Utility of immune monitoring in heart transplant recipients on everolimus-based immune suppression.

BACKGROUND: Everolimus provides effective immune suppression (IS) after heart transplant (HTx). Its pharmacologic properties differentiate everolimus from other IS drugs. A non-invasive immune monitoring (IM) assay test appears to predict the immune state in HTx recipients on standard calcineurin-inhibitor-based IS. The utility of IM in HTx recipients on everolimus-based IS was evaluated. METHODS: Between June 2005 and June 2011, 34 adult HTx recipients followed up at our center received everolimus and had 381 IM assays that were performed at six months to 16-yr post-transplant. Results of the IM assay were correlated with infection and rejection episodes that occurred during the IM testing. RESULTS: In the everolimus-based IS group, there were 18 infectious episodes and four rejection episodes. The average IM score was significantly lower during infection than at steady state (188 ± 122 vs. 338 ± 137 ng/mL ATP, p < 0.001) and not significantly different during rejection when compared with steady state (430 ± 132 vs. 338 ± 137 ng/mL ATP, p = 0.5). CONCLUSIONS: The non-invasive IM assay predicts infectious risk in HTx recipients on everolimus-based IS. Its inconclusive association with rejection was probably due to the small number of rejections. Serial longitudinal IM may allow proper adjustment of everolimus doses.

Individualized immune monitoring of cardiac transplant recipients by noninvasive longitudinal cellular immunity tests.

BACKGROUND: Common immunosuppression strategies after heart transplantation (HTx) are based on accepted target drug levels, disregarding that drug levels do not correlate with the individual patient's pharmacokinetics or with the actual immunosuppressive drug effect on the patient. The Immuknow assay is used for immune monitoring and management of organ transplant recipients. This study evaluated the Immuknow assay for longitudinal immune monitoring of HTx patients throughout various clinical settings. METHODS: The functional immune response as measured by the Immuknow assay was determined in 327 samples collected from 50 HTx patients at the Rabin Medical Center and was analyzed together with common clinical parameters. RESULTS: The median Immuknow levels measured throughout the infection episodes and the episodes of biopsy-proven acute rejection were 129 and 619 ng ATP/mL, respectively. These values were significantly dissimilar to the median Immuknow level measured during clinical quiescence, which was 351 ng ATP/mL (P<0.05). Calcineurin inhibitors drug-level measurements did not provide a reliable depiction of the patients' immune function, because the median deviation from the recommended drug trough levels range was significantly higher than the median deviation of Immuknow levels from their expected immune response zones. Longitudinal monitoring of Immuknow levels through serial testing proved to be a reliable method for individual patient immune management. CONCLUSIONS: The Immuknow assay reliably reflects the cellular immune function of HTx patients, thereby supporting the immune monitoring and management of these patients. Serial longitudinal Immuknow monitoring allows immune management of therapy according to the individual patient's immune status.

Augmentation of low-frequency ultrasound-induced clot disruption by hydroxyethyl starch is dependent on the duration and intensity of ultrasound exposure; an in vitro study.

UNLABELLED: We investigated the synergistic effect between low-frequency ultrasound (US) and hydroxyethyl starch (HAES) on blood clot disruption, using different HAES concentrations, US duration and intensity. Human blood clots, 200 to 400 mg in weight, were placed in tubes containing 10 mL of normal saline alone or with HAES 0.1%, 1% or 2%. Clots were randomized to four intensities of US exposure: none, low, medium and high (maximal amplitude of motion at the tip of the horn: 0, 96, 144 and 192 micro m, respectively), and for three durations of US exposure (10, 20 and 40 s). After treatment, the clots were reweighed, and the percent differences in weights were calculated. US intensity, US duration and HAES concentration had a significant effect on the blood clot dissolution (p < 0.001 for all three variables). HAES augmented clot dissolution only when US intensity was medium or high. With low intensity, HAES did not augment clot lysis. CONCLUSIONS: microparticle-containing solutions, such as HAES, have a potential for augmenting clot disruption by US. This effect is highly dependent on US intensity.

Correlation between the electrocardiogram and regional wall motion abnormalities as detected by echocardiography in first inferior acute myocardial infarction.

We assessed the correlation between ST deviation in each of the six precordial leads and the presence of regional wall motion abnormalities (RWMA) as assessed by transthoracic echocardiography in 109 patients with first inferior acute myocardial infarction. ST depression in lead V1 and V2 was associated with higher incidence of RWMA of the mid-posterior segment (p < 0.02 for both leads). The specificity of ST segment depression in leads V1 and V2 for RWMA in mid-posterior segment was 87 and 57%, and the sensitivity 36 and 70%, respectively. Patients with ST depression in leads V2 or V3 had worse global RWMA score than patients without ST depression in these leads (p = 0.009 and p = 0.025, respectively). Patients with an ST elevation in lead V1, but not in leads V2 or V3, had a higher prevalence of right ventricular involvement (p < 0.0001). ST elevation in lead V5 was associated with more frequent involvement of the apical portion of the inferior wall (p < 0.02), with specificity of 88% and sensitivity of 33%. Global RWMA score was significantly worse for patients with ST elevation than for patients with isoelectric ST in lead V5 (p = 0.024). ST elevation in lead V6 was associated with RWMA in the mid-posterior segment (p < 0.006), with specificity of 91% and sensitivity of 33%, and worse global RWMA score (p = 0.022).

In vitro ultrasound augmented clot dissolution--what is the optimal timing of ultrasound application?

The mechanism of ultrasound augmentation of pharmacological thrombolysis is yet unknown. The goal of this study is to find the best timing regimen for in-vitro ultrasound augmented clot dissolution by streptokinase, heparin and their combination. Blood clots from 4 donors were cut into 200-400 mg sections and randomized to no treatment with ultrasound; pre-treatment with ultrasound (before immersion); early treatment with ultrasound; or late treatment with ultrasound. Clots were placed in tubes containing either saline; heparin; streptokinase or streptokinase +heparin. All groups showed significant weight reduction (p < 0.001). Using the one way ANOVA test, we showed that ultrasound application resulted in a significantly higher rate of clots dissolution (p < 0.05) than without ultrasound in all of the solutions tested. We found no statistically significant difference between the three ultrasound regimens tested. In conclusion, in our in-vitro model, no single ultrasound timing schedule was found to provide better clot dissolution than the other schedules. This finding may suggest an additive effect between the ultrasound and the different solutions rather than a synergistic effect.