Jacqueline Cornelissen

Immunosuppression, eotaxin and the diagnostic changes in eosinophils that precede early acute heart allograft rejection

Peripheral blood eosinophil counts (EOS) are undetectable in 40% blood samples sent for routine haematology at Papworth Hospital during the first 3 months after heart transplantation (HTx). Increases in EOS usually precede the development of allograft rejection by a median of 4 days. We compared the effects of cyclosporin (dose and total blood concentration), prednisolone (dose and both total and unbound plasma concentrations) and azathioprine, as well as plasma concentrations of the CCR-3 chemokines, eotaxin and RANTES, on changes in EOS in 47 consecutive HTx recipients, with a median follow-up of 90 (IQR 85-95) days. Multivariate analysis confirmed the independent association between both prednisolone dose (P<0.0001) and eotaxin (P<0.0001) and changes in EOS. The plasma eotaxin concentration was, in turn, most closely associated with the cyclosporin dose (P<0.001) and plasma prednisolone concentration (P=0.022). The blood cyclosporin concentration (P=0.028), EOS (P=0.012) and prednisolone dose (P=0.015) were all independently associated with the risk of treated acute rejection. When prednisolone pharmacokinetic parameters were substituted for the prednisolone dose in this multivariate model, only the pharmacokinetic parameter retained a significant association with the risk of rejection. Changes in EOS preceding cardiac allograft rejection are directly associated with plasma eotaxin concentrations and indirectly with prednisolone dosage. Cyclosporin may also indirectly influence these changes by inhibiting eotaxin production. EOS, prednisolone dose and blood cyclosporin concentrations were independently associated with the risk of acute rejection. The total and unbound fractions of prednisolone in plasma appear to be even more closely related to rejection but are difficult to measure. Monitoring EOS, as a surrogate measure of prednisolone immunosuppression, may be more cost-effective for controlling rejection than conventional cyclosporin monitoring in the first 6 weeks after HTx.

Biological efficacy of low versus medium dose aspirin after coronary surgery: results from a randomized trial [NCT00262275]

BackgroundThe beneficial effect of aspirin after coronary surgery is established; however, a recent study reported the inability of low doses (100 mg) to inhibit postoperative platelet function. We conducted a double-blind randomised trial to establish the efficacy of low dose aspirin and to compare it against medium dose aspirin.MethodsPatients undergoing coronary surgery were invited to participate and consenting patients were randomised to 100 mg or 325 mg of aspirin daily for 5 days. Our primary outcome was the difference in platelet aggregation (day 5 – baseline) using 1 μg/ml of collagen. Secondary outcomes were differences in EC50 of collagen, ADP and epinephrine (assessed using the technique of Born).ResultsFrom September 2002 to April 2004, 72 patients were randomised; 3 patients discontinued, leaving 35 and 34 in the low and medium dose aspirin arms respectively. The mean aggregation (using 1.1 μg/ml of collagen) was reduced in both the medium and low dose aspirin arms by 37% and 36% respectively. The baseline adjusted difference (low – medium) was 6% (95% CI -3 to 14; p = 0.19). The directions of the results for the differences in EC50 (low – medium) were consistent for collagen, ADP and epinephrine at -0.07 (-0.53 to 0.40), -0.08 (-0.28 to 0.11) and -4.41 (-10.56 to 1.72) respectively, but none were statistically significant.ConclusionContrary to recent findings, low dose aspirin is effective and medium dose aspirin did not prove superior for inhibiting platelet aggregation after coronary surgery.

Difficulty in managing cyclosporin C2 monitoring in de novo lung transplant recipients

95% CI 11.5-6.7). We also determine whether the above risk factors plus AR, mean CsA trough, mean steroid dose, creatinine level 200umol/mL, triglyceride 4.5 mmol/L, cholesterol 6.2 mmol/L, CMV, statin, ACE inhibitor, or calcium channel blockers (CCB) influenced the subsequent occurrence of IVUS-defined cardiac allograft vasculopathy (CAV) at one year (y), an endpoint studied because of its value as a surrogate for survival and MACE at 5 y after transplant. CAV was defined as an increase in maximal intimal thickness of 0.5 mm or more in any segment studied at both baseline and 1 y. Among the 211 patients with baseline and 1 y IVUS, there were too few patients with CMV or without statin use to determine whether these factors affected CAV. AR, and choice of statin were not risk factors for the occurrence of CAV. Of the risk factors analyzed donor age 50 y ((p 0.005, OR 3.6, CI 1.5-9.0) was associated with increased risk of CAV as was recipient CD (p 0.04, OR 1.83, CI 1.02-3.25) Conclusion: Metabolic risk factors did not influence AR or CAV at 1 y. In this mixed population, LVAD use emerged as a significant risk factor for AR, but AR itself did not influence the occurrence of CAV during the same interval. Patients receiving hearts from older donors, or whose reason for transplant is related to a diagnosis of CD may need their regimen tailored to address CAV.

419: Initial cyclosporin C2 monitoring following lung transplantation provides long-term clinical benefits: A prospective randomised study

Tacrolimus in 33 patients, group B; Pre-LT lymphocyte depletion with anti-CD3 Ab (Thymoglobulin), followed by Tacrolimus in 33 patients, group C; No induction, followed by post-LT triple-drug therapy (Tacrolimus/ Cyclosporine A Azathioprine steroids) in 49 patients, group D. The presence of preand post-transplant HLA-Ab was prospectively determined by ELISA, while the specificity of HLA-Ab by single-antigen ELISA and/or Luminex. Results: The prevalence of de novo HLA-Ab in the first year after LT was only 5% in patients who received MMF (group A), significantly lower than in the other groups (18-30%, table). There were no statistically differences between the groups without MMF regarding the prevalence of de novo HLA-Ab. Conclusions: In lung transplantation, the addition of MMF in the immunosuppressive regimen was associated with a lower humoral sensitization.