of increasing endogenous taurine content, i.e., chicken, cod, crab and scallop, for 6 weeks. The energy intake was lower in crab and scallop-fed mice than in chicken and cod-fed mice, but only scallop-fed mice gained less body and fat mass. Liver mass was reduced in scallop-fed mice, but otherwise no changes in lean body mass were observed between the groups. Feed efficiency and apparent nitrogen digestibility were reduced in scallop-fed mice suggesting alterations in energy utilization and metabolism. Overnight fasted plasma triacylglyceride, non-esterified fatty acids, glycerol and hydroxy-butyrate levels were significantly reduced, indicating reduced lipid mobilization in scallop-fed mice. The plasma HDL-to-total-cholesterol ratio was higher, suggesting increased reverse cholesterol transport or cholesterol clearance in scallop-fed mice in both fasted and non-fasted states. Dietary intake of taurine and glycine correlated negatively with body mass gain and total fat mass, while intake of all other amino acids correlated positively. Furthermore taurine and glycine intake correlated positively with improved plasma lipid profile, i.e., lower levels of plasma lipids and higher HDL-to-total-cholesterol ratio. In conclusion, dietary scallop protein completely prevents high-fat, high-sucrose-induced obesity whilst maintaining lean body mass and improving the plasma lipid profile in male C57BL/6J mice.

The Postprandial Effects of a Moderately High-Fat Meal on Lipid Profiles and Vascular Inflammation in Alzheimer's Disease Patients: A Pilot Study.

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disease of aging with unknown causative factors. Accumulating evidence suggests that inflammation and neurovascular dysfunction play important roles in AD. The postprandial period following a moderately high-fat meal is associated with vascular inflammation in young, healthy individuals; however, this relationship has not been investigated in Alzheimer's patients despite their exaggerated inflammatory state. METHODS: Patients with AD and age-matched control subjects were recruited through the UC Davis Alzheimer's Disease Center. All subjects consumed a moderately high-fat breakfast meal. Fasting and postprandial blood samples were collected for lipid, lipoprotein, and oxylipin analyses, as well as assays for cytokine levels and monocyte activation. RESULTS: The plasma lipid analyses revealed similar levels of triglycerides and esterified oxylipins between groups, but there was an interaction between postprandial non-esterified fatty acid (NEFA) levels and body mass index in the AD group compared to the control subjects. The AD group also had increased behenic acid and decreased linoleic and oleic acids in the postprandial period; however, these were not significantly different. Inflammatory assays revealed elevated fasting levels of interleukin (IL)-10 and IL-12 p70, but no change in monocyte activation in the AD group. CONCLUSION: The postprandial period following a moderately high-fat meal is not associated with an exaggerated inflammatory state in Alzheimer's patients, and basal esterified oxylipin profiles do not indicate elevated oxidative stress. However, the baseline inflammatory state during fasting in AD patients includes elevated levels of plasma IL-10 and IL-12 p70, which may indicate a balance between immune responses mediated by these interleukins.

Decreased zinc availability affects glutathione metabolism in neuronal cells and in the developing brain.

A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells. This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA). GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells. γ-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD). The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls. The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD. Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells. Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration. Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low. In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels. This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors.

Dietary eicosapentaenoic acid supplementation accentuates hepatic triglyceride accumulation in mice with impaired fatty acid oxidation capacity.

Reduced mitochondrial fatty acid (FA) ß-oxidation can cause accumulation of triglyceride in liver, while intake of eicosapentaenoic acid (EPA) has been recommended as a promising novel therapy to decrease hepatic triglyceride content. However, reduced mitochondrial FA ß-oxidation also facilitates accumulation of EPA. To investigate the interplay between EPA administration, mitochondrial activity and hepatic triglyceride accumulation, we investigated the effects of EPA administration to carnitine-deficient mice with impaired mitochondrial FA ß-oxidation. C57BL/6J mice received a high-fat diet supplemented or not with 3% EPA in the presence or absence of 500 mg mildronate/kg/day for 10 days. Liver mitochondrial and peroxisomal oxidation, lipid classes and FA composition were determined. Histological staining was performed and mRNA level of genes related to lipid metabolism and inflammation in liver and adipose tissue was determined. Levels of pro-inflammatory eicosanoids and cytokines were measured in plasma. The results showed that mildronate treatment decreased hepatic carnitine concentration and mitochondrial FA ß-oxidation and induced severe triglyceride accumulation accompanied by elevated systemic inflammation. Surprisingly, inclusion of EPA in the diet exacerbated the mildronate-induced triglyceride accumulation. This was accompanied by a considerable increase of EPA accumulation while decreased total n-3/n-6 ratio in liver. However, inclusion of EPA in the diet attenuated the mildronate-induced mRNA expression of inflammatory genes in adipose tissue. Taken together, dietary supplementation with EPA exacerbated the triglyceride accumulation induced by impaired mitochondrial FA ß-oxidation. Thus, further thorough evaluation of the potential risk of EPA supplementation as a therapy for NAFLD associated with impaired mitochondrial FA oxidation is warranted.

Daily consumption of orange-fleshed sweet potato for 60 days increased plasma ß-carotene concentration but did not increase total body vitamin A pool size in Bangladeshi women.

We assessed the effect of daily consumption of orange-fleshed sweet potatoes (OFSP), with or without added fat, on the vitamin A (VA) status of Bangladeshi women with low initial VA status. Women (n = 30/group) received one of the following for 6 d/wk over 10 wk: 1) 0 µg retinol activity equivalents (RAE)/d as boiled white-fleshed sweet potatoes (WFSP) and a corn oil capsule, 2) 600 µg RAE/d as boiled OFSP and a corn oil capsule, 3) fried OFSP and a corn oil capsule, or 4) boiled WFSP and a retinyl palmitate capsule in addition to their home diets. Plasma concentrations of retinol and ß-carotene and total body VA pool size were assessed before and after the 60-d intervention. Initial and final plasma retinol concentrations (mean ± SD) were 0.75 ± 0.18 µmol/L and 0.84 ± 0.19 µmol/L, respectively (P = 0.31); final means did not differ by group. Initial and final plasma ß-carotene concentrations were 0.10 ± 00 µmol/L and 0.18 ± 0.09 µmol/L, respectively (P < 0.0001); final mean plasma ß-carotene concentrations were higher in groups that received OFSP (P < 0.0001), and final mean plasma ß-carotene was marginally higher in the group that received fried OFSP compared with boiled OFSP (P = 0.07). Initial and final total body VA pool sizes were 0.060 ± 0.047 mmol and 0.091 ± 0.070 mmol, respectively (P = 0.05, n = 110) and did not differ by group. Despite an increase in plasma ß-carotene concentration, the impact of OFSP on VA status appears to be limited in Bangladeshi women residing in a resource-poor community.

Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers.

A subject's baseline FA composition may influence the ability of dietary highly unsaturated omega-3 FAs (n3-HUFA) to change circulating profiles of esterified FAs and their oxygenated metabolites. This study evaluates the influence of basal n3-HUFA and n3-oxylipin status on the magnitude of response to n3-HUFA consumption. Blood was collected from fasting subjects (n = 30) before and after treatment (4 weeks; 11 ± 2 mg/kg/day n3-HUFA ethyl esters). Esterified FAs were quantified in erythrocytes, platelets, and plasma by GC-MS. Esterified oxylipins were quantified in plasma by LC-MS/MS. Treatment with n3-HUFAs increased n3-HUFAs and decreased n6-HUFAs in all reservoirs and increased plasma n3-oxylipins without significantly changing n6-oxylipin concentrations. As subject basal n3-HUFAs increased, treatment-associated changes decreased, and this behavior was reflected in the percentage of 20:5n3 + 22:6n3 in red blood cell membrane FAs (i.e., the omega-3 index). To maintain an omega-3 index of 8% and thus reduce cardiovascular disease risk, our analyses suggest a maintenance dose of 7 mg/kg/day n3-HUFA ethyl esters for a 70-kg individual. These results suggest that the basal n3 index may have clinical utility to establish efficacious therapeutic experimental feeding regimens and to evaluate the USDA Dietary Guidelines recommendations for n3-HUFA consumption.

Evolution of hemostatic agents in surgical practice.

OBJECTIVE: Topical hemostatic agents are used in a wide variety of surgical settings, and the evolution of this class of surgical tools is an interesting topic. We reviewed and outlined the historical progress of topical hemostats into present day surgery and urology, and highlight opportunities for future research. MATERIALS AND METHODS: A MEDLINE search of all available literature concerning several classes of topical hemostatic agents was performed. Fibrins sealants, Gelatin sponge hemostatics, cyanoacrylate adhesives, oxidized regenerated cellulose, and microfibrillar collagen were included. References were chosen from a broad range of surgical literature. RESULTS: Topical hemostatic agents have historically taken advantage of a wide variety of mechanisms for hemostasis. Fibrin sealants have a rich history and large potential for further applications. Gelatin sponge hemostatics have been widely used since their introduction, but have changed little. Cyanoacrylate adhesives have a unique mechanism and opportunity for novel applications of existing products. Oxidized cellulose was original in the use of plant-based components. Microfibrillar collagen hemostats have evolved to a wide variety of formats. CONCLUSIONS: A review of the evolution of topical hemostatic agents highlights opportunities for potential novel research. Fibrin sealants may have the most opportunity for advancement, and understanding the history of these products is useful. With the drive in urology for minimally invasive surgical techniques, adaptation of topical hemostatic agents to this surgical approach would be valuable and offers an opportunity for novel contributions.

Gestational zinc deficiency affects the regulation of transcription factors AP-1, NF-κB and NFAT in fetal brain.

Transcription factors AP-1, nuclear factor κB (NF-κB) and NFAT are central to brain development by regulating the expression of genes that modulate cell proliferation, differentiation, apoptosis and synaptic plasticity. This work investigated the consequences of feeding zinc-deficient and marginal zinc diets to rat dams during gestation on the modulation of AP-1, NF-κB and NFAT in fetal brain. Sprague-Dawley rats were fed from gestation day (GD) 0 a control diet ad libitum (25 µg zinc/g diet, C), a zinc-deficient diet ad libitum (0.5 µg zinc/g diet, ZD), the control diet in the amounts eaten by the ZD rats (restrict fed, RF) or a diet containing a marginal zinc concentration ad libitum (10 µg zinc/g diet, MZD) until GD 19. AP-1-DNA binding was higher (50-190%) in nuclear fraction isolated from ZD, RF and MZD fetal brains compared to controls. In MZD fetal brain, high levels of activation of the upstream mitogen-activated protein kinases JNK and p38 and low levels of ERK phosphorylation were observed. Total levels of NF-κB and NFAT activation were higher or similar in the ZD and MZD groups than in controls, respectively. However, NF-κB- and NFAT-DNA binding in nuclear fractions was markedly lower in ZD and MZD fetal brain than in controls (50-80%). The latter could be related to zinc deficiency-associated alterations of the cytoskeleton, which is required for NF-κB and NFAT nuclear transport. In summary, suboptimal zinc nutrition during gestation could cause long-term effects on brain function, partially through a deregulation of transcription factors AP-1, NF-κB and NFAT.

The role of zinc in the modulation of neuronal proliferation and apoptosis.

Although a requirement of zinc (Zn) for normal brain development is well documented, the extent to which Zn can modulate neuronal proliferation and apoptosis is not clear. Thus, we investigated the role of Zn in the regulation of these two critical events. A low Zn availability leads to decreased cell viability in human neuroblastoma IMR-32 cells and primary cultures of rat cortical neurons. This occurs in part as a consequence of decreased cell proliferation and increased apoptotic cell death. In IMR-32 cells, Zn deficiency led to the inhibition of cell proliferation through the arrest of the cell cycle at the G0/G1 phase. Zn deficiency induced apoptosis in both proliferating and quiescent neuronal cells via the intrinsic apoptotic pathway. Reductions in cellular Zn triggered a translocation of the pro-apoptotic protein Bad to the mitochondria, cytochrome c release, and caspase-3 activation. Apoptosis is the resultant of the inhibition of the prosurvival extracellular-signal-regulated kinase, the inhibition of nuclear factor-kappa B, and associated decreased expression of antiapoptotic proteins, and to a direct activation of caspase-3. A deficit of Zn during critical developmental periods can have persistent effects on brain function secondary to a deregulation of neuronal proliferation and apoptosis.

Effects of unfractionated heparin and glycoprotein IIb/IIIa antagonists versus bivalirdin on myeloperoxidase release from neutrophils.

UNLABELLED: OBJECTIVES The objective of this study was to determine whether adjunctive therapy during percutaneous coronary intervention (PCI) affects markers of systemic inflammation or platelet activation. Despite different mechanisms of action, direct-thrombin inhibition with bivalirudin during PCI provided similar protection from periprocedural and chronic ischemic complications as compared with unfractionated heparin (UFH) plus planned use of GPIIb/IIIa antagonists in the REPLACE-2 and ACUITY trials. METHODS AND RESULTS: Patients undergoing nonurgent PCI of a native coronary artery were randomized to receive adjunctive therapy with bivalirudin or UFH+eptifibatide. Interleukin (IL)-6 and C-reactive protein (CRP) transiently increased in both groups after PCI. In the UFH+eptifibatide, but not the bivalirudin group, myeloperoxidase (MPO) levels were elevated 2.3-fold above baseline (P=0.004) immediately after PCI. In an in vitro assay, heparin and to a lesser extent enoxaparin, but not bivalirudin or eptifibatide, stimulated MPO release from and binding to neutrophils and neutrophil activation. A mouse model of endoluminal femoral artery denudation was used to investigate further the importance of MPO in the context of arterial injury. CONCLUSIONS: Adjuvant therapy during PCI may have undesired effects on neutrophil activation, MPO release, and systemic inflammation.