Post-surgical infections and perioperative antibiotics usage in pediatric genitourinary procedures.

BACKGROUND: Post-surgical infections (PSIs) are a source of preventable perioperative morbidity. No guidelines exist for the use of perioperative antibiotics in pediatric urologic procedures. OBJECTIVE: This study reports the rate of PSIs in non-endoscopic pediatric genitourinary procedures at our institution. Secondary aims evaluate the association of PSI with other perioperative variables, including wound class (WC) and perioperative antibiotic administration. STUDY DESIGN: Data from consecutive non-endoscopic pediatric urologic procedures performed between August 2011 and April 2014 were examined retrospectively. The primary outcome was the rate of PSIs. PSIs were classified as superficial skin (SS) and deep/organ site (D/OS) according to Centers for Disease Control and Prevention guidelines, and urinary tract infection (UTI). PSIs were further stratified by WC1 and WC2 and perioperative antibiotic usage. A relative risk and chi-square analysis compared PSI rates between WC1 and WC2 procedures. RESULTS: A total of 1185 unique patients with 1384 surgical sites were reviewed; 1192 surgical sites had follow-up for inclusion into the study. Ten total PSIs were identified, for an overall infection rate of 0.83%. Of these, six were SS, one was D/OS, and three were UTIs. The PSI rate for WC1 (885 sites) and WC2 (307 sites) procedures was 0.34% and 2.28%, respectively, p < 0.01. Relative risk of infection in WC2 procedures was 6.7 (CI 1.75-25.85, p = 0.0055). The rate of infections in WC1 procedures was similar between those receiving and not receiving perioperative antibiotics (0.35% vs. 0.33%). All WC2 procedures received antibiotics. DISCUSSION: Post-surgical infections are associated with significant perioperative morbidity. In some studies, PSI can double hospital costs, and contribute to hospital length of stay, admission to intensive care units, and impact patient mortality. Our study demonstrates that the rate of PSI in WC1 operations is low, irrespective of whether the patient received perioperative antibiotics (0.35%) or no antibiotics (0.33%). WC2 operations were the larger source of morbidity with an infection rate of 2.28% and a 6.7 fold higher increase in relative risk. CONCLUSIONS: WC1 procedures have a rate of infection around 0.3%, which is independent of the use of perioperative antibiotics. WC2 procedures have a higher rate of infection, with a relative risk of 6.7 for the development of PSI, and should be the target of guidelines for periprocedural prophylaxis.

Three testicles in one hemiscrotum: an unusual presentation of polyorchidism.

Polyorchidism, or more than one testicle in a hemiscrotum, is a relatively rare phenomenon. It is often associated with several other conditions, including inguinal hernia, testicular maldescent, testicular torsion, hydrocele or hypospadias. In this report, we describe a patient who presented with three testicles in one hemiscrotum, which is a highly unusual presentation for an already uncommon condition. We also review the relevant literature as it relates to the need for surveillance due to the increased risk for malignancy.

Simvastatin suppresses cyclophosphamide-induced changes in urodynamics and bladder inflammation.

OBJECTIVE: To assess the ability of daily oral simvastatin administration to reduce the negative urodynamic changes associated with cyclophosphamide (CP)-induced cystitis and to prevent bladder inflammation. Patients undergoing CP chemotherapy frequently develop cystitis, leading to urinary dysfunction and hemorrhage. Recent studies have suggested statins possess anti-inflammatory properties and might be uroprotective. MATERIALS AND METHODS: Urodynamic properties were analyzed in 4 groups of female Sprague-Dawley rats: group 1, vehicle (300 µL, 0.5% methylcellulose, orally for 7 days); group 2, simvastatin (1 mg/rat/d); group 3, vehicle plus CP (intraperitoneally 80 mg/kg, 24 h before cystometry); and group 4, simvastatin plus CP. The inflammation in the groups was assessed using Evans blue extravasation. RESULTS: CP stimulated significant increases in the number of nonvoiding contractions (0.83±0.26 vs 4.97±1.90; P=.03) and decreases in the peak voiding pressure (53.46±5.08 vs 33.34±4.37 cm H2O; P=.01). Simvastatin returned these parameters to the control levels of 1.62±0.73 (P=.70) and 45.98±7.78 cm H2O (P=.38). CP at this level caused a slight, but significant, increase in the voided volume (0.82±0.13 vs 1.16±0.14 mL; P=.04), which returned to control levels (0.74±0.12 mL; P=.65) with simvastatin. Other urodynamic parameters, such as the threshold pressure, were not affected by simvastatin or CP, or the combination of the 2. CP-induced inflammation in the bladder (Evans blue extravasation) was suppressed by simvastatin. CONCLUSION: Simvastatin was effective at ameliorating the negative urodynamic changes and inflammation in the bladder after CP administration and is a potential therapy for preventing side effects in patients undergoing this chemotherapy.

Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation.

Steatotic livers are sensitive to ischemic events and associated ATP depletion. Hepatocellular necrosis following these events may result from mitochondrial uncoupling protein-2 (UCP2) expression. To test this hypothesis, we developed a model of in vitro steatosis using primary hepatocytes from wild-type (WT) and UCP2 knockout (KO) mice and subjected them to hypoxia/reoxygenation (H/R). Using cultured hepatocytes treated with emulsified fatty acids for 24 h, generating a steatotic phenotype (i.e., microvesicular and broad-spectrum fatty acid accumulation), we found that the phenotype of the WT and UCP2 KO were the same; however, cellular viability was increased in the steatotic KO hepatocytes following 4 h of hypoxia and 24 h of reoxygenation; Hepatocellular ATP levels decreased during hypoxia and recovered after reoxygenation in the control and UCP2 KO steatotic hepatocytes but not in the WT steatotic hepatocytes; mitochondrial membrane potential in WT and UCP2 KO steatotic groups was less than control groups but higher than UCP2 KO hepatocytes. Following reoxygenation, lipid peroxidation, as measured by thiobarbituric acid reactive substances, increased in all groups but to a greater extent in the steatotic hepatocytes, regardless of UCP2 expression. These results demonstrate that UCP2 sensitizes steatotic hepatocytes to H/R through mitochondrial depolarization and ATP depletion but not lipid peroxidation.

Toll-like receptor 4 is a key mediator of murine steatotic liver warm ischemia/reperfusion injury.

Steatotic donors are routinely rejected for transplantation because of their increased rate of primary nonfunction. These grafts are more sensitive to ischemia/reperfusion (I/R) during transplantation. Removal of endotoxin before reperfusion improves liver performance post-I/R. We hypothesize that the main modality of injury in steatotic livers is toll-like receptor 4 (TLR4) signaling. We fed 4-week-old control and TLR4-deficient (TLR4KO) mice a normal diet (ND) or a 60% high-fat diet (HFD) for 4 weeks to induce steatosis. Mice were subjected to total hepatic ischemia (35 minutes) and reperfusion (1 or 24 hours). Survival improved and liver pathology decreased at 24 hours in TLR4KO HFD animals compared to control HFD animals. An investigation of infiltrates showed that neutrophils and CD4+ cells were increased at 24 hours in control HFD animals, whereas TLR4KO HFD animals were similar to ND controls. Messenger RNA levels of interleukin 6 (IL-6), IL-12, and interferon gamma were elevated at 1 hour in control HFD animals, whereas TLR4KO HFD animals were similar to ND controls. IL-10 levels at 1 hour of reperfusion in control HFD and TLR4KO animals were decreased versus control ND animals. In conclusion, these improvements in liver function in TLR4KO HFD animals implicate TLR4 as a mediator of steatotic graft failure after I/R.

The use of the Papworth cocktail is detrimental to steatotic livers after ischemia-reperfusion injury.

BACKGROUND: Hormonal resuscitation, specifically administration of levothyroxine (T4) and methylprednisolone (steroid, i.e., the "T4 Protocol") in organ transplant donors, is becoming increasingly used. Previous studies have shown that this maximizes the number of usable organs by reducing metabolic disturbances post-brain death. However, anecdotal evidence has shown that steatotic livers are adversely affected by this protocol. Therefore, we sought to investigate the hypothesis that the use of T4 and steroid is detrimental to steatotic livers in a model of total hepatic warm ischemia-reperfusion (I/R). METHODS: We subjected 8- to -10-week-old male C57BL/6 and ob/ob mice to injections of T4 and steroid 48 hr before 15 min of total hepatic ischemia, followed by 24 hr of reperfusion. RESULTS: We saw a significant decrease in survival in ob/ob animals given T4 and steroid as compared with single-treated or vehicle-treated animals. This decrease in survival was accompanied by a dramatic increase in liver necrosis (as measured on a scale from 0 to 3) in these animals as compared with controls. Previous work in our lab has shown that uncoupling protein-2 is a major mediator of I/R in steatotic animals, as it upsets normal energy homeostasis. Following with this hypothesis, we see a dramatic increase in uncoupling protein-2 levels in the combination treated animals, which is accompanied by a concomitant decrease in ATP levels after reperfusion. CONCLUSIONS: The T4 protocol is detrimental to steatotic livers subjected to I/R, likely because of a decreased ability to recover after reperfusion caused by decreased ability to form ATP.

Mitochondrial uncoupling protein-2 mediates steatotic liver injury following ischemia/reperfusion.

Steatotic livers are not used for transplantation because they have a reduced tolerance for ischemic events with reduced ATP levels and greater levels of cellular necrosis, which ultimately result in total organ failure. Mitochondrial uncoupling protein-2 (UCP2) is highly expressed in steatotic livers and may be responsible for liver sensitivity to ischemia through mitochondrial and ATP regulation. To test this hypothesis, experiments were conducted in lean and steatotic (ob/ob), wild-type, and UCP2 knock-out mice subjected to total warm hepatic ischemi-a/reperfusion. Although ob/ob UCP2 knock-out mice and ob/ob mice have a similar initial phenotype, ob/ob UCP2 knock-out animal survival was 83% when compared with 30% in ob/ob mice 24 h after reperfusion. Serum alanine aminotransferase concentrations and hepatocellular necrosis were decreased in the ob/ob UCP2 knock-out mice when compared with ob/ob mice subjected to ischemia. Liver ATP levels were increased in the ob/ob UCP2 knock-out animals after reperfusion when compared with the ob/ob mice but remained below the concentrations from lean livers. Lipid peroxidation (thiobarbituric acid-reactive substances) increased after reperfusion most significantly in the steatotic groups, but the increase was not affected by UCP2 deficiency. These results reveal that UCP2 expression is a critical factor, which sensitizes steatotic livers to ischemic injury, regulating liver ATP levels after ischemia and reperfusion.

Viral IL-10-mediated immune regulation in pancreatic islet transplantation.

Protection of transplanted pancreatic islet grafts in recipients with autoimmune diabetes depends on the suppression of autoimmune recurrence and allogeneic rejection. The aim of this study was to investigate the efficiency of viral IL-10 gene delivery in the prevention of autoimmune recurrence following islet transplantation. We evaluated the effectiveness of a systemically delivered adeno-associated viral vector (AAV vIL-10) carrying viral IL-10 in protecting islet engraftment. We observed significant prolongation of graft survival after treatment with AAV vIL-10 when using islets from donors lacking autoimmunity. We found that the mechanism of vIL-10-mediated protection was associated with suppression of T cell activation and that donor immune cells that were simultaneously transferred with the islet grafts could induce autoimmune recurrence. AAV vIL-10 gene transfer suppressed previously activated T cells and protected grafted islets from autoimmune-mediated destruction. We conclude that vIL-10 can regulate autoimmune activity and that transfer of its gene may have potential for therapeutic islet transplantation.

The novel anti-inflammatory compound, lisofylline, prevents diabetes in multiple low-dose streptozotocin-treated mice.

INTRODUCTION: Proinflammatory cytokines play an important role in the development of type 1 diabetes. Lisofylline (LSF) is a novel anti-inflammatory compound that specifically inhibits proinflammatory cytokine production and action. AIM: To investigate the effect of LSF on diabetes prevention. METHODOLOGY: A mouse with diabetes induced by multiple low doses of streptozotocin (STZ) can be used as an animal model for type 1 diabetes. In this study, we used this method to induce diabetes in C57BL/6J mice. The daily LSF treatment started 5 days before STZ injections and lasted for 2 weeks. The incidence of diabetes was monitored. Insulin secretion was assessed in pancreatic islets isolated from experimental mice. Cytokine production was measured in mouse sera. Islet apoptosis was assessed quantitatively. RESULTS: In LSF-treated mice, there was a significant reduction of diabetes incidence (25% vs. 91.6%). This protection was associated with suppression of systemic levels of IFN-gamma and TNF-alpha, inhibition of macrophage infiltration in islets, restoration of islet insulin secretion, and reduction of beta-cell apoptosis. CONCLUSIONS: This study suggests that treatment with LSF suppresses proinflammatory cytokines and protects beta-cells from inflammation. LSF may be useful for prevention of type 1 diabetes and other disorders associated with excessive proinflammatory cytokines.