A randomized trial of everolimus-based quadruple therapy vs standard triple therapy early after lung transplantation.

Calcineurin inhibitor (CNI) therapy after lung transplantation increases risk of kidney failure. Early everolimus-based quadruple low CNI immunosuppression may improve renal function without compromising efficacy or safety. A prospective, randomized, open-label, 12-month multicenter trial was conducted at 8 German sites. Patients 3-18 months after lung transplantation were randomized (1:1), stratified by baseline estimated glomerular filtration rate (eGFR). In the quadruple low CNI regimen, patients received everolimus (target trough level 3-5 ng/mL) with reduced CNI (tacrolimus 3-5 ng/mL or cyclosporine 25-75 ng/mL) and a cell cycle inhibitor plus prednisone. In the standard triple CNI regimen, patients received tacrolimus (target trough level >5 ng/mL) or cyclosporine (>100 ng/mL) and a cell cycle inhibitor plus prednisone. Of the 180 patients screened, 130 were randomized: 67 in the quadruple low CNI group and 63 in the standard triple CNI group. The primary endpoint (eGFR after 12 months) demonstrated superiority of the quadruple low CNI regimen: 64.5 mL/min vs 54.6 mL/min for the standard triple group (least squares mean, analysis of covariance; P < .001). Key efficacy parameters (biopsy-proven acute rejection, chronic lung allograft dysfunction, and death) and safety endpoints were similar between both groups. Quadruple low CNI immunosuppression early after lung transplantation was demonstrated to be efficacious and safe. Clinical trials registry: ClinicalTrials.gov NCT01404325.

Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine.

Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism.

Assessment of sub-clinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy.

OBJECTIVE: Comparing the diagnostic value of multi-sequential cardiac magnetic resonance imaging (CMR) with endomyocardial biopsy (EMB) for sub-clinical cardiac allograft rejection. METHODS: One hundred and forty-six examinations in 73 patients (mean age 53 ± 12 years, 58 men) were performed using a 1.5 Tesla system and compared to EMB. Examinations included a STIR (short tau inversion recovery) sequence for calculation of edema ratio (ER), a T1-weighted spin-echo sequence for assessment of global relative enhancement (gRE), and inversion-recovery sequences to visualize late gadolinium enhancement (LGE). Histological grade ≥1B was considered relevant rejection. RESULTS: One hundred and twenty-seven (127/146 = 87 %) EMBs demonstrated no or mild signs of rejection (grades ≤1A) and 19/146 (13 %) a relevant rejection (grade ≥1B). Sensitivity, specificity, positive predictive, and negative predictive values were as follows: ER: 63 %, 78 %, 30 %, and 93 %; gRE: 63 %, 70 %, 24 %, and 93 %; LGE: 68 %, 36 %, 13 %, and 87 %; with the combination of ER and gRE with at least one out of two positive: 84 %, 57 %, 23 %, and 96 %. ROC analysis revealed an area under the curve of 0.724 for ER and 0.659 for gRE. CONCLUSION: CMR parameters for myocarditis are useful to detect sub-clinical acute cellular rejection after heart transplantation. Comparable results to myocarditis can be achieved with a combination of parameters. KEY POINTS: • Magnetic resonance imaging is useful for the assessment of cardiac allograft rejection. • CMR has a high negative predictive value for exclusion of allograft rejection. • Diagnostic performance is not yet good enough to replace endomyocardial biopsy.

Usability of ventricular assist devices in daily experience: a multicenter study.

In daily life, the safe, intuitive use of ventricular assist devices (VADs) and especially their peripheral components is not only a question of life quality, but also sometimes crucial for survival. To investigate the advantages and disadvantages of different systems and to get patient feedback on preferred features, a multicenter study was initiated. Based on previous single-center studies, a questionnaire was developed to ascertain patients' experiences, difficulties with, and desires concerning use of the system. This questionnaire was provided both to ongoing patients and to new VAD patients after a minimum hospital discharge time of 6 weeks, at a regular checkup. Additionally, the patients completed a standardized questionnaire on life quality (Kansas City Cardiomyopathy Questionnaire). The centers that contributed to this study were Bad Oeynhausen, Berlin, Hannover, and Vienna. Three hundred fifty-two completed questionnaires on eight different pump types were obtained. An important result is that 42% of those questioned dropped their controller bag at least once. Depending on the device, between 2 and 55% disconnected it unintentionally. Confidence in safe use of the system decreased significantly with age, from 80% at age 20-30 years to 33% at 70-80 years. In devices with an LCD display, 94% considered the readability sufficient. Ninety-four percent considered the training adequate. Between 22 and 88% of the patients called the emergency telephone hotline, depending on the device, and 23-46% depending on the center. This first multicenter study on VAD usability reveals considerable differences among devices and centers. The comparative assessment aims to help optimize device design, patient management, and training.

Interhospital air transport of a blind patient on extracorporeal life support with consecutive and successful left ventricular assist device implantation.

The use of extracorporeal life support systems (ECLS) in patients with postcardiotomy low cardiac output syndrome (LCO) as a bridge to recovery and bridge to implantation of ventricular assist device (VAD) is common nowadays. A 59-year-old patient with acute myocardial infarction received a percutaneous transluminal angioplasty and stenting of the circumflex artery. During catheterization of the left coronary artery (LAD), the patient showed ventricular fibrillation and required defibrillation and cardiopulmonary resuscitation. After implantation of an intra-aortic balloon pump, the patient immediately was transmitted to the operating room. He received emergency coronary artery bypass grafting in a beating heart technique using pump-assisted minimal extracorporeal circulation circuit (MECC). Two bypass grafts were performed to the LAD and the right posterior descending artery. Despite initial successful weaning off cardiopulmonary bypass with high-dose inotropic support, the patient presented postcardiotomy LCO and an ECLS was implanted. The primary setup of the heparin-coated MECC system was modified and used postoperatively. As a result of the absence of an in-house VAD program, the patient was switched to a transportable ECLS the next day and was transferred by helicopter to the nearest VAD center where the patient received a successful insertion of a left VAD 3 days later.

Lung function early after lung transplantation is correlated with the frequency of regulatory T cells.

PURPOSES: Outcomes following lung transplantation are limited by bronchiolitis obliterans syndrome (BOS). As the number of circulating regulatory T cells (Treg) is lower in lung recipients with BOS than in stable lung recipients, we hypothesized that Treg is also correlated with lung function in the early post-transplantation period. METHODS: This prospective study included 18 consecutive patients whose lung function parameters were recorded 3 weeks and 3 months after transplantation, between February and July 2007. Peripheral blood mononuclear cells were stained with anti-CD3, -CD4, -CD8, -CD19, -CD25, -CD28, -CD45RA, -CD45RO, -CD69, -CD127, -CTLA4, and -Foxp3 antibodies and FACS assays were performed. In addition, intracellular cytokines were stained for FACS. RESULTS: Treg-specific markers (Foxp3, CD127(lo), and CTLA4) in the CD25+ CD4+ population were correlated with both forced expiratory volume in 1 s and forced vital capacity. Th1-cytokine secretion was more dominant in CD4+ CD25+ T cells than in CD4+ CD25- T cells. In contrast, Th2 and Treg cytokine secretion was the dominant response in stable recipients. CONCLUSIONS: The frequency of Treg cells was positively correlated with good lung function in the early period after lung transplantation.

Viremia after lung transplant: a cohort study on risk factors and symptoms associated with detection of Epstein-Barr virus.

Background-The frequency and impact of detection of Epstein-Barr virus in the blood of lung and heart-lung transplant recipients in the postoperative period is poorly characterized.Objective-To investigate the frequency of virus detection, associated clinical symptoms and risk factors, and influence of virus detection on outcome.Methods-A cohort of 98 lung transplant recipients were monitored for Epstein-Barr virus in blood before transplant and during their posttransplant hospital stay (median 4 weeks, range 1-21 weeks). Patients were followed up for retransplant or death for a median of 17 months.Results-Epstein-Barr virus DNA was detected in 15 recipients (18.1%) before and in 39 recipients (41.5%) after transplant. Median viral load after transplant was 2300 copies per milliliter of blood (range, 900-45 000 copies/mL). Detection of Epstein-Barr virus DNA before transplant and mechanical ventilation before transplant were associated with detection of Epstein-Barr virus DNA after transplant. Shortness of breath, fatigue, and hoarseness were associated with detection of viral DNA after transplant. The incidence of retransplant or death was not increased in recipients who had viral DNA detected in their blood.Conclusions-Epstein-Barr virus DNA in the blood before transplant and mechanical ventilation before transplant were associated with detection of viral DNA after transplant. Detection of viral DNA after transplant was frequent and clinically relevant.

Combination of everolimus with calcineurin inhibitor medication resulted in post-transplant haemolytic uraemic syndrome in lung transplant recipients--a case series.

BACKGROUND: Post-transplant haemolytic uraemic syndrome (HUS) is a rare but serious disease with a high mortality rate, when left untreated. Immunosuppressive drugs like calcineurin inhibitors as well as mammalian target of rapamycin inhibitors have been reported as causative agents for post-transplant HUS. METHODS: A retrospective observational study was performed in lung transplant recipients, who took part in an interventional study, in two centres. Haemoglobin, platelets, creatinine and lactate dehydrogenase levels were monitored during routine follow-up and patients with deteriorating kidney function were screened for post-transplant HUS. All cases of post-transplant HUS were identified by clinical and laboratory findings. Outcome was recorded until 6 months after diagnosis. RESULTS: A total of 2188 visits in 512 lung transplant recipients (outpatients) were analysed. Out of those, 126 patients took part in an interventional study. In this study, 67 were switched to everolimus in combination with calcineurin inhibitors 4 weeks after transplantation, 59 patients remained on standard immunosuppression (calcineurin inhibitors, mycophenolate mofetil and prednisolone). Five cases of post-transplant HUS were identified in the everolimus group. None of the patients had evidence of gastrointestinal infection or preexisting renal disease. Post-transplant HUS was treated with therapeutic plasma exchange and methylprednisolone pulse therapy. Everolimus was discontinued in all five patients. This treatment regimen led to normalization of haemoglobin, platelets and improved renal function. Two patients developed end-stage renal failure and were maintained on haemodialysis. One patient died due to multiorgan failure. Improvement of renal function was seen in two patients. No further cases were recorded in patients without everolimus during the study period. CONCLUSIONS: Our data should raise the awareness of post-transplant HUS in lung transplant recipients. Post-transplant HUS is a rare disease, but it is a serious cause of acute renal failure in lung transplant recipients treated with a combination of everolimus and calcineurin inhibitors.

[Left ventricular assist devices in chronic therapy of heart failure. Indication, results, risks]. / Chronische Therapie durch linksventrikuläre Unterstützungssysteme bei terminaler Herzinsuffizienz. Indikation, Ergebnisse, Risiken.

Three generations of left ventricular assist devices are available for the therapy of heart failure. In the current development, pulsatile devices are being displaced by axial flow pumps. Intentions for left ventricular assist device implantations are bridge to transplantation or to recovery and destination therapy. Already the mechanical support has the drop on the conservative medical therapy; furthermore, improvements in the devices are registered. In addition, by implanting a left ventricular assist device the quality of life was improved. Consequently, the importance of left ventricular assist devices in the therapy of heart failure is increasing.

HeartMate II left ventricular assist device; early European experience.

OBJECTIVE: The novel axial flow left ventricular assist device HeartMate II was introduced into clinical practice in Europe as part of the pilot study and after CE approval in November 2005. In order to get an overview of the use and performance of the device in Europe a group of investigators was founded to compare the initial results. METHODS: In a retrospective analysis of the first 101 consecutive cases in Europe, data were collected with regard to postoperative outcome and severe adverse events and anticoagulation protocols. Results were stratified by intention to treat as a bridge to transplant or as chronic support therapy in heart failure (destination therapy). RESULTS: In 70% of patients, the HeartMate II was intended as a bridge to transplant therapy, in 30%, it was used as a destination therapy device. The perioperative mortality post implant was 20% in the bridge to transplant patients and 7% in the destination therapy arm. However, after 1 year a comparable survival was observed in both groups (69% destination therapy, 63% bridge to transplant). Main causes of death were multiple organ failure (n=12) and cerebrovascular accidents (n=5). All, but one cerebrovascular accident occurred in the first 9 days after surgery. Only one other death was reported thereafter and there was no mechanical failure of the device. CONCLUSIONS: Even in the early experience the HeartMate II was used as a chronic support device in a substantial number of patients in Europe. Although the total experience is still limited, the incidence of cerebrovascular accidents is very low and the survival beyond the perioperative period is excellent.

Comparison of inhaled iloprost and nitric oxide in patients with pulmonary hypertension during weaning from cardiopulmonary bypass in cardiac surgery: a prospective randomized trial.

OBJECTIVE: The objective of this study was to compare the efficacy of inhaled iloprost and nitric oxide (iNO) in reducing pulmonary hypertension (PHT) during cardiac surgery immediately after weaning from cardiopulmonary bypass (CPB). DESIGN: A prospective randomized study. SETTING: A single-center university hospital. PARTICIPANTS: Forty-six patients with PHT (mean pulmonary artery pressure (mPAP) > or = 26 mmHg preoperatively at rest, after anesthesia induction, and at the end of CPB) scheduled to undergo cardiac surgery were enrolled. INTERVENTIONS: Patients were randomly allocated to receive iloprost (group A, n = 23) or iNO (group B, n = 23) during weaning from CPB. MEASUREMENTS AND MAIN RESULTS: Heart rate, mean arterial pressure, central venous pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure, and left atrial pressure were recorded continuously. Iloprost and iNO were administered immediately after the end of CPB before heparin reversal. Both substances caused significant reductions in mean PAP (mPAP) and pulmonary vascular resistance (PVR) and significant increases in cardiac output 30 minutes after administration (p < 0.0001). However, in a direct comparison, iloprost caused significantly greater reductions in PVR (p = 0.013) and mPAP (p = 0.0006) and a significantly greater increase in cardiac output (p = 0.002) compared with iNO. CONCLUSIONS: PHT after weaning from CPB was significantly reduced by the selective pulmonary vasodilators iNO and iloprost. However, in a direct comparison of the 2 substances, iloprost was found to be significantly more effective.

Five-year results of patients supported by HeartMate II: outcomes and adverse events.

OBJECTIVES: Improved outcomes over the past decade have increased confidence of physicians and patients in extended duration of left ventricular assist device (LVAD) support. This single-centre cohort study reports 5-year outcomes with the HeartMate II (HMII) LVAD. METHODS: We describe a cohort of 89 patients who received a HMII LVAD between February 2004 and December 2010. The causes of death and adverse events were assessed by examination of medical records. A total of 202.74 patient-years were analysed. RESULTS: After 5 years, of the 89 patients, 15 patients remained on device therapy, 39 patients died, 28 patients underwent heart transplantation and 7 patients underwent explantation of the HMII for recovery. One year after the HMII implantation, there was a survival of 71% in the study cohort. In the following years, the survival rate was 65% in the 2nd year, 63% in the 3rd year, 56% in the 4th year and 54% after 5 years of LVAD support. Ten LVAD exchanges were performed in 8 (11%) patients. Currently (March 2017), 12 patients still remain on their original device. The longest ongoing patient on the HMII has been supported for over 11 years (4097 days). The most common adverse events were bleeding (68%; 1.5837 events per patient-year) and LVAD infection [49%; 1.0666 events per patient-year]. Seven cases of pump thrombosis were described (8%; 0.1131 events per patient-year). CONCLUSIONS: This is the first single-cohort study to describe a 5-year survival of HMII patients on extended duration of support. A 5-year survival of 54% was observed in this single-centre cohort.

Splenocyte Infusion and Whole-Body Irradiation for Induction of Peripheral Tolerance in Porcine Lung Transplantation: Modifications of the Preconditioning Regime for Improved Clinical Feasibility.

BACKGROUND: Preoperative low-dose whole-body irradiation (IRR) with 1.5 and 7 Gy thymic IRR of the recipient, combined with a perioperative donor splenocyte infusion lead to reliable donor specific peripheral tolerance in our allogeneic porcine lung transplantation model. To reduce the toxicity of this preconditioning regime, modifications of the IRR protocol and their impact on allograft survival were assessed. METHODS: Left-sided single lung transplantation from major histocompatibility complex and sex mismatched donors was performed in 14 adult female minipigs. Recipient animals were exposed to 3 different protocols of nonmyeloablative IRR within 12 hours before transplantation. All animals were administered a donor splenocyte infusion on the day of lung transplantation. Intravenous pharmacologic immunosuppression was withdrawn after 28 postoperative days. Allograft survival was monitored by chest radiographs and bronchoscopy. RESULTS: IRR prolonged transplant survival in a dose- and field-dependent manner. Shielding of the bone marrow from IRR (total lymphoid IRR at 1.5 and 7 Gy thymic IRR) significantly reduced protocol toxicity defined as thrombocytopenia and consecutive increased bleeding propensity, but had a less effective impact on graft survival. Whole-body IRR at 0.5 and 7 Gy thymic IRR proved to be ineffective for reliable tolerance induction. Eventually, high levels of circulating CD4+CD25high regulatory T cells were present in long-term survivors. CONCLUSIONS: These data show that the infusion of donor-specific alloantigen in combination with IRR is efficient once a threshold dose is exceeded.

Preoperative low-dose irradiation promotes long-term allograft acceptance and induces regulatory T cells in a porcine model of pulmonary transplantation.

BACKGROUND: A simplified conditioning protocol including single-dose preoperative thymic and low-dose whole body irradiation with or without subsequent donor bone marrow transplantation (BMTx) can be applied in porcine lung transplantation. We hypothesized that this protocol would prolong allograft survival. METHODS: Left-sided single lung transplantation from major histocompatibility complex (MHC)-mismatched donors was performed in 27 minipigs. Recipients received whole body (1.5 Gy) and thymic irradiation (7 Gy) before transplantation (IRR group, n=6), intravenous immunosuppression with methylprednisolone, cyclosporine, and azathioprine for 27 postoperative days (IS group, n=5) or both (IRR+IS group, n=10). BMTx group recipients were treated with irradiation, immunosuppression and a donor bone marrow infusion on postoperative day 1. Peripheral blood leukocyte phenotype and donor cell chimerism were monitored by flow cytometry. Purified CD25+ T cells from long-term survivors or rejecting animals were used for in vitro MLR suppression assays. RESULTS: Median graft survival was: IRR 12 days, IS 55 days, IRR+IS 239 days, and BMTx 80 days (P<0.0001). Early peripheral blood macrochimerism was substantial in both the IRR+IS and the BMTX group but was lost in all groups after day 80. The frequency and suppressive function of CD4+CD25+ T cells were enhanced in IRR+IS group long-term survivors. CONCLUSION: Although donor bone marrow infusion was not beneficial in our model, a substantial proportion of the animals treated with irradiation and a 28-day course of immunosuppression accepted their lung allografts long term. The mechanism involved in maintaining allograft tolerance may be based on peripheral T-cell regulation.

Glutathione improves the function of porcine pulmonary grafts stored for twenty-four hours in low-potassium dextran solution.

BACKGROUND: Flush perfusion with low-potassium dextran is the standard strategy in clinical lung preservation. Despite improved outcome, endothelial cell injury and surfactant dysfunction remain a significant problem after lung transplantation. The radical scavenger glutathione has been shown to be responsible for the efficacy of Celsior solution in lung preservation. We tested the hypothesis that the addition of glutathione to low-potassium dextran might further improve graft function by ameliorating ischemia-reperfusion injury. METHODS: In 12 domestic pigs, lungs were flush preserved with either low-potassium dextran (n = 6) or low-potassium dextran supplemented by 5 mmol glutathione (n = 6). Left single lung transplantation was performed after 24-hour storage in low-potassium dextran at 8 degrees C. After 15 minutes of reperfusion the right main bronchus and pulmonary artery were crossclamped. Hemodynamic and respiratory measures were recorded in 30-minute intervals for a total observation period of 7 hours. Bronchoalveolar lavage fluid was obtained from the native lung and 2 hours after reperfusion from the graft. Bronchoalveolar lavage fluid and surfactant composition, and surfactant function analyses were performed. Neutrophil sequestration was assessed by myeloperoxidase activity assay. Tissue water content was calculated from wet/dry weight ratios at the end of the experiment. RESULTS: In the low-potassium dextran group, 2 animals died during reperfusion. After reperfusion, pulmonary vascular resistance (P = .01) and pulmonary artery pressure remained lower in the glutathione/low-potassium dextran group, which was associated with a higher cardiac output (P = .05) in this group. Also, the oxygenation index at the end of the observation period was higher in the glutathione/low-potassium dextran group compared with the low-potassium dextran group (430 +/- 130 vs 338 +/- 184, respectively; P < .05). The graft water content representing postreperfusion lung edema was not different between the 2 study groups. Alteration of surfactant was less in the glutathione/low-potassium dextran group with a significantly decreased small to large aggregate ratio (P = .03) versus low-potassium dextran group. Myeloperoxidase activity was twice as high in the low-potassium dextran group when compared with the glutathione/low-potassium dextran group (glutathione/low-potassium dextran: 134 +/- 110 mU/g vs low-potassium dextran: 274 +/- 168 mU/g, P = .07). CONCLUSION: The addition of glutathione to low-potassium dextran preservation solution reveals beneficial effects on vascular function and surfactant composition in transplanted lungs. Therefore, glutathione ameliorates ischemia-reperfusion injury in a preclinical model of lung transplantation. Future studies are needed to evaluate this promising modification in clinical lung transplantation.

Lung transplantation with lungs from donors fifty years of age and older.

BACKGROUND: A shortage of donors has led to the progressive expansion of criteria for donor selection in lung transplantation. The outcome of recipients of lungs from donors aged 50 years or older is analyzed systematically. METHODS: From March 1998 to June 2003, 49 recipients received lungs from donors aged 50 years or older (range 50-64 years, mean 54 +/- 3 years). This group of recipients was compared with 244 patients receiving lungs from donors aged less than 50 years (range 7-49 years, mean 32 +/- 11 years). This study was undertaken on all 293 patients at our institution who received Perfadex-preserved lungs (Vitrolife, Goteborg, Sweden). RESULTS: Recipient age, sex, and indications for transplant did not differ significantly between groups. Also, the percentage of the different types of transplants (bilateral or single lung transplantation) performed was equal in both cohorts. Donor Pa(O2) /F(IO2) ratios before lung retrieval (415 +/- 91 vs 439 +/- 113, respectively) and length of ischemic time (347 +/- 67 minutes vs 351 +/- 84 minutes, respectively) did not differ significantly between the older and younger donor groups. The following posttransplant parameters were also not statistically different: first Pa(O2)/F(IO2) at intensive care unit arrival (274 +/- 125 in the older donor group vs 253 +/- 119 in the younger donor group, respectively), mechanical ventilation time (328 +/- 427 hours vs 269 +/- 425 hours, respectively), and length of stay in the intensive care unit (16 +/- 18 days vs 14 +/- 18 days, respectively). Recipient survival in the older and younger donor groups at 30 days, 3, 6, 12, 24, and 60 months was 77% +/- 6%, 75% +/- 6%, 73% +/- 7%, 73% +/- 7%, 68% +/- 5%, and 68% +/- 4% versus 86% +/- 2%, 83% +/- 3%, 80% +/- 3%, 78% +/- 3%, 71% +/- 4%, and 66% +/- 4%, respectively. CONCLUSIONS: Lung grafts from elderly donors have been considered as marginal organs for transplantation. However, this study indicates that transplantation of lungs from carefully selected donors aged 50 years or more may lead to similar short- and long-term outcomes compared with lungs from younger donors. The use of lungs from elderly donors may help to increase the number of donor organs in lung transplantation.

Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine.

OBJECTIVE: Tacrolimus has been shown to provide superior immunosuppression in various solid organ transplant settings. The purpose of our study was to compare the survival of porcine lung allografts after induction with either cyclosporine A (CsA) or tacrolimus. METHODS: Single lung transplantation from MHC mismatched donors was performed in 10 minipigs. Immunosuppression included 1.5 mg/kg per day methylprednisolone and 1.0 mg/kg per day azathioprine. CsA (n=5) was adjusted to trough levels of 300-500 ng/ml, tacrolimus (n=5) was adjusted to 16-26 ng/ml. All immunosuppressive drugs were discontinued on postoperative day (POD) 28. Allograft survival was monitored by sequential chest radiographs, bronchoscopy and transbronchial biopsy histology. Peripheral blood leukocytes were scanned for donor chimerism and CD3, CD4, CD8 and CD25 expression. RESULTS: The animals survived a 4-week course of immunosuppression without radiological or histological signs of rejection on POD 28. Median allograft survival in CsA-treated animals was 55+/-15 days and all animals rejected their grafts within 42 days after withdrawal of immunosuppression. In tacrolimus-treated animals, median survival was 152+/-65 days with the longest survivor being electively sacrificed on POD 390 (P=0.0064). The degree of donor leukocyte chimerism and the frequency of CD4+CD25+ T-cells were higher in the tacrolimus group, however, these differences were not statistically significant. CONCLUSION: The results of our study show that primary immunosuppression with tacrolimus is superior to cyclosporine after pulmonary allotransplantation in a large animal model.

Consulting the "experts": a pilot study on perceptions of professional support among lung transplant recipients and accompanying relatives.

BACKGROUND: Lung transplantation is extremely stressful for patients and accompanying support persons. PURPOSE: To improve delivery of care, we designed a cross-sectional study about unmet needs and perceived helpfulness of staff. METHODS: The sample consisted of 30 adult lung transplant recipients with cystic fibrosis (and 22 relatives) and 20 age-matched recipients with other reasons for transplantation (and 17 relatives). Mean survival since transplantation was 5 years. Data were collected via questionnaires (numerical rating scales and fill-in-the-blank items). RESULTS: Most patients in both groups were satisfied with staff support (nurse, doctor) especially during the acute stage of illness. Relatives were less satisfied at all stages. Patients' satisfaction with doctors' support was higher after than before transplantation, but the opposite was true for relatives. Insufficient continuity of care was the most frequent critical comment from patients and support persons. Recommendations to improve delivery of care included providing access to psychosocial professionals and broadening the information provided before transplantation. CONCLUSIONS: Regular screening of customer satisfaction should become routine. Particular attention should be paid to support persons.

Liver stiffness measurements and short-term survival after left ventricular assist device implantation: A pilot study.

BACKGROUND: Hepatic dysfunction can contribute to the clinical outcome of patients with end-stage chronic heart failure (HF). This pilot study evaluated the importance of liver stiffness (LS) measurements by acoustic radiation force impulse (ARFI) imaging elastography in patients with end-stage chronic HF who underwent left ventricular assist device (LVAD) implantation. METHODS: The study enrolled 28 patients (23 men), mean age of 54 ± 11 years, with end-stage chronic HF selected for LVAD implantation. At baseline, all patients received LS measurements using ARFI elastography. Hepatic venous pressure gradient measurements and transjugular liver biopsies were performed in 16 patients. Liver stiffness was measured 21 days (Follow-up 1, n = 23) and 485 ± 136 days (Follow-up 2, n = 13) after LVAD implantation. Patients were classified according to their baseline LS into Group I (low baseline LS [no significant fibrosis = Metavir F < 2]) or Group II (high baseline LS [significant fibrosis = Metavir F ≥ 2]). RESULTS: LS at baseline was higher in Group II than in Group I (p < 0.001) and decreased significantly after LVAD implantation (Follow-up 1, p = 0.002; Follow-up 2, p = 0.002). Baseline LS correlated with liver fibrosis (p = 0.049) and central venous pressure (p = 0.001). Non-survivors showed higher LS (p = 0.019), bilirubin (p = 0.018), Model for End-Stage Liver Disease score (p = 0.001), and liver fibrosis (p = 0.004) compared with the survivors. In the univariate analysis, LS was a significant factor (p = 0.017) in predicting survival after LVAD implantation. CONCLUSIONS: ARFI elastography shows that LS is influenced by central venous congestion and histologic changes of the liver in patients with end-stage chronic HF. LS may predict the outcome in patients after LVAD implantation.