Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.

Incidence and impact of herpes simplex and cytomegalovirus detection in the respiratory tract after lung transplantation.

Herpesvirus infections cause morbidity in lung transplant recipients. The study was conducted to investigate the incidence and impact of herpes simplex virus (HSV) and cytomegalovirus (CMV) detection in the respiratory tract (RT) of lung and heart-lung transplant recipients (LTR) during the postoperative phase. In a prospective cohort study, 91 LTR having at least 1 nasopharyngeal swab (NPS) sent for virus diagnostics were monitored for CMV and HSV detection in NPS during their post-transplant hospital stay on cardiothoracic surgery wards (median 4 weeks) by direct immunofluorescence testing for HSV, virus culture, and CMV and HSV polymerase chain reaction (PCR). Bronchoalveolar lavages (BALs) were analyzed with the same protocol except that HSV PCR was only performed on request. Risk factor analysis for the outcome '90-day mortality' was performed. Fifteen LTR had virus detection in NPS (16.5%): 9 had CMV, 5 had HSV, and 1 had both CMV and HSV. Four of 84 LTR had CMV detection in BAL (4.8%). Absence of CMV detection in NPS had a negative predictive value of 98.8% for absence of CMV detection in BAL. HSV DNA detection in NPS, especially if detected within 8 days after transplantation, was associated with 90-day mortality. In conclusion, detection of herpesviruses in the RT was clinically relevant and frequent, despite antiviral prophylaxis.

Management and outcomes after multiple corneal and solid organ transplantations from a donor infected with rabies virus.

BACKGROUND: This article describes multiple transmissions of rabies via transplanted solid organ from a single infected donor. The empirical Milwaukee treatment regimen was used in the recipients. METHODS: Symptomatic patients were treated by deep sedation (ketamine, midazolam, and phenobarbital), ribavirin, interferon, and active and passive vaccination. Viral loads and antibodies were continuously monitored. RESULTS: Recipients of both cornea and liver transplants developed no symptoms. The recipient of the liver transplant had been vaccinated approximately 20 years before transplantation. Two recipients of kidney and lung transplants developed rabies and died within days of symptomatic disease. Another kidney recipient was treated 7 weeks before he died. The cerebrospinal fluid viral load remained at constant low levels (<10,000 copies/mL) for approximately 5 weeks; it increased suddenly by almost 5 orders of magnitude thereafter. After death, no virus was found in peripheral compartments (nerve tissue, heart, liver, or the small intestine) in this patient, in contrast to in patients in the same cohort who died early. CONCLUSIONS: Our report includes, to our knowledge, the longest documented treatment course of symptomatic rabies and the first time that the virus concentration was measured over time and in different body compartments. The postmortem virus concentration in the periphery was low, but there was no evidence of a reduction of virus in the brain.

[Fast track in cardiac surgery]. / Fast Track in der Herzchirurgie.

Fast track in cardiac surgery is not well defined. In the past early or immediate extubation was used as a marker. After cardiac surgery this parameter is not sufficient. In addition to cardiorespiratory stability, circulatory and haemostatic homeostasis are also required. Therefore the current Fast Track concept includes a period of intensive monitoring of the patient postoperatively to establish stability. Thereafter intensive care medicine should not be required. Evolving new surgical concepts in combination with appropriate anaesthesiologic management will lead to wide application of fast track cardiac surgery in the future.

Intentional ABO-incompatible lung transplantation.

We report on a case of intentional blood group incompatible lung transplantation. A blood group O cystic fibrosis patient was mechanically ventilated and put on interventional lung assist for severe respiratory decompensation. Since timely allocation of a blood group O donor lung was impossible, an AB deceased donor lung rescue allocation was accepted and the transplant performed using a pre-, peri- and postoperative antibody depletion protocol including plasmapheresis, ivIg administration, rituximab and immunoadsorption. Nine months after the transplant the patient is at home and well.

Effects of ivabradine on allograft function and exercise performance in heart transplant recipients with permanent sinus tachycardia.

Aim of this retrospective analysis was to evaluate the effects of ivabradine given primarily as a heart rate-lowering agent on allograft function and cardiopulmonary performance in heart transplant recipients with permanent sinus tachycardia. Starting May 2006, 26 heart transplant recipients with permanent sinus tachycardia received ivabradine (5 mg bid). It was discontinued early in 3 patients (11.5%) due to adverse events. In the remaining 23 patients, resting heart rate (HR) was significantly lowered from 106.3 +/- 9.1 to 82.2 +/- 6.3 bpm after 3 weeks of treatment. The effect remained constant during the remaining treatment period, whereas resting blood pressure was not affected. After 12 weeks of ivabradine treatment, the corrected QT interval was significantly reduced into the range seen in normal individuals. Left ventricular (LV) end-diastolic posterior wall thickness, LV mass and LV mass index were also found to have decreased significantly. There was a trend to improvement of cardiopulmonary performance and LV ejection fraction, both of which did not reach statistical significance, however. It may be concluded that ivabradine successfully reduced the resting HR of heart transplant recipients with sinus tachycardia without negatively influencing the blood pressure. The definitive impact of ivabradine on LV mass regression and cardiopulmonary performance require further prospective, randomized and controlled trials.

Impact of bacterial and fungal donor organ contamination in lung, heart-lung, heart and liver transplantation.

We investigated to which extent bacterial and fungal donor organ contamination (DOC) caused posttransplant nosocomial infections (NI) in solid organ transplant (Tx) recipients. Between January 2002 to December 2003 (lung and heart Tx) and October 2003 to September 2004 (liver Tx), NIs were determined according to modified CDC criteria for NIs for all transplantations performed at Hannover Medical School. Organisms of the same species cultured from donor organs and infected transplantees were genotyped if available. Out of 282 solid organ recipients (140 lung-Tx, 16 heart-lung-Tx, 51 heart-Tx, 75 liver-Tx), 150 recipients (53.2%) received contaminated donor organs. Incidences of NIs were 33.7% in lung, 68.8% in heart-lung, 21.6% in heart, and 28% in liver recipients. In 11 out of 282 transplantees (3.9%, CI (95%) 2.0-6.9%) organisms of NIs and of contamination of the donor organ were of the same species. Even if assuming five missing pairs of organisms as genetically identical, incidences of DOC-related posttransplant infections were only between 1.3% (CI(95%) 0.0; 7.2) in liver-Tx and 18.8% (CI(95%) 4; 45.6) in heart-lung Tx, and DOC related mortality was 0.4% (CI(95%) 0.0;1.9). Despite high DOC rates, posttransplant infections due to DOC were rare under the condition of adequate preoperative antibiotic prophylaxis and aseptic organ retrievement.

Alternatives to heart transplantation. Symposium of the "Treatment of End-stage Heart and Lung Failure" working group on October 22, 2005 in Munich.

Heart transplantation is currently the treatment of first choice in patients with end-stage refractory heart failure. But already the demand for donor organs cannot be met, and patients face long waiting times for transplantation. In the future waiting times will become even longer as life expectancy increases and the number of heart-failure patients requiring transplantation grows. Consequently, in view of the poor prognosis of the disease in its advanced stages, alternatives to heart transplantation are increasingly gaining importance. In recent years new innovative treatment methods and techniques have been developed which have already proved clinically successful in patients with end-stage heart failure, especially as bridging measures. Some of these techniques appear suitable for long-term use and could therefore serve as an alternative to heart transplantation in some patients. Interesting new avenues of research may even lead to cardiac cell replacement therapies in the future. These approaches are currently undergoing initial clinical trials. This report presents surgical and cardiologic treatments for end-stage heart failure that have already been clinically investigated as well as techniques that are still in the preclinical stage and discusses their potential as alternatives to heart transplantation.

Adverse effects of rabies pre- and postexposure prophylaxis in 290 health-care-workers exposed to a rabies infected organ donor or transplant recipients.

The recent unfortunate rabies transmissions through solid organ transplants of an infected donor in Germany required the initiation of a vaccination program to protect health care workers (HCWs) with close contact to rabies-infected patients. A systematic follow-up of adverse effects was initiated. Rabies postexposure prophylaxis (PEP) was started in 269 HCWs at four German hospitals. Pre-exposure prophylaxis (PreEP) was administered to 74 HCWs caring for an already diagnosed rabies patient. At each vaccination date, HCWs were interviewed for symptoms possibly representing adverse effects. Adverse effects of PEP and PrePEP were compared. Out of 269 HCWs, 216 were included for the investigation of adverse effects. Of these 216 HCWs, 114 (53%) individuals developed at least one systemic adverse effect. Incidences of tiredness (30.6%), malaise (26.4%), headache (26.9%), dizziness (14.8%), and chills (13.0%) declined in the course of PEP (p < 0.05), whereas incidences of fever (7.4%), paraesthesias (7.9%), arthralgias (1.9%), myalgias (4.2%), nausea (9.3%), diarrheas (2.8%) and vomiting (1.4%) did not. In 11 (5.1%) HCWs PEP was discontinued mostly due to adverse reactions (four suffered strong headaches, two HCWs meningeal irritations, two chills, one paraesthesia, one malaise, and one a rush). Systemic effects of PEP or PreEP did not differ significantly. Despite relatively high incidences of moderate severe adverse reactions rabies PEP is safe. Strong headache, tiredness, dizziness, and paraesthesias are the most important postvaccinal symptoms. Vaccinees suffering from adverse effects of PEP must be strongly encouraged to complete PEP, as it is to date the only protection against fatal rabies.

[Infection control measures and surveillance of patients with ventricular assist devices]. / Infektionsprävention und -Surveillance bei Kunstherzpatienten.

Ventricular assist devices (VAD) are a new routine therapy option for end-stage heart failure. However, the incidence of VAD-related infections varies between 20 and 188% and makes a major contribution to VAD-related morbidity. Therefore, optimised infection control policies should be applied to prevent VAD-related infections. As to date only a few studies exist investigating particular prevention measures for VAD recipients, we have tried to adapt evidence-based guidelines. In detail the following preventive measures are discussed: antibiotic prophylaxis, endocarditis prophylaxis, dressing technique for the driveline-exit site and education of patients and medical staff. A new patient-based surveillance system is proposed which reflects the different times since implantation of VADs and therefore allows a fair method for interhospital comparison.

Pressure-controlled versus volume-controlled one-lung ventilation for MIDCAB.

One-lung ventilation is limited by hypoventilation and hypoxemia because of increasing airway pressure and intrapulmonary shunt. Previous clinical studies compared pressure-controlled versus volume-controlled ventilation during one-lung ventilation in patients with pre-existing pulmonary disease. We studied 50 patients undergoing thoracotomy and one-lung ventilation because of cardiovascular disease. After two-lung ventilation with volume-controlled ventilation, patients were divided randomly into two groups. In one group, ventilation was switched to pressure-controlled ventilation after starting one-lung ventilation. In the other group, volume-controlled ventilation was continued. Parameters of ventilation, pulmonary function and systemic and pulmonary hemodynamics were recorded. We observed, that peak airway pressure, dead space ventilation and arterial carbon dioxide partial pressure were significantly higher during volume-controlled ventilation. After one-lung ventilation patients with pressure controlled ventilation had lower alveolar-arterial oxygen tension difference and a higher arterial oxygen partial pressure with significant differences for those patients in the intensive care unit. We conclude that pressure-controlled ventilation may be useful to improve gas exchange and alveolar recruitment during one lung ventilation.

Outcome following single vs bilateral lung transplantation in recipients 60 years of age and older.

AIMS: The significant shortage of donor organs in lung transplantation necessitates a careful selection of lung transplant recipients. The outcome of lung transplant recipients aged 60 years and older has not been analyzed systematically. METHODS: We retrospectively reviewed our experience with older recipients. Between January 1999 and July 2003, 248 patients underwent lung transplantation at our institution, of which 18 were aged 60 years and older (7.3%, range 60-66, mean 62 +/- 1.1). RESULTS: Eleven (61%) of the recipients 60 years and older received a single (SLTx) and seven (39%), a bilateral lung transplant. Donor age in the single transplant cohort was 30 +/- 4 years. It was 33 +/- 3 years in bilateral patients. Posttransplant ventilation time was significantly different among groups, with 282 +/- 32 hours after bilateral and 56 +/- 13 hours after transplant (P < .05). Also significantly longer was the length of the ICU stay in the bilateral group. First PaO2 in the ICU was not different among the two groups. The 1-year survival in the single transplant group was significantly better compared to the bilateral group with 73% versus 43%, respectively. CONCLUSIONS: The 1-year survival following lung transplantation in patients older than 60 years is markedly reduced compared to recipients under 60 years of age. If a lung transplant is considered in a recipient above the age of 60 years, a single transplant should be favoured. If that is not indicated, patients over 60 should be very carefully selected for bilateral transplant.

[Lung transplantation. Possibilities and limitations]. / Lungentransplantation. Möglichkeiten und Grenzen.

Lung transplantation is an option for patients with endstage pulmonary diseases without contraindications. Recent European studies showed a survival benefit for patients with cystic fibrosis, fibrosis and emphysema after lung transplantation. Early mortality has been reduced recently by surgical improvements. Life expectancy after lung transplantation has improved in recent years but is still lower than in patients with other solid organ transplantations. Quality of life is consistently improved but exercise tolerance keeps reduced in comparison to the normal population. Specific problems described in detail are frequent organ rejections and infections, airway problems and a high incidence of malignant diseases. 5-year survival after lung transplantation is in average 60%.

[Quality of life and exercise capacity in lung transplant recipients]. / Lebensqualität und körperliche Leistungsfähigkeit bei Patienten nach Lungentransplantation.

BACKGROUND: Quality of life in lung transplant recipients (LTR) is reported to be comparable with that of the general population. However, previous studies have shown that exercise capacity was reduced to 30 - 40 % of normal values. The purpose of this study was to investigate the gap between good self-reported quality of life and reduced exercise capacity in LTR, to describe possible correlations and to compare the results with those of a control group (CG). METHODS: 27 LTR 208 +/- 67 days after bilateral lund transplantation (16 male, 11 female; age: 46 +/- 10 years; body mass index: 24 +/- 3 kg x m (- 2), FEV (1) % 75 +/- 27 %) and 30 controls (17 male 13 female; age 47 +/- 15 years; BMI: 26 +/- 4 kg x m (- 2), FEV (1) % 103 +/- 15 %) performed cardiopulmonary exercise testing and were interviewed with the standardized German "Quality of life profile for chronic disease" self-rating questionnaire. RESULTS: Significant differences were shown in objective exercise related variables (peak oxygen consumption: LTR 15.1 +/- 1.8, CG 34.5 +/- 9.1 ml x min (- 1) x kg (- 1); p < 0,01); peak workload: LTR 1.0 +/- 0.2; CG 2.4 +/- 1.0 W. kg (- 1); p < 0.01); percentage of predicted workload: LTR 44 +/- 12, CG 115 +/- 33 %; p < 0.01). The rating of subjective quality of life in physical, psychological and social domains of LTR did not differ from values of the CG or of the general population (n = 1143). The quality of life in the physical domain correlated significantly with peak exercise capacity (LTR r = 0.44, p < 0.05; CG r = 0.37; p < 0.05). CONCLUSION: Patients 7 months after lung transplantation described their physical, social and psychological quality of life as equally good as the healthy control group. However, peak exercise capacity and oxygen consumption were markedly reduced. To improve physical capacity in the range of daily activities, an exercise training program should be offered to patients after lung transplantation.

The experience of the support person involved in a lung transplant programme: results of a pilot study.

UNLABELLED: In contrast to the high priority most transplant programmes give to the recipient's support system there is a paucity of studies referring to the experience of the respective support persons. This study sought to focus on the subjective burden of support persons and their unmet needs. METHOD: A questionnaire was designed for a cross-sectional study using numerical rating scales and fill-in-the-gap-items concerning subjective burden, stress symptoms, unmet needs, suggestions to improve the support person's situation. Participants were 39 relatives of adult transplant patients (22 cystic fibrosis transplant recipients, 17 recipients with other aetiologies) who had transplants 5 years ago (mean). RESULTS: The acute illness stage was rated as extremely stressful by most of the respondents. However, even during the rehabilitation period, one third described themselves as very stressed. Stress related symptoms at or post transplant were reported by 82% of respondents (more mothers than partners). Symptoms mostly referred to depressive and anxiety states. Most support persons had to tackle organizational difficulties in order to stay with the recipient and faced financial burdens not refunded by agencies. Support persons made suggestions to improve the recipient's situation and those of other support persons. Regarding the recipient their advice referred to enhanced information giving, aspects of communication and better access to psychosocial professionals. Regarding another support person they suggested to be well-informed beforehand and to remain optimistic. CONCLUSIONS: Mothers in this study seemed to be particularly vulnerable as support persons and thus deserve special attention. Few resources may be needed to achieve considerable benefit for the support person, such as arranging accommodation or identifying a team member to relate to.