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J Vanhaecke

Publications and source records attributed to J Vanhaecke.

At least 19 recordsLinked to original sources

To transplant or not? The importance of psychosocial and behavioural factors before lung transplantation.

The gratifying results of lung transplantation in terms of survival and quality of life stimulate the referral of an ever-increasing number of patients with end-stage lung disease. This in turn compounds the organ shortage, which is the limiting factor in the transplantation rate. In the absence of good alternative treatment modalities, an evidence-based pretransplant screening process is a prerequisite to determine which patients will benefit most from transplantation. Within this evidence-based screening process, medical selection criteria are well established. There is a growing awareness that psychosocial and behavioural factors may determine outcome after transplantation as well. This paper reviews the available evidence for psychosocial and behavioural factors in the screening process for lung transplantation. The relation of various factors with post-transplant outcome was explored. Psychosocial characteristics before transplantation consist of 1) anxiety and depression, 2) personality disorders, 3) neurocognitive problems, and 4) lack of social support. Pretransplant behavioural factors include 1) noncompliance with medication, 2) alcohol abuse or dependence, 3) smoking, 4) noncompliance with dietary guidelines, and 5) noncompliance with monitoring of vital parameters and infections. It appears that the lack of rigorous studies limit the feasibility of an evidence-based screening process. Prospective studies are crucial to this further investigation of the relationship between psychosocial and behavioural determinants before transplantation and outcomes after transplantation, in terms of compliance, morbidity, and mortality. Identification of modifiable risk factors for poor outcome before transplantation is a first step in developing interventions.

Alcoholism↗

Mortality rates after heart transplantation: how to compare center-specific outcome data?

BACKGROUND: Studies of outcome in cardiac transplantation have focused primarily on identifying patient- and donor-related factors associated with patient mortality. Less consideration has been given to the impact of the transplant center. This study was undertaken to assess variability in heart transplantation outcome in Eurotransplant centers to provide a framework for auditing. METHODS AND RESULTS: In a 2-year period, 1,401 adult patients underwent heart transplantation in 45 centers. The 1-year patient survival rate was 76% (95% CI, 74%-78%) with a range of 0% to 100% at the center level. The risk-adjusted center effect on mortality was estimated by calculating a standardized difference between the observed number of deaths 1 year after transplantation and the expected number of deaths based on the case mix. By assessing within- and between-center variations with empirical Bayes (EB) methods, after adjustment for all registered prognostic factors, an improved estimate of the true center effect was obtained. Compared with the standard risk-adjusted center effect method, fewer outlying centers were identified with the EB method. CONCLUSION: EB methods, because they are known to incorporate more information from the data, enable a more precise and realistic portrayal of heart transplant centers' performances, compared with other risk-adjusted center effect methods. In the context of auditing procedures, EB methods should preferably be used for the identification of centers that deviate significantly from quality standards.

Adolescent↗

Exhaled nitric oxide after lung transplantation: impact of the native lung.

It has already been demonstrated that exhaled nitric oxide (eNO) is increased in lung transplant patients with chronic rejection, although it is not known whether the diseased native lung after single lung transplantation (SLTx) contributes to the increased eNO values. This study aimed to compare the eNO values in stable lung transplant patients (SLTx versus sequential (S)SLTx and heart (H)LTx) and in patients with established chronic rejection. Altogether, 42 LTx patients (25 females, 13 SLTx, 18 SSLTx, 11 HLTx), with a mean follow-up of 1149 days and a mean age of 44.6 yrs at transplantation, were included. Twenty-six patients had no signs of chronic rejection (five SLTx and 21 SSLTx/HLTx). There was no difference in their eNO values (10.2 in SLTx versus 12.2 (parts per billion) ppb in SSLTx/HLTx). Sixteen patients (eight SLTx and eight SSLTx/HLTx) had a chronic rejection (eight bronchiolitis obliterans syndrome (BOS) potential stage, four BOS stage 1, three BOS stage 2 and one BOS stage 3). Their eNOs were 18.1 (SLTx) and 17.0 (SSLTx/HLTx) ppb, respectively, which were significantly different to the stable LTx patients and showed a trend towards significance for SSLTx/HLTx. There was no significant difference in eNO between the patients with chronic rejection who underwent SLTx and those who underwent SSLTx/HLTx. The diseased native lung after single lung transplantation probably does not contribute much to the exhaled nitric oxide values, either in stable lung transplant patients or in lung transplant patients with chronic rejection.

Adolescent↗

Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine--results at 24 months after transplantation.

BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events.

Adolescent↗

Profiles of patients who experienced a late acute rejection due to nonadherence with immunosuppressive therapy.

The purpose of this study was to determine the significance and patient profiles of nonadherence with immunosuppressive therapy in the etiology of late acute rejections (LARs), more than 1 year after heart transplantation. Nonadherence was assessed in 101 heart transplant recipients (14 females, 87 males) with a median age of 56 (Q1=50; Q3=61) and a median posttransplant status of 3 (range, 1-6) years, using electronic event monitoring and self-report. The influence of depression, perceived self-efficacy, knowledge, perceived health, symptom frequency and distress, perceived social support, and adherence with outpatient appointments on medication nonadherence was examined. Ten LARs occurring in six patients were observed. Nine of the rejections, emerging in five patients, appeared to be caused by medication nonadherence. Nonadherence with immunosuppressive therapy is a major risk factor in the etiology of LAR. Patient profiles allow the identification of patients at risk.

Adult↗

Psychosocial and behavioral selection criteria for solid organ transplantation.

An evidence-based selection process for organ transplantation may be a valuable approach to improve posttransplant outcomes. This paper reviews state-of-the-art psychosocial and behavioral selection criteria and assesses their validity in view of predicting outcomes after transplantation. Psychosocial factors addressed are psychiatric disorders, mental retardation, irreversible cognitive dysfunction, and lack of social support. Behavioral selection criteria discussed are alcoholism, smoking, drug abuse, and obesity. This review reveals that the evidence concerning these selection criteria in scarce. There is a definite need for more longitudinal research to strengthen the scientific basis of the psychosocial and behavioral dimension of transplantation.

Evidence-Based Medicine↗

Peak oxygen uptake better predicts outcome than submaximal respiratory data in heart transplant candidates.

BACKGROUND: Many studies have focused on the prognostic power of peak oxygen uptake VO(2) in patients with chronic heart failure, but maximal exercise testing is not without risk. The purpose of the present study was, therefore, to assess the prognostic significance of the steepness of changes in ventilation and carbon dioxide output VO(2) during submaximal exercise in comparison with VO(2). METHODS AND RESULTS: The study population consisted of 284 adult heart transplant candidates who performed a graded maximal bicycle ergometer test with respiratory gas analysis. Using the respiratory data up to a gas exchange ratio of 1.0, 3 submaximal slopes were calculated in each patient. During follow-up (median, 1.33 years), 57 patients died and 149 had >/=1 cardiovascular event. When using Cox proportional hazards analysis, both peak VO(2) and submaximal respiratory slopes predicted outcome before and after accounting for age, sex, and body mass index. However, whereas the prognostic power of peak VO(2) was independent of submaximal respiratory data, the prognostic significance of the slopes was lost after controlling for peak VO(2). Stepwise regression analysis even selected peak VO(2) as an independent prognostic index among the following factors: cause of heart failure, ejection fraction, pulmonary vascular resistance, natremia, and the forced expiratory volume in 1 s. CONCLUSIONS: Respiratory data during submaximal exercise are significant predictors of outcome in patients with chronic heart failure, but their prognostic power is inferior to that of peak VO(2). However, these data may be useful when maximal exercise is contraindicated or not achievable.

Adolescent↗

Oxidized low density lipoprotein is a prognostic marker of transplant-associated coronary artery disease.

Retrospective studies identified oxidized low density lipoprotein (LDL) in the blood as a diagnostic marker of coronary artery disease (CAD). This prospective study sought to determine the prognostic value of oxidized LDL for CAD in cardiac transplant patients. Oxidized LDL was measured in 99 cardiac transplant patients with normal coronary angiograms at baseline and was measured again after a median follow-up of 2 years at the time of a second angiogram. Twenty-one patients developed angiographically detectable cardiac transplant vasculopathy (cases), and 78 individuals did not (controls). Cases had significantly higher baseline plasma levels of oxidized LDL than did controls: 1.18+/-0.70 versus 0.57+/-0.20 mg/dL (mean+/-SD, P<0.0001). The increase of oxidized LDL at the end of the follow-up was significantly higher in cases than in controls: 0. 75+/-0.73 mg/dL versus 0.14+/-0.27 mg/dL (P<0.0001). Baseline levels of oxidized LDL predicted cardiac transplant vasculopathy (chi(2)=16, P<0.0001) independent of pretransplant ischemic cardiomyopathy, time after transplantation, age, and serum levels of LDL and high density lipoprotein cholesterol. The development of transplant CAD was associated with a further increase of plasma levels of oxidized LDL (chi(2)=14, P=0.0002). Oxidized LDL is a prognostic marker of transplant CAD.

Adult↗

Clinical risk associated with appointment noncompliance in heart transplant recipients.

This study examined the prevalence of appointment noncompliance in 101 heart transplant recipients and how appointment noncompliance is related to patient profile and clinical risk. Appointment noncompliance was defined as patients not showing up at 1 or more planned clinic appointments (at a minimal frequency of every 3 months) during the previous year. Clinical variables were collected from medical files. Psychosocial variables were measured using established instruments. Medication noncompliance was assessed using electronic event monitoring. Paired t test, Wilcoxon 2-sample test, chi-square test, or Fisher exact test were used for statistical analysis as appropriate. The prevalence of appointment noncompliance was 7%. Appointment noncompliers were significantly younger, were less likely to live in a stable relationship with a partner, were more depressed, perceived their health as poorer, experienced more symptom distress, and had significantly more drug holidays. Fifty-seven percent of the appointment noncompliers experienced 1 or more late acute rejection episodes, compared to 2% of the appointment compliers. Appointment noncompliance is a critical behavioral risk factor in the occurrence of late acute rejection episodes in heart transplant patients. Patient profiles allow the identification of patients at risk for appointment noncompliance.

Adult↗

Personality disorders: a challenge for transplantation.

Evidence concerning personality disorders is limited in the transplant literature, but the existence of a personality disorder in a transplant candidate does appear to be a risk factor for poor outcome after transplantation. This article addresses the issue of personality disorders in transplantation, including a definition and diagnostic criteria of personality disorders and the value of possible interventions to treat patients with personality disorders. Directions for treating personality disorders as part of the broader clinical management of transplant recipients are also provided.

Humans↗

Safety, tolerability and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil based formulation of cyclosporine--results at six months after transplantation.

BACKGROUND: The introduction of cyclosporine has resulted in significant improvement in the survival of cardiac allograft recipients due to decreased mortality from infection and rejection. The original oil-based cyclosporine formulation exhibits variable and unpredictable bioavailability that correlates with an increased incidence of acute and chronic rejection in those patients in whom this is most pronounced. The primary objectives of this prospective, multicenter, randomized, double-blind study in cardiac transplant patients were: to compare the efficacy of cyclosporine microemulsion (CsA-NL) with oil-based cyclosporine (CsA-SM) as measured by cardiac allograft and recipient survival and the incidence and severity of acute rejection episodes; and to assess the safety and tolerability of CsA-NL compared with CsA-SM in this population. This report represents the analysis of results 6 months after transplantation. METHODS: A total of 380 patients undergoing their first cardiac transplant at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial examining the safety and efficacy of CsA-NL versus CsA-SM. Rejection was diagnosed using endomyocardial biopsy and were graded according to standardized criteria of the International Society of Heart and Lung Transplantation (ISHLT). Clinical parameters were monitored during the study. Survival and freedom from were used for analysis as was Fisher's exact test for comparisons between groups. RESULTS: At 6 months after transplantation, allograft and patient survival were the same for both groups. The frequency of ISHLT grade 3A or greater episodes in the two groups was identical. Fewer CsA-NL patients (5.9%) required antilymphocyte antibody (ATG or OKT-3) therapy for rejection compared with the CsA-SM-treated patients (14.1%, P=0.01). Females with ISHLT rejection grade > or = 3A treated with CsA-NL had a 46% lower incidence of rejection compared with the CsA-SM-treated group (31.3% vs. 57.6%, P=0.032). Fewer infections were seen in the CsA-NL. With the exception of baseline and 1 week posttransplant creatinines which were higher in the CsA-NL group, the overall creatinine was not significantly different between the two groups. CONCLUSIONS: This multicenter, randomized study of cardiac transplant recipients documented less severe rejection (in particular those requiring antibody therapy) and a lower incidence of infection in CsA-NL-treated patients. Results from the female subgroup analysis suggest that the improved bioavailability of CsA-NL might reduce the frequency of rejection episodes in female patients. The use of CsA-NL was not associated with an increased risk of adverse events.

Adolescent↗

Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction.

OBJECTIVE: The aim of this study was to characterize a regional myocardial flow-function relationship in collateral dependent myocardium produced by multiple coronary artery obstruction. METHODS: Ameroid constrictors were placed around the proximal right (RC) and circumflex (CX) coronary arteries and a silicon tubing cuff around the proximal LAD (left anterior descending artery) (luminal stenosis +/- 77%) in 18 dogs. Weekly two-dimensional echocardiography was performed for regional function (anterior [A], inferoposterior [IP], wall thickening [WT]), and fractional shortening (FS). Colored microspheres injected at baseline and before sacrifice, before and after dipyridamole (0.5 mg/kg) injection, determined resting flow (RF) and coronary reserve (CR), respectively. RESULTS: Coronary angiography performed at four weeks after surgery confirmed occlusion of RC and CX with collateralization and a tight stenosis of LAD. Initially, an episodic reduction in A and IP WT was observed which became persistent later (AWT: 16 +/- 3%; IPWT: 16 +/- 4%, FS: 20 +/- 4%, p < 0.005 vs. baseline [BS]). With dobutamine a biphasic response (improvement in A and IP WT between 5-15 and dysfunction between 20-30 microg/kg/min) was observed. Seven dogs were sacrificed at eight weeks and showed normal RF but reduced transmural CR (A: 75 +/- 18%; IP: 46 +/- 22% of control). Seven dogs underwent PTCA of the LAD at eight weeks and showed gradual improvement in AWT with normalization at 12 weeks (AWT: 30 +/- 5%, p < 0.001 vs. eight weeks). At sacrifice RF and CR in the A wall were normal but there was reduced subendocardial RF in the IP region (64% of BS). Further, biopsy samples showed normal histological findings and high energy phosphate content in all dogs. Radioligand binding assays using 125I-iodocyanopindolol showed downregulation of beta-adrenergic receptor density in the dysfunctional regions compared with control. CONCLUSIONS: In this canine model of viable, collateral dependent and reversibly dysfunctional myocardium, there was early episodic dysfunction followed by persistent dysfunction which was initially associated with normal RF and later with subendocardial hypoperfusion.

Animals↗

Cyclophosphamide rescue therapy for chronic rejection after lung transplantation.

BACKGROUND: Obliterative bronchiolitis remains the leading cause of late mortality after heart-lung and lung transplantation. Although several treatment options have been advocated, none has proven to be very successful. Cyclophosphamide is effective in the treatment of idiopathic pulmonary fibrosis, and chronic rejection after lung transplantation is also a fibroproliferative process. We therefore conducted an open, uncontrolled study to look at the effect of cyclophosphamide rescue therapy in the treatment of chronic rejection in lung transplant recipients. METHODS: Between October 1996 and March 1998 cyclophosphamide was prescribed to 7 patients with chronic and persistent rejection who failed to respond to conventional therapy (pulse steroids or antilymphocyte products or both). RESULTS: Cyclophosphamide therapy was initiated on postoperative day 478+/-366. At that time 2 patients were in bronchiolitis obliterans syndrome stage 0, 3 patients in stage 1, and 2 patients in stage 2. Their best postoperative forced expiratory volume in one second (FEV1) was 2.19+/-0.75 L. Three months before the start of cyclophosphamide the FEV1 had declined to 1.90+/-0.83 L, with a further decline to 1.63+/-0.64 L at the time of initiating cyclophosphamide. In 6 of the 7 patients the FEV1 stabilized or increased after cyclophosphamide had been started (mean FEV1 3 and 6 months after cyclophosphamide of 1.77+/-0.58 L and 1.79+/-0.48 L, respectively). One patient died 18 months after the introduction of cyclophosphamide due to progressive obliterative bronchiolitis. In one patient cyclophosphamide had to be stopped because of persistent leucopenia. CONCLUSIONS: Cyclophosphamide might be a promising therapeutic alternative for the treatment of chronic persistent rejection after lung transplantation.

Adult↗

Protein kinase C expression and subcellular distribution in chronic myocardial ischemia. Comparison of two different canine models.

We studied protein kinase C (PKC) isozyme expression and activity distribution in two models of chronically ischemic canine myocardium: (1) single vessel obstruction (SVO), produced by tight stenosis of LAD followed by preconditioning and acute ischemia (40 min); (2) three vessel obstruction (3VO), produced by LAD-stenosis and gradual occlusion of right coronary artery and left circumflex. In both models after 8 weeks of chronic ischemia the dogs were either sacrificed or had PTCA of the LAD with a follow up of another 4 weeks. Control dogs were sham operated. PKC activity was measured in subcellular fractions of tissue samples from anterior and posterior regions in the presence of histone and gamma-[32P]-ATP. PKC isozymes were detected by Western blotting. All regions perfused by the obstructed coronaries were dysfunctional at 8 weeks when compared to baseline, with improvement of anterior wall function after PTCA of LAD. PKC activity was elevated in the membrane fraction of SVO, but unchanged in the 3VO model. PKCs alpha, epsilon, and zeta prevailed in cytosol fraction of the controls (cytosol/membrane ratios were +/- 3.34, 1.38 and 4.56 for alpha, epsilon and zeta, respectively), consistent with PKC activity distribution, while delta was not detected. There was no significant difference between the groups concerning the relative membrane amount of the isozymes. PKCs alpha and epsilon were decreased in the cytosol fraction of both models at 8 weeks (for anterior region, by 56 and 57% in SVO and by 49 and 46% in 3VO, respectively) without there being any differences between anterior and posterior regions, and were low also in the PTCA group. PKC zeta distribution however varied between the two models. The amount of PKC zeta isozyme was downregulated by 45% after 8 weeks of chronic ischemia and returned towards the control values after PTCA in the anterior region of SVO, while it did not change in anterior wall after 8 weeks in 3VO but was significantly decreased (by 47%) in posterior region after PTCA. In conclusion, our results suggest modified PKC signalling in chronically ischemic canine myocardium.

Animals↗

Out-patient versus in-hospital ambulatory 24-h blood pressure monitoring in heart transplant recipients.

OBJECTIVE: To study the effect of the environment--in-hospital vs. out-patient situation--on blood pressure as measured by ambulatory blood pressure monitoring (ABPM). PATIENTS AND METHODS: Twenty-four hour ABPM was performed sequentially in-hospital and again 9+/-3 days later on an out-patient basis, in 30 consecutive heart transplant recipients (27 men, median age 56 years, median time post-transplant 3 years). The same equipment was used on both occasions, without any interim change in medical treatment. RESULTS: Both systolic and diastolic blood pressure were higher in-hospital than as an out-patient: +7+/-7 and +6+/-5 mm Hg respectively for the 24-h average (P<0.001). Daytime and night-time pressures were affected similarly. Depending on the specific cut-off values used, 37 to 87% of the individual patients were hypertensive in-hospital; 31 to 73% of these had an acceptable blood pressure as an out-patient. The converse was very rare (0 to 3% of the total group). CONCLUSIONS: In heart transplant patients blood pressure as assessed from 24-h ABPM is lower in the home environment than during a hospital stay. The post-transplant attenuation of the circadian variation in blood pressure is not influenced by the environment. Checking an unsatisfactory in-hospital ABPM with an outpatient recording may obviate the need for an (intensified) antihypertensive treatment in a substantial number of patients.

Adolescent↗