Jingyuan Feng

Chemokine and chemokine receptor gene expression indicates acute rejection of human cardiac transplants.

Background. Factors directing T-cell infiltration into allografts during acute rejection remain poorly defined. Chemokines have been shown to mediate leukocyte recruitment into allografts in animal models of rejection. The goal of this study was to test the presence and levels of chemokine and receptor gene expression in serial endomyocardial biopsy specimens from heart transplant patients and to correlate the levels observed with histopathologic rejection grade. Methods. Three hundred sixteen serial endomyocardial biopsy specimens from 30 heart transplant patients were obtained during the clinically scheduled surveillance heart biopsy program. The follow-up period was 1 year. The expression of interferon (IFN)-&ggr; inducible protein (IP)-10, monokine induced by IFN-&ggr; (Mig), interferon-inducible T-cell alpha chemoattractant (I-TAC), regulated on activation normal T-cell expressed and secreted (RANTES), monocyte chemotactic protein (MCP)-1, interleukin (IL)-8, and the receptors CXCR3 and CCR5 were tested using quantitative, real-time polymerase chain reaction. Biopsy samples were examined histologically to assign rejection grade. Results. Expression of IP-10, Mig, I-TAC, RANTES, CXCR3, and CCR5, but not MCP-1 and IL-8, increased significantly in both grade 2 and grade 3 rejection (P ≤0.0096). These increases returned to normal after treatment with pulse steroid therapy to treat the rejection episode. Conclusion. The expression of IP-10, Mig, I-TAC, RANTES, CXCR3, and CCR5 in cardiac allografts significantly correlates with the presence and grade of acute rejection.

Chemokine and receptor-gene expression during early and late acute rejection episodes in human cardiac allografts.

Background. The expression levels of several chemokine genes in heart allografts correlate with histologic rejection grade. Potential molecular differences between early and late rejection (grade ≥2) episodes were examined by testing chemokine and receptor-gene expression. Methods. Expression of inducible protein (IP)-10, monokine induced by IFN-&ggr; (Mig), interferon inducible-T cell alpha chemoattractant (I-TAC), regulated on activation normal T-cell expressed and secreted (RANTES), and their receptors CXCR3 and CCR5 was tested in 60 endomyocardial biopsies from 24 patients using quantitative (Taqman) real-time polymerase chain reaction (PCR). The biopsies were taken in the first 3 months or from the 9th to the 12th month following transplantation. Results. IP-10, Mig, RANTES, CXCR3, and CCR5 expression levels were increased in the later versus earlier biopsies (P ≤0.01) despite no change in histologic rejection-grade status. Conclusion. These results demonstrate significantly increased expression of T-cell chemoattractants in heart allografts during later rejection when compared with episodes occurring shortly after transplantation. The findings suggest increased intensity of inflammation in rejection occurring at later times posttransplant that are revealed by molecular analyses of the graft.

A randomized trial of massage therapy after heart surgery.

OBJECTIVES To determine whether massage therapy improves postoperative mood, pain, anxiety, and physiologic measurements; shortens hospital stay; and decreases occurrence of atrial fibrillation. METHODS Two hundred fifty-two adults undergoing cardiac surgery were randomized to usual postoperative care (n=126) or usual care plus two massages (n=126). Assessments of mood, depression, anxiety, pain, physiologic status, cardiac rhythm, and hospital length of stay were completed. Logistic and linear regressions were performed. RESULTS Preoperative pain, mood, and affective state scores were positively associated with postoperative scores; however, there were no postoperative differences between groups for any measures (P=.11 to .93). There were no differences in physiologic variables except lower postoperative blood pressure after massage (P = .01). Postoperative atrial fibrillation occurrence (P = .6) and median postoperative hospital length of stay (P = .4) were similar between groups. CONCLUSION Massage therapy is feasible in cardiac surgical patients; however, it does not yield therapeutic benefit. Nevertheless, it should be a patient-selected and -paid option.

Induction Chemoradiotherapy Increases Pleural and Pericardial Complications after Esophagectomy for Cancer

Hypothesis: Limited information is available on late complications of multimodality therapy for locally advanced esophageal cancer. This study focuses on postesophagectomy benign pleural and pericardial complications to determine their prevalence, temporal pattern, and treatment, and their association with induction chemoradiotherapy and influence on survival. Methods: Between March 1987 and November 2001, 291 patients with clinical stage ≥IIA esophageal cancer underwent esophagectomy; 106 received induction chemoradiotherapy. A propensity score incorporating clinical stage and histopathology was used to identify 100 matched pairs of induction chemoradiotherapy and surgery-only patients. Among these, occurrence of pleural effusion, pericardial effusion, and pericarditis was ascertained by follow-up. Time-related occurrence, risk factors, and association with survival were assessed by repeated-events analyses. Results: During follow-up, 61 induction chemoradiotherapy patients experienced at least one pleural or pericardial complication, as did 46 propensity-matched surgery-only patients. Most occurred within 1 year, with 1-year freedom from occurrence only 34% after induction chemoradiotherapy and 59% after surgery only (p = 0.02). Risk of pleural effusion was nearly twice as great (hazard ratio 1.7, p = 0.0004) and pericardial complications 5 times greater (hazard ratio 5.3, p = 0.0005) after induction chemoradiotherapy than after surgery alone. Complications after induction chemoradiotherapy required intervention somewhat more frequently (58% versus 47%, p = 0.18), although they did not diminish subsequent survival (p > 0.8). Conclusions: Benign pleural and pericardial complications occur surprisingly frequently after esophagectomy, particularly when induction chemoradiotherapy is employed. This must be factored into discussions of morbidity for multimodality treatment strategies for locally advanced esophageal cancer and should be considered distinct from acute toxicity of induction chemoradiotherapy reported.

Decortication After Lung Transplantation

BACKGROUND Compromise of a pulmonary allograft by restrictive or infectious pleural-space pathology may be amenable to surgical intervention; however, the role of decortication in this patient population has not yet been substantiated. To address this issue, indications and outcomes of decortication after lung transplantation were examined at our institution. METHODS From February 1990 to December 2006, 553 patients underwent lung transplantation; postoperative decortications were performed 27 times in 24 patients (4.3%). RESULTS Indications for decortication included presumed empyema (15), loculated effusion (7), hemothorax (3), and fibrothorax (2). Decortication was performed at a median of 81 days after transplantation (range, 12 days to 7.8 years). Complete lung reexpansion was achieved after 19 of 27 decortications (70%). Infection was cleared from the pleural space in 9 of 15 empyema patients (64%). Survivals at 1, 3, 6, and 12 months after decortication were 85%, 73%, 65%, and 60%, respectively. Operative mortality (30-day or in-hospital) was 23%, and median length of stay was 19 days. CONCLUSIONS Decortication may alleviate the compromise of a transplanted lung by restrictive or infectious pleural-space disease, but operative risk is substantial.

The effect of two different cyclosporine formulations on the long-term progression to chronic rejection in renal allograft recipients

Abstract: Introduction:  The introduction of the microemulsion formulation of cyclosporine (CsA) (Neoral – NEO) has been shown to provide improved absorption and less intrapatient variability than the previous formulation (Sandimmune – SIM) in kidney transplant recipients. It has been suggested that the use of the microemulsion formulation results in less acute rejection, and therefore permits better long‐term transplant outcomes. Our aim was to determine whether the microemulsion formulation of cyclosporine has reduced the long‐term (5 yr or more) rates of chronic rejection (allograft nephropathy) in a renal transplant population.

1079-78 Preoperative QRS widening and ventricular dysrhythmia predict adverse outcomes following left ventricular reconstruction for ischemic cardiomyopathy

Background: Bone marrow-derived mononuclear cells (BM-MNCs) can give rise to endothelial progenitor cells and localized transplantation of BM-MNCs in ischemic myocardium may augment neovascularization. However, not much is known of the arrhythmogenic potential of BM-MNCs after intramyocardial transplantation. Objective: Evaluate the threshold for ventricular arrhythmia induction with conventional electrophysiologic study (EPS) with programmed stimulation in swine with chronic myocardial ischemia treated with autologous BM-MNCs. Methods: Adult Yucatan swine underwent left circumflex (LCX) ameroid implantation. At 4 weeks, animals were randomized to receive either BMMNCs (n=8) or DMEM culture medium as control (n=8). Bone marrow (30-50ml) was aspirated from sternum and if necessary, iliac crest. Mononuclear cells were isolated using density gradient centrifugation. Catheter-based (Boston Scientific StilettoTM) intramyocardial injections were performed with combined fluoroscopic and intracardiac echocardiography (ICE) guidance. The treatment group received total of 1 x 108 BMMNCs at 10 sites, 5 in ischemic (LCX), and 5 in non-ischemic (LAD) region. Four weeks after cell treatment, global wall motion score index (GWMSI) was evaluated by dobutamine stress echocardiography. Subsequently, electrophysiologic study was performed with right ventricle stimulation at apex and outflow tract, using a basic cycle length of 500 and 400msec and 1-3 extrastimuli. Results: No difference was found in total number of cases with inducible arrhythmias in BM-MNC and control groups: 3 out of 8 animals (38%) in BM-MNC group (2 polymorphic VT and 1 VF) and 3 out of 8 animals (38%) in control group (1 monomorphic VT and 2 VF). There was also no difference in global wall motion (GWMSI=1.03 in BM-MNCs; 1.17 in sham, p=0.38) and there was no correlation between GWMSI and ventricular arrhythmia induction (1.29 for induced pigs; 1.01 for non-induced, p=0.09). Conclusion: Transplantation of autologous BM-MNCs into ischemic myocardium did not alter the threshold for ventricular arrhythmia. Left ventricular dysfunction was not related to arrhythmia inducibility.