Intraventricular versus intravenous colistin for the treatment of extensively drug resistant Acinetobacter baumannii meningitis.

BACKGROUND AND PURPOSE: Reports on the safety and efficacy of intraventricularly administered (IVT) colistin for the treatment of Acinetobacter baumannii ventriculomeningitis in adults are limited and no comparative studies of IVT colistin versus intravenous (IV) therapy alone have been published. This study compared outcomes of patients with postneurosurgical ventriculomeningitis caused by extensively drug-resistant A. baumannii treated with IV colistin or IV plus IVT colistin. METHODS: In an 11-year period, information on 18 consecutive patients with extensively drug-resistant A. baumannii ventriculomeningitis was collected. Infection was defined on the basis of (i) isolation of A. baumannii from the cerebrospinal fluid (CSF); (ii) laboratory evidence of CSF infection; (iii) signs/symptoms of central nervous system (CNS) infection. Patients were divided into group 1 (nine patients, IV colistin alone) and group 2 (nine patients, IV plus IVT colistin). RESULTS: Cerebrospinal fluid sterilization was documented for 12 of 18 patients (66.6%). The CSF sterilization rate was 33.3% in group 1 and 100% in group 2 (P = 0.009). The mean time to CSF sterilization was 21 days (range 8-48). Five patients died due to A. baumannii CNS infection (all in group 1), and five deaths were unrelated to A. baumannii ventriculomeningitis. Intensive care unit mean length of stay was shorter in group 2 (20.7 vs. 41.6 days, P = 0.046). Crude relative risk ratio of cumulative incidence of persistent CNS infection in group 1 versus group 2 was 13. No cases of chemical meningitis due to intrathecal colistin administration were encountered. CONCLUSIONS: Intraventricular colistin administration is much more effective than IV therapy alone and does not seem to add further toxicity.

An experimental study on minimally occlusive laser-assisted vascular anastomosis in bypass surgery: the importance of temperature monitoring during laser welding procedures.

Laser welding has been proposed as an alternative technique to conventional stitching in microvascular anastomosis, with the advantages of improving the vascular healing process and reducing the risk of malfunction of a bypass. Our group recently proposed a laser-assisted end-to-side anastomotic technique, providing the advantages of laser welding and reducing the occlusion time of the recipient vessel, that is important in neurosurgical bypass procedures, in order to reduce the risk of cerebral ischemia. This in vivo study focuses on the control of the temperature dynamics developing in the welded tissue. A jugular vein graft was harvested and implanted on the rabbit carotid artery by means of two end-to-side anastomosis. Laser welding procedure was then carried out to implant the bypass. A real-time monitoring of the temperature during welding was performed with an infrared thermocamera, in order to control the laser-induced heating effect on the external surface of the vessel walls. The temperature analysis highlighted the dynamic of the heating effect in space and time and enabled us to define an optimal temperature range in operative conditions. The temperature control provided safe tissue heating confined within the directly irradiated area, with negligible damage to surrounding tissues, as well as effective sealing and welding of the vessel edges at the anastomotic sites. The average occlusion time of the carotid artery was about 11 minutes. After a follow-up of 30 days, all the bypasses were patent and no signs of thrombosis or leak point pressure were present, thus confirming the safety of this laser-assisted anastomotic procedure.

Comparative evaluation of genome-wide gene expression profiles in ruptured and unruptured human intracranial aneurysms.

Few studies have evaluated the over or the underexpression of genes directly in samples of aneurysmal wall and extracranial pericranial vascular tissue to investigate the genetic influence in formation and rupture of intracranial aneurysms. We present the results obtained using the DNA microarray technique analysis on sample tissues collected during surgery. We collected and analyzed 12 aneurismal and 9 peripheral arteries (superficial temporal (STA) and middle meningeal artery (MMA) specimens from ruptured aneurysm group patients (13 cases), 10 aneurismal and 12 STA and MMA samples from unruptured aneurysm group patients (14 cases) and 5 STA and MMA artery specimens from control group patients (4 cases). Total RNA was isolated from samples and subjected to cDNA microarray analysis with the use of the human genome U133A GeneChip oligonucleotide microarray (Affymetrix, Santa Clara, CA), which allows to analyze a total number of 14,500 genes in the same time. For genes of interest, real-time RT-PCR was performed to confirm their expression level. Total RNA was isolated from samples and subjected to DNA microarray analysis with the use of the human genome U133A GeneChip oligonucleotide microarray, which allows to analyze a total number of 14,500 genes at the same time. For genes of interest, real-time RT-PCR was performed to confirm their expression level. Regarding ruptured aneurysms, genes were identified showing differential expressions (overexpressed or downregulated) pertaining to specific pathways, particularly those for the structural proteins of the extracellular matrix, members of matrix metalloproteinase (MMP) family (which resulted as being overexpressed) and genes involved in apoptotic phenomena. Particularly, real-time RT-PCR analysis confirmed the upregulation of MMP-2, MMP-9 and pro-apoptotic genes, such as Fas, Bax and Bid, and the downregulation of anti-apoptotic genes, such as Bcl-X(L) and Bcl-2. In a compared analyses of ruptured vs unruptured aneurysms, a different expression was also detected regarding gene coding the tissue inhibitor of matrix metalloproteinases 3 (TIMP-3), which appeared markedly downregulated in unruptured aneurysms, where its expression in unruptured aneurysms was similar to that observed in controls. Another gene differently expressed is nitric oxide synthase (iNOS), which appeared overexpressed in ruptured aneurysms when compared to unruptured aneurysms. Our study is the first, to our knowledge, that compares gene expression profiles (genoma-wide) in intracranial aneurysms. The results of our study suggest that the inhibitor of the metalloproteinase, the pathway of nitric oxide and the apoptotic process play a key-role in reducing the resistance of the arterial wall, that can result in formation and rupture of the intracranial aneurysms.