Intravascular US-guided direct intrahepatic portocaval shunt with an expanded polytetrafluoroethylene-covered stent-graft

PURPOSE: To retrospectively evaluate the midterm patency rate of the nitinol (Viatorr, W.L. Gore and Associates, Flagstaff, Ariz) stent-graft for direct intrahepatic portacaval shunt (DIPS) creation. MATERIALS AND METHODS: Institutional Review Board approval for this retrospective HIPAA-compliant study was obtained with waiver of informed consent. DIPS was created in 18 men and one woman (median age, 54 years; range, 45-65 years) by using nitinol polytetrafluoroethylene (PTFE)-covered stent-grafts. The primary indications were intractable ascites (n = 14), acute variceal bleeding (n = 3), and hydrothorax (n = 2). Follow-up included Doppler ultrasonography at 1, 6, and 12 months and venography with manometry at 6-month intervals after the procedure. Shunt patency and cumulative survival were evaluated by using the Kaplan-Meier method and survival curves were plotted. Differences in mean portosystemic gradients (PSGs) were evaluated by using the Student t test. Multiple regression analysis for survival and DIPS patency were performed for the following parameters: Child-Pugh class, model of end-stage liver disease score, pre- and post-DIPS PSGs, pre-DIPS liver function tests, and pre-DIPS creatinine levels. RESULTS: DIPS creation was successful in all patients. Effective portal decompression and free antegrade shunt flow was achieved in all patients. Intraperitoneal bleeding occurred in one patient during the procedure and was controlled during the same procedure by placing a second nitinol stent-graft. The primary patency rate was 100% at all times during the follow-up period (range, 2 days to 30 months; mean, 256 days; median, 160 days). Flow restrictors were deployed in two (11%) of 19 patients. The 1-year mortality rate was 37% (seven of 19). CONCLUSION: Patency after DIPS creation with the nitinol PTFE-covered stent-graft was superior to that after TIPS with the nitinol stent-graft.

[Survival, clinical data and quality of life 10 years after heart transplantation: a prospective study]

AIM: To study prospectively patients after heart transplantation with respect to quality of life, mortality, morbidity, and clinical parameters before and up to 10 years after the operation. METHODS: Sixty patients (47.9 +/- 10.9 years, 57 men, 3 women) were transplanted at the University of Vienna Hospital, Department for Heart and Thorax Surgery and were included in this study. They were assessed when set on the waiting list, then exactly one, 5 and 10 years after the transplantation. The variables evaluated included physical and emotional complaints, well-being, mortality and morbidity. In the sample of patients who survived 10 years (n = 23), morbidity (infections, malignancies, graft arteriosclerosis, and rejection episodes) as well as quality of life were evaluated. RESULTS: Actuarial survival rates were 83.3, 66.7, 48.3% at 1, 5, and 10 years after transplantation, respectively. During the first year, infections were the most important reasons for premature death. As a cause of mortality, malignancies were found between years 1 and 5, and graft arteriosclerosis between years 5 and 10. Physical complaints diminished significantly after the operation, but grew significantly during the period from 5 to 10 years (p < 0.001). However, trembling (p < 0.05) and paraesthesies (p < 0.01) diminished continuously. Emotional complaints such as depression and dysphoria (both p < 0.05) increased until the tenth year after their nadir at year 1. In long-time survivors, 3 malignancies (lung, skin, thyroidea) were diagnosed 6 to 9 years postoperatively. Three patients (13%) had signs of graft arteriosclerosis at year 10; 9 (40%) patients suffered from rejection episodes during the course of 10 years. There were no serious rejection episodes deserving immediate therapy. Quality of life at 10 years is good in these patients. CONCLUSIONS: Heart transplantation is a successful therapy for patients with terminal heart disease. Long-term survivors feel well after 10 years and report a good quality of life.

Noncompliance in organ transplant recipients: a literature review

The consequences of failing to comply to doctor's instructions can be damaging and devastating for the individual patient and their family. Noncompliance also leads to waste, as it reduces the potential benefits of therapy, and to the extra cost of treating avoidable consequent morbidity. Life-long immunosuppression is a prerequisite for good graft function, and noncompliance is often associated with late acute rejection episodes, graft loss, and death. It might be assumed that transplant patients constitute a highly motivated group, and that compliance would be high. Unfortunately, this is not the case: overall noncompliance rates vary from 20 to 50%. This overview includes literature on heart, liver, and kidney transplants in adult and pediatric transplant patients. Compliance behavior after transplantation, noncompliance and its relationship to organ loss and death, retransplantation outcome after graft loss due to noncompliance, and reasons for postoperative noncompliance will be addressed.

[Noncompliance in organ transplantation: a review]

The effectiveness of medical treatment depends not only on the appropriateness of the treatment modality but also on the patient's compliance with the intended regimen. The consequences of failing to comply can be damaging and devastating for the individual patient and his/her family. Noncompliance also leads to waste in two areas: first, a reduction of the potential benefits of therapy, and second, the additional cost of treating the avoidable consequent morbidity. A dramatic example of the consequences of noncompliance with the treatment regimen concerns patients who have had organ transplants: life-long immunosuppression is a pre-requisite for good graft function, and noncompliance is often associated with the occurrence of late acute rejection episodes, graft loss, and death. Here it might be assumed that these patients constitute a highly motivated group, and that compliance would be high. Unfortunately, this is not the case: overall noncompliance rates vary from 20 to 50%. There is no systematic and comprehensive review of the literature on noncompliance and its consequences in organ transplant patients to date. This overview includes literature on heart, liver and kidney transplants in adult and paediatric transplant patients and addresses the following issues: preoperative behaviour patterns as predictors of postoperative compliance problems, compliance behaviour after transplantation, noncompliance and its relationship to organ loss and death, retransplantation outcome after graft loss due to noncompliance, reasons for postoperative noncompliance, and ways to promote compliance.

Vascular adaptation of the internal thoracic artery graft early and late after bypass surgery

OBJECTIVE: Flow mismatch between the supplying artery and the myocardial perfusion region has been observed in patients with internal thoracic artery grafts. Thus coronary flow changes of arterial (internal thoracic artery grafts) and saphenous (saphenous vein grafts) bypass grafts were studied early and late after coronary artery bypass grafting. METHODS: Thirty patients undergoing elective bypass surgery (internal thoracic artery and saphenous vein grafts) were studied intraoperatively and (17 patients) 3 to 10 months postoperatively. Coronary flow was measured intraoperatively with the transit-time Doppler scanning technique. Postoperatively, flow velocity and coronary flow reserve were determined with the Doppler flow wire technique. Quantitative angiographic analysis was used to determine vessel size for calculation of absolute flow. RESULTS: Intraoperatively, internal thoracic artery graft flow was significantly lower than saphenous vein graft flow (31 +/- 8 vs 58 +/- 29 mL/min, P < .01). Postoperatively, internal thoracic artery graft flow increased significantly to 42 +/- 24 mL/min at 3 months and to 56 +/- 30 mL/min (P < .02 vs intraoperative value) at 10 months, respectively. However, saphenous vein graft flow remained unchanged over time (58 +/- 29 to 50 +/- 27 mL/min at 3 months and 46 +/- 27 mL/min at 10 months). Coronary flow reserve was abnormally low intraoperatively in the internal thoracic artery (1.3 +/- 0.3) and saphenous vein (1.6 +/- 0.5) grafts but increased significantly to normal values in both types of graft at follow-up. CONCLUSIONS: Bypass flow of the internal thoracic artery graft is significantly reduced intraoperatively when compared with that of the saphenous vein graft. However, 3 and 10 months after the operation, flow of the internal thoracic artery graft increases significantly and is similar to saphenous vein graft flow. This finding can be explained by an early flow mismatch of the native internal thoracic artery in the presence of a large perfusion territory. During follow-up, there is vascular remodeling of the internal thoracic artery, probably because of endothelium-mediated mechanisms.

Reflection, refraction, and rejection : copper smelting heritage and the execution of environmental policy

This dissertation examines the global technological and environmental history of copper smelting and the conflict that developed between historic preservation and environmental remediation at major copper smelting sites in the United States after their productive periods ended. Part I of the dissertation is a synthetic overview of the history of copper smelting and its environmental impact. After reviewing the basic metallurgy of copper ores, the dissertation contains successive chapters on the history of copper smelting to 1640, culminating in the so-called German, or Continental, processing system; on the emergence of the rival Welsh system during the British industrial revolution; and on the growth of American dominance in copper production the late 19th and early 20th centuries. The latter chapter focuses, in particular, on three of the most important early American copper districts: Michigan’s Keweenaw Peninsula, Tennessee’s Copper Basin, and Butte-Anaconda, Montana. As these three districts went into decline and ultimately out of production, they left a rich industrial heritage and significant waste and pollution problems generated by increasingly more sophisticated technologies capable of commercially processing steadily growing volumes of decreasingly rich ores. Part II of the dissertation looks at the conflict between historic preservation and environmental remediation that emerged locally and nationally in copper districts as they went into decline and eventually ceased production. Locally, former copper mining communities often split between those who wished to commemorate a region’s past importance and develop heritage tourism, and local developers who wished to clear up and clean out old industrial sites for other purposes. Nationally, Congress passed laws in the 1960s and 1970s mandating the preservation of historical resources (National Historic Preservation Act) and laws mandating the cleanup of contaminated landscapes (CERCLA, or Superfund), objectives sometimes in conflict – especially in the case of copper smelting sites. The dissertation devotes individual chapters to the conflicts that developed between environmental remediation, particularly involving the Environmental Protection Agency and the heritage movement in the Tennessee, Montana, and Michigan copper districts. A concluding chapter provides a broad model to illustrate the relationship between industrial decline, federal environmental remediation activities, and the growth of heritage consciousness in former copper mining and smelting areas, analyzes why the outcome varied in the three areas, and suggests methods for dealing with heritage-remediation issues to minimize conflict and maximize heritage preservation.

Interferon-gamma regulates idiopathic pneumonia syndrome, a Th17+CD4+ T-cell-mediated graft-versus-host disease

RATIONALE: Pulmonary complications of hematopoietic stem cell transplantation include infections and graft-versus-host diseases, such as idiopathic pneumonia syndrome (IPS). Conflicting data exist regarding the role of the interferon (IFN)-gamma-producing Th1 CD4(+) T-cell subset and IL-17A in IPS. OBJECTIVES: To determine the role of IFN-gamma and IL-17A in the establishment of pulmonary graft-versus-host disease. METHODS: A semiallogeneic murine model based on C57BL/6 x BALB/c as recipients with transplantation of BALB/c RAG2(-/-) bone marrow and transfer of different genetic knockout T cells (T-bet(-/-), IFN-gamma(-/-), IFN-gammaR(-/-)) on a BALB/c background. Lung tissue was examined for parenchymal changes and infiltrating cells by histology and fluorescence-activated cell sorter analysis. MEASUREMENTS AND MAIN RESULTS: After transfer of semiallogeneic bone marrow together with donor CD4(+) T cells lacking IFN-gamma or T-bet-a T-box transcription factor controlling Th1 commitment-we found severe inflammation in the lungs, but no enhancement in other organs. In contrast, wild-type donor CD4(+) T cells mediated minimal inflammation only, and donor CD8(+) T cells were not required for IPS development. Mechanistically, the absence of IFN-gamma or IFN-gamma signaling in pulmonary parenchymal cells promoted expansion of IL-17A-producing CD4(+) T cells and local IL-17A release. In vivo depletion of IL-17A reduced disease severity. CONCLUSIONS: One mechanism of IFN-gamma protection against IPS is negative regulation of the expansion of pathogenic IL-17A-producing CD4(+) T cells through interaction with the IFN-gamma receptor on the pulmonary parenchymal cell population.

Analysis of independent microarray datasets of renal biopsies identifies a robust transcript signature of acute allograft rejection

Transcriptomics could contribute significantly to the early and specific diagnosis of rejection episodes by defining 'molecular Banff' signatures. Recently, the description of pathogenesis-based transcript sets offered a new opportunity for objective and quantitative diagnosis. Generating high-quality transcript panels is thus critical to define high-performance diagnostic classifier. In this study, a comparative analysis was performed across four different microarray datasets of heterogeneous sample collections from two published clinical datasets and two own datasets including biopsies for clinical indication, and samples from nonhuman primates. We characterized a common transcriptional profile of 70 genes, defined as acute rejection transcript set (ARTS). ARTS expression is significantly up-regulated in all AR samples as compared with stable allografts or healthy kidneys, and strongly correlates with the severity of Banff AR types. Similarly, ARTS were tested as a classifier in a large collection of 143 independent biopsies recently published by the University of Alberta. Results demonstrate that the 'in silico' approach applied in this study is able to identify a robust and reliable molecular signature for AR, supporting a specific and sensitive molecular diagnostic approach for renal transplant monitoring.

Dextran sulfate facilitates anti-CD4 mAb-induced long-term rat cardiac allograft survival after prolonged cold ischemia

Ischemia/reperfusion injury leads to activation of graft endothelial cells (EC), boosting antigraft immunity and impeding tolerance induction. We hypothesized that the complement inhibitor and EC-protectant dextran sulfate (DXS, MW 5000) facilitates long-term graft survival induced by non-depleting anti-CD4 mAb (RIB 5/2). Hearts from DA donor rats were heterotopically transplanted into Lewis recipients treated with RIB 5/2 (20 mg/kg, days-1,0,1,2,3; i.p.) with or without DXS (grafts perfused with 25 mg, recipients treated i.v. with 25 mg/kg on days 1,3 and 12.5 mg/kg on days 5,7,9,11,13,15). Cold graft ischemia time was 20 min or 12 h. Median survival time (MST) was comparable between RIB 5/2 and RIB 5/2+DXS-treated recipients in the 20-min group with >175-day graft survival. In the 12-h group RIB 5/2 only led to chronic rejection (MST = 49.5 days) with elevated alloantibody response, whereas RIB 5/2+DXS induced long-term survival (MST >100 days, p < 0.05) with upregulation of genes related to transplantation tolerance. Analysis of the 12-h group treated with RIB 5/2+DXS at 1-day posttransplantation revealed reduced EC activation, complement deposition and inflammatory cell infiltration. In summary, DXS attenuates I/R-induced acute graft injury and facilitates long-term survival in this clinically relevant transplant model.

Tricuspid valve regurgitation attributable to endomyocardial biopsies and rejection in heart transplantation

In the present report the prevalence, severity, and risk factors of tricuspid valve regurgitation (TR) in 251 heart transplant recipients have been analyzed retrospectively. Tricuspid valve function was studied by color-flow Doppler echocardiogram and annual heart catheterization. The presence or severity of TR was graded on a scale from 0 (no TR) to 4 (severe). Additional postoperative data included rate of rejection, number of endomyocardial biopsies, incidence of transplant vasculopathy, and preoperative and postoperative hemodynamics. The incidence of grade 3 TR increases from 5% at 1 year to 50% at 4 years after transplantation. Multivariate analysis showed rate of rejection and donor heart weight to be significant risk factors. The ischemic intervals as well as the preoperative and postoperative pulmonary hemodynamics did not affect the severity or prevalence of TR. These results indicate that various factors appear to have an impact on the development of TR and that the prevalence might be lowered by a reduction of the number of biopsies performed and when possible, oversizing of donor hearts.