Odd Geiran

Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens

Abstract Background: Nonmelanoma skin cancer occurs frequently in organ transplant recipients, but the relative importance of different immunosuppressive therapy regimens is unclear. Objective: We studied the risk of skin cancer in the complete, single-center Norwegian cohort of kidney and heart transplant recipients (n = 2561). Methods: We determined cancer risk estimation by means of standardized incidence ratios and multivariate Cox regression. Results: Transplant recipients had an increased risk of cutaneous squamous cell carcinoma (SCC) (65-fold), malignant melanoma (3-fold), and Kaposis sarcoma (84-fold), and of lip SCC (20-fold), compared with the general population. After adjustment for age, kidney transplant recipients receiving cyclosporine, azathioprine, and prednisolone had a significantly (2.8 times) higher risk of cutaneous SCC relative to those receiving azathioprine and prednisolone. After adjustment for age and type of immunosuppressive regimen, heart transplant recipients had a significantly (2.9 times) higher risk than kidney transplant recipients. Conclusion: The risk of cutaneous SCC, malignant melanoma, Kaposis sarcoma, and lip SCC is increased in kidney and heart transplant recipients. The risk of posttransplant cutaneous SCC is related to the degree of immunosuppression caused by long-term immunosuppressive therapy. (J Am Acad Dermatol 1999;40:177-86.)

Myocardial expression of CC- and CXC-chemokines and their receptors in human end-stage heart failure

OBJECTIVES Chemokines regulate several biological processes, such as chemotaxis, collagen turnover, angiogenesis and apoptosis. Based on the persistent immune activation with elevated circulating levels of chemokines in patients with congestive heart failure (CHF), we have hypothesised a pathogenic role for chemokines in the development of CHF. The objective of this study was to examine mRNA levels and cellular localisation of chemokines and chemokine receptors in human CHF. METHODS We examined explanted hearts from ten patients with end-stage heart failure (all chambers) and in ten organ donors using an RNase protection assays and immunohistochemical techniques. RESULTS Our main findings were: (i) expression of eight chemokine and nine chemokine receptor genes in both failing and nonfailing myocardium, (ii) particularly high mRNA levels of monocyte chemoattractant protein (MCP)-1 and CXC-chemokine receptor 4 (CXCR4), in both chronic failing and nonfailing myocardium, (iii) decreased mRNA levels of MCP-1 and interleukin (IL)-8 in the failing left ventricles compared to failing left atria, (iv) decreased chemokine (e.g., MCP-1 and IL-8) and increased chemokine receptor (e.g., CCR2, CXCR1) mRNA levels in failing left ventricles and failing left atria compared to corresponding chambers in the nonfailing hearts and (v) immunolocalisation of MCP-1, IL-8 and CXCR4 to cardiomyocytes. CONCLUSION The present study demonstrates for the first time chemokine and chemokine receptor gene expression and protein localisation in the human myocardium, introducing a new family of mediators with potentially important effects on the myocardium. The observation of chemokine dysregulation in human end-stage heart failure may represent a previously unknown mechanism involved in progression of chronic heart failure.

Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris ☆: Clinical results from The Norwegian Randomized Trial

OBJECTIVES The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris. BACKGROUND Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published. METHODS One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2. RESULTS Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.) CONCLUSIONS Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.

Balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension

Objective To examine the effect of balloon pulmonary angioplasty (BPA) on chronic thromboembolic pulmonary hypertension (CTEPH) in patients with inoperable disease or persistent pulmonary hypertension after pulmonary endarterectomy. Design Observational cohort study. Setting Referred patients with inoperable or persistent CTEPH. Patients Twenty consecutive CTEPH patients (10 females), aged 60±10 years. Interventions BPA. Main outcome measures Right heart catheterisation, functional capacity (cardiopulmonary exercise testing (CPET) and NYHA class) and blood sampled biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T examined at the time of diagnosis and repeated in all patients 3 months after the last BPA. Results Seventy-three catheterisations were performed with 18.6±6.1 BPAs per patient on segmental and subsegmental arteries. Two deaths occurred following the first BPA, with an overall 10% periprocedural death rate. Reperfusion oedema complicated seven procedures. Comparisons before and after BPA showed significant haemodynamic improvements, including decreased mean pulmonary artery pressure (mPAP) (45±11 mm Hg vs 33±10 mm Hg; p<0.001) and increased cardiac output (4.9±1.6 L/min vs 5.4±1.9 L/min; p=0.011). Reduced right ventricular strain was indicated by significantly lower plasma levels of NT-proBNP and troponin T. Significant improvement in functional capacity was evident as assessed by NYHA class (3.0±0.5 vs 2.0±0.5; p<0.001) and CPET (13.6±5.6 mL/kg/min vs 17.0±6.5 mL/kg/min; p<0.001). Seventeen patients (85%) were alive after 51±30 months of follow-up. Conclusions BPA may offer an alternative form of treatment in selected CTEPH patients. While prognostic markers such as haemodynamics, functional capacity and biomarkers improve, significant periprocedural complications must be recognised. Randomised trials are warranted.

Mechanism of complement activation and its role in the inflammatory response after thoracoabdominal aortic aneurysm repair

Background—Complement activation contributes to ischemia-reperfusion injury. Patients undergoing thoracoabdominal aortic aneurysm (TAAA) repair suffer extensive ischemia-reperfusion and considerable systemic inflammation. Methods and Results—The degree and mechanism of complement activation and its role in inflammation were investigated in 19 patients undergoing TAAA repair. Patients undergoing open infrarenal aortic surgery (n=5) or endovascular descending aortic aneurysm repair (n=6) served as control subjects. Substantial complement activation was seen in TAAA patients but not in controls. C1rs-C1-inhibitor complexes increased moderately, whereas C4bc, C3bBbP, C3bc, and the terminal SC5b-9 complex (TCC) increased markedly after reperfusion, reaching a maximum 8 hours after reperfusion. Interleukin (IL)-1&bgr;, tumor necrosis factor &agr; (TNF-&agr;), and IL-8 increased significantly in TAAA patients but not in controls, peaking at 24 hours postoperatively and correlating closely with the degree of complement activation. IL-6 and IL-10 increased to a maximum 8 hours after reperfusion in the TAAA patients, were not correlated with complement activation, and increased moderately in the control subjects. Myeloperoxidase and lactoferrin increased markedly before reperfusion in all groups, whereas sICAM-1, sP-selectin, and sE-selectin were unchanged. No increase was observed in complement activation products, IL-1&bgr;, TNF-&agr;, or IL-8 in a mannose-binding lectin (MBL)–deficient TAAA patient, whereas IL-6, IL-10, myeloperoxidase, and lactoferrin increased as in the controls. Two other MBL-deficient TAAA patients receiving plasma attained significant MBL levels and showed complement and cytokine patterns identical to the MBL-sufficient TAAA patients. Conclusions—The data suggest that complement activation during TAAA repair is MBL mediated, amplified through the alternative pathway, and responsible in part for the inflammatory response.

Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure.

Background Studies in different animal models and plasma analyses in humans suggest that members of the interleukin‐6 (IL‐6) cytokine family may be involved in the pathogenesis of congestive heart failure (CHF). Accordingly, we have examined IL‐6‐related cytokines in chronic CHF in humans by analysing gene and protein expression in myocardium derived from patients with end‐stage heart failure and donor hearts.

Health-Related Quality of Life in Lung Transplant Candidates and Recipients

Background: Studies on the health-related quality of life in lung transplantation have used general questionnaires, although lung-specific instruments might be more sensitive to small differences. Objectives: To compare the health-related quality of life of lung transplant recipients with lung transplant candidates, using lung-specific and general instruments, and to assess the reliability and validity of these questionnaires. Methods: The study is a cross-sectional postal survey of 31 lung transplant recipients and 15 candidates, using the following outcome measures: St. George’s Respiratory Questionnaire (SGRQ), a lung-specific health status instrument; the Short Form 36 (SF-36), a general measure, and the Hospital Anxiety and Depression scale (HAD). Results: The SGRQ showed a significantly better score (p < 0.05) for transplant recipients in the impacts and activity dimensions and the total score than for candidates. SF-36 scores showed a similar improvement in all subscales of the SF-36 except bodily pain. Cronbach’s α for all dimensions of the SGRQ, SF-36, and HAD were 0.77–0.95. Conclusions: Patients surviving lung transplantations can expect a considerable improvement in most dimensions of health-related quality of life. This finding was consistent using both lung-specific and general measures. The reliability of the questionnaires was acceptable. The associations between scales support the validity of the questionnaires in this setting.

Plasma C-reactive protein as a marker of cardiac allograft vasculopathy in heart transplant recipients.

OBJECTIVES This study was initiated to determine whether heart transplant recipients (HTRs) with cardiac allograft vasculopathy (CAV) have increased levels of high-sensitivity C-reactive protein (hsCRP) and to examine whether an increase in hsCRP after heart transplantation predicts the development of CAV. Furthermore, the effect of pravastatin on plasma levels of hsCRP in HTRs was investigated. BACKGROUND The relationship between CAV and hsCRP, as well as the effect of statins on hsCRP in HTRs, has not been well established. METHODS On referral for their annual angiographic control study, 150 consecutive HTRs (mean 6.5 years since transplantation) were included. Plasma levels of hsCRP were measured before angiography and compared with patients with (n = 52) and without (n = 98) CAV. In 49 of these patients, we additionally analyzed hsCRP in blood samples stored from their six-month visit after the transplantation procedure. Furthermore, in a randomized, crossover study, hsCRP was analyzed in 17 male HTRs before and after six weeks of treatment with 20 mg pravastatin. RESULTS Median levels of CRP were elevated among patients with CAV compared with those with normal angiograms [3.86 (1.78 to 7.00) vs. 1.08 (0.72 to 2.13) mg/l, p < 0.001]. Prospectively evaluated hsCRP levels from six months to follow-up were significantly higher among those who developed CAV compared with those with normal angiograms [+2.76 (1.56 to 5.00) vs. +0.07 (-0.57 to 0.41) mg/l, p < 0.001]. On multivariate analysis, the increase in hsCRP was the only significant predictor of CAV. Six weeks of treatment with pravastatin significantly reduced hsCRP levels by 25%, without any relation to changes in lipid values. CONCLUSIONS Elevated plasma levels of CRP are associated with angiographic evidence of CAV, and the increase in hsCRP is a strong predictor of development of CAV. Statin treatment reduces levels of hsCRP and should be used in HTRs, regardless of their lipid levels.

Intraaortic balloon pumping for predominantly right ventricular failure after heart transplantation.

BACKGROUND Right ventricular failure from elevated pulmonary vascular resistance in the recipient is a main cause of early mortality after heart transplantation. When pharmacologic treatment is insufficient, mechanical circulatory assistance has been used to support the failing right ventricle. Considering right and left ventricular interdependence, we investigated whether intraaortic balloon counterpulsation (IABP) might also alleviate predominantly right ventricular dysfunction after heart transplantation. METHODS Among 278 cardiac recipients, 12 adult patients underwent mechanical circulatory support for cardiac allograft dysfunction. Five patients were treated with percutaneous IABP for early postoperative low cardiac output syndrome characterized by predominantly right ventricular failure. Clinical data and hemodynamic variables were recorded before and during IABP treatment. RESULTS Cardiac index (CI) and mean arterial pressure (MAP) increased (CI 1.7 +/- 0.1 to 2.5 +/- 0.2, MAP 53 +/- 12 to 71 +/- 7, p < 0.05) within 1 hour after IABP, whereas central venous pressure (CVP) and pulmonary artery wedge pressure (PAWP) decreased (CVP 21.6 +/- 1.7 to 13.8 +/- 3.1, p < .05; PAWP 14.8 +/- 4.9 to 12.4 +/- 3.7, nonsignificant). Within the next 12 hours, CI and mixed venous oxygen saturation increased (p < 0.05) and pulmonary artery pressure decreased (p < 0.05). All 5 patients were weaned successfully and 4 are long-term survivors with adequate cardiac performance at 1 year follow-up. CONCLUSIONS Intraaortic balloon pumping is a minimally invasive circulatory assist device with proved efficiency in low cardiac output syndromes. This report shows that low output syndrome caused by predominantly right ventricular allograft failure may be an additional indication for IABP.

Intraaortic Balloon Pump in Open Heart Operations: 10-Year Follow-up With Risk Analysis

BACKGROUND The intraaortic balloon pump (IABP) is the primary mechanical device used for perioperative cardiac failure. METHODS We analyzed the prognostic predictors and long-term survival of 344 patients undergoing cardiac operations who required the perioperative use of an IABP at our institution from January 1980 to December 1989. Hospital survivors (163 patients) were followed up for a mean of 7.45 years (range, 1 month to 15.3 years); cumulative follow-up included 1,167 patient-years. RESULTS The early mortality rate was 52.6% (181 patients). From parameters available at the time of IABP insertion, logistic regression analysis identified preoperative serum creatinine level, left ventricular ejection fraction, perioperative myocardial infarction, timing of IABP insertion, and indication for operation as independent predictors of early (30-day) death (p < 0.05). Cox regression analysis of hospital survivors identified timing of IABP insertion, perfusion time, and preoperative serum creatinine level as independent prognostic factors for late death (p < 0.05), whereas patient age was only marginally significant (p < 0.06). There was no association between IABP-related complications and death. Survival analysis demonstrated a 10-year actual survival rate of 22.04% +/- 0.023%, with 57 patients still at risk and significantly improved survival among those who received an IABP before operation (p < 0.02). CONCLUSIONS The early mortality rate in patients who received an IABP was high. Hospital survivors had a relatively good long-term prognosis. The significantly better short- and long-term survival of patients who received an IABP before operation may justify more liberal preoperative use of the IABP in high-risk patients.