Jan Ankersmit

Pretransplant cachexia and morbid obesity are predictors of increased mortality after heart transplantation

Background. Extremes in body weight are a relative contraindication to cardiac transplantation. Methods. We retrospectively reviewed 474 consecutive adult patients (377 male, 97 female, mean age 50.3±12.2 years), who received 444 primary and 30 heart retransplants between January of 1992 and January of 1999. Of these, 68 cachectic (body mass index [BMI]<20 kg/m2), 113 overweight (BMI=>27–30 kg/m2), and 55 morbidly obese (BMI>30 kg/m2) patients were compared with 238 normal-weight recipients (BMI=20–27 kg/m2). We evaluated the influence of pretransplant BMI on morbidity and mortality after cardiac transplantation. Kaplan-Meier survival distribution and Cox proportional hazards model were used for statistical analyses. Results. Morbidly obese as well as cachectic recipients demonstrated nearly twice the 5-year mortality of normal-weight or overweight recipients (53% vs. 27%, respectively, P =0.001). An increase in mortality was seen at 30 days for morbidly obese and cachectic recipients (12.7% and 17.7%, respectively) versus a 30-day mortality rate of 7.6% in normal-weight recipients. Morbidly obese recipients experienced a shorter time to high-grade acute rejection (P =0.004) as well as an increased annual high-grade rejection frequency when compared with normal-weight recipients (P =0.001). By multivariable analysis, the incidence of transplant-related coronary artery disease (TCAD) was not increased in morbidly obese patients but cachectic patients had a significantly lower incidence of TCAD (P =0.05). Cachectic patients receiving oversized donor hearts had a significantly higher postoperative mortality (P =0.02). Conclusions. The risks of cardiac transplantation are increased in both morbidly obese and cachectic patients compared with normal-weight recipients. However, the results of cardiac transplantation in overweight patients is comparable to that in normal-weight patients. Recipient size should be kept in mind while selecting patients and the use of oversized donors in cachectic recipients should be avoided.

Impact of retrograde cerebral perfusion on aortic arch aneurysm repair

OBJECTIVE Protection of the brain is a primary concern in aortic arch surgery. Retrograde cerebral perfusion is a relatively new technique used for cerebral protection during profound hypothermic circulatory arrest. This study was designed to compare, retrospectively, the outcome of 109 patients undergoing aortic arch operation with and without the use of retrograde cerebral perfusion. METHODS Fifty-five patients had profound hypothermic circulatory arrest alone, and 54 patients had supplemental cerebral protection with retrograde cerebral perfusion. Mean age was 61 +/- 13 years and 58 +/- 14 years, respectively (mean +/- standard deviation). Twenty-two preoperative and intraoperative characteristics, including age, sex, acuity, presence of aortic dissection, and aneurysm rupture, were similar in the 2 groups (P >.05). RESULTS Mean circulatory arrest times (in minutes) were 30 +/- 19 in the group without retrograde cerebral perfusion and 33 +/- 19 in the group with retrograde cerebral perfusion, respectively. chi(2) Analysis revealed that patients operated on with the use of retrograde cerebral perfusion had significantly lower hospital mortality (15% vs 31%; P =.04) and in-hospital permanent neurologic complications (9% vs 27%; P =.01). Retrograde cerebral perfusion failed to reduce the prevalence of temporary neurologic dysfunction (17% vs 18%; P =.9). Stepwise multiple logistic regression revealed that extracorporeal circulation time, age, and lack of retrograde cerebral perfusion were statistically significant independent risk factors for hospital mortality. The same analysis revealed that lack of retrograde cerebral perfusion was the only significant independent risk factor for permanent neurologic dysfunction. CONCLUSION Retrograde cerebral perfusion decreased the prevalence of permanent neurologic complications and the hospital mortality in patients undergoing aortic arch operations.

Long-term survival (>10 years) of patients >60 years with induction therapy after cardiac transplantation.

OBJECTIVE Cardiac transplantation has become an established method for end-stage heart disease. Short- and mid-term outcome has been known to be similar between younger and older (>60 years) recipients. So far, nothing is known about long-term outcome of old patients and the potential long-term effects of antibody induction therapy in these patients. The purpose of this study was to analyse long-term outcome of old cardiac transplant recipients who underwent antibody induction therapy. METHODS Since 1989, 203 patients (total n = 882) above 60 years have been transplanted at our center. On these patients n = 66 were above 65 years. Survival, incidences of rejection, infection, cancer, graft arteriosclerosis and the amount of renal insufficiency were compared with patients <60 years (n = 679), transplanted during the same period of time. Freedom from specific event was computed by Kaplan-Meier analysis and compared by log-rank test. RESULTS Ten year survival was similar in all groups (<60 years: 53.7%; 60-64 years: 53.1% and >65 years: 60.2%; P = NS). Causes of death were similar in all patient groups. There were significant fewer rejection episodes in the older patient group (freedom from rejection: 74.9 vs. 83.5 vs. 90.6; P = 0.03). Yet significantly more number of patients >65 years were without steroid maintenance therapy (43.1%) compared to other patient groups (8.2 vs. 9.3%; P < 0.05). There was no difference in overall freedom from severe infection (74.1 vs. 67.7 vs. 85.3%; P = NS), whereas there was a trend towards more CMV disease in the oldest patient group (82.7 vs. 88.6 vs. 70.8%; P=0.06). The incidence of cancer was similar in all groups (freedom from cancer: 82.2 vs. 84.7 vs. 79.1%; P = NS), as well as there was no difference in severe graftsclerosis between all patients (79.2 vs. 93.7 vs. 93.3%; P = NS). There was no difference in development of chronic renal dysfunction (creatinine > 2.0 mg/dl) between the three groups (10 vs. 14 vs. 16%; P = NS). CONCLUSIONS Old recipients of cardiac transplants have a similar long-term outcome than younger recipients. They were less prone to rejections, had a similar incidence of severe infections and showed a trend towards more CMV disease. All patients had a very low rate of graft arteriosclerosis that was similar amongst the groups. Age-related decline of the immune system further enhanced by immunomodulation of antibody induction therapy might be accounted for the results as well as steroid-free immunosuppression.

Is the transpulmonary pressure gradient a predictor for mortality after orthotopic cardiac transplantation

Elevated pulmonary vascular resistance (PVR) is a well‐known risk factor for right ventricular failure after orthotopic cardiac transplantation. The influence of preoperative transpulmonary pressure gradient (TPG) and PVR on post‐transplant 30 days mortality was evaluated. To analyze the response of PVR and TPG to cardiac transplantation, we analyzed 718 adult patients undergoing primary cardiac transplantation. Indications for operation were: 35.2% ischemic cardiomyopathy (ICM), 61.2% idiopathic dilated cardiomyopathy (DCM), and 3.3% other diagnosis (e.g. hypertrophic cardiomyopathy). The mean age (51.9) and the mean ischemic time (169.7 min) were comparable between 30 days survivors and nonsurvivors. Students t‐tests and chi‐square analysis were used to compare data from 30‐day survivors and nonsurvivors. Statistical significance was defined as P < 0.05. Fishers exact test and multiple logistic regression analysis was performed to evaluate the relationship between hemodynamic parameters and outcome after transplantation. Primary end‐point was 30 days mortality and secondary end‐point long‐term survival of patient groups with different TPG and PVR values. In survivors the mean TPG was 10.3 ± 5.1 (mean ± SD) vs. 13 ± 6.6 in patients who died after transplantation (P = 0.0012). The PVR was 2.6 ± 1.4 vs. 3.5 ± 2.2 (P = 0.0012). In multivariate logistic regression, the parameters TPG and PVR exhibit a significant influence between survivors and nonsurvivors after cardiac transplantation within 30 days (TPG: P = 0.0012; PVR: P = 0.0012). The mortality rates in patients with TPG > 11 mmHg and PVR < 2.8 Wood units or TPG < 11 mmHg and PVR > 2.8 Wood units were comparable to those with TPG < 11 mmHg and PVR < 2.8 mmHg. The TPG is an important predictor in nonrejection‐related early mortality after orthotopic cardiac transplantation. The determination of TPG in combination with PVR is a more reliable predictor of early post‐transplant survival than PVR alone.

Effect of obesity on outcome after cardiac transplantation

OBESITY is a well-described and significant risk factor for postoperative medical complications in surgery. High incidences of wound infection and dehiscence, thrombophlebitis, and pulmonary insufficiency have been reported. Obese surgical patients have abnormalities in cardiac, pulmonary, endocrine, and gastrointestinal function, as well as abnormalities in pharmacokinetics and pharmacodynamics. Obesity is also associated with the development of some of the most prevalent diseases of modern society: Cardiovascular as well as cerebrovascular disease, diabetes, and hypertension. More postoperative complications and the same comorbidities might also be expected in obese transplant recipients, which could lead to increased postoperative morbidity and mortality. In fact, reports on solid organ transplantation, including kidney, liver, and pancreas indicated in agreement a poorer outcome in obese organ recipients in terms of graft and patient survival. There is little information, however, on the impact of obesity on outcome after cardiac transplantation. Organ donor shortages mandate careful assessment of preoperative risk for heart transplantation to enable appropriate patient selection for this procedure. Therefore the purpose of the present study was to determine the impact of preoperative overweight and obesity as defined by body mass index (BMI 5 kg/m) on outcome after heart transplantation with regard to patient survival, surgical complications, incidence of infection, acute rejection and development of transplant coronary artery disease.

Non-melanoma skin cancer and its risk factors in an Austrian population of heart transplant recipients receiving induction therapy

Background  Solid organ transplant recipients have a high risk of developing nonmelanoma skin cancers (NMSC). We describe the characteristics and incidence of skin tumors in an Austrian population of heart transplant recipients (HTR).

Combined heart and kidney transplantation using a single donor: a single center's experience with nine cases.

BACKGROUND Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single centers experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. METHODS From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. RESULTS One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44+/-28 months. CONCLUSION HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.

The receptor for advanced glycation endproducts and its ligands in patients with myasthenia gravis.

OBJECTIVE Myasthenia gravis (MG) is a T- and B-cell mediated autoimmune disorder affecting the neuromuscular junction. The receptor for advanced glycation endproducts (RAGE) plays a role in the amplification of chronic inflammatory disorders and autoimmune diseases. We sought to investigate the role of RAGE and its ligands in the pathophysiology of MG. METHODS In this cross-sectional study we enrolled 42 patients with MG and 36 volunteers. We employed enzyme-linked immunosorbent assays to determine the concentration of soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1) in serum of patients and volunteers. In a subpopulation of patients we measured the serum levels of endogenous secretory (es) RAGE and various RAGE ligands, such as S100B, S100A8 and advanced glycation endproducts (AGE-CML). Reported are means and standard error mean. RESULTS We found significantly reduced levels of the soluble receptors sRAGE and esRAGE in patients with MG compared to volunteers without MG (sRAGE [pg/ml] 927.2 ± 80.8 vs. 1400.1 ± 92.4; p<0.001; esRAGE [pg/ml] 273.5±24.6 vs. 449.0 ± 22.4; p<0.001). Further categorization of patients with MG according to the distribution of muscle involvement revealed the following sRAGE concentrations: generalized MG 999.4 ± 90.8 and ocular MG 696.1 ± 161.8 (vs. control; One-way ANOVA: p<0.001; Post hoc analysis: generalized vs. ocular MG: p=0.264, generalized MG vs. control: p=0.008, ocular MG vs. control: p=0.001). In patients with detectable antibodies specific for acetylcholine receptors (Anti-AChR positive) the sRAGE concentration was 970.0 ± 90.2 compared to those without (seronegative) 670.6 ± 133.1 (vs. control; One-way ANOVA: p<0.001; Post hoc analysis: Pos vs. Neg.: p=0.418, Pos vs. control: p=0.003, Neg. vs. control: p=0.008). We next investigated the role of RAGE ligands in MG. The concentrations of RAGE ligands in patients with MG and controls were as follows: (HMGB1 [ng/ml] 1.7 ± 0.1 vs. 2.1 ± 0.2; p=0.058; S100B [pg/ml] 22.5 ± 22.5 vs. 14.4 ± 9.2; p=0.698; S100A8 [pg/ml] 107.0 ± 59.3 vs. 242.5 ± 103.6; p=0.347; and AGE-CML [ng/ml] 1100.8 ± 175.1 vs. 1399.8 ± 132.8; p=0.179). CONCLUSIONS Our data suggest a role for the RAGE pathway in the pathophysiology of MG. Further studies are warranted to elucidate more about this immunological axis in patients with MG.

Thymomas and Thymic Carcinomas: Prognostic Factors and Multimodal Management

BACKGROUND Thymomas and thymic carcinomas are rare malignant tumors. We report the experience with the resection and multimodal treatment at a single department in Central Europe in the years 2001 to 2010. OBJECTIVE We sought to determine prognostic factors in this patient population. METHODS A 10-year retrospective analysis of 84 resections on 72 patients for thymomas/thymic carcinomas or their recurrences was performed. RESULTS Patients admitted to a single thoracic surgery center presented with Masaoka-Koga stage I (29.2%), II (43.1%), III (13.9%), and IV (13.9%). In approximately 88.9% of cases, a complete resection could be reached. Using overall survival as an outcome measure, the 5-year survival rate was 87%. Of all the cases presented, 9.7% cases showed tumor recurrence and 6.9% cases showed tumor progression. There was decreased survival rate with increasing Masaoka-Koga stage (p = 0.017) and incomplete resection (p < 0.001). CONCLUSION Completeness of resection and Masaoka-Koga stage were significant prognostic factors. Multidisciplinary treatments of patients with thymoma or thymic carcinoma result in good patient care, and global efforts with larger number of patients are needed to elucidate more about the biology, diagnosis, and treatment of these tumors.

Alemtuzumab in Lung Transplantation: An Open‐Label, Randomized, Prospective Single Center Study

Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil. Group B received thymoglobulin in association with standard dose IS. Patient and graft survival, freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, kidney function, infectious complications and posttransplant lymphoproliferative disorder were analyzed. Alemtuzumab induction therapy resulted in complete the absence of ACR episodes ≥ A2 within the first year post‐TX. The difference to thymoglobulin was significant (alemtuzumab 0 vs. ATG 0.33; p = 0.019). All other factors studied did not show any differences between the two groups. Alemtuzumab induction therapy after LUTX in combination with reduced maintenance IS significantly reduces higher‐grade rejection rates. This novel therapeutic agent had no impact on survival, infections rates, kidney function and incidence of malignancies.