Conservative management of azygous vein rupture in blunt thoracic trauma.

We report a case of successful conservative management of acute traumatic rupture of the azygous vein. A 48-year-old male was involved in a motor vehicle collision. Primary survey revealed acute right intrathoracic haemorrhage. He remained haemodynamically stable with rapid infusion of warmed crystalloid solution and blood. Computed tomographic imaging showed a contained haematoma of the azygous vein. The patient was managed conservatively in the intensive care. Azygous vein laceration resulting from blunt thoracic trauma is a rare condition that carries a universally poor prognosis unless the appropriate treatment is instituted. Clinical features include acute hypovolaemic shock, widened mediastinum on chest radiograph, and a right-sided haemothorax. Haemodynamic collapse necessitates immediate resuscitative thoracotomy. Interest in this injury stems from the severity of the clinical condition, difficulty in diagnosis, the onset of a rapidly deteriorating clinical course all of which can be promptly reversed by timely and appropriate treatment. Although it is a rare cause of intramediastinal haemorrhage, it is proposed that a ruptured azygous vein should be considered in every trauma case causing a right-sided haemothorax or widened mediastinum. All cases described in the literature to date involved operative management. We present a case of successful conservative management of this condition.

Should cardiac surgery be delayed among carriers of methicillin-resistant Staphylococcus aureus to reduce methicillin-resistant Staphylococcus aureus-related morbidity by preoperative decolonisation?

OBJECTIVES: Preoperative methicillin-resistant Staphylococcus aureus (MRSA) carriage is associated with higher rates of postoperative MRSA infection. Carriage can be eradicated but this requires delaying surgery, which presents a dilemma when the surgery is urgent. We analysed the incidence of preoperative MRSA carriage and the impact on postoperative outcomes in a cardiac surgery population. PATIENTS AND METHODS: Patient data were collected prospectively from 2000 to 2007 (n=3789). MRSA screening is performed at a preadmission clinic for elective patients and on admission to the hospital for all patients. Three groups of MRSA carriers were identified: patients who were identified as carriers at a preadmission clinic (n=22, group 1), patients whose admission screening was positive but where the result was received postoperatively (n=103, group 2) and patients who acquired an MRSA infection or colonisation more than 48 h after admission (n=60, group 3). RESULTS: MRSA eradication measures prior to admission were successful in 21 of 22 in group 1 (95.4%). There were no MRSA infections in group 1. However, in group 2 there were 11 patients with an MRSA infection (10%) even though eradication measures were started on confirmation of carriage. In group 3, 19 of the 60 patients had an MRSA infection. The intensive care stay and mortality were significantly greater in groups 2 and 3 than in group 1 or compared with the overall patient population. However, groups 2 and 3 also had a significantly higher risk profile (European System for Cardiac Operative Risk Evaluation (EuroSCORE)). When matched with similar risk patients, patients in groups 2 and 3 had mortality outcomes that were consistent with matched risk patients. CONCLUSION: Patients who were MRSA carriers were older, more likely to have been on haemodialysis and to have been admitted from another hospital and underwent more complex surgical procedures. Carriage of MRSA was associated with a very high rate of MRSA infection, particularly among patients with diabetes. This suggests that delaying surgery may be warranted in patients expected to require implantation of prosthetic material such as valves, especially with diabetes. However, the survival outcomes for MRSA carriers are determined by their EuroSCORE rather than their MRSA status. This suggests that urgent cardiac surgery should not be delayed in patients with MRSA carriage.

Regulation of EP receptors in non-small cell lung cancer by epigenetic modifications.

BACKGROUND: Cyclooxygenase (COX)-2 is frequently overexpressed in non-small cell lung cancer (NSCLC) and results in increased levels of prostaglandin E2 (PGE(2)), an important signalling molecule implicated in tumourigenesis. PGE(2) exerts its effects through the E prostanoid (EP) receptors (EPs1-4). METHODS: The expression and epigenetic regulation of the EPs were evaluated in a series of resected fresh frozen NSCLC tumours and cell lines. RESULTS: EP expression was dysregulated in NSCLC being up and downregulated compared to matched control samples. For EPs1, 3 and 4 no discernible pattern emerged. EP2 mRNA however was frequently downregulated, with low levels being observed in 13/20 samples as compared to upregulation in 5/20 samples examined. In NSCLC cell lines DNA CpG methylation was found to be important for the regulation of EP3 expression, the demethylating agent decitabine upregulating expression. Histone acetylation was also found to be a critical regulator of EP expression, with the histone deacteylase inhibitors trichostatin A, phenylbutyrate and suberoylanilide hydroxamic acid inducing increased expression of EPs2-4. Direct chromatin remodelling was demonstrated at the promoters for EPs2-4. CONCLUSIONS: These results indicate that EP expression is variably altered from tumour to tumour in NSCLC. EP2 expression appears to be predominantly downregulated and may have an important role in the pathogenesis of the disease. Epigenetic regulation of the EPs may be central to the precise role COX-2 may play in the evolution of individual tumours.

Comparative analysis and outcomes of sleeve resection versus pneumonectomy.

To compare the outcome of sleeve resection or complex sleeve resection versus (Vs) pneumonectomy for lung cancer in a single unit. Between 1998 and 2006, 664 lung resections were carried out. There were 129 (19.4%) pneumonectomies and 79 (11.9%) sleeve resections; Twenty one patients (26.5%) underwent a complex sleeve resection. Operative mortality for the sleeve resections (SR) was 2.5% and for the pneumonectomies 8.53%. Overall 5-year survival after SR was 46.8% and after pneumonectomy 37.1%. The survival curves for the 2 procedures after adjusting for risk factors are different. The area under the curve is higher for the SR (Hazard ratio 1.78 C.I.: 0.92-3.46). The 5-year survival for early stages favors SR. The survival for the complex SR was not influenced by the complexity of the procedure but from the TNM stage of each individual case. Multivariate analysis of risk factors affecting survival after surgery showed: male sex Hazard ratio (HR) 1.19, 0.63-2.27(95%CI), Age >63 1.38(HR), 0.78-2.48, Pneumonectomy 1.78(HR), 0.92-3.46 and stage III 4.44(HR), 1.94-10.16(95% CI). For comparative stages survival appears to be better after sleeves, moreover male sex, sleeve resection, age younger that 63 and early TNM stage are positive predictors for survival.

Transcriptional regulation of IRS5/DOK4 expression in non-small-cell lung cancer cells.

The insulin-receptor substrate family plays important roles in cellular growth, signaling, and survival. Two new members of this family have recently been isolated: IRS5/Dok4 and IRS6/Dok5. This study examines the expression of IRS5/DOK4 in a panel of lung cancer cell lines and tumor specimens. The results demonstrate that expression of IRS5/DOK4 is frequently altered with both elevated and decreased expression in non-small-cell lung cancer (NSCLC) tumor specimens. The altered expression of IRS5/DOK4 observed in tumor samples is not due to aberrant methylation. In vitro cell culture studies demonstrate that treatment of NSCLC cell lines with the histone deacetylase inhibitor trichostatin A (TSA) upregulates IRS5/DOK4. This finding indicates that expression is regulated epigenetically at the level of chromatin remodeling. Chromatin immunoprecipitation experiments confirm that the IRS5/DOK4 promoter has enhanced histone hyperacetylation following treatments with TSA. Finally, hypoxia was demonstrated to downregulate IRS5/DOK4 expression. This expression was restored by TSA. The clinical relevance of altered IRS5/DOK4 expression in NSCLC requires further evaluation.

DOK4/IRS-5 expression is altered in clear cell renal cell carcinoma.

The insulin-receptor substrate family plays important roles in cellular growth, signaling, and survival. We have previously shown the dysregulation of the IGF-axis in clear cell renal cell carcinoma. In this manuscript, we examine the expression of the insulin receptor substrate family in clear cell RCC, and demonstrate that the expression of 2 members of this family are significantly altered in tumors. The most striking finding is that expression of the new IRS family member IRS-5 is significantly upregulated in 90% of examined clear cell RCCs. Studies on this gene has shown that it is regulated through chromatin remodeling in kidney cells.