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Transmission of infection via transplantation of allografts including solid organs, eyes, and tissues are uncommon but potentially life-threatening events. Donor-derived infections have been documented following organ, tissue, and ocular transplants. Each year, more than 70 000 organs, 100 000 corneas, and 2 million human tissue allografts are implanted worldwide. Single donors may provide allografts for >100 organ and tissue recipients; each allograft carries some, largely unquantifiable, risk of disease transmission. Protocols for screening of organ or tissue donors for infectious risk are nonuniform, varying with the type of allograft, national standards, and availability of screening assays. In the absence of routine, active surveillance, coupled with the common failure to recognize or report transmission events, few data are available on the incidence of allograft-associated disease transmission. Research is needed to define the optimal screening assays and the transmissibility of infection with allografts. Approaches are reviewed that may contribute to safety in allograft transplantation.

Glycopeptides have been considered the antimicrobials of choice for serious meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-resistant coagulase-negative staphylococci (MR-CoNS) infections for several years. Daptomycin is a new option for the treatment of these infections, including those exhibiting reduced susceptibility to glycopeptides. The aim of this study was to compare glycopeptides and daptomycin for the treatment of infections caused by MRSA or MR-CoNS. Data for 106 patients with bloodstream infections (bacteraemia or infective endocarditis) or skin and soft-tissue infections (SSTIs) were retrospectively reviewed, of which 43 were treated with daptomycin (DAP group) and 63 were treated with vancomycin or teicoplanin (GLYCO group). Patients included in the two comparison groups were homogeneous in terms of age, risk factors and clinical severity. Aetiology was mainly represented by MRSA in both groups, followed by various species of MR-CoNS. Daptomycin was used more frequently in patients with central venous catheter-associated bacteraemia or pacemaker-associated infection. Patients with SSTIs included in the GLYCO group had a longer mean duration of antibiotic therapy (18.2 days vs. 14.6 days; P=0.009) and a longer mean length of hospital stay (28.2 days vs. 19.6 days; P=0.01) compared with those included in the DAP group. A longer mean duration of antibiotic therapy was also observed in patients with bloodstream infections receiving glycopeptide therapy (25.6 days vs. 18 days; P=0.004). In conclusion, the good clinical efficacy of daptomycin is associated with a more rapid resolution of the clinical syndrome and a reduced length of hospitalisation. This latter aspect may have important pharmacoeconomic implications, promoting the use of daptomycin in the clinical setting.

Paolo A. Grossi, Alessandro Nanni Costa, Deirdre Fehily, Emily A. Blumberg, Matthew J. Kuehnert, Jay A. Fishman, Michael G. Ison, Roberta Lattes, Camille N. Kotton, Daniele Lilleri, Anne Kabanova, Antonio Lanzavecchia, Giuseppi Gerna, Raymund R. Razonable, Patrizia Comoli, Marco Zecca, Sabrina Basso, Fabrizio Ginevri, Alessandra Grossi, Francesco P. Schena, Antoni Rimola, Patrizia Burra, Elenora De Martin, Kryssia Isabel Rodriguez-Castro, Stefano Fagiuoli, Luisa Pasulo, Raffaele Bruno, Pietro Andreone, Elisabetta Loggi, Fabio Arena, Gian Maria Rossolini, Gabriele Sganga, and Valerio Cozza

The advent of combined antiretroviral therapy (cART) dramatically changed the view of human immunodeficiency virus (HIV) infection as an exclusion criterion for solid organ transplantation, resulting in worldwide reports of successful transplants in HIV-infected individuals. However, there are few reports on simultaneous pancreas-kidney transplant in HIV-positive recipients detailing poor outcomes. A series of four pancreas-kidney transplant performed on HIV-infected individuals between 2006 and 2009 is presented. All recipients reached stably undetectable HIV-RNA after transplantation. All patients experienced early posttransplant infections (median day 30, range 9-128) with urinary tract infections and bacteremia being most commonly observed. In all cases, surgical complications led to laparotomic revisions (median day 18, range 1-44); two patients underwent cholecystectomy. One steroid-responsive acute renal rejection (day 79) and one pancreatic graft failure (month 64) occurred. Frequent dose adjustments were required due to interference between cART and immunosuppressants. At a median follow-up of 45 months (range, 26-67) we observed 100% patient survival with CD4 cell count300 cells/mm(3) for all patients. Although limited by its small number, this case series represents the largest reported to date with encouraging long-term outcomes in HIV-positive pancreas-kidney transplant recipients.

Objective: The aim of the present study was to evaluate the virological response to a new antiretroviral treatment (ART2) after failure of a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs)-containing regimen. Design: Retrospective observational study based on the Italian ARCA cohort database. Adult patients were included if they had a virological failure (defined as plasma viral load above 500 copies/ml in two subsequent visits) while on a treatment with one NNRTI plus 2 NRTIs, had an available HIV genotype. Results: Patients on ART2 were followed up for 791 person/year and median follow up was 10.8 months(IQR 5.2-26). Variables associated with reduced risk of ART2 virological failure at univariable analysis had started the treatment in recent years (HR 0.90; 95% CI 0.86-0.94, p

BACKGROUND: The characteristics of patients with infective endocarditis (IE) vary significantly by region of the world. The aim of this study was to evaluate the contemporary epidemiology, characteristics, and outcome of IE in a large, nationwide cohort of Italian patients. METHODS: We conducted a prospective, observational study at 24 medical centers in Italy, including all the consecutive patients with a definite or possible diagnosis of IE (modified Duke criteria) admitted from January 2004 through December 2009. A number of clinical variables were collected through an electronic case report form and analyzed to comprehensively delineate the features of IE. We report the data on patients with definite IE. RESULTS: A total of 1,082 patients with definite IE were included. Of these, 753 (69.6%) patients had infection on a native valve, 277 (25.6%) on a prosthetic valve, and 52 (4.8%) on an implantable electronic device. Overall, community-acquired (69.2%) was more common than nosocomial (6.2%) or non-nosocomial (24.6%) health care-associated IE. Staphylococcus aureus was the most common pathogen (22.0%). In-hospital mortality was 15.1%. From the multivariate analysis, congestive heart failure (CHF), stroke, prosthetic valve infection, S. aureus, and health care-associated acquisition were independently associated with increased in-hospital mortality, while surgery was associated with decreased mortality. CONCLUSIONS: The current mortality of IE remains high, and is mainly due to its complications, such as CHF and stroke.

Infectious complications remain a significant cause of morbidity and mortality among solid organ transplant recipients. The recent development of powerful immunosuppressive agents such as tacrolimus, mycophenolate mofetil, rapamycin, and monoclonal antibodies has altered current regimens for the prevention and treatment of allograft rejection. The goals of modern immunosuppressive treatment are no longer limited to controlling episodes of rejection but also include the reduction in associated side effects and long-term complications. The impact of these newer regimens in terms of effects on host defense and susceptibility to opportunistic infections is matter of current investigation.

We report four cases of West Nile virus (WNV) transmission following a single multiorgan donation in north-eastern Italy. The transmissions were promptly detected by local transplant centres. The donor had been tested for WNV by nucleic acid amplification test (NAT) prior to transplantation and was negative. There were no detected errors in the nationally implemented WNV safety protocols.

Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of immunosuppression. We evaluated the risk of HHV8 transmission from liver donors, and its clinical impact in southern Italy, where its seroprevalence in the general population is reported to be as high as 18.3%. We tested 179 liver transplant recipients and their donors for HHV8 antibodies at the time of transplantation, and implemented in all recipients a 12-month posttransplant surveillance program for HHV8 infection. Of the 179 liver transplant recipients enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ donor's seroprevalence was 4.4%. Eight seronegative patients received a liver from a seropositive donor, and four of them developed primary HHV8 infection. Two of these patients had lethal nonmalignant illness with systemic involvement and multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral reactivation after liver transplantation. In addition, an HHV8 seronegative recipient of a seronegative donor developed primary HHV8 infection and multicentric Castleman's disease. In conclusion, primary HHV8 infection transmitted from a seropositive donor to a seronegative liver transplant recipient can cause a severe nonmalignant illness associated with high mortality. Donor screening for HHV8 should be considered in geographic areas with a high prevalence of such infection.

Background & Aims The main limitation of orthotopic liver transplantation (OLT) is the scarcity of available donor organs. A possibility to increase the organ pool is to use grafts from hepatitis B virus surface antigen (HBsAg) positive donors, but few data are currently available in this setting. We assessed the clinical, serovirological, and immunological outcomes of liver transplant from HBsAg positive donors in a single centre study. Methods From 2005 to 2009 10 patients underwent OLT from HBsAg positive donors, for HBV-related disease (n=6) or HBV-unrelated disease (n=4). The median follow-up was 42months (range 12–60). All recipients were HBcAb positive and were given antiviral prophylaxis. Results Patients transplanted for HBV-related disease never cleared HBsAg. Two HBsAg negative patients never tested positive for HBsAg, whereas the others experienced an HBsAg appearance, followed by spontaneous production of anti-HBs, allowing HBsAg clearance. No patient ever had any sign of HBV hepatitis. HBV replication was effectively controlled by antiviral therapy. The immunologic sub-study showed that a most robust anti-HBV specific T cell response was associated with the control of HBV infection. Conclusions OLT from HBsAg positive donors seems to be a safe procedure in the era of highly effective antiviral therapy.

The aim of this research was to study the consequences of ω3 fatty acids (FA) administration around calving on inflammatory response and on productive performances. In this period dairy cows undergo a metabolic challenge, coming with an inflammatory-like status triggering the release of pro-inflammatory mediators (e.g. eicosanoids, cytokines). Eicosanoids synthesis may be modulated by altering the ratio of their precursors (ω3 and ω6 FA). Ten cows received 22 g/d of rumen-protected ω3 FA from -21 to +21 days from calving (OPT), while 10 (CTR) received no supplement. Cows were frequently monitored for health status, body condition score (BCS), blood (metabolic, inflammatory and FA profiles), milk yield. OPT (vs CTR) showed a similar milk production, a numerically smaller BCS drop, lower postpartum levels of non-esterified fatty acids (P

Seven cases of Pneumocystis carinii pneumonia (PCP) (two in 1988, three in 1989, one in 1990 and one in 1991) have been observed in a group of 241 heart transplant recipients transplanted in Pavia, Italy, from November 1985 through December 1991. Median time to onset of symptoms was 100 days after transplantation (range 59-333 days). Diagnosis was achieved in all patients by cytological examination of bronchoalveolar lavage (BAL) fluid and/or transbronchial biopsy. Clinical and roentgenographic features were remarkably similar in all PCP-affected heart transplant recipients. A dry, persistent hacking cough associated with dyspnoea was consistently observed. Fever ranged from 37.6 to 39.4 degrees C, median leukocyte count and median arterial oxygen saturation (SaO2) values were 7,300/mm3 (range 3,000-16,000/mm3) and 61% (range 49.3-93%), respectively. Median CD4+ count at the onset of symptoms was 211/mm3 (range 28-739/mm3). The only patient experiencing a recurrence of PCP had a CD4+ cell count of 28/mm3 at the end of treatment with trimethoprim-sulfamethoxazole (TMP-SMX). In all patients human cytomegalovirus was isolated from BAL fluids; however, treatment with TMP-SMX alone (20 mg/kg/day of TMP) was consistently followed by a complete recovery.

Viral, bacterial, parasitic, prion and fungal infections havebeen transmitted via organ and tissue allografts (1). De-spite screening programs utilizing serologic testing and ona review of the potential donor’s medical records and be-havioral history, clusters of donor-derived infections in re-cipients persist although these are uncommon. Recent im-provements in the microbiologic screening of donors havereduced this risk. However, requirements for microbiologictesting of organ donors are nonuniform. Behavioral defini-tions of the ‘high-risk donor’ designed to reduce the riskfor HIV transmission are dated (1994) but, coupled withmicrobiologic screening, have resulted in a low incidenceof disease transmission through exclusion of donors withrecent intravenous drug use, incarceration and certain sex-ual contacts. However, the accuracy of exposure historymay be suspect. The availability of viral nucleic acid testing(NAT) has the capacity to reduce the risk of disease trans-mission by detecting early stages of many infections in-cluding those due to human immunodeficiency virus (HIV),hepatitis B virus (HBV) and hepatitis C virus (HCV) in the‘window’ period before antibody seroconversion develops(II-2).Despite the development of new policies and the use ofhighly sensitive assays, reports of the transmission of in-fection to organ transplantation recipients remain uncom-mon but occur with sufficient frequency to suggest thatcurrent approaches to screening of donors are inadequate.The role of geographically restricted microorganisms hasalso increased as a consequence of travel and migrationof populations. The commercialization of transplantationin some regions may also minimize the incentive to testand exclude potentially infected donors. Recent clusters oforgan-associated viral transmissions illustrate the vulnera-bility of immunosuppressed recipients to infections dueto organisms of limited native virulence for normal indi-viduals (2–4). Many potential exposures are too commonor too nonspecific to allow appropriate decision-makingregarding the risk of transmission. Furthermore, in someclusters of documented transmissions (e.g. due to lym-phocytic choriomeningitis, LCMV), no clear exposure orevidence of donor infection could be demonstrated evenin retrospective investigation (2).In contrast with solid organ screening, blood and tissuescreening policies have adopted more consistent labora-tory testing of donors for a wider array of pathogens withthe flexibility to introduce additional assays when indicatedby changing epidemiologic patterns. However, any strategyadopted for organ donors must be cost-effective, highlysensitive and specific and available at all times with rapidturn around times. The selection of the ‘list’ of pathogensfor screening of organ donors might be shaped by a seriesof specific questions: (1) Is the pathogen prevalence suffi-ciently high in the general population for the positive pre-dictive value of the screening test to be useful? (2) Is thereevidence that the pathogen can be transmitted by organtransplantation? (3) Does transmission result in significantmorbidityandmortality?and(4)Isthereareliableandlogis-tically applicable test available for screening? (II-3). For themajority of recent transmission events, including LCMV,other reported arenaviruses and rabies, the above criteriaare not fulfilled. Therefore while disease transmission byorgan transplantation may lead to serious morbidity andmortality, there are no currently available diagnostic testsfor these pathogens that could be readily applied to donorscreening. The inability to detect potential pathogens re-flects the low level of viremia in immunologically normaldonors compared with the rapid amplification of infectionin the immunosuppressed recipients. Thus, given the levelof viremia and the low frequency of these agents in thegeneral population, it is unlikely that a sufficiently rapid,sensitive and specific screening test could be developedand applied in the short term. Even for a pathogen such asWest Nile virus (WNV) for which disease outbreaks may be

The authors discuss the experience of another group with rapamycin as the principal immunosuppressive drug in HIV positive recipients of liver transplantation. We would suggest that control of HIV-RNA viremia in liver transplanted patients is still a matter of the choice of the best ART independently from the type of the antirejection treatment.

Background: Bacterial brain abscesses remain a serious central nervous system problem despite advances in neurosurgical, neuroimaging, and microbiological techniques and the availability of new antibiotics. The successful treatment of brain abscesses requires surgery, appropriate antibiotic therapy, and eradication of the primary source; nevertheless many controversial issues on the management of this serious infection remain unresolved. Controversial issues: The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group - a panel of multidisciplinary experts - was to define recommendations for some controversial issues using an evidence-based and analytical approach. The controversial issues were: (1) Which patients with bacterial brain abscesses can be managed safely using medical treatment alone? (1a) What is the efficacy in terms of outcome, tolerability, cost/efficacy, and quality of life of the different antibiotic regimens used to treat bacterial cerebral abscesses? (1b) Which antibiotics have the best pharmacokinetics and/or tissue penetration of brain and/or brain abscess? 2) What is the best surgical approach in terms of outcome in managing bacterial brain abscesses? Results are presented and discussed in detail. Methods: A systematic literature search using the MEDLINE database for the period 1988 to 2008 of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle-Ottawa Quality Assessment Scale for case-control studies, longitudinal cohorts, and retrospective studies. The GRADE method for grading quality of evidence and strength of recommendation was applied. © 2010 International Society for Infectious Diseases.

From November 1985 to December 1990, 2,552 endomyocardial biopsy specimens from 209 heart transplant patients were studied. Forty-four (21%) patients developed 45 episodes of major human cytomegalovirus infection (HCMV). Human cytomegalovirus infection was primary in 13 of 44 patients. Thirty-one patients developed episodes of recurrent major infection. One patient had both primary and recurrent infections. Conventional histopathologic and immunohistochemical study, in situ hybridization, and polymerase chain reaction were used to diagnose HCMV myocardial involvement on corresponding endomyocardial biopsy specimens performed during infection. Conventional morphologic study showed typical viral inclusion bodies in four biopsy specimens. Two cases had myocyte HCMV localization with necrotizing myocarditis, whereas two had endothelial cell involvement without any inflammatory reaction. In these four biopsy specimens, immunohistochemistry showed a higher number of infected cells than that recognized by conventional histopathologic study. In situ hybridization detected infected cells with no evidence of cytopathic effect. Polymerase chain reaction gave HCMV amplification products in two additional biopsy specimens otherwise interpreted as moderate and mild rejection, respectively. Therefore, 6 biopsies showed HCMV myocardial involvement (6 of 45; 13.3%): all were from patients with primary HCMV infection (6 of 13; 46%). None of 32 major recurrent infections showed any myocardial involvement. In conclusion, our study is the first to demonstrate that myocardial HCMV involvement preferentially occurs in primary infection and HCMV endothelial localization can be free from inflammatory reaction, whereas HCMV myocyte localization leads to necrotizing myocarditis. Polymerase chain reaction has a higher diagnostic sensitivity than in situ hybridization. However, polymerase chain reaction findings of HCMV DNA on otherwise negative endomyocardial biopsy specimens remains of questionable significance because polymerase chain reaction-positive biopsy samples do not necessarily indicate tissue infection. It is impossible to determine whether amplified sequences derive from circulating leukocytes or from tissue cells.

Prior to the advent of highly active antiretroviral therapy (HAART), HIV-infected patients were usually not considered as transplant candidates because of the poor prognosis of their underlying disease and concerns regarding the potential detrimental effects of immunosuppression on viral load and immune status. However, with the significant HAART-associated improvements in morbidity and mortality, good short-term outcomes after liver and kidney transplantation for patients with HIV infection have been reported. Nevertheless, HIV infection is currently considered a contraindication to lung transplantation in most transplant centers worldwide. The results of a double lung transplant performed in an HIV and HBV co-infected patient with cystic fibrosis (CF) and end-stage respiratory failure (ESRF) are presented after a 2-year follow-up. Approval of and recommendations for the management of this patient were obtained from the Italian National Center for Transplantation as an extension of the ongoing Italian protocol for liver and kidney transplantation in HIV-infected individuals. The operation was successful and the patient recovered rapidly after surgery. A cautious infectious and immunosuppressive management allowed so far the avoidance of major infectious complications and rejection. To the best of our knowledge, this is the first report of lung transplantation in an HIV and HBV co-infected patient.

Abs #032

Background: Concomitant hepatitis C virus infection (HCV) needs caution when selecting systemic treatments in psoriasis patients as some agents confer a risk of liver toxicity and/or are immunosuppressant. Phototherapy may provide a therapeutic choice but it is not always a practical option. Limited evidence supports the use of cyclosporine or TNF-α blockers. No data are available concerning the safety of efalizumab in patients with HCV infection. Objective: To describe the clinical characteristics and evolution of 5 adult patients with severe chronic plaque psoriasis and concomitant HCV infection who were treated with efalizumab. Method: A retrospective clinical case report. Results: Five adult patients with severe chronic plaque psoriasis and concomitant HCV infection were treated successfully using efalizumab with no increased viral replication and progression of liver disease for a follow-up of 8–20 months. Conclusion: Although further confirmation is needed, this report provides preliminary evidence to support also a cautious use of efalizumab in patients with HCV infection.

For the first time in Italy, two patients with meningoencephalitis were diagnosed with West Nile virus (WNV) infection in September 2008 [1]. The patients live in the Bologna and Ferrara provinces of Emilia Romagna where WNV infections had previously been noted in horses, crows and magpies [2]. The Italian National Transplant Centre (CNT), which is responsible for the procurement, processing and distribution of organs and tissues in Italy, has now reviewed the risks of transmission of WNV by organ, tissue and cell transplantation and, taking into account the advice and recommendations of the relevant authorities in other countries, issued guidance to the transplant community.

Thromboembolic complications in HIV-infected patients have been reported. To our knowledge, no case–control studies have compared the prevalence of thromboembolic events between HIV-positive and HIV-negative individuals. One hundred and sixty-nine HIV-infected patients and 180 randomly selected blood donors were enrolled. Selected patients completed a specific questionnaire and were subsequently interviewed. Information was collected on family and personal history of cardiovascular disorders and the presence of personal risk factors for venous and arterial thrombosis. All reported events were adjudicated only if adequate documentation of objective tests was available. Mean age and sex were similar in the two groups. A vascular event was documented in six HIV-infected patients (3.55%) and in none of the controls (P = 0.0108). Family history of cardiovascular disorders, cigarette smoking and hypertriglyceridemia were more prevalent in HIV patients than in controls. In multivariate analysis, neither family traditional cardiovascular risk factors nor HIV infection were independently associated with the presence of thromboembolic events. The results confirm the hypothesis that HIV-positive patients have an increased risk of thromboembolic disorders. Whether this increased risk has been provoked by HIV infection itself or by other associated risk factors for cardiovascular events, such as cigarette smoking and hypertriglyceridemia, remain to be clarified.

Limited access to scarce resources, such as organs for transplantation, has increasingly prompted the use of elderly donors, with a consequent growth of possible risk factors linked to their particular features. Acceptable organ quality must therefore be guaranteed, without exposing recipients to unacceptable risks. For this reason, a set of guidelines for assessing donor suitability has been drawn up. This document standardizes the operative steps in the donor evaluation process and provides precise instructions for center staff. A pool of experts is available round the clock to offer advice on doubtful clinical cases. Such measures have allowed more effective use of available donors for transplantation.

Delia Colombo,1 Sergio Chimenti,2 Paolo Antonio Grossi,3 Antonio Marchesoni,4 Federico Bardazzi,5 Fabio Ayala,6 Lucia Simoni,7 Donatella Vassellatti,1 Gilberto Bellia1 On behalf of SYNERGY Study Group 1Novartis Farma Italia, Origgio (VA), 2Tor Vergata Polyclinic Rome, 3Macchi Hospital and Foundation, Varese, 4Orthopaedic Institute Pini, Milan, 5S Orsola-Malpighi Polyclinic, Bologna, 6University Federico II Naples, 7MediData srl, Modena, Italy Background: Sex medicine studies have shown that there are sex differences with regard to disease characteristics in immune-mediated inflammatory diseases, including psoriasis, in immune response and susceptibility to viral infections. We performed a post hoc analysis of the Observational Study of infectious events in psoriasis complicated by active psoriatic arthritis (SYNERGY) study in patients with psoriatic arthritis (PsA) treated with immunosuppressive regimens including cyclosporine, in order to evaluate potential between-sex differences in severity of disease and prevalence of viral infections.Methods: SYNERGY was an observational study conducted in 24 Italian dermatology clinics, which included 238 consecutively enrolled patients with PsA, under treatment with immunosuppressant regimens including cyclosporin A. In this post hoc analysis, patients' demographical data and clinical characteristics of psoriasis, severity and activity of PsA, prevalence of seropositivity for at least one viral infection, and treatments administered for PsA and infections were compared between sexes.Results: A total of 225 patients were evaluated in this post hoc analysis, and 121 (54%) were males. Demographic characteristics and concomitant diseases were comparable between sexes. Statistically significant sex differences were observed at baseline in Psoriasis Area and Severity Index score (higher in males), mean number of painful joints, Bath Ankylosing Spondylitis Disease Activity Index, and the global activity of disease assessed by patients (all higher in females). The percentage of patients with at least one seropositivity detected at baseline, indicative of concomitant or former viral infection, was significantly higher among women than among men. No between-sex differences were detected in other measures, at other time points, and in treatments. Patients developed no hepatitis B virus or hepatitis C virus reactivation during cyclosporine treatment.Conclusion: Our post hoc sex analysis suggests that women with PsA have a greater articular involvement and a higher activity of disease compared to males. Immunosuppressive treatment with cyclosporine seems not to increase susceptibility to new infections or infectious reactivations, with no sex differences. Keywords: psoriatic arthritis, sex, viral infections, SYNERGY, cyclosporine

Critically ill patients are on the increase in the present clinical setting. Aging of our population and increasingly aggressive medical and therapeutic interventions, including implanted foreign bodies, organ transplantation and advances in the chemotherapy of malignant diseases, have created a cohort of particularly vulnerable patients. Pseudomonas aeruginosa is one of the leading gram-negative organisms associated with nosocomial infections. This organism is frequently feared because it causes severe hospital-acquired infections, especially in immunocompromised hosts, and is often antibiotic resistant, complicating the choice of therapy. The epidemiology, microbiology, mechanisms of resistance and currently available and future treatment options for the most relevant infections caused by P. aeruginosa are reviewed.

Background: Sepsis is a major cause of morbidity and death in hospitalized patients worldwide and one of the largest current challenges in critical care. Method: Review of the pertinent English-language literature. Results: Treatment goals conventionally have included maintenance of systemic perfusion and eradication of sources of infection. Initial empiric antimicrobial regimen should be broad enough to cover all likely pathogens, as there is little margin for error in critically ill patients. Conclusion: A multidisciplinary team, including the critical care physician, the microbiologist, the infectious disease specialist, the surgeon, and the clinical pharmacologist, is necessary for optimal patient outcome.

We performed a meta-analysis to determine whether antifungal prophylaxis decreases infectious morbidity and mortality in liver transplant patients. We searched for randomized trials dealing with prophylaxis with systemic antifungal agents. We used a fixed effect model, with risk ratio (RR) and 95% confidence interval (CI); we assessed study quality for heterogeneity and publication bias. Six studies (5 double-blind), for a total of 698 patients, compared fluconazole, itraconazole, or liposomal amphotericin to placebo (5 studies) or oral nystatin. Prophylaxis reduced colonization (RR, 0.45; CI, 0.37-0.55), total proven fungal infections (RR, 0.31; CI, 0.21-0.46), which included both superficial (RR, 0.27; CI, 0.16-0.45) and invasive (RR, 0.33; CI, 0.18-0.59) infections, and mortality attributable to fungal infection (RR, 0.30; CI, 0.12-0.75). Prophylaxis did not affect overall mortality (RR, 1.06; CI, 0.69-1.64) or empiric treatment for suspected fungal infection (RR, 0.80; CI, 0.39-1.67). The beneficial effect of antifungal prophylaxis was predominantly associated with the reduction of Candida albicans infection and mortality attributable to C. albicans. Compared to controls, however, patients receiving prophylaxis experienced a higher proportion of episodes of non-albicans Candida, and in particular of C. glabrata. No beneficial effect on invasive Aspergillus infection was observed. In conclusion, our analysis shows a clear, though limited, beneficial effect of antifungal prophylaxis in liver transplant patients. Concerns about the selection of triazole-resistant Candida strains, however, are realistic, and the potential disadvantages of prophylaxis should be weighed against the established benefits.

Left ventricular assist device (LVAD) support is an established therapy for patients with end-stage heart failure as a bridge to transplant; its usage as an alternative for those patients not eligible for transplant is not an established therapy yet. A 68-year-old male had a Thoratec-Heartmate LVAD implanted as destination therapy. After an uneventful (apart from early fever) recovery in the intensive care unit, the patient developed an intractable high temperature, and generalized sepsis and died 21 days following implant. The white cell blood count never exceeded the guard limits, and the patient succumbed with severe LVAD valve malfunction. At post-mortem examination friable material consisting of fungal hyphae was found on the inflow and outflow valves. According to published clinical trials, infection accounts for more than 40% of mortality in LVAD supported patients. Fungal LVAD endocarditis is a particularly deadly disease. Successful management requires a high level of suspicion and timely institution of antifungal therapy to control the infection. This has led some authors to recommend empiric antifungal therapy in LVAD recipients with culture-negative sepsis unresponsive to broad-spectrum antibiotics.

1. O titulo desta comunicacao nao e meu, mas do incansavel e admiravel organizador do nosso encontro; porem, e titulo muito oportuno por colocar em questao a existencia de uma dimensao epistemologica que deve ser enfrentada com urgencia, seja pelo cientista do direito, seja pelo docente chamado a ensinar disciplinas juridicas em nivel universitario. Pesquisa cientifica e ensino, se nao se quiser trair a verdadeira essencia da Universidade, estao de fato numa relacao de indefectivel simbiose. Alguem, cansado – e nao sem razao – dos demasiados apelos, e frequentemente de forma vazia, as imponentes palavras que sao ‘epistemologia’ e ‘epistemologico’, podera A FORMACAO DO JURISTA E A EXIGENCIA DE UM HODIERNO “REPENSAMENTO”* EPISTEMOLOGICO

Preemptive therapy of human cytomegalovirus (HCMV) infections has gained popularity in transplantation centers. However, standardized protocols are not available. In particular, whether a qualitative molecular assay for detection of a late (pp67) HCMV mRNA represents a valuable alternative to quantitative antigenemia remains to be defined.Overall, 82 heart (HTR) and lung (LTR) transplant recipients were randomized into two arms, where therapy was guided by qualitative pp67 mRNA NASBA (40 patients) or quantitative antigenemia (42 patients). In the NASBA arm, both primary and recurrent infections were treated upon first confirmed positive NASBA result. In the antigenemia arm, primary infections were treated upon first confirmed positive result, while recurrent infections were treated upon cutoff of 100 pp65-positive leukocytes. In both arms, therapy was stopped upon virus disappearance. Primary endpoint was duration of therapy.The number of treated/infected patients was significantly higher in the NASBA arm (25/30 vs. 15/39; P=0.015), as was the number of treated/relapsing patients (5/8 vs. 1/11; P=0.040), whereas the number of HCMV-infected/total number of patients was significantly higher in the antigenemia arm (39/42 vs. 30/40; P=0.026). Thus, in the NASBA arm, although the median duration of therapy was shorter compared to antigenemia (17 vs. 21 days, P0.05), the overall number of days of therapy was significantly higher. No patient developed HCMV disease.pp67 mRNA NASBA can safely replace antigenemia, with some apparent advantages (semiautomation and objectivity of test results) and disadvantages (overtreatment of patients and greater duration of overall treatment).

Epstein-Barr virus (EBV)–associated posttransplantation lymphoproliferative disorders (PTLDs) are a well-recognized complication of immunosuppression in solid organ transplant recipients. The reported therapeutic approaches are frequently complicated by rejection, toxicity, and other infectious pathologies, and overall mortality in patients with unresponsive PTLD remains high. Thus, low-toxicity treatment options or, preferably, some form of prophylactic/preemptive intervention are warranted to improve PTLD outcome in this setting. We assessed whether transfer of EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from the peripheral blood of allograft recipients receiving immunosuppression could increase EBV-specific killing in vivo without augmenting the probability of graft rejection. Autologous EBV-specific CTLs were generated for 23 patients who were identified as being at risk of developing PTLD through the finding of elevated EBV DNA load. Of the 23 patients, 7 received 1 to 5 infusions of EBV-specific CTLs. CTL transfer was well tolerated, and none of the patients showed any evidence of rejection. An increase of the EBV-specific cytotoxicity was observed after infusion, notwithstanding continuation of immunosuppressive therapy. EBV DNA levels had a 1.5- to 3-log decrease in 5 patients, whereas in the other 2 graft recipients CTL transfer had no apparent stable effect on EBV load. Our data suggest that the infusion of autologous EBV-specific CTLs obtained from peripheral blood mononuclear cells recovered at the time of viral reactivation is able to augment virus-specific immune response and to reduce viral load in organ transplant recipients. This approach may, therefore, be safely used as prophylaxis of EBV-related lymphoproliferative disorders in these patients, following a strategy of preemptive therapy guided by EBV DNA levels.

To investigate whether early liver regeneration after resection in patients with hepatic tumors might be influenced by post-operative infective complications.A retrospective analysis of 27 liver resections for tumors performed in a single referral center from November 2004 to January 2010. Regeneration was evaluated by multidetector computed tomography at a mean follow-up of 43.85 d. The Clavien-Dindo classification was used to evaluate postoperative events in the first 6 mo after transplantation, and Centers for Disease Control and Prevention definitions were used for healthcare associated infections data. Generalized linear regression models with Gaussian family distribution and log link function were used to reveal the principal promoters of early liver regeneration.Ten of the 27 patients (37%) underwent chemotherapy prior to surgery, with a statistically significant prevalence of patients with metastasis (P = 0.007). Eight patients (30%) underwent embolization, 3 with primary tumors, and 5 with secondary tumors. Twenty patients (74%) experienced complications, with 12 (60%) experiencing Clavien-Dindo Grade 3a to 5 complications. Regeneration ≥ 100% occurred in 10 (37%) patients. The predictors were smaller future remnant liver volume (-0.002; P0.001), and a greater spleen volume/future remnant liver volume ratio (0.499; P = 0.01). Patients with a resection of ≥ 5 Couinaud segments experienced greater early regeneration (P = 0.04). Nine patients experienced surgical site infections, and in 7 cases Clavien-Dindo Grade 3a to 4 complications were detected (P = 0.016). There were no significant differences between patients with primary or secondary tumors, and either onset or infections or severity of surgical complications.Regardless of the onset of infective complications, future remnant liver and spleen volumes may be reliable predictors of early liver regeneration after hepatic resection on an otherwise healthy liver.

The accuracy of diagnosis of subacute rumen acidosis (SARA) with a single measurement of the ruminal pH remains contradictory. To clarify this aspect, a large assessment of rumen, faecal and blood parameters was performed in several herds characterised by diets rich in non-structural carbohydrates. Rumen fluid was collected by rumenocentesis 6 h after feeding from 114 dairy cows (half 30–90 and half 150–250 days in milk) from 10 herds. In the same day, blood and faecal samples were collected and milk yield was recorded. The herds were ex-post classified as healthy (CTR n = 6) or as at risk for SARA (n = 4), based on ruminal pH. SARA versus CTR herds had lower rumen pH (5.67 vs 5.97 P < 0.01) and higher concentration of VFA, with lower acetate (P < 0.01) and higher propionate and valerate (P < 0.05) proportions. Moreover, the faecal DM was lower (P < 0.05), whereas the milk yield was higher with a lower concentration of fat (P < 0.05). At blood level, no significant differences were observed between the groups on positive acute-phase proteins, whereas SARA herds showed higher concentrations of paraoxonase and Ca and lower of cholesterol, total proteins, nitrates, Na and Zn (P < 0.01). Therefore, SARA herds did not show any evident symptom of ruminal disorder or systemic inflammation. On the contrary, these herds had a higher milk yield and a better inflammometabolic profile. These data confirm the difficulties to diagnose the SARA by a single measurement of ruminal pH in commercial herds and suggest the need of more specific indices to identify herds at risk.

THE USE OF ventricular assist devices (VADs) as a bridge to transplantation has improved the quality of life and decreased the morbidity and mortality in patients awaiting transplantation. The success of VADs for longterm support in patients with heart failure has made the use of VADs for permanent cardiac assistance a promising therapy. However, infectious complications, often arising from the percutaneous driveline exit site, remain the single most important obstacle for widespread use of VADs. The incidence of infection following left VAD (LVAD) implantation has been reported to be 13% to 80%. According to a review of .2000 patients worldwide, clinically relevant infections occurred in 25% of LVAD recipients. Fortunately, these infections do not preclude heart transplantation. The aim of the present study was to evaluate the incidence of infectious complications and the impact of infection on outcome in a series of patients on circulatory mechanical assistance with the Novacor N100 LVAD (Baxter Healthcare, Inc, Novacor Division) at the Charles Dubost Cardiac Surgery Center, IRCCS San Matteo, University of Pavia, Italy.

Human cytomegalovirus (CMV) was the first “opportunistic” virus described in renal transplant recipients under azathioprine and prednisone (1). It has been the most frequent cause of infectious complications after whole organ transplantation with all subsequent immunosuppressive regimens (2-11). In seronegative recipients, latently infected allografts and leukocyte-containing blood products are documented means of virus transmission (12-16). Among pre-transplant CMV seropositive transplant recipients, CMV infection may occur after reactivation of latent infection or after reinfection (17). Coinfection with multiple strains has also been detected in immunocompromised individuals (18-20). These so called secondary infections occur in about 50% to 80% of pre-transplant seropositive transplant recipients but a smaller proportion of the patients, ranging from 10 to 40% according to the transplanted organ, develop a CMV disease (11). Active CMV infection occurs during the first three months after transplantation and may be accompanied by a broad spectrum of disease manifestations ranging from a mononucleosis like syndrome to severe pneumonia. In the scientific literature the definitions used for CMV infection, CMV viremia and CMV disease vary greatly. Since this can make comparison between different studies difficult, a consensus definition was achieved during the fourth and fifth CMV conference in Paris 1993 and Stockholm 1995 (21).