Secondary listing for deceased-donor kidney transplantation does not increase likelihood of engraftment at a large transplant center.

The supply of donor organs has not increased as fast as has the number of patients awaiting kidney transplantation. Few organs are shared outside the areas of recovery. This trend has caused some ESRD patients to seek listing at multiple centers. We examined UNOS registry data and transplant registry data at the University of Alabama at Birmingham (UAB) for the 576 patients listed at multiple centers over an 8-year span ending December 31, 2005. We identified 72 multilisted patients who received a deceased-donor renal allograft at UAB and reviewed their records for demographics, HLA matching and transfer of listing time. The only predictors for transplantation at UAB were initial listing at UAB or transfer of waiting time. Fifty-one of the 72 patients had listed at UAB first; the other 21 had transferred waiting time. None of the 176 patients who listed elsewhere first and did not transfer waiting time had been transplanted at UAB. Aggregate cost of listing and evaluation for the 176 patients listed elsewhere first who did not transfer waiting time was $1 254 528. Secondary listing at UAB, with a large cohort awaiting transplantation, without transfer of waiting time from another center was an expensive and futile process.

Differential pharmacokinetic interaction of tacrolimus and cyclosporine on everolimus.

OBJECTIVE: We characterized the pharmacokinetics of tacrolimus and everolimus in a combined immunosuppressive regimen. METHODS: This was an open-label exploratory trial in eight maintenance renal transplant patients with calcineurin inhibitor intolerance initially receiving mycophenolate mofetil (MMF) and tacrolimus. At enrollment, MMF was discontinued and replaced with everolimus 1.5 mg twice a day in study period 1 (days 1 to 10). In period 2 (day 11 to month 3), tacrolimus dose was reduced by half. RESULTS: At study entry tacrolimus trough level (C0) was 7.9 +/- 3.9 ng/mL and area under the curve over a dosing interval (AUC) was 132 +/- 56 ng x h/mL. The addition of everolimus in period 1 did not change tacrolimus exposure: C0 8.4 +/- 4.0 ng/mL, AUC 134 +/- 70 ng x h/mL. Everolimus pharmacokinetics in the presence of tacrolimus in period 1 were: C0 3.3 +/- 1.2 ng/mL, Cmax 10.4 +/- 5.1 ng/mL, AUC 58 +/- 20 ng x h/mL. When compared to pharmacokinetic data from a previous study in 47 renal transplant patients receiving everolimus at the same fixed dose (1.5 mg twice a day) with cyclosporine, everolimus exposure was 2.5-fold higher with cyclosporine relative to the data in this study with tacrolimus. After tacrolimus dose reduction in period 2, there was no clinically relevant change in everolimus exposure: C0 3.0 +/- 1.1 ng/mL, Cmax 8.2 +/- 1.3 ng/mL, AUC 49 +/- 10 ng x h/mL. CONCLUSIONS: Tacrolimus appears to have a minimal effect on everolimus blood levels compared with the influence of cyclosporine. The dose of everolimus when combined with tacrolimus needs to be higher than when combined with cyclosporine in order to reach a given everolimus blood level.

Ageism and kidney transplantation.

The growing shortage of deceased-donor kidneys and the rapid growth in the number of patients with end-stage renal failure aged 65 years and older is impacting the current policies for allocation of allografts. The utilitarian and egalitarian philosophies may clash in times of limited resources. Organ transplantation can be viewed as a microcosm concerning healthcare issues facing an aging population and limited resources. The limited resources in organ transplantation are not merely financial. The limits on supply of deceased-donor organs will force the transplant community to deal with allocation issues before the more general population faces other limits in health care. Our discussions may clarify some of the problems.

Experience with cyclosporine.

Cyclosporine ended the azathioprine-prednisone era of transplantation. For years prior to cyclosporine, regimens in transplant centers were relatively fixed and all patients received the same two drugs in nearly the same doses with adjustments made primarily for toxicities. Transplant physicians became expert in the side effects of steroids and azathioprine. Cyclosporine changed everything. Change is never easy, however, and initial resistance to changing protocols (especially for a new nephrotoxic drug) was only overcome by randomized, controlled trials. Cyclosporine increased allograft and patient survival rates without increasing opportunistic infections. However, as important were the changes in thinking that came about. It can be argued that cyclosporine contributed to expanding multicenter controlled trials in the transplant community. It also helped bring about concepts such as tailoring drugs to individual patients, drug minimization or elimination, use of polypharmacy, and focus on the first few weeks after transplant. Understanding of T-cell function and causes of renal dysfunction were brought into clearer focus by this exciting new agent.

Cystic lesions of the pericardium. Review of the literature and classification.

Pericardial cystic lesions (PCLs) occur infrequently but are significant for their varying clinical presentation and pathological multitude. A review of the literature (including Medline and Current Contents database searches, and search of existing bibliographies) finds confusion in nomenclature and an absence of appropriate classification. A new classification system is proposed based on exo- or endophytic growth, presence of adhesions, and compression of myocardium or great vessels. A multitude of pathological entities with diverse pathogenesis, disease courses, and prognoses may present as PCLs. Detailed knowledge of lesion types and alternatives among diagnostic and therapeutic options permits a selective approach to patient management. The usefulness of a unified classification system should be evaluated in a substantial patient population, with detailed statistical analysis.

Tracheostomy: a risk factor for mediastinitis after cardiac operation.

BACKGROUND: We studied whether tracheostomy after coronary artery bypass grafting (CABG) is associated with higher incidence of mediastinitis and mortality, and whether shorter intervals between median sternotomy and tracheotomy are associated with higher incidence of mediastinitis. METHODS: Patients (n = 6,057) undergoing CABG since March 1977 were reviewed. Patients requiring tracheostomy and those developing mediastinitis were identified. Mediastinitis diagnosis required positive culture of mediastinal tissue or fluid. RESULTS: After CABG, 88 patients had tracheostomy performed (1.45%). Seven patients receiving tracheostomy after developing mediastinitis were excluded. Of the remaining 81 patients, 7 developed mediastinitis (8.6%) compared with 44 of 5,969 (0.7%) who did not require tracheostomy (p < 0.001). Mortality in tracheostomy patients was 24.7% (20 of 81) compared with 5.2% in patients not requiring tracheostomy (316 of 5,969; p < 0.001). Patients not developing mediastinitis had tracheostomy placement an average of 25 days after CABG compared with 18.7 days for those developing mediastinitis (p = 0.141). CONCLUSIONS: Tracheostomy after CABG is associated with increased incidence of mediastinitis and mortality. In this review, the time interval between CABG and tracheostomy was not predictive of mediastinitis. A larger sample size would be required to be confident that there is no correlation.

Variables affecting weight gain in renal transplant recipients.

Previous studies of renal transplant recipients have suggested that weight gain after transplantation is relatively common, especially among certain populations. We conducted a retrospective review of 977 renal transplant recipients at the University of Alabama at Birmingham to identify patterns of weight change (as mean percentage of body weight at transplantation) attributed to race, sex, income, age at transplantation, pretransplantation time on dialysis, incidence of diabetes, rejection episode(s), and/or obesity (body mass index >/= 30 kg/m(2)) at transplantation. Patients were evaluated at 3, 6, 9, and 12 months posttransplantation and at 2 and 3 years, when available. Univariate analysis at 1 year showed that blacks achieved a greater weight change than whites (P = 0.0004), women had greater gains than men (P = 0.0001), and low-income patients had greater mean gains versus medium- (P = 0.0001) and high-income patients (P = 0.0001). Advancing age and weight gain were inversely correlated (P = 0.0002). Having one or more rejection episode indicated less weight gain than having no rejection episode (P = 0.0220). Incidence of diabetes or time on dialysis was not a significant predictor of weight gain. Black race, female sex, low income, younger age, and no incidence of rejection episodes were significantly associated with weight gain at 1 year in the multivariate analysis.

Tolerance in renal transplantation after allogeneic bone marrow transplantation-6-year follow-up.

Despite significant advancements in clinical transplantation, very few reports describe the long-term acceptance of transplanted solid organs without indefinite immunosuppression. The immunosuppressive agents used are nonspecific and have serious potential side effects. We present a patient who received a living-donor renal allograft from the same person who had donated bone marrow to her several years earlier. Tolerance was expected based on previous acceptance of full-thickness skin grafts from the donor. Indeed, there has been no evidence of rejection during a 6-year follow-up period, and no induction or maintenance immunosuppression has been given. All noninvasive parameters of graft function remain normal. This and similar reports prove that genetically disparate solid organs can coexist without pharmacological immunosuppression.

Mechanical circulatory support for acute heart failure.

Circulatory support devices are frequently required in postcardiotomy shock, postmyocardial infarction shock, and acute myocarditis. A panel of cardiac surgeons addressed the use of these devices in 4 patients. Cardiogenic shock after mitral valve replacement was considered best served by a left ventricular assist device (VAD) with apical rather than atrial cannulation. A left VAD should be placed first and a right VAD only if needed. Acute myocardial infarction shock was considered best treated with a left VAD with left ventricular cannulation to avoid thrombosis. If cardiac transplantation is an option, a long-term device must be considered. Young patients with acute fulminant myocarditis should be implanted with VADs in anticipation of recovery, and transplantation should be delayed. Patients with severe heart failure after coronary bypass grafting were considered best served by an extracorporal membrane oxygenation (ECMO) system or a VAD. Current postcardiotomy survival rates of postcardiotomy patients of 20% to 40% are worthwhile, but can be improved. Temporary devices such as ECMO can be changed to more long-term devices when necessary.

Ross procedure for complex left ventricular outflow tract obstruction.

BACKGROUND: Complex left ventricular outflow tract (LVOT) obstruction in children continues to pose a significant therapeutic challenge to cardiac surgeons. The Ross procedure, in combination with resection of subaortic stenosis or a Konno type septal incision, is an important option for these difficult patients. METHODS: Recently two children aged 14 and 5 years with LVOT obstruction involving combined subaortic and valvar stenosis underwent surgical correction using the pulmonary autograft. Clinical presentation, operative technique, outcome and intermediate follow-up are detailed. RESULTS: One patient had resection of an isolated subaortic membrane in combination with a pulmonary autograft and the second a Ross Konno procedure. Postoperative hospital stays were without complication. Both patients were discharged at 5 days and have no significant obstruction nor semilunar valve insufficiency at 3 years' follow-up. CONCLUSIONS: Pulmonary autografts can be used in combination with resection of subaortic tissue or a septal incision for reconstruction of complex left ventricular outflow tract obstruction. This technique renders excellent short term valve function, relief of obstruction, avoids anticoagulation and provides potential for future growth.

The best way to manage hypertension after renal transplantation.

Hypertension in renal allograft recipients is a common problem arising from multiple factors, including peripheral vascular damage caused by pretransplant hypertension, side effects of immunosuppressive medications, allograft dysfunction, renal artery stenosis, recurrent glomerulonephritis, synthesis of vasoconstrictive hormones by the native kidneys, and excessive dietary salt intake. Identification of modifiable factors causing hypertension and concurrent medical conditions, and measurement of glomerular filtration rate, cyclosporine/tacrolimus blood levels, and magnitude of proteinuria are essential to tailor treatment for an individual patient. Lifestyles that exacerbate hypertension should be modified. For pharmacological therapy, diuretics and calcium channel blockers are first-line agents in patients on cyclosporine shortly after transplant. Angiotensin-converting enzyme inhibitors are good choices for patients with significant proteinuria. Reduction of immunosuppression will improve hypertension in some patients, but entails a potential risk of rejection or graft loss. Angioplasty is necessary in patients with a functionally significant stenosis of the allograft renal artery. Other patients on maximal medical therapy may benefit from native nephrectomy.

Differences in bioavailability between oral cyclosporine formulations in maintenance renal transplant patients.

Previous studies of healthy volunteers and small numbers of transplant recipients have suggested that the oral solution formulation of Sandimmune (cyclosporine [CsA]; Sandoz Pharmaceuticals, East Hanover, NJ) is bioequivalent to the soft gelatin capsule (SGC) formulation. However, there is conflicting evidence as to whether the two formulations are bioequivalent in all patients; to date, there are no published studies that explicitly address their bioequivalence in patients. We conducted a randomized, open-label, two-sequence, two-period, crossover study. Of 20 maintenance renal transplant recipients shown by a screening pharmacokinetic (PK) profile to be poor absorbers of CsA, half were randomized to receive first the SGC formulation and half the oral solution formulation for a period of 7 days. Each patient then underwent a 12-hour PK profile on the last day of the assigned formulation before a crossover to receive the other formulation and repeat the 7-day treatment and PK profile cycle. The results showed that peak and total exposure to CsA was greater with the SGC formulation. The SGC-oral solution ratios indicated an average 38% greater peak and 11% greater total exposure for the SGC formulation (P < 0.01 and P = 0.09, respectively). Trough levels were more similar between formulations, with SGC showing an average of 5% greater troughs (P > 0.10). In our selected population of malabsorbers, the SGC formulation made a difference in drug exposure.

Centrifugal pumps: description of devices and surgical techniques.

BACKGROUND: Because of simplicity of application, universal access, and low cost, centrifugal pumps are commonly used for short-term mechanical cardiac assist. Indications and techniques for application of this technology continue to evolve. METHODS: The clinical experience with 151 patients undergoing centrifugal mechanical cardiac assist at the University of Missouri-Columbia has been reviewed. We have compared commonly available centrifugal pumping systems in vitro and in vivo for characteristics that might distinguish them. RESULTS: Centrifugal pumps have been found to be well suited for use in surgery on the thoracic aorta, for extracorporeal membrane oxygenation and for postcardiotomy cardiac mechanical assist. Complications associated with centrifugal mechanical assist are predictable and common but potentially can be reduced by improved surgical techniques and anticoagulation strategies. In vitro and in vivo experimentation with available centrifugal pumps reveals nuances characteristic of each of the devices. CONCLUSIONS: All centrifugal pumps presently available are less destructive to blood cellular elements compared with roller pumps. With familiarity, all can function satisfactorily for short-term mechanical assist with no compelling evidence that favors any particular centrifugal pump system clinically available. Centrifugal pumps are ideally suited for left heart bypass during surgery on a thoracic aorta and for short-term application as may be required for postcardiotomy mechanical assist. Centrifugal pump technology should be part of the armamentarium of all cardiothoracic surgeons.

Minimally invasive lobectomy directed toward frail and high-risk patients: a case-control study.

BACKGROUND: To compare minimally invasive video-assisted thoracic surgery (VATS) with thoracotomy, cases were matched from a pool of pulmonary lobectomies performed by one surgeon who offered VATS for patients with unfavorable risk factors. METHODS: A thoracotomy case was paired to each of 19 VATS cases by age, sex, lobe, side, and forced expiratory volume in 1 second. Eleven VATS and 5 thoracotomy patients with severe activity impairments or reduced forced expiratory volume in 1 second (< 1.5 L or 50% predicted) were classified as higher risk than the others. RESULTS: Despite more high-risk cases, VATS yielded shorter hospitalizations (5.3+/-3.7 versus 12.2+/-11.1 days, p = 0.02), chest tube durations (4.0+/-2.8 versus 8.3+/-8.9 days, p = 0.06), and earlier returns to full preoperative activities (2.2+/-1.0 versus 3.6+/-1.0 months, p < 0.01). The VATS operations had no intraoperative complications and lasted 229+/-59 minutes. Pain 3 weeks later was dramatically better for the VATS group (none or mild, 63% versus 6%; severe, 6% versus 63%; p < 0.01). Six complications or deaths occurred in each group and were related to forced expiratory volume in 1 second, steroid usage, age, active smoking, and upper lobe resection (p < 0.01). Three VATS deaths occurred only in elderly, performance status 3 patients, with two caused by gastrointestinal-related problems masked by steroid use. CONCLUSIONS: A VATS lobectomy is less painful and may offer faster recovery for the frail or high-risk patient. Further study, particularly of its safety in severely activity-impaired patients, is warranted.

The heartmate left ventricular assist system: first successful implantation in Missouri.

We report a case of the first successful implantation of the HeartMate left ventricular assist system as a bridge to heart transplant in the state of Missouri. Indications, technique of insertion, patient selection, outcomes and future applications are discussed.