Twenty-year comparison of tissue and mechanical valve replacement.

OBJECTIVE: We sought to compare outcomes with tissue and St Jude Medical mechanical valves over a 20-year period. METHODS: Valve-related events and overall survival were analyzed in 2533 patients 18 years of age or older undergoing initial aortic, mitral, or combined aortic and mitral (double) valve replacement with a tissue valve (Hancock, Carpentier-Edwards porcine, or Carpentier-Edwards pericardial) or a St Jude Medical mechanical valve. Total follow-up was 13,390 patient-years. There were 666 St Jude Medical aortic valve replacements, 723 tissue aortic valve replacements, 513 St Jude Medical mitral valve replacements, 402 tissue mitral valve replacements, 161 St Jude Medical double valve replacements, and 68 tissue double valve replacements. The mean age was 68 +/- 13.3 years (St Jude Medical valve, 64.5 +/- 12.9; tissue valve, 72.0 +/- 12.6). RESULTS: There were no overall differences in survival between tissue and mechanical valves. Multivariable analysis indicated that the type of valve did not affect survival. Analysis by age less than 65 years or 65 years or older and presence or absence of coronary disease revealed similar long-term survival in all subgroups. The risk of hemorrhage was lower in patients receiving tissue aortic valve replacements but was not significantly different in patients receiving mitral valve or double valve replacements. Thromboembolism rates were similar for tissue and mechanical valve recipients. However, reoperation rates were significantly higher in patients receiving both aortic and mitral tissue valves. The reoperation hazard increased progressively with time both in patients receiving aortic and in those receiving mitral tissue valves. Overall valve complications were initially higher with mechanical aortic valves but not with mechanical mitral valves. However, valve complication rates later crossed over, with higher rates in tissue valve recipients after 7 years in patients undergoing mitral valve replacement and 10 years in those undergoing aortic valve replacement. CONCLUSIONS: Tissue and mechanical valve recipients have similar survival over 20 years of follow-up. The primary tradeoff is an increased risk of hemorrhage in patients receiving mechanical aortic valve replacements and an increased risk of late reoperation in all patients receiving tissue valve replacements. The risk of tissue valve reoperation increases progressively with time.

Pre-transplant donor-specific transfusions induce allograft rejection and IL-2 gene expression in the WKY-->F344 functional tolerance model of rat lung transplantation.

Our previous studies have shown that a spontaneous functional tolerance develops in a rat model of lung transplantation (WKY-->F344). The tolerance observed in this model may be due to the minor histocompatible differences in this combination, however, the possibility of a tolerogenic effect related specifically to the lung allograft must be considered. To further examine this model, the effect of pre-transplant donor-specific spleen cell transfusions (DSTs) was examined on the functional tolerance state seen in this model. F344 rats received WKY spleen cells on days -45 and -30 before lung transplantations. Control F344 rats received lung transplants without DSTs. Recipients in both groups were killed on day 7, 14, 21 and 49 post-transplant, and allograft rejection (AR) was graded histologically (stage 0-IV). Intragraft cytokine gene transcripts were examined on day 7 and 14 post-transplant using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques to investigate the underlying immunological events occurring in each group. In addition, allogeneic (WKY) and third party (BN) skin grafts were placed on lung recipients at day 35 post-transplant to evaluate the development of systemic tolerance. It was seen that control animals showed moderate to severe lymphocytic infiltrations (stage II-III AR) in the first 3 weeks followed by spontaneous recovery with stage I-II AR on day 49. In marked contrast, DST-treated animals showed more aggressive AR with severe lymphocytic infiltration and haemorrhagic infarction (stage III-IV AR) by day 14-21, without any evidence of recovery on day 49. WKY skin grafts showed prolonged survival in control animals, but were promptly rejected in DST-treated animals. Intragraft cytokine gene expression in control animals was characterized by no or weak expression of IL-2 and high IL-10, while DST-treated animals showed high levels of IL-2 transcripts. IL-2:IL-10 and IL-2:IL-4 ratios were significantly increased in DST-treated animals compared with controls on day 7 post-transplant. It was concluded that pre-transplant DSTs did not enhance allograft survival, but actually induced AR and ablated any immunological benefit of the lung allograft on induction of tolerance in the WKY-->F344 lung transplant model. It was found that the DST-induced AR was associated with a deviation of cytokine immune responses from a predominant Th2 to Th1 profile characterized by increased IL-2 gene expression in the allografts. We also conclude that factors other than the degree of histocompatibility matching, such as the route and timing of alloantigen exposure, and the amount or nature of alloantigens associated specifically with lung allografts, are involved in deviating native immune responses toward acceptance or rejection of lung allografts in this model of lung transplantation.

Postinfarction ventricular septal defect.

Despite improved screening and diagnostic capabilities for the presence of coronary artery disease (CAD), with the promise of improved outcomes from earlier therapeutic interventions, postinfarction ventricular septal perforation (VSD) continues to be a very difficult therapeutic challenge. In our experience with VSD, the incidence of this complication per year has decreased, almost certainly related to earlier and more effective medical therapy in patients with CAD. By contrast, the outcomes of surgical repair have not improved, even with an aggressive strategy about bypassing involved coronary arteries. Furthermore, the earliest possible surgical approach and the incorporation of a number of technical advances, especially those relating to myocardial preservation, have not had an apparent effect. Because the number of patients who underwent operation is small, it is not possible from our single-institutional experience to define statistical significance to our continuing observations of this condition, suggesting that the clinical spectrum of postinfarction VSD is still evolving. Important changes appear to be associated with an increase in the number of female patients observed (60%), in contrast to their lesser frequency of uncomplicated coronary bypass (18%) and a change in the anatomic substrate, with posterior infarctions and rupture now accounting for 73% of cases at Cedars-Sinai. For the present, earliest possible surgical intervention to minimize the severity of multi-organ failure and use all of the advanced therapeutic modalities of cardiac support and surgical therapy that are available continues to be indicated. For the long term, continuing advances in the earlier diagnosis and more aggressive management of CAD, especially in females, may hold the best promise for a continued decrease in the occurrence of this very difficult-to-treat postinfarction complication.

Clinical and nonclinical predictors of the cost of coronary bypass surgery: potential effects on health care delivery and reimbursement.

BACKGROUND: Health care providers are being pressured to lower the cost of care. Because of the inherent cost variability in providing health care, as reimbursement falls, providers may not be able to cover all costs. Understanding the underlying causes of this wide variability is important in determining optimum pricing. Prior studies on the cost of coronary bypass surgery have determined which clinical variables affect cost, yet none have studied nonclinical variables that can influence the cost of coronary bypass surgery. METHODS: In a cohort of 882 consecutive patients with treatment classified in the diagnosis-related group (DRG) 107, we examined 55 clinical and nonclinical variables obtained from our prospective database. For explanatory purposes, we used multiple linear regression to determine the variables that were predictive of direct cost and the magnitude of contribution of each variable. RESULTS: Eleven clinical and 4 nonclinical variables were predictive of direct cost. Nonclinical variables added significant cost-predictive information beyond that of the traditional clinical variables, and their magnitude of effect was equal to or greater than the traditional clinical variables. CONCLUSIONS: Nonclinical patient characteristics add important predictive information concerning the cost of coronary bypass surgery to traditional clinical variables. These data will be important in developing contracting strategies, in the evaluation of individual physician performance, and in modifying national methods of reimbursement.

Perivascular delivery of a nitric oxide donor inhibits neointimal hyperplasia in vein grafts implanted in the arterial circulation.

OBJECTIVE: Nitric oxide has been reported to reduce intimal hyperplasia as a response to arterial injury. This study was designed to assess the possible effect of perivascular application of a nitric oxide donor on neointimal proliferation occurring in veins exposed to the dynamics of the arterial circulation in a hypercholesterolemic rabbit model. METHODS: Autologous jugular vein grafts were implanted in the carotid circulation of 20 hypercholesterolemic rabbits. A mixture of a biodegradable polymer and the nitric oxide donor, spermine/nitric oxide, which releases nitric oxide with a half-life of 39 minutes, was applied periadventitially at the time of implantation. Controls were veins bathed in saline solution, polymer alone, and polymer plus the carrier vehicle spermine without nitric oxide. Animals (n = 5 in each group) were put to death on day 28 for morphometric analysis, cell count, and immunohistochemical staining. RESULTS: Treatment with perivascular nitric oxide donor significantly decreased wall thickness (126 +/- 24 microm vs 208 +/- 45 microm, p = 0.0017) and area (124 +/- 22 microm2/microm vs 211 +/- 37 microm2/microm, p = 0.005). With the carrier vehicle spermine alone, there was a trend toward reduced intimal thickness, but the change was not statistically significant. In the grafts treated with nitric oxide donor, expression of insulin-like growth factor, fibroblast growth factor, thrombospondins, fibronectin, and tenascin was reduced. CONCLUSION: The periadventitial delivery of nitric oxide donor produces a reduction of neointimal hyperplasia in veins implanted in the arterial circulation. The mechanism of action is not entirely clear, but the reduction cannot be explained on the basis of decreased cell proliferation alone. Other possibilities are modulation of protein synthesis of vascular smooth muscle cells and production of extracellular matrix components.

Cardiac operations in patients 90 years of age and older.

BACKGROUND: Growth of the elderly population worldwide, and specifically in the United States, will continue to accelerate and will have a profound impact on the cost and delivery of health care resources in the future. A medical strategy that allows the elderly to live independently is essential to most cost-effective use of our resources. The question remains as to what will be the future of surgical therapy for this increasing population. METHODS: We retrospectively studied the cases of 30 consecutive nonagenarians (mean age, 92.3 +/- 1.8 years) who underwent a cardiac operation within a 9-year period. All patients were in New York Heart Association class III or IV and underwent operation urgently or emergently. RESULTS: The 30-day mortality rate was 10%, and the actuarial survival rates were 81% +/- 8% and 75% +/- 9% at 1 year and 2 years, respectively. Seventy-eight percent of survivors were in New York Heart Association class I or II within 2 years after operation and had an improved quality of life. The cost of providing care in this age group was 24% higher than in octogenarians. CONCLUSIONS: Advanced age in and of itself (>90 years) should not be a contraindication to an open-heart operation, although morbidity, mortality, and cost may be higher. However, selective criteria identifying risks and benefits for individual patients should be applied. The aging of our population will have a profound impact on the cost and delivery of health care resources in the future. This issue must be addressed in the current debate on the provision of expensive procedures under a realigned national health-care system.

Clinical experience with one hundred consecutive patients undergoing orthotopic heart transplantation with bicaval and pulmonary venous anastomoses.

OBJECTIVE: Our objective was to assess survival, need for pacemaker insertion, and rejection frequency with a new surgical technique of orthotopic heart transplantation using bicaval and pulmonary venous anastomoses. METHODS: We retrospectively reviewed 100 consecutive patients who had orthotopic heart transplantation with this technique between July 1991 and September 1995. RESULTS: The mean age was 57.0 +/- 11.1 years, with 51 patients being 60 years or older. The mean donor/recipient weight ratio was 0.92, and in 28 patients the ratio was less than 0.8. The early (30-day) survival was 100% and the 1- and 2-year survivals were 98% +/- 2% and 96% +/- 2%, respectively. Survival was not affected by age or by the duration of the OKT3 therapy (p > 0.2 for each of these parameters). The seven late deaths were due to infection (n = 2), graft atherosclerosis (n = 3), acute rejection (n = 1), and nonspecific graft failure (n = 1). No permanent pacemaker was required in the first 6 months after the operation, and all the patients were discharged in normal sinus rhythm. Freedom from treated rejection was significantly greater in patients with 7 days of OKT3 therapy than in patients with 14 days of therapy (p < 0.0001). CONCLUSIONS: Orthotopic heart transplantation with bicaval and pulmonary venous anastomoses offers an improved alternative to the standard biatrial technique, with a 30-day mortality of 0,% in 100 consecutive patients, excellent intermediate-term survival, and elimination of the need for pacemaker insertion. More normal anatomic configuration and synchronous function of the atria may have contributed to these results.

Heart transplantation in patients 70 years of age and older: initial experience.

BACKGROUND: Heart transplantation has become a highly successful therapeutic option for patients with end-stage cardiomyopathy. Consequently, the criteria for patient selection, particularly regarding recipients' upper age limits, have been expanded, with an increasing number of people older than 60 years of age now undergoing transplantation. METHODS: A retrospective analysis of 6 patients 70 years of age and older who underwent heart transplantation was done; their clinical courses and outcomes were compared with those of younger patients, with a special emphasis on their posttransplantation quality of life. RESULTS: All 6 patients are alive and clinically well at a mean follow-up of 12 months. No age-related complications have been observed, and their quality of life is excellent. There has been a very low incidence of rejection, as well as few episodes of rejection. CONCLUSIONS: Heart transplantation in selected people 70 years of age and older can be performed successfully with a morbidity comparable to that seen in younger patients and excellent short-term survival. This initial experience is encouraging, but further studies and long-term follow-up are needed to validate the more routine application of this therapy.

Heart transplantation in patients 65 years of age and older: a comparative analysis of 40 patients.

BACKGROUND: Advanced age has traditionally been considered a relative contraindication to heart transplantation because of the potential for increased morbidity and decreased long-term survival. METHODS: We analyzed the results in 40 patients 65 years of age and older who underwent heart transplantation and compared them with those in 138 patients younger than 65 years. RESULTS: The older age group had a higher incidence of diabetes mellitus (p = 0.01), donor-recipient weight mismatch (< 0.80) (p = 0.004), lower donor-recipient weight ratio (p = 0.02), and longer allograft ischemic time (p = 0.008), among other differences. However, the 30-day operative mortality was similar in both groups (2.5% in older versus 2.2% in younger patients). Actuarial survival at 12, 24, and 36 months was not statistically different between the older and younger patients (86% +/- 6% versus 93% +/- 2%, 78% +/- 8% versus 89% +/- 3%, and 72% +/- 9% versus 81% +/- 4%, respectively; p = 0.26). The posttransplantation intensive care unit stay, total hospital stay, and associated hospital costs were also similar. The incidence of rejection during the first posttransplantation year was similar in both groups. CONCLUSIONS: Heart transplantation in selected patients 65 years of age and older can be performed successfully, with a morbidity and mortality comparable with those seen in younger patients. Advanced age should not be an exclusion criterion for heart transplantation, but selective criteria should be applied that identify risks and benefits individually.

Adverse 5-year outcome after coronary artery bypass surgery in blacks.

BACKGROUND: Coronary heart disease is the leading cause of death among blacks, but little is known about the late results of coronary artery bypass surgery in this population. It is not known whether differences in preoperative medical characteristics or medical health insurance affect outcome. We studied the effects of medical risk factors on survival outcome after coronary artery bypass surgery in a population of medically insured black and white patients. METHODS: Racial status and outcomes from surgery were determined in 3728 consecutive patients who had coronary artery bypass surgery at the authors' institution from January 1, 1984, to June 30, 1992. Coronary artery bypass surgery (excluding valve replacement) was performed in 115 black and 3113 white patients. RESULTS: Late survival probability was worse for blacks than whites at 1 year (84% vs 92%) and at 5 years (64% vs 82%, P=.001, Wilcoxon test). Most deaths were due to cardiac events in both groups (68% in blacks vs 67% in whites). Blacks had more hypertension (84% vs 54%), diabetes mellitus (36% vs 23%), and more were current smokers (21% vs 14%) (all P<.05, Fisher's exact test). Medical insurance coverage for blacks and whites was as follows: Medicare (60% vs 57%), private (38% vs 42%), and Medi-Cal (2% vs 2%). Operative mortality (30 days) was similar (5.2% for blacks vs 4.1% for whites; P=.48, Fisher's exact test). In a Cox regression model, race predicted long-term survival and persisted as an important risk factor after adjusting for preoperative factors related to patient survival (adjusted hazard ratio, 2.10; 95% confidence interval, 1.43 to 3.07). CONCLUSIONS: In this group of predominantly medically insured patients undergoing coronary artery bypass surgery, the risk of death in blacks at 5 years was twice that of whites.

Revascularization alone or combined with suture annuloplasty for ischemic mitral regurgitation. Evaluation by color Doppler echocardiography.

To determine the effectiveness of revascularization alone or combined with mitral valve repair for ischemic mitral regurgitation, we performed color Doppler echocardiography intraoperatively before and after cardiopulmonary bypass in 49 patients (mean age, 70 +/- 9 years) with concomitant mitral regurgitation and coronary artery disease (triple vessel or left main in 88%; prior infarction in 90%). After revascularization alone (n = 25), the mitral annulus diameter (2.88 +/- 0.44 cm vs 2.88 +/- 0.44 cm), leaflet-to-annulus ratio (1.44 +/- 0.30 vs 1.44 +/- 0.29), and mitral regurgitation grade (1.7 +/- 0.9 vs 1.8 +/- 0.7) remained unchanged (p = NS, postpump vs prepump); mitral regurgitation decreased by 2 grades in only 1 patient (4%). After combined revascularization and mitral valve suture annuloplasty (Kay-Zubiate; n = 24), the annulus diameter decreased (to 2.57 +/- 0.45 cm from 3.11 +/- 0.43 cm), the leaflet-to-annulus ratio increased (to 1.46 +/- 0.25 from 1.20 +/- 0.21), and the mitral regurgitation grade decreased significantly (to 0.9 +/- 0.9 from 2.8 +/- 1.0) (p < 0.01); mitral regurgitation decreased by 2 grades or more (successful repair) in 75%. The origin of the jet correlated with the site of prior infarction (p < 0.05), being inferior in cases of posterior or inferior infarction (67%), and central or broad in cases of combined anterior and inferior infarction (70%). Despite a slightly higher 30-day mortality in the repair group (p = 0.10), there was no significant difference in survival between the 2 surgical groups at 5 years or 8 years. Therefore, in this study of patients with mitral regurgitation and coronary artery disease, reduction in regurgitation grade with revascularization alone was infrequent. Concomitant suture annuloplasty significantly reduced regurgitation by reestablishing a more normal relationship between the leaflet and annulus sizes. The failure rate after suture annuloplasty was 25%; alternative repair techniques such as ring annuloplasty may have a lower failure rate.

Influence of vein valves in the development of arteriosclerosis in venoarterial grafts in the rabbit.

Coronary saphenous vein grafts in human beings have a more limited long-term patency rate than internal thoracic artery grafts, primarily because of more rapid development of arteriosclerosis. The factors responsible for this increased susceptibility are not completely understood. To test the hypothesis that vein valves may influence this process, we studied 48 hypercholesterolemic rabbits with jugular vein grafts interposed into the carotid arterial circulation. In 24 animals (group A), the vein segments did not contain a vein valve. In the other 24 animals (group B), a vein valve was present. Both groups were further divided in four subgroups of six to be put to death at 2, 4, 6, and 8 weeks after the operation. All animals were fed a 2% cholesterol diet. At postmortem examination, alternate 2 mm sections were either stained with hematoxylin and eosin for histologic and morphometric studies or frozen in liquid nitrogen for immunohistochemistry and in situ hybridization studies. Proliferating cell nuclear antigen immunostaining was used to study cell proliferation. Wall thickness of vein grafts increased with time. During the first 2 weeks intimal and medial thickening was primarily due to an increase in numbers of cells. Between 2 and 6 weeks further intimal and medial thickening occurred, but without additional increase in cell numbers. After 6 weeks, foam cells and lipid deposits started to appear. By 8 weeks, changes identical to those seen in arteriosclerotic plaques in human beings were evident. These changes developed sooner and with more intensity in group B animals (p < 0.01 to 0.001), and they developed faster and with more severity in segments of vein located distal to the valve than in the segments located proximal to the valve (p < 0.001). This is the first controlled experiment demonstrating that the presence of valves in the vein segments is associated with augmented and accelerated intimal changes leading to vein atheromatosis.

Hospital-based group: ideal practice for the future?

The format for future cardiothoracic surgical practices includes the option of a hospital-based group where provider groups and the hospital share the responsibilities and obligations of clinical care and the cost of that care. Based on personal experience at the Cedars-Sinai Medical Center, Los Angeles, three separate contract relationships during our tenure have reflected the evolution of cardiothoracic surgeons' relationship to our patients and the hospital in which we work. Although other organizational modes may prove equally successful, the hospital-based group practice is a viable structure that supports the preservation of quality in the work performed. This relationship helps to maintain a steady volume of patients enabling research endeavors, which are primarily funded through practice incomes, to continue and it also provides a platform for networking with defined patient referrals, shared services, and bench-marking with other centers.

Optimizing cardiothoracic surgery information for a managed care environment.

The rapid change occurring in American healthcare is a direct response to rising costs. Managed care is the fastest growing model that attempts to control escalating costs through limitations in patient choice, the active use of guidelines, and placing providers at risk. Managed care is an information intensive system, and those providers who use information effectively will be at an advantage in the competitive healthcare marketplace. There are five classes of information that providers must collect to be competitive in a managed care environment: patient satisfaction, medical outcomes, continuous quality improvement, quality of the decision, and financial data. Each of these should be actively used in marketing, assuring the quality of patient care, and maintaining financial stability. Although changes in our healthcare system are occurring rapidly, we need to respond to the marketplace to maintain our viability, but as physicians, we have the singular obligation to maintain the supremacy of the individual patient and the physician-patient relationship.

Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation.

Lung transplantation is now routinely performed for a wide range of end-stage cardiopulmonary disorders. Despite overcoming the problems associated with early acute rejection, chronic rejection (CR) in the form of obliterative bronchiolitis has emerged as the primary cause of late graft loss. The mechanisms involved in the development of CR of lung allografts are poorly understood, and no effective therapy is currently available. To better understand the pathological events associated with CR and tolerance, we examined two models of lung allograft rejection established in our laboratory. First, we exchanged left lung allografts between moderately histoincompatible inbred rat strains (WKY-->F344: n = 42 and F344-->WKY: n = 40). The WKY-->F344 model was previously shown to develop spontaneous tolerance, while the converse model (F344-->WKY) showed persistent acute rejection. The purpose of this investigation was to assess histopathological changes associated with long-term grafts left in place up to 140 days after transplant. To confirm that tolerance had developed, skin-grafting experiments were performed. Five skin grafts from each strain were placed on lung allograft recipients on day 35 after transplant and skin allograft survival was assessed and compared with controls. Acute rejection (AR) was graded histologically (stage O-IV) and the pathologic intensity of inflammation and CR were graded (0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = 76-100%) on percentage of involvement with the following categories being examined: (a) lymphocytic infiltration (perivascular, peribronchial, and peribronchiolar) and (b) vasculitis, edema, hemorrhage, and necrosis. Finally, chronic rejection was diagnosed by the presence of intimal hyperplasia, interstitial fibrosis, peribronchiolar fibrosis, bronchiolitis obliterans, and bronchiectasis. The WKY-->F344 animals showed progressive AR (stage III, day 21). Thereafter, the AR subsided spontaneously and was stage 0 on day 140. There were no signs of CR in these animals. In the F344-->WKY model, the AR progressed up to stage III-IV (day 21) and maintained for several weeks at stage III. Thereafter, pictures of the lungs showed CR on days 49, 70, and 98. There were significant differences between the two models during the chronic phase, such as interstitial fibrosis (0 +/- 0 vs. 1.8 +/- 1.3, P < 0.005), peribronchiolar fibrosis (0 +/- 0 vs. 3.6 +/- 0.55, P < 0.01), vasculitis (0.2 +/- 0.45 vs. 2.0 +/- 0, P < 0.008), and intimal hyperplasia (0.2 +/- 0.45 vs. 2.6 +/- 0.9, P < 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Soluble CTLA4Ig modifies parameters of acute inflammation in rat lung allograft rejection without altering lymphocytic infiltration or transcription of key cytokines.

The efficacy of CTLA4Ig in blocking immune activation and allograft rejection (AR) was tested in an aggressive and rapid model of rat lung AR (Brown Norway [BN]-->Lewis [LEW]). CTLA4Ig is a recombinant soluble protein that binds with high affinity to rat B7/BB1 and other surface molecules on APCs, subsequently blocking the binding of B7/BB1 to CD28/CTLA4 on T cells. This interrupts the costimulatory pathway critical for complete T cell activation and completion of the AR process. Left single-lung transplants were performed between BN-->Lew. Five allograft recipients were examined in each group. At transplantation, animals received 250 micrograms of CTLA4Ig or 250 micrograms of control Ig intraperitoneally daily until sacrifice. Animals were sacrificed on days 2, 4, and 7 after transplant. Control (BN-->Lew) grafts show irreversible rejection by day 7. Syngeneic (Lew-->Lew) grafts show no AR on day 7. AR episodes were graded histologically (stages 0-IV) and pathologic intensity of inflammation was graded on percentage of involvement. Cytokine transcript levels were measured in control and CTLA4Ig-treated animals (n = 5 in each group) on day 7 using reverse transcriptase polymerase chain reaction techniques. The most profound differences were found on day 7 after transplant. The degree of lymphocytic infiltration was greater in the CTLA4Ig group (perivascular: 4 +/- 0 vs. 2.6 +/- 0.6, peribronchial: 4 +/- 0 vs. 2.2 +/- 0.4, and peribronchiolar: 3.6 +/- 0.5 vs. 2 +/- 0.3, P < 0.01). However, in striking contrast, the stage of AR (3 +/- 0 vs. 4 +/- 0, P < 0.01), vasculitis (1 +/- 0.7 vs. 2.6 +/- 0.6, P < 0.05), hemorrhage (0.4 +/- 0.6 vs. 3.2 +/- 0.4, P < 0.01), and necrosis (0 +/- 0 vs. 2.4 +/- 0.5, P < 0.005) were significantly reduced in animals treated with CTLA4Ig. Since CTLA4Ig blocks Th1 cell activation in vitro, we compared the levels of Th1 inflammatory cytokines IL-2, gamma-IFN, and TNF-alpha in the two models. The intragraft ratios (CTLA4Ig/control) were IL-2:0.77, gamma-IFN: 1.29, and TNF-alpha:1.33. Thus, CTLA4Ig did not significantly block intragraft production of Th1 cytokines on day 7.(ABSTRACT TRUNCATED AT 400 WORDS)

A cardiothoracic surgery information system for the next century: implications for managed care.

The United States health care system is under tremendous pressure to cut costs while maintaining quality. One mechanism to reduce costs is managed care--a system with both risks and benefits for patients, providers, and payors, and one that requires large volumes of data to ensure optimal medical and financial decision-making. In this review, we describe the types of information needed by managed care systems, including medical outcome data (satisfaction, survival, quality of life, and complications) and financial data (costs and long-term resource utilization). From a provider's point of view, the customers for these data range from individual patients to large self-insured corporations, and we describe the data required for each potential customer. Finally, as a concrete example of how data can be collected and analyzed to improve a provider's competitiveness, we describe the Cedars-Sinai Medical Center cardiothoracic surgery database from a managed care perspective. The concepts presented are generalizable to other subspecialties, and will become more important in the increasingly competitive milieu of American health care.