Intestinal ischaemia and reperfusion (I/R) contributes to the pathogenesis of
numerous clinical conditions in all age groups. Many of these diseases, including
neonatal necrotizing enterocolitis (NEC), result in significant morbidity and
mortality through multiple organ dysfunction, and available treatment is currently
limited to supporting vital functions.
My aims were: to investigate novel therapeutic strategies such as moderate
hypothermia and peroxynitrite decomposition catalyst FeTMPyP [5,10,15,20-
tetrakis(N-methyl-4'-pyridyl)porphyrinato iron (III)] in experimental models of
adult and infant intestinal I/R; and to characterise the inflammatory process in
human NEC, evaluating its relationship with clinical outcome.
In an adult rat model, total-body moderate hypothermia applied throughout
ischaemia and reperfusion counteracts oxidative stress in both the intestine and
distant organs. This suggests that hypothermia could be beneficial as a preventative
measure when intestinal ischaemia can be foreseen. However, in clinical practice
therapy can usually be commenced only after ischaemia has occurred. In two sets
of experiments, I showed that rescue hypothermia applied after mesenteric
ischaemia improves outcome in both adult and neonatal rats, and this benefit is
maintained after rewarming. Hypothermic protection could result from prevention
of multiple organ dysfunction through several different pathways, including
modulation of hepatic phosphoenergetics, pulmonary inflammatory infiltrate,
cardiac energy metabolism, and systemic oxidative stress.
Administration of peroxynitrite decomposition catalyst FeTMPyP as a rescue
therapy at reperfusion also exerts a protective effect in neonatal rats, possibly via
inhibition of adhesion molecule expression, leukocyte recruitment, and lipid
peroxidation in the intestine, leading to prevention of systemic oxidative stress.
In a study conducted on human specimens from neonates with NEC, tissue
injury seems to be mediated via increased expression of endothelial adhesion
molecules ICAM-1 and P-Selectin, leading to macrophage and neutrophil
infiltration. Endothelial E-Selectin is expressed exclusively in NEC patients, and
appears to be a marker of rapidly evolving disease and distant organ failure.
The diagnosis of acute appendicitis remains a critical challenge for paediatric surgeons. White Blood Cell (WBC) count, once considered a basic exam, is still routinely performed in most institutions, despite its lack of accuracy. Aim of this study is to assess the additional value of WBC count in the diagnosis of acute appendicitis.We retrospectively reviewed the charts of children who underwent appendectomy for acute appendicitis in the last two years at our institution. In the patients treated in 1999 (Group A), WBC count was assessed routinely after admission. The surgeons relied on leukocytosis as well as on clinical findings and on ultrasound abdominal scan for the diagnosis of acute appendicitis. In the patients treated in 2000 (Group B), blood cell count was not tested or deliberately ignored by the surgeons.There were 65 children in Group A and 70 in Group B; the two groups of patients were similar in terms of gender (p = 0.989) and age (p = 0.758). Criteria for operation were similar in the two groups (p = 0.222). No differences were found in the number of perforated (p = 0.989) and normal (p = 0.217) appendixes in the two groups as well as in the duration of hospital stay after surgery (p = 0.849).WBC count at admission has no proven additional value in the diagnosis of acute appendicitis and can be omitted without modifying diagnostic pathway and without affecting diagnostic accuracy.
CPT I (outer membrane carnitine palmitoyltransferase I) is a crucial enzyme in myocardial substrate selection. Two isoforms exist in the heart, the liver (L-) and muscle (M-) isoforms, which have different kinetic characteristics and alter in relative amounts during the neonatal/weaning/adult transition. CPT I is a point for control and regulation of fatty acid oxidation via modulation of its activity by malonyl-CoA, the concentration of which is set by acetyl-CoA carboxylase, AMP-activated protein kinase and malonyl-CoA decarboxylase in response to, for example, alterations in glucose supply. Systemic inflammatory responses and sepsis lead to myocardial dysfunction as part of multiple system organ failure. We have shown that: (i) myocardial CPT I activity is inhibited during neonatal sepsis; (ii) on the basis of inhibitor studies this inhibition appears to be of M-CPT I rather than L-CPT I; (iii) nitration of M-CPT I occurs, probably by peroxynitrite, and this may be responsible for the decrease in CPT I activity; (iv) myocardial CPT I activity is also inhibited in another model of systemic inflammatory response, namely intestinal ischaemia/reperfusion injury, but this can prevented by whole-body moderate hypothermia. Inhibition of M-CPT I would be predicted to alter myocardial substrate selection but there are several questions that remain to be answered.
Urokinase is an enzyme with a fibrinolytic effect that facilitates pleural empyema drainage through a chest tube. The aim of this study was to assess the risk of pneumothorax, the need for pleural debridement surgery, the persistence of fever, and the number of days in hospital in a group of children with parapneumonic pleural empyema treated with urokinase. This was an uncontrolled retrospective study on children suffering from parapneumonic empyema. Data collected on 17 children treated with urokinase were compared with 11 children treated prior to the advent of urokinase (the "historic" group). The urokinase was instilled in the pleural cavity over a period ranging from 2-8 days, amounting to a median total dose per kilogram of body weight of 18,556 IU (range, 7,105-40,299). Surgical treatment of the empyema involved drainage tube placement and/or debridement of the pleural cavity. Three children developed pneumothorax during their hospital stay, and one more case occurred 6 months after the child had recovered from his empyema; there were 3 cases of pneumothorax during the acute phase in the "historic" group (P = 0.54). Five children in the urokinase group were debrided and 12 were only drained, as opposed to 9 and 2, respectively, in the "historic" group (P = 0.02). The overall hospital stay was 17 days for the urokinase group, and 24 for the "historic" group (P = 0.02). No bleeding or other major complications were reported in the group treated with urokinase. In conclusion, urokinase treatment does not carry a risk of pneumothorax, while it does reduce hospital stay and the need for pleural debridement.
Pelvic fractures constitute between 0.3% and 4% of all paediatric injuries, with a mortality rate up to 25%. This study aims to review the experience with pelvic fractures at Starship Children's Hospital and demonstrate its role as a marker of severe trauma.A retrospective review of children with pelvic fractures managed at our institution in the 20-year period between July 1995 and May 2015 was performed. The search identified 179 consecutive children admitted with a pelvic fracture. Data fields collected included patient details, mechanisms of injury, investigations performed, length of hospital stay, management and complications. Data was also collected on Injury Severity Score (ISS), Glasgow coma scale (GCS), transfusion requirements and details of associated injuries (both orthopaedic and non-orthopaedic).Median age was eight years (IQR 5-12 years) with 65% boys. The median Injury Severity Score (ISS) was 9 (IQR 4-22). Pedestrian-motor vehicle injuries were most common at 46% of cases, followed by passengers injured in motor vehicle accidents accounting for 23% (n=41). Associated injuries were present in 68% (n=122) of patients, with other orthopaedic fractures (42%, n=75) and thoracic injuries (33%, n=59) most common. Management of pelvic fractures was primarily non-operative, with only 7% (n=13) requiring operative intervention. In comparison, operative procedures for associated injuries were much more common and were required in 38% (n=68) of cases.Pelvic fractures represent an important marker for severe trauma. Patterns of paediatric pelvic fractures reported by other studies around the world are very similar. Understanding the patterns in which pelvic fractures and their associated injuries occur and the outcome of treatment is fundamental to the establishment of effective preventative, diagnostic and therapeutic interventions.
INTRODUCTION Thoracoscopy is an important option in the treatment of many thoracic pathologies; its use in children, however, is still limited. We have retrospectively evaluated the thoracoscopic activity in our pediatric surgery department in the last six years. METHODS AND PROCEDURES Video-Assisted Thoracoscopy (VATS) has been routinely adopted in our institutions since 1997. The data of 115 patients who have undergone VATS were reviewed and analysed. RESULTS There were 47 males and 68 females. Mean age at surgery was 66.08 (SD: 58.23) months. Mean body weight at surgery was 21.85 (SD: 16.26) Kg. The patients were divided in four groups according to the pathologies: Patent Ductus Arteriosus (PDA) (n = 95), Pleural Empyema (n = 14), Mediastinal Mass (n = 3) and Lung Disease (n = 3). Complicances were seen in two patients in the PDA group (one laryngeal nerve paralysis and one chylothorax) and one in the pleural empyema group (post-operative bleeding which required blood transfusion). CONCLUSIONS VATS can be performed safely and with minimal morbidity. In our experience, early and late complications turned out to be quite low. This survey would support on-going development of thoracoscopy in children.
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