S. Schaffellner

Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates.

There is in vitro proof that mTOR proteins play a role in protecting HCV infected cells from apoptosis. The aim of this cohort study was to evaluate the effect of sirolimus as an mTOR inhibitor on hepatitis C recurrence in liver transplant recipients. Hepatitis C virus positive patients were followed prospectively regarding transaminases, immunosuppressive target levels, HCV RNA and influence of donor and recipient factors on viral recurrence and survival. Viral recurrence was defined as elevated liver enzymes combined with active hepatitis diagnosed on the basis of increasing viral load and/or biopsy-proven HCV relapse in the transplanted organ. Sixty-seven HCV positive patients were included: 39 received a regimen including sirolimus; 28 patients received calcineurin inhibitors. Sirolimus patients showed a significant decrease in the HCV PCR levels (p<0.05). Survival of the sirolimus patients was significantly higher (p<0.03) than in the other patient cohort. Sirolimus has been shown to be a potent immunosuppressive agent after liver transplantation, though nothing is known about its effect on HCV. This analysis suggests that sirolimus has potential to suppress viral recurrence in HCV positive liver transplant candidates.

Dyslipidemia during sirolimus therapy in patients after liver transplantation

Abstract:  Introduction:  Sirolimus (SRL) is an immunosuppressive agent of potential benefit in clinical liver transplantation (LTX). One of the major side effects of SRL is hyperlipidemia, which is reported in up to 44% of patients. In this report, we describe the lipid profiles of 20 stable liver transplant recipients who received SRL for immunosuppression.

Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.

Wagner D, Adunka C, Kniepeiss D, Jakoby E, Schaffellner S, Kandlbauer M, Fahrleitner‐Pammer A, Roller RE, Kornprat P, Müller H, Iberer F, Tscheliessnigg KH. Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.
Clin Transplant 2011: 25: E396–E3400.

Morphological and functional characterization of a pancreatic beta-cell line microencapsulated in sodium cellulose sulfate/poly(diallyldimethylammonium chloride).

Abstract:  Background:  Late diabetic complications cannot be prevented totally by current antidiabetic strategies. Therefore, new therapeutic concepts of insulin replacement such as pancreas transplantation are evolving. Due to the shortage of human donor organs, transplantation of microencapsulated xenogeneic pancreatic islet cells has attracted considerable attention. Sodium cellulose sulfate/poly(diallyldimethylammonium chloride) (NaCS/PDADMAC) is a material with favorable biogenic properties that has been used for microencapsulation of various cell types. However, there are no data on the suitability of NaCS/PDADMAC for microencapsulation of pancreatic β‐cells.

Intramyocardial Electrogram Variability in the Monitoring of Graft Rejection After Heart Transplantation

The ventricular evoked response is a well‐standardized electrophysiological signal that can be used for noninvasive, long‐term cardiac transplant monitoring. Rejection‐sensitive and infection‐specific parameters extracted from intramyocardial electrograms correlate with clinical results. The influences of pacing rate, transition from intrinsic to paced rhythm and positional changes on the diagnostic parameters were studied. Increasing the pacing rate shortened the ventricular evoked response and directly influenced the infection specific parameter. The rejection‐sensitive parameter remained stable at pacing rates between 100 and 120 beats/min. Measurements made immediately after the patient assumed a supine position and after switching to paced rhythm showed a decrease in the rejection‐sensitive parameter. A change in position from supine to upright did not influence the rejection‐sensitive parameter, but higher values were measured after returning to the supine position. In conclusion, noninvasive recordings of the ventricular evoked response for monitoring of cardiac allograft should be done at the same time of day, at the same pacing rate, and with the patient resting for at least 5 minutes before measurements are made.

Non-invasive cardiac allograft monitoring: the Graz experience

Based on previous reports by our group, initial studies on non-invasive cardiac graft monitoring have been presented recently. In this study we define new parameters to monitor rejection and infection after heart transplantation (HTX) the ventricular evoked response (VER) T-slew rate parameter is defined as the maximum negative slope in the descending part of the repolarization phase of the VER. We calculated the VER duration parameter in milliseconds and defined it as the time between the pacemaker spike and the cross-over of the baseline, with the slope line used to calculate the VER T-slew rate. During the HTX procedure, we implant wide-band telemetric pacemakers and fractally coated, epimyocardial electrodes (Physios CTM 01 and ELC 54-UP, Biotronik; Berlin, Germany). During each follow-up and on biopsy days, intramyocardial electrogram sequences were obtained and sent via the Internet to the central data-processing unit in Graz. We scored the infection status of the patients before data acquisition. The VER parameters were automatically calculated and send back within a few minutes. We prospectivly compared 1,613 follow-ups from 42 patients with biopsy (International Society of Heart and Lung Transplantation grading) and infection classification. The VER duration parameter did not change during rejection; however, we found an increase during clinically apparent infection. The VER T-slew rate parameter was lower during rejection grade 2 or higher, as well as during clinically apparent infection. The negative predictive value to rule out rejection was 99%. Our results indicate that rejection and infection cause different, reproducible effects on the electrical activity of the transplanted heart. Non-invasive cardiac graft monitoring may reduce the need for surveillance biopsies and may offer a tool to optimize immunosuppressive therapy after HTX.

Creation of a prevascularized site for cell transplantation in rats

Stiegler P, Matzi V, Pierer E, Hauser O, Schaffellner S, Renner H, Greilberger J, Aigner R, Maier A, Lackner C, Iberer F, Smolle‐Jüttner F‐M, Tscheliessnigg K, Stadlbauer V. Creation of a prevascularized site for cell transplantation in rats. Xenotransplantation 2010; 17: 379–390.

Myeloperoxidase as serum marker for detection of CMV infections and rejections in patients after liver or heart transplantation

Rejection episodes and infections are common problems after organ transplantations (TX). Rejection can be diagnosed in liver-transplant (LTX) patients when liver-specific enzymes in the serum are elevated. As endomyocardial biopsy (EMB) is the gold standard for detecting heart transplant (HTX) rejection, serum parameters would permit more selective use of this invasive procedure. Cytomegalovirus (CMV) infections can have serious consequences for TX patients and so should be diagnosed and treated timely. At present, there are no suitable diagnostic methods other than CMV antigen pp65 and CMV polymerase chain reaction (PCR). Our study aimed to test the sensitivity of myeloperoxidase (MPO), an enzyme of neutrophilic granulocytes, as a new serum parameter in addition to established serum parameters and EMB for diagnosis of infection and rejection episodes after LTX and HTX. MPO in plasma from 246 blood samples (103 used for statistical analysis) from 27 patients (18 LTX and 9 HTX) was determined using ELISA; C-reactive protein (CRP), gamma-glutamyl-transpeptidase (GGT), white blood count and CMV pp65 antigen were monitored routinely. EMBs were performed at defined intervals after HTX. Results were analyzed with descriptive statistics, T-test, Wilcoxon test and Cox regression analysis, whereby a p<0.05 was viewed as significant. MPO values in TX patients with an infection (7 LTX, 2 HTX) were significantly higher than in TX patients without complications (control group) (253.9 microg/l vs. 116.6 microg/l, p=0.0194). In TX patients with rejections (6 LTX, 6 HTX), there is also a significant increase in comparison to controls (429.7 microg/l vs. 116.6 microg/l, p=0.0001). Data from individual TX patients, however, indicate that MPO levels rise distinctly earlier with infection (CMV) than with rejection, enabling earlier detection of the complication and initiation of suitable treatment. Our findings suggest that a larger and prospective study should be designed to evaluate the usefulness of MPO levels in assessing organ transplant recipients.

Non-invasive graft monitoring after heart transplantation: rationale to reduce the number of endomyocardial biopsies.

Abstract The endomyocardial biopsy is invasive, reduces quality of life and cannot be repeated daily. Initial studies on noninvasive cardiac graft monitoring have been presented recently. During the heart transplant procedure, we implanted wideband telemetric pacemakers and fractally coated, epimyocardial electrodes. On biopsy days and during each follow‐up, intramyocardial electrogram sequences were obtained. The maximum T‐slew rate from the ventricular evoked response (VER) was automatically calculated and compared to the biopsy results (n = 331, ISHLT grading). The VER T‐slew rate was significantly lower during rejection grade 2 or higher. The negative predictive value to exclude rejection was 98%. Using a single threshold diagnosis model, 74% of the biopsies could have been avoided. Noninvasive cardiac graft monitoring can reduce the need for surveillance biopsies and may offer a tool to optimize immunosuppressive therapy after heart transplantation

Occurance of apoptosis during ischemia in porcine pancreas islet cells.

Purpose Pancreas islet transplantation is a potential treatment of diabetes mellitus and porcine organs provide an easily available source of cells. Unfortunately quality and quantity of isolated islets are still not satisfactory. Apoptosis occurs in freshly isolated islets and plays a significant role in early graft loss. We evaluated the influence of four storage solutions on porcine pancreas islets. Method After warm ischemia of 15–20 minutes 12 organs were stored in 4 cold preservation solutions: Histidine-Tryptophan-Ketoglutarate solution (HTK), Hanks buffered saline solution (HBSS), University of Wisconsin (UW) solution and Ringer-Lactate (R). After cold ischemia for 100 minutes, organs were fixed in 3% formalin. Apoptotic cells were counted on hematocylin-eosin stainings. Results Most apoptotic cells were found in organs stored in R. Low numbers were found in the other groups. The difference between organs stored in R and organs stored in UW, HTK, or HBSS was highly significant. No significant difference could be found between UW, HTK and HBSS. Conclusion Cold and warm ischemia of the pancreas seems to induce apoptosis in islet cells. Preservation solutions cause less apoptosis than electrolyte solution. No significant differences could be found among the preservation solutions.