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Agostino Pierro

Publications and source records attributed to Agostino Pierro.

At least 19 recordsLinked to original sources
PubMed2006

Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis.

OBJECTIVES: (1) To characterise neurodevelopmental outcome of neonates with necrotizing enterocolitis (NEC); (2) to define whether NEC increases risk of neurodevelopmental impairment in very low birth weight neonates; (3) to investigate whether stage of disease or need for surgery increase risk of poor outcome. DESIGN: A systematic review was performed. Searches identified 182 relevant papers. Ten studies compared extremely low birthweight neonates with NEC to infants of similar age and gestation who did not develop NEC. Data are reported as OR (95% CIs, p values for test for overall effect) and compared by chi2. RESULTS: 7843 children (821 with NEC) were included in the meta-analysis. Median follow-up was 20 months (range 12 to 156). Overall, 45% of children who had neonatal NEC were neurodevelopmentally impaired. Infants with NEC were significantly more likely than infants of similar age and gestation who did not develop NEC to be neurodevelopmentally impaired (1.6 (1.3 to 2.0), p = 0.0001) including a higher risk of cerebral palsy (1.5 (1.2 to 2.0), p = 0.001), visual (2.3 (1.0 to 5.1), p = 0.04), cognitive (1.7 (1.4 to 2.2), p<0.0001) and psychomotor impairment (1.7 (1.3 to 2.2), p<0.0001). The odds ratio of neurodevelopmental impairment was also 2.3 times higher in neonates with Bell's stage III disease or requiring surgery ((1.5 to 3.6), p = 0.0001). CONCLUSIONS: NEC is associated with significantly worse neurodevelopmental outcome than prematurity alone. Presence of advanced NEC and need for surgery increase the risk of neurological impairment.

Cognition Disorders↗
PubMed2006

An investigation of minimisation criteria.

BACKGROUND: Minimisation can be used within treatment trials to ensure that prognostic factors are evenly distributed between treatment groups. The technique is relatively straightforward to apply but does require running tallies of patient recruitments to be made and some simple calculations to be performed prior to each allocation. As computing facilities have become more widely available, minimisation has become a more feasible option for many. Although the technique has increased in popularity, the mode of application is often poorly reported and the choice of input parameters not justified in any logical way. METHODS: We developed an automated package for patient allocation which incorporated a simulation arm. We here demonstrate how simulation of data can help to determine the input parameters to be used in a subsequent application of minimisation. RESULTS: Several scenarios were simulated. Within the selected scenarios, increasing the number of factors did not substantially adversely affect the extent to which the treatment groups were balanced with respect to the prognostic factors. Weighting of the factors tended to improve the balance when factors had many categories with only a slight negative effect on the factors with fewer categories. When interactions between factors were included as minimisation factors, there was no major reduction in the balance overall. CONCLUSION: With the advent of widely available computing facilities, researchers can be better equipped to implement minimisation as a means of patient allocation. Simulations prior to study commencement can assist in the choice of minimisation parameters and can be used to justify those selections.

Age Distribution↗
PubMed2006

The effects of moderate hypothermia on energy metabolism and serum inflammatory markers during laparotomy.

The objective of this study was to investigate energy metabolism of the gut and liver as well as serum inflammatory cytokines following exploratory laparotomy at moderate hypothermia. Two groups of rats were studied, (n=6-8/group); laparotomy at normothermia for 120 min and laparotomy at hypothermia (32-33 degrees C) for 120 min. Study 1: Intestinal glucose, succinate, lactate, phosphocreatine, and ATP as well as hepatic glucose, succinate, lactate, and ATP were measured in terms of micromole per gram using magnetic resonance spectroscopy. Study 2: Serum levels of TNF-alpha, IL-1beta, LPS-inducible chemokine (LIX), and sICAM-1 were measured by ELISA. Histology of the gut and liver were interpreted. Data are expressed as mean and SEM. In Study 1, laparotomy at hypothermia caused an increase in intestinal glucose levels (0.78+/-0.03 vs. 1.29+/-0.11, P=0.0012) with a decrease in hepatic lactate levels (0.82+/-0.04 vs. 0.44+/-0.06, P<0.001). There were no differences in the other metabolites between the two groups. In Study 2, there were no differences in serum TNF-alpha, IL-1beta, LIX, or sICAM-1 between the two groups. Histological features of the gut and liver among groups were comparable. In conclusion, the intestine and liver react to hypothermia differently. However, levels of high-energy phosphates in both organs are not affected by hypothermia suggesting adequate energy for the organs. It is unlikely that hypothermia induces either systemic inflammatory response or hypoxic damage to the intestine and liver in this model.

Animals↗
PubMed2006

Oesophageal atresia: improved outcome in high-risk groups?

PURPOSE: The Spitz classification of oesophageal atresia (OA) based on the birth weight and the presence of a major cardiac anomaly was proposed 1994. Advances in neonatal care have led us to question if these outcome figures are still valid. We tested the hypothesis that the outcome of neonates with OA has improved during the last decade. METHODS: The records of all neonates (n = 188) born with OA and treated in a single institution between 1993 and 2004 were reviewed and compared with data from the original Spitz study. Data were obtained on the birth weight, presence of a major cardiac anomaly, and survival. Differences in survival were compared using the Yates-corrected chi2 test. RESULTS: In the early period, 326 neonates survived (87.6%) compared with 174 (91.5%) in the most recent decade (P = .10). Based on Spitz classification, the outcome comparing both periods was the following: group I, 97% (283/293) and 98.5% (130/132) (P = .44); group II, 59% (41/70) and 82% (41/50) (P = .01); group III, 22% (2/9) and 50% (3/6) (P = .57), respectively. CONCLUSIONS: The Spitz classification remains valid. It may be of use when counselling parents and in comparing outcome among centres. In our centre, the overall survival of neonates with OA has not significantly changed in the recent decade. The improvement in survival of neonates in group II, however, demonstrated the recent advances in neonatal, paediatric surgical, and cardiac care.

Esophageal Atresia↗
PubMed2005

Juvenile papillomatosis of the breast in a male infant with Noonan syndrome, café au lait spots, and family history of breast carcinoma.

Juvenile papillomatosis (JP) of the breast is a rare condition, usually affecting women under 30 years of age. Although this is considered a benign lesion, follow-up is recommended for the patient and family since there is an association with a family history of breast carcinoma and increased risk of development of breast carcinoma. We report an infant with JP, Noonan syndrome (NS), café au lait spots, and family history of breast carcinoma. Seven previously reported cases of JP in males exist, two occurring in infants. The association between JP and NS has not been previously reported.

Breast Neoplasms, Male↗
PubMed2005

The surgical management of necrotising enterocolitis.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates. The disease affects mainly premature neonates. The pathogenesis is still unknown but predisposing factors are prematurity, formula feeding and sepsis. The disease can lead to gangrene and intestinal perforation requiring surgery. The options for surgery are between primary peritoneal drainage or laparotomy. However, the optimum choice between peritoneal drainage and laparotomy remains controversial, particularly in low-birth-weight infants (<1000 g). Peritoneal drainage offers temporary decompression, drainage and stabilization of patients whilst awaiting surgery, or in patients too unstable to be able to tolerate surgery or anaesthesia. Those weighing >1000 g who have no associated morbidities and are clinically stable are preferentially treated by primary laparotomy. The principal surgical objectives of laparotomy in acute NEC are to control sepsis and removal of gangrenous bowel preserving as much bowel length as possible. The surgical options at laparotomy include resection with enterostomy, resection with primary anastomosis, proximal jejunostomy and "clip and drop" technique. The option exercised is influenced by the clinical status of the patient and the extent of the disease.

Anastomosis, Surgical↗
PubMed2005

Total glutathione is not decreased in infants with necrotizing enterocolitis.

BACKGROUND: Glutathione (GSH) is the major intracellular antioxidant protecting against free radical-mediated damage. Oxidative stress is implicated in the pathogenesis of necrotizing enterocolitis (NEC), and damage could be enhanced by a relative deficiency of GSH. We hypothesized that infants with NEC would have lower levels of erythrocyte GSH when compared with controls. METHODS: Total erythrocyte GSH concentration (per gram of hemoglobin [g Hb]) was determined in blood samples from infants with NEC (n = 16) referred for surgical intervention. Nonseptic infants referred for other conditions (eg, patent ductus arteriosus ligation) served as controls (n = 10). RESULTS: Controls and infants with NEC were demographically similar. Mean erythrocyte GSH concentration in infants with NEC was 0.076 +/- 0.004 micromol/g Hb and in controls it was 0.078 +/- 0.005 micromol/g Hb (P = .73). There was no significant correlation between GSH concentration and weight, gestational age, or C-reactive protein levels. In infants with NEC, there was no difference in GSH levels between infants with stage 2 and stage 3 diseases nor between those who died and survived, but a trend toward lower GSH levels in infants with more extensive diseases exists. CONCLUSIONS: Total GSH levels are similar in infants with NEC and controls. It is possible that a relative rather than absolute deficiency of antioxidant compounds exists and may contribute to the development of NEC.

Birth Weight↗
PubMed2005

Staged repair of giant omphalocele in the neonatal period.

BACKGROUND/PURPOSE: The aim of this study was to analyze the outcome of giant omphalocele repaired in the neonatal period. METHODS: Twelve consecutive (1997-2004) neonates with giant omphalocele (defect >6 cm with liver herniation) were reviewed. A silo of Prolene mesh (Ethicon) was attached to the fascia and the defect was closed without opening the amniotic sac after sequential reduction. In 2 neonates with ruptured omphalocele a plastic sheet was inserted below the mesh. Data are reported as median and range. RESULTS: Gestational age was 38 weeks (range, 32-40 weeks) and birth weight was 2.9 kg (range, 1.0-3.1 kg). The final closure was achieved at 26 days (range, 16-62 days). Three neonates (25%) died before final closure (causes: ruptured omphalocele, lung hypoplasia, cardiac anomalies, and intestinal failure). In the 9 surviving neonates, mechanical ventilation was required for 8 days (range, 2-20 days), hospital stay was 42 days (range, 23-73 days), and full enteral feeding was achieved on day 12 (range, 4-53 days). Complications included wound infection in 5 neonates and midgut volvulus in 1. Prophylactic Ladd's procedure was performed laparoscopically at a later stage in 4 children. At laparoscopy, intraperitoneal adhesions were minimal and the central liver did not preclude the operation. The 9 survivors are all well after 46 months (range, 12-67 months). CONCLUSIONS: Giant omphalocele can be safely repaired in the neonatal period without opening the amniotic sac. Intestinal malrotation should be excluded and Ladd's procedure can be performed laparoscopically at a later stage.

Abnormalities, Multiple↗
PubMed2005

Inflammatory response in children after laparoscopic vs open Nissen fundoplication: randomized controlled trial.

UNLABELLED: We performed a randomized controlled trial to compare the inflammatory and immune responses to Nissen fundoplication in infants and children undergoing either open or laparoscopic surgery. METHODS: Forty children undergoing Nissen fundoplication were randomized to laparoscopy or open surgery using minimization with respect to age, neurologic status, and operating surgeon. Intraoperative and postoperative analgesias were standardized. Inflammatory markers (plasma malondialdehyde, nitrate plus nitrite level, and cytokines) and monocyte class II major histocompatibility complex expression were measured preoperatively, at end of surgery, 4, 24, and 48 hours postoperatively. Postoperative changes were compared between open and laparoscopic groups. RESULTS: There were no significant changes in circulating malondialdehyde, nitrates plus/ nitrite, interleukin-10, or tumor necrosis factor alpha in the postoperative period in either group. Interleukin-1 receptor antagonist (IL-1rA) and IL-6 were significantly increased in both groups, with a tendency for greater elevation of IL-1rA in the open group. Monocyte major histocompatibility complex expression fell significantly in both groups; however, this fall appeared to be slightly more marked in the open group. CONCLUSIONS: The postoperative cytokine response is similar in children undergoing open and laparoscopic Nissen fundoplication. This trial indicates that laparoscopy may partly reduce postoperative immune suppression.

Child↗
PubMed2005

P-selectin expression, neutrophil infiltration, and histologic injury in neonates with necrotizing enterocolitis.

BACKGROUND/PURPOSE: P-selectin promotes adherence of leukocytes to the endothelium in inflammatory processes. The aim of this study was to investigate the expression of P-selectin and its role in the development of inflammation in neonates with necrotizing enterocolitis (NEC). METHODS: Twenty-nine intestinal specimens from 13 neonates with NEC and 7 control neonates with congenital gastrointestinal abnormalities were studied. Histologic damage, immunohistochemical expression of P-selectin, and polymorphonuclear cell infiltrate were graded blindly. Mann-Whitney U and Spearman rank tests were used to compare grades. RESULTS: Expression of P-selectin was increased in NEC compared with controls in both medium-sized vessels (P = .03) and in the microcirculation (P = .03). P-selectin expression on medium-sized vessels correlated with the degree of histologic injury (P = .02, r = 0.425). P-selectin expression was greatest in areas of active inflammation but markedly lower in necrotic areas. The degree of polymorphonuclear cell infiltration strongly correlated with P-selectin expression on both medium-sized vessels (P = .004, r = 0.513) and the microcirculation (P = .001, r = 0.578). CONCLUSIONS: Expression of P-selectin is increased in medium-sized vessels and in the microcirculation in intestinal specimens of neonates with NEC compared with neonatal controls. Expression of P-selectin is associated with the recruitment of polymorphonuclear cells and the severity of histologic injury, although P-selectin expression is lost in necrotic tissue.

Enterocolitis, Necrotizing↗
PubMed2005

The surgical treatment of gastro-esophageal reflux in neonates and infants.

Gastro-esophageal reflux (GER) is a physiological process characterized by the involuntary passage of gastric contents into the lower esophagus not induced by noxious stimuli. It represents a common condition in preterm infants and may occur in healthy neonates. The phenomenon is only considered as GER disease when it causes the patient to be symptomatic or results in pathological complications. Fundoplication is recommended in symptomatic neonates and infants with GER that does not respond to medical treatment. The presence of respiratory symptoms related to GER is the primary indication for fundoplication in this selected population. The Nissen fundoplication is the antireflux procedure of choice and the experience concerning other procedures, including laparoscopic techniques, is limited in this age group. The best results are achieved in newborn infants with isolated GER, as the recurrence rate of GER in infants with associated anomalies is high. Further studies are necessary to evaluate the benefit of laparoscopic fundoplication in this age group.

Esophagoscopy↗
PubMed2005

Moderate hypothermia protects against systemic oxidative stress in a rat model of intestinal ischemia and reperfusion injury.

Multisystem organ failure represents a major cause of mortality in intestinal ischemia and reperfusion (I/R), and oxidative stress plays a key role in its pathogenesis. Hypothermia is beneficial in I/R injury, but its effects on systemic oxidative stress have not been elucidated. The aim of this study was to evaluate the effects of moderate hypothermia on systemic oxidative stress after intestinal I/R injury. Anaesthetized adult rats (n = 10 per group) underwent 60 min of intestinal ischemia followed by 120 min of reperfusion or sham operation at normothermia (36 degrees C-38 degrees C) or moderate hypothermia (30 degrees C-32 degrees C). At sacrifice, ileum, liver, lungs, and kidneys were removed to determine the concentration of malondialdehyde (a marker of lipid peroxidation), reduced and oxidized glutathione (a major endogenous antioxidant), and glutathione redox state. Plasma malondialdehyde and nitrate plus nitrite (reflecting nitric oxide production) were also analyzed. A marked elevation of malondialdehyde was observed after I/R at normothermia in plasma, ileum, and lungs; however, hypothermia during I/R prevented this increase. I/R at normothermia caused a profound decrease in reduced glutathione and glutathione redox state in the ileum, but this was not observed in I/R at hypothermia. Interestingly, hypothermia increased glutathione content of control intestine. Nitric oxide production was increased only in normothermic I/R animals. Moderate hypothermia attenuates systemic oxidative stress associated with experimental intestinal I/R in an animal model by decreasing lipid peroxidation in plasma, ileum, lungs, and kidneys, by preventing the depletion of gut glutathione, and by reducing systemic nitric oxide production. However, whether these effects persist after rewarming is unknown.

Animals↗
PubMed2004

Tyrosine nitration of carnitine palmitoyl transferase I during endotoxaemia in suckling rats.

Heart carnitine palmitoyl transferase I (CPTI) is inhibited in vivo during endotoxaemia and in vitro by peroxynitrite but the biochemical basis of this inhibition is not known. The aim of this study was to determine which isoform of CPT I is inhibited during endotoxaemia and whether the inhibition is due to increased tyrosine nitration. Cardiac mitochondria were isolated from endotoxaemic suckling rats. To determine whether M- or L-CPTI was inhibited, we carried out titrations with DNP-etomoxir-CoA. Slopes of the titration curves with DNP-etomoxir-CoA were no different between control and endotoxaemia, suggesting that M-CPTI was specifically inhibited. Immunoprecipitation was carried out using an anti-nitrotyrosine antibody. Immunoprecipitated proteins were identified by Western blotting with L- and M-CPTI specific antibodies. L-CPTI was nitrated both in control and in 2- and 6-h endotoxaemia mitochondria but there was no significant difference in the level of nitration. M-CPTI was also nitrated in control mitochondria but nitration was significantly increased at both 2- and 6-h endotoxaemia. Either 10 mM 3-nitrotyrosine plus 40 microg nitrated-albumin or 0.5 M dithionite, during immunoprecipitation, greatly decreased immunopositivity for M- and L-CPTI on WB. M-CPTI appears to be a novel target for peroxynitrite during endotoxaemia, which would alter myocardial substrate selection.

Acyl Coenzyme A↗
PubMed2004

Melatonin protects from, but does not reverse, the effects of mediators of sepsis on liver bioenergetics.

BACKGROUND: Reactive oxygen species (ROS) have been reported to play a significant role in the pathogenesis of sepsis and liver dysfunction. In particular, neonates are at risk for sepsis and have less protection against oxidation. Melatonin has been reported to reduce the oxidative stress status in neonates with sepsis. Little is known about the effect of melatonin on liver bioenergetics. The aim of this study was to investigate the protective effect of melatonin on hepatocyte oxidative energy metabolism against hydrogen peroxide (H2O2), a free radical mediator of septic damage. METHODS: Hepatocytes were isolated from neonatal suckling rats (11-15 days old). The cells, respiring on palmitate, were exposed to H2O2 at the concentration of 2 mmol/l, melatonin alone at 1 micromol/l or 10 micromol/l, or H2O2 plus melatonin at each of the two concentrations. Oxygen consumption was measured polarographically. In subsequent experiments, melatonin was added after the hydrogen peroxide. RESULTS: Hydrogen peroxide significantly reduced hepatocyte oxygen consumption ( p<0.001), but melatonin added at the same time was able to prevent this effect ( p<0.001). However, melatonin at a low dose significantly inhibited hepatocyte oxygen consumption ( p<0.001), an effect which has not been previously described. When melatonin was added to cells after they had been exposed to hydrogen peroxide, a beneficial effect was not observed, indicating that melatonin is not able to reverse the effects of hydrogen peroxide. CONCLUSION: Melatonin has a protective effect on hepatocyte oxidative metabolism, improving mitochondrial function by counteracting oxidative stress.

Animals↗
PubMed2004

Heart energy metabolism after intestinal ischaemia and reperfusion.

BACKGROUND/PURPOSE: Multiple organ failure subsequent to intestinal ischaemia and reperfusion (I/R) includes cardiac failure, but little is known about heart energy metabolism in this setting. This study investigates the effects of intestinal I/R on heart energy metabolism and evaluates the effects of moderate hypothermia. METHODS: Adult rats underwent intestinal ischaemia for 60 minutes followed by 120 minutes of reperfusion. Animals were maintained at either normothermia (36 degrees to 38 degrees C) or moderate hypothermia (30 degrees to 32 degrees C). In experiment A, 2 groups were studied: (1) sham at normothermia; (2) I/R at normothermia. After death, the heart was removed. Cardiac phosphoenergetics were assessed by 31P magnetic resonance spectroscopy; data are expressed as micromoles per gram. In experiment B, 4 groups were studied: (1) sham at normothermia, (2) I/R at normothermia, (3) sham at hypothermia, (4) I/R at hypothermia. At the end of the experiment, the heart was harvested. The activity of carnitine palmitoyl transferase I (CPT I), an important enzyme in the control of fatty acid oxidation, was measured; data are expressed as nanomoles per minute per unit citrate synthase. Results are expressed as mean +/- SEM. RESULTS: In experiment A, there were no differences between the 2 study groups in cardiac phosphocreatine, inorganic phosphate, adenosine triphosphate (ATP), or in the ratio of inorganic phosphate to ATP. In experiment B, CPT I activity was decreased significantly after I/R at normothermia compared with normothermic sham, but this enzyme inhibition was prevented by hypothermia (3.9 +/- 0.2; v I/R). CONCLUSIONS: These results suggest that although cardiac ATP supply was maintained during intestinal I/R at normothermia, the balance of substrate utilisation was shifted from fatty acid oxidation to carbohydrate utilisation. However, moderate hypothermia modified these changes. The beneficial effect of moderate hypothermia on cardiac metabolism during intestinal I/R has potential clinical application in various surgical conditions.

Adenosine Triphosphate↗
PubMed2004

Gastric transposition in children--a 21-year experience.

PURPOSE: The purpose of this study was to analyze the outcome in 173 children (104 M, 69 F) undergoing transposition since 1981. METHODS: The most common indications for esophageal replacement included failed repair of different varieties of esophageal atresia (127), caustic injury (23), and peptic strictures (8). A total of 81% of the patients were referred from other hospitals (50% from other countries). Age at operation ranged from 7 days to 17 years. The gastric transposition was performed using blunt mediastinal dissection only in 90 patients with an additional 81 patients undergoing lateral thoracotomy. The retrosternal position was used in 2 patients. RESULTS: There were no graft failures including those who had previously failed gastric tube or Scharlilike operations. Anastomotic leakage occurred in 12% (all but 1 resolved spontaneously). Anastomotic stricture requiring dilatation occurred in 19.6%. Half of these patients had previous caustic esophageal injury. There were 9 deaths in the group (5.2%). One death occurred intraoperatively, 5 in the early postoperative period, and there were 3 late deaths. In more than 90% of our patients, the outcome was considered good to excellent in terms of absence of swallowing difficulties or other gastrointestinal symptoms. Many, however, preferred to eat small frequent meals. Poor outcome was particularly associated with multiple previous attempts at esophageal salvage. There was no deterioration in the function of the gastric transposition in those patients followed up for more than 10 years. CONCLUSIONS: Gastric transposition for esophageal substitution is an acceptable procedure. It is attended by 5% mortality and a 12% leak rate. A total of 19.6% of the patients needed anastomotic dilatation for stricture. In the long term, good function has been maintained. Gastric transposition compares favorably with alternative methods of esophageal replacement.

Adolescent↗
PubMed2004

Intestinal ischemia reperfusion injury and multisystem organ failure.

Intestinal ischemia-reperfusion is a common pathway for many diseases in infants, children, and adults, and this may lead to multiple organ dysfunction syndrome and death. While several studies have investigated reperfusion injury in cardiac, cerebral, and hepatic disease, limited work has been published on intestinal ischemia-reperfusion and its multiorgan effects. The authors have developed models of intestinal ischemia-reperfusion in rats and have demonstrated that intestinal reperfusion causes liver energy failure at normothermia. This is followed by 100% mortality within 4 hours of reperfusion. Moderate hypothermia (32 degrees C to 33 degrees C) induced throughout ischemia and reperfusion prevents liver energy failure, intestinal damage, and neutrophil infiltration in the lungs. Moderate hypothermia in this model of intestinal ischemia and reperfusion prevents mortality. Further studies are needed to establish whether therapeutic hypothermia is a useful intervention in the treatment of infants and children with intestinal injuries caused by ischemia and reperfusion.

Adenosine Triphosphate↗