Immune status assessment in adult lung transplant candidates

BackgroundLung transplant recipients have an increased susceptibility to a variety of infections due to immunosuppressive therapy. Current guidelines recommend pneumococcal and other vaccinations, prior to lung transplantation to protect against post-transplant infections, but measurement of the antibody response to vaccination is not advised. Immune status investigation in lung transplant candidates, including the response to pneumococcal polysaccharide vaccination, has not been described.MethodsImmune status investigation, including measurement of immunoglobulins, complement and the response to 23-valent pneumococcal polysaccharide vaccination (23vPPV) was performed in 81 adult lung transplant candidates.ResultsEighteen patients had low IgG levels and 32 patients had low IgG1 and/or IgG2 levels. After vaccination with 23vPPV the median antibody concentration of all serotypes increased significantly. Fifty-two patients had protective IgG-post-vaccination antibody levels to at least 10 serotypes. Twenty-nine patients had an impaired response to 23vPPV.ConclusionsIn conclusion, a significant proportion of our cohort of lung transplant candidates had one or more abnormalities in the immune status. It is likely that these patients have an increased risk for infections after transplantation. Revaccination, including measurement of antibody response, and possibly antibody replacement therapy should be considered to minimize infection risk.     

Hypogammaglobulinemia following cardiac transplantation: a link between rejection and infection.

BACKGROUND: Hypogammaglobulinemia (HGG) has been reported after solid organ transplantation and is noted to confer an increased risk of opportunistic infections. OBJECTIVES: In this study, we sought to assess the relationship between severe HGG to infection and acute cellular rejection following heart transplantation. METHODS: Between February 1997 and January 1999, we retrospectively analyzed the clinical outcome of 111 consecutive heart transplant recipients who had immunoglobulin G (IgG) level monitoring at 3 and 6 months post-transplant and when clinically indicated. RESULTS: Eighty-one percent of patients were males, mean age 54 +/- 13 years, and the mean follow-up period was 13.8 +/- 5.7 months. Patients had normal IgG levels prior to transplant (mean 1137 +/- 353 mg/dl). Ten percent (11 of 111) of patients developed severe HGG (IgG < 350 mg/dl) post-transplant. The average time to the lowest IgG level was 196 +/- 125 days. Patients with severe HGG were at increased risk of opportunistic infections compared to patients with IgG > 350 mg/dl (55% [6 of 11] vs. 5% [5 of 100], odds ratio = 22.8, p < 0.001). Compared to patients with no rejection, patients who experienced three or more episodes of rejection had lower mean IgG (580 +/- 309 vs. 751 +/- 325, p = 0.05), and increased incidence of severe HGG (33% [7 of 21] vs. 2.8% [1 of 35], p = 0.001). The incidence of rejection episodes per patient at 1 year was higher in patients with severe HGG compared to patients with IgG >350 (2.82 +/- 1.66 vs. 1.36 +/- 1.45 episodes/patient, p = 0.02). The use of parenteral steroid pulse therapy was associated with an increased risk of severe HGG (odds ratio = 15.28, p < 0.001). CONCLUSIONS: Severe HGG after cardiac transplantation may develop as a consequence of intensification of immunosuppressive therapy for rejection and hence, confers an increased risk of opportunistic infections. IgG level may be a useful marker for identifying patients at high risk.     

Dynamics of soluble interleukin-2 receptor levels immediately after heart transplantation. Attenuation of increase by OKT3 therapy

Quantification of T cell activation after cardiac transplant by measuring serum soluble interleukin 2 receptor levels daily may give insight into immunologic dynamics after cardiac allograft implantation. It was our hypothesis that this protein would demonstrate a characteristic rise after heart transplant not related to severe rejection that was distinct from a control group, and that this increase could be attenuated with OKT3 therapy. We measured soluble interleukin 2 receptor levels daily for two weeks in 26 patients undergoing orthotopic cardiac transplantation (19 receiving triple therapy immunosuppression with cyclosporine, azathioprine, and prednisone, and 7 with OKT3 added days 1 through 5). Interleukin-2 receptor levels for transplant patients were compared with 15 control subjects (14 undergoing bypass surgery and one valve replacement). Mean soluble interleukin-2 receptor level for the entire two-week period was higher for transplants versus controls; 839 +/- 31 U/ml vs. 504 +/- 20 U/ml (mean +/- SEM; P less than .05). Patients receiving OKT3 had a lower level (670 +/- 39 U/ml) than those not (902 +/- 36 U/ml, P less than .05) despite the fact that mean biopsy scores for the observation period were not significantly different. No significant rejection or infection episodes occurred in any patient. These results describe, for the first time, sequential changes in soluble interleukin 2 receptor levels early after heart transplant and demonstrate that the characteristic early rise can be attenuated with short-term OKT3 administration.     

Effect of ureteral stent on urinary tract infections in renal transplantation

A retrospective study was carried out to determine the effect of ureteral intubation during renal transplantation. We noted urinary tract infections in 76 per cent of those patients whose ureters were intubated during transplantation, as opposed to 45 per cent in those transplant recipients without ureteral stents. The incidence of recurrent urinary tract infections also increased from 18 to 34 per cent with the use of ureteral catheters. Ten separate episodes of bacteremia, indirectly related to indwelling catheters, are noted.     

Infectious Complications After Heart Transplantation in Chinese Recipients

Several factors appear to influence the incidence and type of infectious complications among different populations of transplant recipients. This study sought to assess the incidence and type of infection after transplantation in Chinese heart allograft recipients. A total of 130 infectious episodes occurred in 192 consecutive heart transplantation patients between June 1993 and May 2004. The median length of follow-up was 46.7+/-38.4 months. The 1-, 5- and 10-year survival rates were 81.8+/-2.8%, 63.0+/-3.8% and 45.7+/-7.7%. Infection was the leading cause of early and late deaths. Of the infectious episodes, 66 (51%) were caused by bacteria, 35 (27%) by viruses, 10 (8%) by fungi, 7 (5%) by Mycobacterium tuberculosis and 12 (9%) by other pathogens. The most common bacterial infectious episodes were caused by methicillin-resistant Staphylococcus aureus (20 of 66). The most common viral infections were varicella zoster virus infection in 12 (34%), cytomegalovirus infection in 9 (26%) and hepatitis B virus infection in 8 (23%). There was only one episode of clinical syndrome compatible to Pneumocystis jiroveci pneumonia. In conclusion, there was low incidence of Pneumocystis jiroveci pneumonia and cytomegalovirus infection, and high incidence of Mycobacterium tuberculosis infection in Chinese heart allograft recipients.     

Increased infections associated with the use of OKT3 for treatment of steroid-resistant rejection in renal transplantation

We compared the infections encountered in 23 renal transplant patients given the monoclonal anti-T-cell antibody, Orthoclone OKT3 (OKT3), for treatment of steroid-resistant rejection in 1986 and in 23 control patients from 1984 to 1985 with resistant rejection matched demographically, for severity of rejection and for risk factors predisposing to infection, who did not receive OKT3; recipients of OKT3 received substantially less prednisone, cyclosporine, and antilymphocyte globulin (ALG) than control patients for treatment of the rejection episode. Fourteen (61%) patients given OKT3 developed one or more infections in the 3-month period following treatment as compared with 9 control patients (39%) given conventional antirejection therapy with high-dose steroids and, usually, ALG. Patients given OKT3 were significantly more likely to develop serious infections (pneumonia, bacteremia, meningitis, or severe viral infection; 16 episodes vs. 4, P = .02). Six recipients of OKT3 (26%) acquired infections typically encountered in states associated with depressed cell-mediated immunity (CMI)--Listeria sepsis (2), disseminated nocardiosis and Mycobacterium tuberculosis infection (1), cytomegalovirus (CMV) pneumonia (1), Yersinia infection with severe dermatophytosis (1), and Epstein-Barr virus-associated lymphoproliferative syndrome (1)--as compared with 1 case of mild CMV infection in the control group (P = .08). Trimethoprim-sulfamethoxazole (TMP-SMZ) was given to 19 patients in each group; all 4 recipients of OKT3 who did not receive TMP-SMZ prophylaxis developed life-threatening infection, 3, bacteremia (2 with Listeria) and 1, disseminated nocardiosis and M tuberculosis infection. These data suggest that OKT3 given for treatment of resistant rejection in renal transplantation predisposes the patient to serious infection, particularly with opportunistic pathogens characteristically associated with depressed cell-mediated immunity. Prophylaxis with TMP-SMZ, which is safe, well tolerated, and effective for reducing the incidence of infection in renal transplantation, may be especially important during OKT3 therapy.     

OKT3 treatment for steroid-resistant acute rejection in kidney transplantation

Orthoclone (OKT3, Ortho Biotech Inc, USA) monoclonal antilymphocyte antibody is a powerful T-cell-specific immunosuppressive agent. OKT3 has been used for induction therapy in kidney and liver transplantation, as well as to treat acute or steroid-resistant acute rejection episodes (ARE). This study was a retrospective analysis of 43 renal transplant recipients who developed steroid-resistant ARE and were treated with OKT3 between September 1994 and June 2004. The recipients were 36 men and 7 women of mean age 32.7 +/- 11.6 years (range, 19 to 48 years). The mean time from transplantation to OKT3 treatment was 7.2 +/- 6.7 months. Thirty-four episodes (79.1%) responded to OKT3 therapy with improved graft function, but the remaining 9 (20.9%) grafts did not respond. Among the 34 OKT3 responders, the mean serum creatinine decreased from 3.96 +/- 2.5 mg/dL to 2.45 +/- 1.77 mg/dL after treatment. Eleven (25.6%) of the 43 patients experienced minor side effects: fever, dyspnea, tachycardia, bradycardia. One patient (2.3%) developed acute pulmonary edema; one (2.3%), cytomegalovirus infection; and eight (18.6%), bacterial infections. The 1-, 3-, and 5-year graft survival rates for the 34 patients who responded to OKT3 therapy were 96%, 93%, and 85%, respectively. All patients are currently alive. The results indicate that OKT3 is a safe, effective treatment choice for steroid-resistant ARE in kidney transplantation.     

Homocysteine—a treatable risk factor for allograft vascular disease after heart transplantation?

Growing evidence suggests that elevated total plasma homocysteine (tHCY) levels are associated with cardiac allograft vasculopathy following heart transplantation. To assess the effect of folic acid supplementation on tHCY levels, we performed a prospective study in a cohort of 69 patients (7.0 +/- 3.2 years after heart transplantation; mean age, 55.0 +/- 9.6 years; 61 male) treated with 5 mg folic acid/day (n = 34) vs no medication (n = 35). Therapy with folic acid resulted in significantly decreased tHCY levels, from 22.6 +/- 9.6 micromol/liter to 17.3 +/- 5.5 micromol/liter (p = 0.001) within 3 months, whereas values in the control group remained unchanged. We conclude that folic acid supplementation (5 mg per day) provides a simple and effective measure to lower elevated tHCY levels in heart transplant recipients.     

Prevention of herpes simplex virus infection by oral acyclovir after cardiac transplantation.

Infection with herpes simplex virus is common among immunosuppressed patients. In an attempt to prevent such infection, 58 patients (group 1) who underwent cardiac transplantation between 1987 and 1990 were given acyclovir (200 mg orally three times a day) prophylactically throughout their postoperative hospital stay (mean 22 days +/- 1 day). The patients' immunosuppressive protocol included cyclosporine, azathioprine and prednisone. The course of these patients was compared to that of 24 patients (group 2) who underwent cardiac transplantation between 1983 and 1986 but were not given prophylactic antiviral treatment postoperatively. The immunosuppressive protocol in these patients consisted of cyclosporine and prednisone. Herpes infection developed during the 1st year in 5 patients (9%) in group 1 and in 11 patients (46%) in group 2 (p < 0.05). The actuarial rates of freedom from herpes infection at 1, 6 and 12 months after transplantation were 100%, 98% +/- 2% and 95% +/- 3%, respectively, in group 1 and 82% +/- 7%, 58% +/- 11%, 53% +/- 11% in group 2. All viral infections were cutaneous or mucosal, except for one, which developed in a patient with pneumonia. All infections responded well to treatment, although one patient with an infected cornea was left with a permanent visual deficit. The authors conclude that prophylaxis of herpes simplex virus infection with acyclovir administered orally in the early postoperative period is effective in preventing viral infections during the 1st year after cardiac transplantation.     

IMPACT OF FEBRILE INFECTIONS ON THE LONG-TERM FUNCTION OF KIDNEY ALLOGRAFTS

PURPOSE: We prospectively determined the impact of febrile infectious disease on long-term renal graft function compared with a matched control group. MATERIALS AND METHODS: Included in our study were 39 patients who presented with episodes of febrile infection with body temperature greater than 38C on 2 consecutive occasions, necessitating hospitalization. In addition, 39 controls without febrile infection requiring hospitalization within 2 months were chosen from the complete data pool of all renal transplant recipients followed at our transplant clinic using the matched pair technique. Renal function was estimated by serum creatinine and calculated creatinine clearance. RESULTS: Of the 39 patients with infection 15 had urinary tract infection and 24 had other, mostly bacterial infection, including pneumonia/severe bronchitis in 12, oral/dental infection in 2, gastroenteritis in 2, shunt sepsis in 1, herpes zoster in 1, cytomegalovirus in 1 and other in 5. Mean estimated creatinine clearance plus or minus standard deviation was similar in the infection and control groups at the beginning of the study (51 +/- 22 and 51 +/- 23 ml. per minute, respectively). During the infectious episode mean creatinine clearance significantly decreased to 38 +/- 17 ml. per minute in the infection group. After infection resolved creatinine clearance returned to an almost baseline mean value of 50 +/- 23 ml. per minute. However, after 2 years of followup there was a significant difference in mean creatinine clearance in the infection group versus controls (45 +/- 25 versus 52 +/- 25 ml. per minute, p = 0.022). CONCLUSIONS: To our knowledge we have shown for the first time in a prospective controlled study that febrile infectious episodes correlate with poor long-term renal graft function.     

Long-term results in diabetic patients undergoing heart transplantation.

We conducted a retrospective study of 305 nondiabetic patients and 37 diabetic patients who underwent heart transplantation from July 1982 to May 1990. Actuarial survival was similar for both groups of patients at 1 year (76.4% versus 81.3%) and at 2 years (69.6% versus 73.0%). Because we were interested in long-term results, we further analyzed only those patients surviving more than 1 year after transplantation (214 nondiabetic patients and 29 diabetic patients). Mean follow-up for the nondiabetic patients was 31.8 +/- 16.2 months and for the diabetic patients, 32.9 +/- 4.1 months. The respective mean age in each group was 50.4 +/- 10.3 years and 51.6 +/- 9.1 years. No difference was observed between the nondiabetic patients and diabetic patients regarding the rejection rate per patient-month (0.040 +/- 0.041 versus 0.045 +/- 0.051 episodes per patient-month), the infection rate per patient-month (0.056 +/- 0.081 versus 0.081 +/- 0.102 episodes per patient-month), or renal function as evidenced by mean creatinine levels at 1, 2, and 3 years. Twelve patients were insulin-dependent before transplantation; and 1 year after transplantation, they required an insulin dose 2.12 times greater than the dose before operation. Coronary artery disease developed in 32.8% of the nondiabetic patients, compared with 31.0% of the diabetic patients by the fourth year of follow-up. Despite the need for increased insulin doses, the diabetic patients had similar long-term survival to that of the nondiabetic patients, without an increased risk of rejection, infection, renal dysfunction, or coronary artery disease. Our experience supports the feasibility of heart transplantation in selected diabetic recipients.     

Bacterial and fungal pneumonias after lung transplantation

OBJECTIVE: The aim of this study was to evaluate the epidemiology of bacterial and fungal pneumonia in lung transplant (LT) recipients and to assess donor-to-host transmission of these microorganisms. MATERIALS AND METHODS: We retrospectively studied all positive cultures from bronchoalveolar lavage (BAL) of 49 lung transplant recipients and their donors from August 2003 to April 2007. RESULTS: There were 108 episodes of pneumonia during a medium follow-up of 412 days (range, 1-1328 days). The most frequent microorganisms were: Pseudomonas aeruginosa (n = 36; 33.3%), Staphylococcus aureus (n = 29; 26.8%), and Aspergillus spp. (n = 18; 16%). Other fungal infections were due to Fusarium spp., Cryptococcus neoformans, and Paracoccidioides brasiliensis. Of the 31 donors with positive BAL, 15 had S. aureus. There were 21 pretransplant colonized recipients (43%) and 16 of them had suppurative underlying lung disease. P. aeruginosa was the most frequent colonizing organism (59% of pretransplant positive cultures). There were 11 episodes of bacteremia and lungs were the source in 5 cases. Sixteen deaths occurred and 6 (37.5%) were due to infection. Statistical analyses showed association between pretransplant colonizing microorganisms from suppurative lung disease patients and pneumonias after lung transplantation (RR = 4.76; P = .04; 95% CI = 1.02-22.10). No other analyzed factor was significant. CONCLUSIONS: Bacterial and fungal infections are frequent and contribute to higher mortality in lung transplant recipients. P. aeruginosa is the most frequent agent of respiratory infections. This study did not observe any impact of donor lung organisms on pneumonia after lung transplantation. Nevertheless, we demonstrated an association between pretransplant colonizing microorganisms and early pneumonias in suppurative lung transplant recipients.     

Airway anastomosis complications in de novo lung transplantation with sirolimus-based immunosuppression.

A prospective, pilot trial was started to evaluate the effect of a sirolimus-based immunosuppressive regimen on acute and chronic rejection in de novo lung transplant patients. Primary lung transplant (LTx) recipients received a sirolimus- and tacrolimus-based immunosuppressive therapy immediately after transplantation. Both immunosuppressants were administered with trough level adjusted, while steroid administration was minimized. Four patients were enrolled (2 single-lung transplants, 1 double-lung transplant, 1 heart-lung transplant) in the study. Mean ischemia time was 387 +/- 92 minutes. Acute rejection (at least Grade A1 ISHLT) was detected in 1 patient. Incidence of infection was 0.6 infection per 100 patient-days (3 Aspergillus infections). Until hospital discharge mean sirolimus trough level was 6.2 +/- 1.2 ng/ml. Depending upon mean sirolimus trough levels of each patient, severe wound-healing complications were seen in 3 patients, resulting in bronchial airway dehiscence in 2 patients with lethal outcome in 1 patient. As a result of these complications, we revised the study design after inclusion of only 4 patients: Sirolimus administration is now started after completion of bronchial wound-healing. Sirolimus-based immunosuppressive therapy administered immediately after lung transplantation seems to be associated with severe wound-healing complications of the bronchial anastomosis.     

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.     

Pancreas transplantation. A new program

Sixteen pancreatico-duodenal transplants were performed on 15 insulin-dependent diabetics, aged 25-46, during a 20-month period beginning May 1, 1988. Fourteen patients received a combined cadaveric pancreas/renal transplant with bladder drainage. One patient received a second pancreas transplant 24 hours after the first pancreas graft failed due to portal vein thrombosis. One patient received a pancreas graft 3 years after kidney transplantation. Complications included five cases of hematuria, two bladder leaks, two wound infections, one cytomegalovirus pneumonia, three cases of graft pancreatitis, one pseudocyst, one urine reflux pancreatitis requiring conversion to pancreatico-enterostomy, and two late deaths. Average time to discharge was 17 days following transplant, with 2.9 re-hospitalizations per patient and an average of 38 in-hospital days during the first 6-12 months. Seventeen rejection episodes occurred in 12 patients, diagnosed by declining urine amylase and pH and/or finding of rejection on kidney biopsy. Patient and kidney graft survival is 87 per cent. Pancreas graft survival is 81 per cent (1-20 months follow-up). All patients are insulin-independent and normoglycemic. Mean glycosylated hemoglobin concentration is 4.0 +/- 0.9 post-transplant vs. 7.5 +/- 0.6 pretransplant. Mean serum creatinine is 1.4 +/- 0.7 mg/dl. A new program of pancreas transplantation can be successful in carefully selected diabetic patients, with special attention to avoidance of preservation injury to the pancreas during multiorgan donor procurement. Combined pancreatic/renal transplantation is believed to be the therapeutic treatment of choice in Type I diabetic patients who have impaired renal function and have no significant cardiovascular disease.     

Bacterial infections after intestine and multivisceral transplantation

BACKGROUND: The frequency of bacterial infections (BI) in intestinal transplant (IT) patients is high with sepsis being the leading cause of death after this procedure. We herein report our experience with major BI to ascertain the incidence, microbiological and clinical factors, risk factors and outcome. MATERIALS AND METHODS: 124 patients (72 children and 52 adults) received 135 grafts: namely, 39 isolated intestine, 33 liver-intestine and 63 multivisceral. Only major BI were considered, namely, those associated with serious morbidity/mortality requiring specific therapy. Patient data were retrieved from computerized databases, flow-charts, and medical records. RESULTS: 92.7% patients showed BI. There were 327 episodes, representing 2.6 episodes/patient (2.8/patients with infection): 193 episodes of bacteremia (1.7/patient with BI) including 29.5% due to catheter related sepsis, 16.5% from abdominal source, 5.7% from respiratory origin and 4.1% from the wound. The organ locations includes 46 respiratory infections, 33 intraabdominal abscesses or infected fluid collections, 8 diffuse peritonitis, 34 wound infections and other miscellaneous sites: empyema, soft tissue infections, cholangitis em leader etc. Median time of infection was nine days after surgery (mean 22+/-3 days), with 67.7% patients having at least one BI before the end of the first month. Infection was present in 76.2% of the 63 deceased patients. An infectious episode during month 1, a clinically manifest abdominal infection and a positive intraabdominal culture had negative impacts on patient survival. CONCLUSIONS: BI are common and early complications after IT. The high rate of bacteremia, line sepsis and abdominal and respiratory infections reflect the recipient's condition, with chronic deterioration superimposed with the effects of prolonged abdominal visceral surgery.     

Decreased levels of serum immunoglobulins as a risk factor for infection after heart transplantation

OBJECTIVE: We aimed to assess humoral immunity markers that provide prognostic value for the development of infections in heart transplant recipients. PATIENTS AND METHODS: Forty-one heart transplant recipients underwent humoral immunity studies, including Immunoglobulin (IgG, IgA, IgM) and IgG subclasses determined by nephelometry on serum samples obtained before transplantation and 1 month after transplantation. Potential clinical risk factors were evaluated: waiting time for transplantation, pretransplant cytomegalovirus (CMV) serologic status of donor and recipient; recipient age; gender; cardiac disease severity before transplantation; type of immunosuppression; and occurrence of rejection. OUTCOME MEASURES: We measured infections requiring intravenous (IV) drug therapy during the first year. The association between variables and outcome was assessed using Cox proportional hazards modelling. Immunoglobulin levels were split into two groups using the median value observed as the cut-off. RESULTS: Of 41 patients studied, 19 (46%) had at least one episode of infection, 16 of which were CMV infections treated with IV gancyclovir, 1 CMV disease + aspergillosis and 2 bacterial pneumonia. Pretransplant IgG (<1055 mg/dL; RR 5.32; 95% confidence interval [CI] 1.73 to 16.29; P = .0034); pretransplant IgG1 (<695 mg/dL; RR 4.80; CI 1.57 to 14.68; P = .006), and posttransplant IgG levels (<589 mg/dL; RR 3.38; CI 1.21 to 9.44, P = .019) were associated with an increased risk of developing infections. Both waiting time for transplantation (RR 0.95; CI 0.91 to 0.98, P = .007) and pretransplant cardiac disease severity (RR 1.94; CI 1.17 to 3.21, P = .009) were significant risk factors for infection. After adjustment for clinical predictive variables, decreased values of posttransplant IgG remained significant predictors. CONCLUSIONS: The existence of decreased levels of IgG in the setting of heart transplantation was associated with an higher risk for infection. Monitoring of immunoglobulin levels, a rapid and well-standardized nephelometric determination, in heart transplantation, may identify a subset of patients at risk for development of infections.     

Outcome of patients surviving to heart transplantation after being mechanically bridged for more than 100 days.

OBJECTIVE: The effect of long-term mechanical support on subsequent heart transplantation is still debated. METHODS: We report the outcome of 41 patients (42 +/- 12 years) bridged with left ventricular assist devices (VAD; 28 Novacor, 9 HeartMate, 2 Thoratec, and 2 DeBakey) for >100 days (218 +/- 76 days) between April 1994 and March 2000). We compared follow-up with 146 patients (55 +/- 13 years) who underwent heart transplantation during the same time without prior long-term mechanical support. RESULTS: Thirty-two of the 41 patients (78%) underwent heart transplantation, 9 patients (22%) died of multi-organ (n = 5), cardiac (n = 2), or cerebral failure (n = 2). Thirty-day post-transplant mortality includes 5 cases (3 graft failures). Within the following 2 years, another 5 patients expired, 2 of cardiac failure/sudden death. Currently, 21 of 41 patients (51%) are still alive 10 to 77 months (41 +/- 22 months) after heart transplantation (1 patient was lost for follow-up). One-year and 5-year survival rates were compared with the control group (VAD vs control, 1-year survival was 75% vs 74% and 5-year survival was 60% vs 66%). Fifteen patients are doing well in New York Heart Association Class I), and 6 are NYHA Class II despite normal left ventricular ejection fraction. Episodes of moderate acute rejection (International Society for Heart and Lung Transplantation Grade 3) occurred in 10 patients (1.3 episodes per patient), not significantly different from that of the control group (1.2 episodes per patient). Scintigraphy showed regional myocardial ischemia/transplant vasculopathy in 4 patients, and coronary angiography detected the same in 2. One patient has undergone successful retransplantation. Two patients had increased right ventricular pressure. Six patients had impaired kidney function, and 3 had impaired liver function. Seven patients experienced cytomegalovirus infection. CONCLUSIONS: Our data indicate that patients who underwent heart transplantation after long-term mechanical support have a similar survival rate and comparable cardiac morbidity associated with acute rejection episodes.     

Pseudomonas aeruginosa bacteremia in patients undergoing liver transplantation: an emerging problem

In our institution, Pseudomonas aeruginosa bacteremia appeared to occur with increasing frequency in patients undergoing liver transplantation. We thus conducted a prospective study to define risk factors and outcome in these patients. Over a 19-month period 6% of liver transplants were followed by Pseudomonas bacteremia. The mean age was 46 years (range, 24 to 67 years). The interval between transplantation and onset of bacteremia was 3 to 372 days (mean, 80). The incidence of Pseudomonas bacteremia in liver transplants was three times that of other transplants (heart, lung, kidney). Ninety one percent of infections were nosocomial. Polymicrobial bacteremia occurred in 30% of episodes. The portal of entry was respiratory in 30%, abdominal in 35%, and biliary in 13%. Four patients had recurrent Pseudomonas bacteremia: liver abscess (1), biliary obstruction (2), subhepatic abscess (1). Survival at 14 days was 70%. Survival rates were significantly lower for patients with hypotension, on mechanical ventilators, and increasing severity of illness (p less than 0.05). Survival was higher when bacteremia occurred within the first 30 days after transplantation compared to after 30 days. A large number (43.4%) of Pseudomonas bacteremias occurred after transplant surgery of biliary tract manipulation, while the patient was receiving a prophylactic regimen of cefotaxime and ampicillin. P. aeruginosa is an important pathogen in the liver transplant recipient; prevention may be possible for a subgroup of patients with the use of prophylactic antibiotics with activity against P. aeruginosa.     

Cutting Balloon angioplasty for cardiac transplant vasculopathy.

We performed Cutting Balloon angioplasty on 20 lesions in 11 heart transplant recipients 7.5 +/- 3.8 years after transplantation. The mean percentage of diameter stenosis decreased from 88.3% +/- 13.8% to 19.6% +/- 13.7% after Cutting Balloon angioplasty without complication. Seven patients underwent follow-up angiography at 4.9 +/- 1.7 months in a total of 12 lesions, and all lesions showed restenosis with a mean diameter stenosis of 84.4% +/- 19.2%. Cutting Balloon angioplasty can be used to treat obstructions in cardiac transplant coronary arteries; however, it may cause exacerbation and produce a high restenosis rate.