Single-center experience with primary orthotopic liver transplantation with FK 506 immunosuppression

Objective: The efficacy for primary orthotopic liver transplantation of a new immunosuppressive agent, FK 506 (tacrolimus, Prograf, Fujisawa USA, Deerfield, IL), was determined. Summary Background Data: After 3 years of preclinical research, a clinical trial of FK 506 for orthotopic liver transplantation was begun in February 1989, first as a rescue therapy for patients with intractable rejection with conventional immunosuppression, then as a primary drug. Methods: Between August 1989 and December 1993, 1391 recipients (1188 adult and 203 pediatric) of primary liver allografts were treated with FK 506 from the outset. Results from these patients were analyzed and compared with those of 1212 historical control patients (971 adult and 241 pediatric) given cyclosporine-based immunosuppression. Results: Actuarial survival at 4 years was 86.2% with FK 506 versus 65.5% with cyclosporine in the pediatric patients (p < 0.0000) and 71.4% versus 65.5% in the adults (p < 0.0005). The need for retransplantation was reduced significantly for FK 506 patients. Four-year graft survival was 77.0% with FK 506 versus 48.4% with cyclosporine in the pediatric patients (p < 0.0000), and 61.9% with FK 506 versus 51.4% with cyclosporine in the adult recipients (p < 0.0000). Regression analysis revealed that reductions in mortality or graft loss from uncontrollable rejection, sepsis, technical failure, and recurrent original liver disease were responsible for the improved results with FK 506 therapy. Conclusions: FK 506 is a potent and superior immunosuppressive agent for orthotopic liver transplantation

CMV infection of liver transplant recipients: comparison of antigenemia and molecular biology assays

BACKGROUND: CMV is a major clinical problem in transplant recipients. Thus, it is important to use sensitive and specific diagnostic techniques to rapidly and accurately detect CMV infection and identify patients at risk of developing CMV disease. In the present study, CMV infection after liver transplantation was monitored retrospectively by two molecular biology assays - a quantitative PCR assay and a qualitative NASBA assay. The results were compared with those obtained by prospective pp65 antigenemia determinations. MATERIALS AND METHODS: 87 consecutive samples from 10 liver transplanted patients were tested for CMV by pp65 antigenemia, and CMV monitor and NASBA pp67 mRNA assay. RESULTS: CMV infection was detected in all patients by antigenemia and CMV monitor, whereas NASBA assay identified only 8/10 patients with viremia. Furthermore, CMV infection was never detected earlier by molecular biology assays than by antigenemia. Only 5/10 patients with CMV infection developed CMV disease. Using a cut off value of 8 cells/50,000, antigenemia was found to be the assay that better identified patients at risk of developing CMV disease. However, the kinetics of the onset of infection detected by NASBA and CMV monitor seemed to have better identified patients at risk of developing CMV disease. Furthermore, before onset of disease, CMV pp67 mRNA was found to have similar or better negative and positive predictive values for the development of CMV disease. CONCLUSIONS: The present data, suggests that the concomitant use of antigenemia and pp67 mRNA assay gives the best identification of patients at risk of developing CMV disease

Relationship between pp65 antigenemia levels and real-time quantitative DNA PCR for Human Cytomegalovirus (HCMV) management in immunocompromised patients

<p>Abstract</p> <p>Background</p> <p>Quantitative real-time PCR assays, which are more rapid and practical than pp65 antigenemia determination, are progressively becoming the preferred method for monitoring Human Cytomegalovirus (HCMV) reactivation. However, the relationship between HCMV DNA and antigenemia levels is still under investigation. The aim of this study was to analyse the relationship between HCMV DNA and pp65 antigenemia levels in order to identify clinically useful threshold values for the management of patients.</p> <p>Methods</p> <p>475 consecutive samples from 156 immunosuppressed patients were tested for HCMV by pp65 antigenemia and Real-time PCR assay.</p> <p>Results </p> <p>136 out of 475 consecutive samples derived from 48 patients showed evidence of HCMV infection. HCMV DNA was detected in 106 samples, pp65 antigen in 3, and both markers in 27. pp65 antigen detection was associated with higher HCMV DNA levels. The cut-off HCMV DNA level that best predicted pp65 antigenemia in this series of samples was 11,500 copies/ml, but different threshold levels could be observed for specific groups of patients. HCMV disease was observed in 5 out of 48 patients with active HCMV infection. The presence of clinical symptoms was associated with positive pp65 and with higher antigenemia levels. Higher HCMV DNA load at the onset of viral replication was correlated to the development of clinical symptoms.</p> <p>Conclusion</p> <p>Both pp65 antigenemia and HCMV DNA load can be useful for the prospective monitoring of immunocompromised subjects. Specific cut-off levels capable of triggering preemptive antiviral treatment should be determined in accordance to the type of test used and the characteristics of patients and prospectively validated.</p

Fulfilling the promise of the materials genome initiative with high-throughput experimental methodologies

The Materials Genome Initiative, a national effort to introduce new materials into the market faster and at lower cost, has made significant progress in computational simulation and modeling of materials. To build on this progress, a large amount of experimental data for validating these models, and informing more sophisticated ones, will be required. High-throughput experimentation generates large volumes of experimental data using combinatorial materials synthesis and rapid measurement techniques, making it an ideal experimental complement to bring the Materials Genome Initiative vision to fruition. This paper reviews the state-of-the-art results, opportunities, and challenges in high-throughput experimentation for materials design. A major conclusion is that an effort to deploy a federated network of high-throughput experimental (synthesis and characterization) tools, which are integrated with a modern materials data infrastructure, is needed

Five-years surveillance of invasive aspergillosis in a university hospital

<p>Abstract</p> <p>Background</p> <p>As the most common invasive fungal infection, invasive aspergillosis (IA) remains a serious complication in immunocompromised patients, leading to increased mortality. Antifungal therapy is expensive and may result in severe adverse effects.</p> <p>The aim of this study was to determine the incidence of invasive aspergillosis (IA) cases in a tertiary care university hospital using a standardized surveillance method.</p> <p>Methods</p> <p>All inpatients at our facility were screened for presence of the following parameters: positive microbiological culture, pathologist's diagnosis and antifungal treatment as reported by the hospital pharmacy. Patients fulfilling one or more of these indicators were further reviewed and, if appropriate, classified according to international consensus criteria (EORTC).</p> <p>Results</p> <p>704 patients were positive for at least one of the indicators mentioned above. Applying the EORTC criteria, 214 IA cases were detected, of which 56 were proven, 25 probable and 133 possible. 44 of the 81 (54%) proven and probable cases were considered health-care associated. 37 of the proven/probable IA cases had received solid organ transplantation, an additional 8 had undergone stem cell transplantation, and 10 patients were suffering from some type of malignancy. All the other patients in this group were also suffering from severe organic diseases, required long treatment and experienced several clinical complications. 7 of the 56 proven cases would have been missed without autopsy. After the antimycotic prophylaxis regimen was altered, we noticed a significant decrease (p = 0.0004) of IA during the investigation period (2003-2007).</p> <p>Conclusion</p> <p>Solid organ and stem cell transplantation remain important risk factors for IA, but several other types of immunosuppression should also be kept in mind. Clinical diagnosis of IA may be difficult (in this study 13% of all proven cases were diagnosed by autopsy only). Thus, we confirm the importance of IA surveillance in all high-risk patients.</p

In Vitro Susceptibilities of 217 Clinical Isolates of Zygomycetes to Conventional and New Antifungal Agents▿

We evaluated the in vitro susceptibilities of 217 zygomycetes to amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, and flucytosine. The significant in vitro activity of posaconazole against several species appears to support its reported clinical efficacy. Decreased susceptibility to amphotericin B was noted with Cunninghamella bertholletiae