O. Piazza

Antithrombin Reduces Ischemic Volume, Ameliorates Neurologic Deficits, and Prolongs Animal Survival in Both Transient and Permanent Focal Ischemia

Background and Purpose— Antithrombin (AT), a glycoprotein belonging to the serpin family, blocks thrombin formation and activity at several steps. Thrombin, beside its relevant role in the coagulation cascade, exerts neurodetrimental effects through the activation of a family of protease-activated receptors, which can be implicated in stroke pathophysiology. The aims of the present study were to evaluate whether AT could reduce brain damage, ameliorate neurologic deficits, and prolong animal survival. Methods— Two different doses of AT (10 and 30 IU/kg IP) were administered 3 hours, 6 hours, or 3 and 6 hours after an ischemic insult to mice and rats subjected to either transient or permanent focal ischemia. Ischemic volume was evaluated 24 hours or 7 days after the ischemic insult. Neurologic deficits were also scored. Results— In mice, 10 or 30 IU/kg AT administered twice, at 3 and 6 hours after transient ischemia, and 30 IU/kg AT administered 3 hours only after transient ischemia substantially reduced total ischemic volume, significantly improved neurologic deficits evaluated 24 hours after the insult, and prolonged animal survival. In rats, the same doses given at the same time intervals significantly reduced ischemic volume, evaluated 24 hours after permanent ischemia. Conclusions— These results indicate that AT remarkably reduces infarct volume, ameliorates neurologic deficit scores, and prolongs animal survival in 2 rodent models of brain ischemia. Taken together, our data suggest that AT, delivered via systemic administration, an easily achievable route of administration and in a clinically useful time window, could represent a new therapeutic strategy to be validated for the clinical treatment of human stroke.

Toll-like receptor kinetics in septic shock patients: a preliminary study.

The aim of this study is to evaluate some inflammatory parameter changes in septic shock patients and their possible correlation with clinical outcome, in particular when continuous veno-venous hemofiltration (CVVH) treatment is required. Considering the objective difficulty in enrolling this kind of patient, a preliminary study was initiated on seventeen septic shock patients admitted to a medical and surgical ICU. The mRNA expression of Toll-like receptor (TLR)-1, TLR-2, TLR-4, TLR-5, TLR-9, TNFα, IL-8 and IL-1β was assessed, the plasmatic concentrations of IL-18, IL-2, IL-10 and TNFα were measured on the day of sepsis diagnosis and after 72 h. In those patients who developed acute renal failure unresponsive to medical treatment and who underwent CVVH treatment the same parameters were measured every 24 h during CVVH and after completion of the treatment. On sepsis diagnosis, gene expression of TLRs was up-regulated compared to the housekeeping gene in all the patients. After 72 h, in 35% of the patients a down-regulation of these genes was found compared to day 1, but it was not associated with a reduction of cytokine serum levels or improved clinical signs, better outcome or reduced mortality. After high volume hemofiltration treatment, cytokine serum levels and TLR expression were not significantly modified. In conclusion, considering the not numerous number of cases, from our preliminary study, we cannot certainly correlate TLR over-expression in septic shock patients with severity or outcome scores.

Typing of vancomycin-resistant Enterococcus faecium strains in a cohort of patients in an Italian intensive care Unit.

Background:Vancomycin-resistant enterococci (VRE) have become a major cause of nosocomial infections. The increase of vancomycin-resistant Enterococcus faecium (VR-Efm) in an intensive care unit (ICU) of an Italian university hospital from 2003 through 2004, led us to evaluate the phenotypic and genetic features of these strains. The prevalence of different bacterial species in this ICU is described. The antibiotic resistance profiles of VR-Efm strains, their van-genotype and pulsed-field gel electrophoresis (PFGE) profiles were also analyzed.Materials and Methods:From January 2003 to December 2004, VR-Efm strains were collected from several biological samples. Bacteria were identified using standard biochemical reactions and automated systems. Antibiotic susceptibility was evaluated by disk diffusion and microdilution methods. Resistance to glycopeptides was confirmed by the E test. Vancomycin-resistant genotypes (vanA, vanB) were identified by PCR. Strains were typed by PFGE.Results:Fifty E. faecium strains were isolated from a total of 700 patients. Of these, 26 were vancomycin-resistant and were isolated from 26 different patients. We also found one strain with resistance to linezolid. The vanA genotype was identified in 20/26 strains and vanB in the remaining strains. A major pulsed-field cluster (“A”) was identified. In this cluster, 14 strains were identified (A1–A14) and 25 out of 26 VR-Efm belonged to it. Only one strain showed a different pattern (strain type “B”). All isolates with the vanA genotype belonged to cluster “A”, therefore five out of six isolates with the vanB genotype belonged to cluster A. The only strain with type B pattern was the vanB genotype.Conclusions:Isolation of VR-Efm was very frequent (52%) in our cohort of patients and the vanA genotype was the most frequent (77%). We found 25 out of 26 VR-E. faecium strains to be epidemiologically related by PFGE (cluster A). Strains with distinct genotypes shared closely related PFGE profiles. The occurrence of one major cluster among patients of a single unit indicated intra-facility VRE transmission.

S100B Induces the Release of Pro-Inflammatory Cytokines in Alveolar Type I-like Cells

S100B, a 21kDa cytosolic calcium-binding protein of the EF-hand type, present in high abundance in the brain, stimulates inflammatory responses in different cellular types inside and outside the central nervous system. Most of extracellular S100B effects are mediated by Receptor for Advanced Glycation End-products (RAGE). RAGE is highly expressed in lung by Alveolar Type-I (AT-I) cells and its activation contributes to ALI/ARDS pathogenesis. In this in-vitro study, we tested the hypothesis that S100B (0.002μg/L, 0.02μg/L, 0.5μg/L, 5μg/L) stimulates an ATI-derived cell line (R3/1) to secrete inflammatory mediators involved in lung inflammation. Our main result is that S100B stimulates R3/1 cells to secrete TNF-alpha and IL-6 (well-known pro-inflammatory cytokines in lung inflammation and neurogenic pulmonary edema), but not sICAM-1, CINC-1 or CINC-3. Soluble RAGE (sRAGE) reduced SlOOB-dependent secretion of TNF-alpha but did not decrease S100B-dependent secretion of IL-6. Moreover, in absence of S100B, sRAGE enhanced IL-6 release. This study demonstrates that in vitro S100B dose-dependently stimulated R3/1 cells, to enhance the secretion of TNF-alpha and IL-6; S100B pro-inflammatory activity might be mediated at least in part by RAGE. Besides acting as decoy receptor, sRAGE could have pro-inflammatory properties.

Guidelines and the medical “art”

Over the last decade a large number of guidelines have been published. For example, a number of European countries have had National Guidelines for the management of cardiac patients undergoing non-cardiac surgery for many years. In 2007, the American College of Cardiology/ American Heart Association (ACC/ AHA) published comprehensive guidelines on this subject [1]. This was followed in 2010 with the publication of European guidelines (with the sensible absence of any recommendation on the use of volatile anaesthetics) [2]. Which begs the question of whether it was really necessary to offer yet another large document, or would a shorter, more straightforward document have been enough? It has been pointed out that the translation of research into clinical practice is a difficult process due to the vast amount of information published daily, which may actually hinder the dissemination of new knowledge. The abundance of information to be digested by clinicians has brought about a flourishing trade in summaries of the best evidence. Such summaries have often been targeted even by guidelines, decreasing the value of the recommendations contained therein. On the other hand, guidelines have increased their objectives and have become basic tools used by institutions at various administrative levels (e.g., State, regional, and health service) to better allocate resources and optimize treatment. As in other European Countries, the Italian Government has implemented a National Plan (http://www.pnlg.it) that discourages the development of ‘‘niche’’ guidelines and encourages a multidisciplinary approach. The Italian Society of Anesthesia and Intensive Care (SIAARTI) and the Italian Society of Surgery in conjunction with the Italian Health Care Ministry have developed guidelines for antibiotic prophylaxis [3]. These guidelines appear to meet the criteria which elicit the need for a National Guideline: epidemiological criteria (probably the most objective), model of availability of efficacious evidence, and economical criteria. The purpose is noble, but will the effect be good? Last but not least: what do doctors think of guidelines? In many European countries, very few guidelines have been easily translated into clinical practice, and adherence remains suboptimal in too many cases [4, 5]. There are two critical points: the clinician’s perception of the utility and risks of the guidelines and the capacity/capability of the medical care system to implement the recommendations in the document. With respect to the first point, in Europe, guidelines have an ambiguous medical–legal importance. Even if guidelines are based on strong evidence and proof of efficacy, application is not compulsory, although they can assume a normative role in legal debates. In terms of the second point, we draw attention to the following example. The SIAARTI has licensed recommendations on end-of-life care [6]. This topic, which has also been wrestled with in other countries [7–9], is a complex issue in Italy [10–12]. A recent survey on the implementation of the Italian recommendations revealed that even if 84% of the interviewed agreed with the recommendations suggested in the guidelines, more than 50% had problems with implementing them (submitted data). Plato, in ‘‘Politics’’, hypothesized an experiment in which all doctors, with no autonomy, would transform the point of view of the majority into law. However, the same Plato stressed that a codified assistance would lose efficacy because the rules, based on a ‘‘Platonic’’ patient, do not adapt well to a singular patient. If this is what is wanted with current so-called guidelines, ‘‘then it is clear that all the arts would be ruined’’. No one can say if guidelines will cure medicine. They are useful, but we should be alert in not transforming them into a control tool.

Luxatio cordis due to right pericardium tear, a difficult diagnosis: report of a case

AbstractBackground. Dislocation of the heart is a rare complication of thoracic blunt trauma. A high index of suspicion of pericardium rupture is necessary to formulate an early diagnosis to reduce morbidity and mortality. Patients. A 23-year-old man suffered a blunt thoracoabdominal trauma and was admitted 3 days later to a university hospital ICU for right heart luxation due to right pericardial tear. Mechanical ventilation delayed radiological findings. Methods and results. Surgery by repositioning the heart and repairing the pericardial tear allowed restoration of hemodynamic equilibrium.

Warning! Fire in the ICU

At 5:30 pm on December 17, 2010, shortly after a power failure, smoke filled the Intensive Care Unit (ICU) of Federico II University Hospital in Naples, Italy, triggering the hospital emergency alarm system. Immediately, staff began emergency procedures and alerted rescue teams. All patients were transferred without harm. The smoke caused pharyngeal and conjunctival irritation in some staff members. After a brief investigation, firefighters discovered the cause of the fire was a failure of the Uninterruptible Power Supply (UPS).

Removal of inflammatory cytokines with high volume hemofiltration: 12AP3-4

Anesthesia and Intensive Care, Università Degli Studi di Napoli Federico II, Napoli, Italy Background and Goal of the Study: The removal of inflammatory mediators in septic patients treated by high volume hemofiltration might depend by the adsorption of the membrane (1) and by the filtration rate (2). The aim of this study was to evaluate the efficiency of high volume continuous veno-venous hemofiltration (CVVH), with a 12Kd cut-off filter, in removing pro-inflammatory and anti-inflammatory cytokines from the blood compartment of severe sepsis patients. Materials and Methods: We enrolled 31 severe sepsis patients. 6 out of 31 developed ARF and required CVVH (filtration rate of 40 ml/kg/h). Cytokines serum levels were measured at the beginning and after 48 hours of the CVVH treatment. Pre-filter, post-filter venous blood and filtrate samples were collected. Cytokines (IL-2, IL-18, IL-10 and TNF) serum levels were quantified by ELISA. Results: In septic patients not treated by CVVH, at day 1 median cytokines levels (pg/mL) were: IL-18 (1028,9), IL-2 (18,86), TNF(17,92), IL-10 (185,7). Cytokine concentrations (pg/mL) in patients treated by CVVH are expressed, as median, in the table below: