Role of proton pump inhibitors in preventing hypergastrinemia-associated carcinogenesis and in antagonizing the trophic effect of gastrin.

Gastrin is the main hormone stimulating gastric acid secretion, but it exerts proliferative and anti-apoptotic actions on various cancer cell types, in addition to its well-known trophic effect on enterochromaffin-like cells. As treatment with proton pump inhibitors (PPIs) increases the biosynthesis and secretion of gastrin, it has been postulated that treatment with PPIs could increase the risk of cancer, especially in Barrett's esophagus, gastric carcinoids, and colorectal cancer (CRC). Some tumors produce gastrin of their own, which can act in an autocrine manner to promote tumor growth. In addition, gastrin is known to foster the tumor microenvironment. However, in spite of these potentially increased cancer risks due to PPI-induced hypergastrinemia, prospective, large-scale cohort studies did not show an increase in CRC prevalence. The question as to why the long-term use of PPIs was not associated with an increased cancer risk of CRC might be answered by the fact that the PPIs antagonized the trophic effects of hypergastrinemia. Furthermore, the blockade of proton pumps or potassium channels in cancer cells could limit the abnormal glycolytic energy metabolism of cancer cells. Apart from their suppressive effect on gastric acids, PPIs exert an anti-tumor effect through the selective induction of apoptosis as well as an anti-inflammatory effect, and they protect cells from developing chemo- or radiotherapeutic resistance. Moreover, the anti-carcinogenic actions of PPIs were augmented with PPI-induced hypergastrinemia. Together with their potential targeted killing of cancer stem cells, these effects demonstrate their potential anti-cancer actions.

Current status of heart transplantation in Taiwan.

PURPOSE: We reviewed the national results of heart transplantation in Taiwan. METHODS: From July 1987 to December 2012, 1354 patients underwent heart transplantation in 18 qualified heart centers in Taiwan. The transplantation volume and survival rate were reviewed. RESULTS: The median age of recipients was 49 years at surgery, with 37% in the International Society for Heart and Lung Transplantation (ISHLT)-1A, 30% in ISHLT-1B, and 32% in ISHLT-2. The allograft 1-, 3-, 5-, and 10-year survival rates were 78%, 68%, 61%, and 47%, respectively. Mostly difficult recipients were bridged by extracorporeal membrane oxygenation (ECMO) instead of ventricular assist device (VAD). CONCLUSION: The results of heart transplantation in Taiwan are comparable with ISHLT world results. In Taiwan, we use more ECMO than VAD for mechanical circulatory support to bridge critical recipients to heart transplantation.

Predicting hospital mortality in adult patients with prolonged stay (>14 days) in surgical intensive care unit.

BACKGROUND: The aim of this paper was to identify the factors at surgical intensive care unit (SICU) admission and during the following SICU course that influence hospital mortality of patients with prolonged SICU stay (>14 days). METHODS: This prospectively-planned study enrolled 1661 patients over 16 years old with prolonged SICU stay in a tertiary-care teaching hospital over a 4-year period. Data at SICU admission, physiologic factors on the 14th SICU day and the indications of prolonged ICU stay were collected. A multivariate logistic regression model with a least absolute shrinkage and selection operator technique was adopted to identify factors associated with hospital mortality in prolonged-stay patients at the 14th SICU day. RESULTS: Prolonged-stay patients accounted for 9.7% of the total SICU admissions, but consumed 51.7% of total SICU days. The hospital mortality of these patients was 34%. For predicting the hospital mortality in prolonged SICU stay patients, the predictors at ICU admission included gender, longer pre-ICU days, higher Charlson comorbidity index, and not admitted from emergency. Predictors on the 14th SICU day included lower Glasgow coma scale, lower mean arterial pressure, higher dosage of inotropes required, higher serum lactate level, higher serum bilirubin level, lower platelet count, and the use of renal replacement therapy. Among the indications for prolonged SICU stay, predictors included the need for mechanical circulatory support, worsening acute encephalopathy with altered mental status, hemodynamic instability due to bleeding, and sepsis with unstable vital signs. CONCLUSION: This validated predictive model reached clinically accurate discriminatory power, and may serve to improve patient care and resource utilization in the SICU.

Extracorporeal membrane oxygenation and Thoratec pneumatic ventricular assist devices as double bridge to heart transplantation.

INTRODUCTION: Ventricular assist devices have benefited patients with end-stage heart failure as a bridge to heart transplantation (HTx). We present our experiment of HTx using extracorporeal membrane oxygenation (ECMO) with Thoratec pneumatic ventricular assist device (TpVAD). METHODS: From May 1996 to June 2011, among 410 patients who underwent HTx 23 required mechanical circulatory support (MCS) with implantation of the TpVAD and 15 (65%) of them received grafts. RESULTS: The 23 patients included 4 female and 19 male patients of age range 10 to 80 years. Eighteen (78%) of them needed ECMO before TpVAD implantation. Twelve (67%) were implanted with a TpVAD double bridge to HTx. The demand for MCS among patients with acute hemodynamic collapse has led to major improvements in the existing systems such as ECMO with double bridge to TpVAD. CONCLUSION: We used ECMO as a rescue procedure for acute hemodynamic deterioration. However, during ECMO support, left ventricular afterload increased. If prolonged support is required, TpVAD might be required: 15 (65%) of patients supported by ECMO with TpVAD needed to a wait a suitable donor. We recommend the application of ECMO for short-term support (within 1 week), and TpVAD as a bridge for medium- or long-term support.

The influence of the organ allocation policy on a patient's chances of undergoing heart transplantation and the posttransplantation survival rate.

The Taiwan Organ Registry and Sharing Center (TORSC) was established by the Department of Health on June 6, 2002. According to the organ allocation policy, the computer-based organ-matching program began on April 1, 2005. In order to encourage organ donations, "donor hospitals" were given the highest priority. On October 1, 2010, the TORSC implemented a new allocation policy allowing highest priority to the most critically ill patients listed as 1A status. The aim of this study was to investigate the influence of the allocation policy on the likelihood of undergoing a heart transplantation (HTx) as well as the survival after the procedure. Based on the timeline of changes in the organ allocation policy, the patients were divided into three groups: "individual decision," "donor hospital first," and "urgency status first." We observed the waiting time of status 1A patients to decrease and their chance to receive a donor heart increase but their survival rate after HTx to decrease. Further research is needed to define the optimal organ allocation policy.

Ventricular assist device application as a bridge to pediatric heart transplantation: a single center's experience.

OBJECTIVES: There are limited options for mechanical circulatory support to treat end-stage heart failure in pediatric patients. Although extracorporeal membrane oxygenation is commonly used in infants and children, ventricular assist devices (VAD) provide a longer duration of support with fewer complications before recovery or as a bridge to heart transplantation (HTx), as described herein. METHODS: This retrospective chart review of eight patients transplanted from April 2008 to December 2011, after left ventricular assist device (LVAD) implantation due to end-stage heart failure. Their mean age was 12 years (9-15 y) and mean body weight, 48 kg (20-78). All were New York Heart Association functional class IV with mean left ventricular ejection fractions less than 15%. RESULTS: The six patients (75%) received HTx after a mean LVAD support duration of 43.2 days; 2 (25%) died before a suitable heart became available. Their mean duration of LVAD support was 30 days. There were 4 (50%) who experienced clinically evident thromboembolic events: 3 (37.5%) cerebrovascular with 1 mortality and 1 (12.5%) as acute limb ischemia. Transient hemodialysis was performed in 4 (50%). Bloodstream infection identified in 6 (75%) was controlled with intravenous antibiotics. Driveline infection identified in 4 (50%) was treated successfully with local wound dressing changes and intravenous antibiotics. One 9-year-old boy died of rejection at 16 months after transplantation. CONCLUSIONS: Because of the organ shortage, pediatric patients have a low chance to undergo HTx. VAD provides long-term support for children with end-stage heart failure before a suitable heart becomes available. A thromboembolic event remains a major complication influencing their survival.

The outcome of heart transplantation in hepatitis C-positive recipients.

BACKGROUND: Clinical outcomes of heart transplantation (HTx) among recipients with chronic hepatitis C virus (HCV) infection are poorly understood especially in Asia. Therefore, this study evaluated these clinical outcomes. METHODS: Using retrospective chart review we collected data on 385 patients including 20 HCV-positive recipients at the time of transplantation. We obtained information on demographics features, serial transaminases, graft function, patient survival as well as the incidences of acute hepatitis and transplant coronary artery disease. RESULTS: Between 1987 and 2010, the 20 HCV-positive patients had a median age at transplantation of 52 years (range, 30-63). Seventeen were men and three women. All the patients were classified as Child-Pugh class A; two had cirrhosis prior to HTx. Over a mean follow-up of 63 months (range, 2 days to 187 months), there were 11 deaths, including two hospital mortalities and nine subsequent deaths. Only one mortality (5%) was related to Child-Pugh class C cirrhosis, despite liver transplantation. Among the other 19 deceased or surviving recipients, there was no evidence of hepatic dysfunction or hepatocellular carcinoma. Transplant coronary artery disease was detected in six patients (30%). There was no significant difference in Kaplan-Meier actuarial survival between the HCV-positive and HCV-negative recipients (P = .59). CONCLUSIONS: There was no significant difference in patient survival or graft function between HCV-positive and HCV-negative HTx recipients. Additionally, HCV-positive recipients were not at an increased risk of hepatic failure or accelerated transplant coronary artery disease.

Cardiac allograft vasculopathy compared by intravascular ultrasound sonography: everolimus to mycophenolate mofetil--one single-center experience.

UNLABELLED: Cardiac allograft vasculopathy (CAV) remains one of the leading causes of late graft failure and death. Cyclosporine microemulsion Neoral (CsA) had been used in heart transplantation (HTx) recipients. Meanwhile, Everolimus (EVL; Certican, Norvatis Pharmaceuticals; Basel, Switzerland) or mycophenolate mofetil (MMF) have been combined with CsA for maintenance treatment. We compared atherosclerosis in HTx patients showing CAV by intravascular ultrasound (IVUS) in two groups: the CE who received CsA, EVL, and steroid versus the CM group, who received CsA, MMF, and steroid. MATERIALS AND METHODS: We explored IVUS parameters such as plaque thickness (PT), lumen circumference (LC), media adventitial circumference, lumen diameter (LD), and media adventitial diameter to characterize the atherosclerosis among CE versus CM groups. RESULTS: In this study, both the CE and CM groups showed increased plaque thickening in the first year posttransplantation (P < .05). However, MMF significantly reduced LC and LD (P < .05) Upon multivariate linear regression analysis, the CE group seemed to show less effect on the maximal difference in PT between 2 and 12 months after adjusting for age at transplantation and gender (P < .05). There was no acute clinical adverse event of CAV reported in either both group during the follow-up. The atherosclerosis of CAV revealed by LC, LDmax, and LDmin was significantly less among patients treated with CE than CM. CONCLUSION: These results suggested that everolimus-treated patients showed benefits compared with MMF-treated subjects as extrapolated from these IVUS data.

Clinical experience of tacrolimus with everolimus in heart transplantation.

BACKGROUND: Tacrolimus (Tac) in combination with mycophenolate mofetil is widely used after heart transplantation (HT). Everolimus (EVR), a new potent proliferation signal inhibitor can be used with a carcineurin inhibitor to reduce the occurrence of rejection. The purpose of this study was to evaluate the efficacy and safety of Tac combined with EVR in de novo HT. MATERIALS AND METHODS: From January 2009 to April 2011, 33/62 patients who underwent HT were prescribed Tac and EVR as de novo immunosuppression. The main exclusion criteria were poor kidney function (serum creatinine > 2.8 mg/dL), panel-reactive antibodies > 25%, donors > 60 years old, or cold ischemia time > 6 hours. All patients received Tac (C0 blood level 5-10 ng/mL during the first 6 months, then 3-5 ng/mL), EVR (C0 target 3-8 ng/mL), and corticosteroids. After transplantation, routine examinations included echocardiogram and protocol endomyocardial biopsy. RESULTS: There was no operative mortality. The 1- and 3-year actuarial survivals were 95.74% ± 3.49%. One patient who had undergone coronary artery bypass grafting previously and received intra-aortic balloon pumping and extracorporeal membrane oxygenator-assisted cardiopulmonary resuscitation before HT died of Aspergillus septicemia 58 days after HT. No biopsy-proven acute rejection > grade 2R or acute rejection associated with hemodynamic compromise was observed. Hyperlipemia was noted in 16 cases (48.5%), hypertension in 11 (33.3% 5%), and diabetes mellitus in 12 (36.4%). No other severe adverse events were noted. CONCLUSIONS: Concentration-controlled EVR (C0 target 3-8 ng/mL) in combination with Tac achieved good efficacy and safety. The 1- and 3-year actuarial survivals were 95.74% ± 3.49%.

Twenty-four year single-center experience of hepatitis B virus infection in heart transplantation.

OBJECTIVE: Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. We have reported the outcome of (1) recipients with hepatitis B surface antigen (HBsAg)-positive; HBsAg-negative recipients who receive donor hearts from HBsAg-positive donors; and treatment with lamivudine of hepatitis B flare-ups after heart transplantation, using case numbers that range from 100 to 200. METHODS: From July 1987 to May 2011, all 412 orthotopic heart transplant recipients and donors underwent routine preoperative screening for hepatitis B virus markers and liver function parameters. Lamivudine was prescribed prophylactically for recipients with elevated serum enzyme levels or an HBV DNA virus load before transplantation, or when there was evidence of hepatitis B flare-up after transplantation. Postoperative HBV markers and liver function parameters were collected over a mean follow-up time of 7.8 years. RESULTS: Thirty-four recipients were HBsAg-positive before heart transplantation, and 23 experiencing HBV reactivation upon follow-up requiring lamivudine treatment. Clinical responses were achieved in all of them: 15 were complete and two, slow partial responses. Twenty-six recipients with an HBV naïve status at the time of heart transplantation, and three patients received donor hearts from an HBsAg-positive donor under perioperative hepatitis B immunoglobulin prophylaxis. HBV infection was successfully prevented in two patients, but the other one contracted HBV hepatitis, which was successfully treated with lamivudine. CONCLUSIONS: HBV reactivation after the heart transplantation was common but usually well controlled with lamivudine treatment. Although posttransplantation liver function deteriorated for a period, there was no HBV infection-related morbidity or mortality. Perioperative hepatitis B immunoglobulin prophylaxis can successfully prevent HBV naïve recipients from infection in some cases, but HBsAg-positive donors should only be considered in high risk situations.

Heart retransplantation for pediatric primary allograft failure.

PURPOSE: Heart transplantation is indicated for children with end-stage heart failure or complex inoperable congenital defects. When the transplanted heart fails, retransplantation is suggested and herein we have presented the prognosis of these pediatric cases. MATERIALS AND METHODS: From March 1987 to March 2011, we performed 404 heart transplantations including 45 pediatric patients, 6 (13.3%) of whom experienced graft failure requiring retransplantation. Only four of the six patients (66.7%) had a chance for retransplantation. RESULTS: Six of 45 pediatric heart transplant patients (13.3%) experienced graft failure requiring retransplantation. Four of them (66.7%) underwent retransplantation. Only one of the four died due to severe postoperative sepsis with acute respiratory distress. The other three patients recovered well and remain alive with no neurological sequelae; all are in New York Heart Association functional classification I at present. CONCLUSION: Pediatric post-heart graft failure require expectations retransplantation, which shows a good prognosis.

Risk factors for 30-day readmission in general medical patients admitted from the emergency department: a single centre study.

BACKGROUND: Overcrowding in emergency departments (ED) around the world is an increasingly serious problem with an adverse impact on both patient flow and patient outcomes. A significant contributing factor to ED overcrowding is possibly due to readmission. Risk factors for readmission in patients admitted from ED are rarely studied, particularly in Asian countries where the length of stay is reportedly longer. METHODS: A retrospective study of patients admitted to general medical wards from the ED of a referral centre in northern Taiwan from November 2009 to April 2010 was conducted. The primary outcome was 30-day hospital readmission and clinical characteristics were analysed for predictors of readmission. RESULTS: Of the recruited 2698 patients, 451 (16.7%) were readmitted within 30 days after discharge. Age, gender, marital status and the activities of daily living (Barthel's score) were not associated with 30-day readmission. Higher Charlson score ((score 2-4) hazard ratio (HR): 1.42, 95% confidence interval (CI): 1.07-1.89; (score >4) HR: 1.93, 95% CI: 1.37-2.73), longer hospital stay ((8-14 days) HR: 1.51, 95% CI: 1.17-1.95; (15-28 days) HR: 1.64, 95% CI: 1.22-2.19; (>28 days) HR: 1.97, 95% CI: 1.43-2.71), and presence of underlying active malignancy (HR: 1.66, 95% CI: 1.27-2.16) and anaemia (HR: 1.26, 95% CI: 1.02-1.55) were independently associated with readmission. CONCLUSION: Medical patients admitted from the ED of a referral centre have a 30-day readmission rate of 16.7%. Post-discharge care should focus on patients with higher Charlson score, longer hospitalisation, anaemia and underlying active malignancy, which are independent predictive factors for 30-day readmission.

Definition, risk factors and outcome of prolonged surgical intensive care unit stay.

There is no generally accepted definition for a "prolonged surgical intensive care unit (SICU) stay". The aims of the current study were to: (1) define prolonged SICU stay; (2) identify risk factors of prolonged SICU stay; and (3) identify risk factors of hospital mortality in patients with a prolonged SICU stay. All SICU patients aged >16 years and with an intensive care unit (ICU) stay longer than three days without ICU readmission between 1 January 2004 and 30 November 2006 at the National Taiwan University Hospital were recruited to the study. A total of 2598 patients were recruited. ICU stay >16 days was defined as a prolonged SICU stay since rates of ICU mortality, hospital mortality and mortality one year after ICU discharge remained stationary after ICU stay was >16 days. A multivariate logistic regression model identified factors associated with a prolonged SICU stay, including age more than 70 years old, (odds ratio 1.587, 95% confidence interval 1.246 to 2.022), increasing pre-ICU hospital days (odds ratio 1.009, 95% confidence interval 1.003 to 1.015), admission from emergency (odds ratio 1.925, 95% confidence interval 1.455 to 2.548), use of mechanical circulation support (odds ratio 2.314, 95% confidence interval 1.458 to 3.674) and renal replacement therapy (odds ratio 5.140, 95% confidence interval 3.781 to 6.987). A multivariate logistic regression model identified factors associated with ICU mortality in patients with ICU stay >16 days, including renal replacement therapy (odds ratio 4.780, 95% confidence interval 2.687 to 8.504). An ICU stay >16 days could be used to define prolonged SICU stay when hospital and one-year mortality rates are considered. Prevention of organ failure requiring renal replacement therapy might prove a useful goal to avoid prolonged ICU stay and even hospital mortality.

Pediatric heart transplantation bridged with ventricular assist devices.

Heart transplantation (HTx) is indicated in children with end-stage heart failure or complex inoperable congenital defects. Because of the shortage of pediatric donor hearts, various bridge techniques have been used in pediatric patients to prolong patient survival until a suitable heart becomes available. We reviewed medical records of several pediatric patients in whom bridging with ventricular assist devices was used. All of the patients survived HTx, and are alive and well with no neurologic sequelae. They are NYHA functional class I. Thus, morbidity and mortality were acceptable in this high-risk group of pediatric patients with a ventricular assist device bridging to HTx.

Outcome in children bridged and nonbridged to cardiac transplantation.

BACKGROUND: Heart transplantation (HTx) in children with end-stage heart disease has become an accepted treatment option. OBJECTIVE: To evaluate our results of pediatric cardiac transplantation with vs without bridge methods. PATIENTS AND METHODS: The study included 31 patients (34 transplantations) younger than 18 years who underwent orthotopic HTx between March 1995 and December 2008. Ten patients were girls, and 21 were boys. Preoperative diagnoses included cardiomyopathy (n=20), congenital heart disease (n=7), hypertrophic cardiomyopathy (n=2), restrictive cardiomyopathy (n=1), and ischemic cardiomyopathy (n=1). Mean (SD) ischemia time was 185 (72) minutes. Thirty-day mortality was 6%, and was due to primary graft failure (n=2). Overall follow-up was 4.36 (3.93) years. Eleven patients underwent bridge techniques before HTx, and 11 patients required perioperative extracorporeal membrane oxygenation or ventricular assist device support. RESULTS: In the group that received extracorporeal membrane oxygenation, 8 patients (73%) were successfully weaned and discharged with excellent functional class. There were no differences in operative mortality, functional class, survival, rejection, and infection rates between the bridged and nonbridged groups. Overall actuarial 1- and 5-year survival rates were 93% and 83%, respectively. All survivors had good functional class. CONCLUSION: Our findings demonstrate satisfactory medium-term outcome of HTx in selected pediatric patients with end-stage heart disease. Using bridge methods in children at high risk can increase the opportunity to receive a donor heart. These bridge methods achieve similar postoperative outcomes.

Extracoporeal membrane oxygenation hybrid with Thoratec ventricular-assist devices as double bridge to heart transplantation.

Ventricular-assist devices (VADs) have benefitted patients with end-stage heart failure as a bridge to heart transplantation (HTx). Herein, we describe our experience with HTx in the presence of extracorporeal membrane oxygenation (ECMO) together with the Thoratec VAD (Thoratec Corp, Pleasanton, California). From May 1996 to June 2009, mechanical circulatory support with the Thoratec VAD was provided in 20 patients. Before implantation of the VAD, circulation in 17 patients was maintained using ECMO. Although 350 patients underwent HTx during that period, only 13 patients (65%) received suitable donor organs for orthotopic HTx. The 20 patients ranged in age from 10 to 80 years; 3 were female, and 17 were male; and 17 (85%) required ECMO before VAD implantation. In 11 of 17 patients (65%), the VAD was implanted as a double bridge to HTx. The demand for mechanical circulatory support in patients with acute hemodynamic collapse has led to major improvements in clinically available systems such as ECMO as a double bridge to VAD implantation. We use ECMO as a rescue procedure in patients with acute hemodynamic deterioration. However, during ECMO support, left ventricular afterload increases. If prolonged support is necessary, a VAD may be required. We observed that 65% of patients who received support from an ECMO hybridized with the Thoratec VAD could wait for a suitable donor for HTx. We recommend use of ECMO for short-term support (<1 week) and the Thoratec VAD for medium- or long-term support as a bridge to HTx.

Heart transplantation in patients with amyloidosis.

Cardiac transplantation is currently the only established surgical approach to the treatment of refractory heart failure. Heart transplantation because of amyloid cardiomyopathy continues to generate controversy because of donor shortage and concerns about disease recurrence in the allograft. We reviewed the medical records for all patients who underwent heart transplantation at our institution from 1987 to 2007, and found that 4 patients were diagnosed as having amyloid cardiomyopathy after pathologic examination of the excised hearts. No operative mortality was noted; however, all of the patients died of sepsis after transplantation. Because of the poor results, we do not recommended performing transplantation in patients with amyloidosis. Preoperative surveys and evaluation for amyloidosis must be emphasized in patients with hypertrophic cardiomyopathy.

Can cyclosporine blood level be reduced to half after heart transplantation?

BACKGROUND: Cyclosporine (CsA) is widely used after heart transplantation. The purpose of this prospective randomized study was to evaluate the safety and efficacy of reduction of CsA blood level to one-half of the traditional blood concentration under a regimen of everolimus (EVL), CsA, and steroid. MATERIALS AND METHODS: This prospective, 6 month, randomized, open-label study included adult (aged 18 to 65 years) recipients of a primary heart transplant with serum creatinine60 years old, had cold ischemia time>6 hours, or had plasma renin activity>or=25%. All patients received CsA (C2 blood level 1000-1400 ng/mL), EVL (C0 target 3-8 ng/mL), and corticosteroids to day 60, before random entry into one of 2 groups: SE (C2 blood level from days 60-149=800-1200 ng/mL, and days 150-180 C2=600-1000 ng/mL), or RE group with CsA reduced by one-half after 3 months (days 90-149 C2=400-600 ng/mL, and from days 150-180 C2=300-500 ng/mL). RESULTS: The 25 recipients eligible for this study included 13 patients in the SE and 12 in the RE group. There was no operative mortality in either group. No death or graft loss was noted within 6-months in either group. Mean serum creatinine at month 6 tended to be lower in the RE cohort (1.23+/-0.44 mg/dL versus 1.55+/-0.85 mg/dL; P=.093). Biopsy-proven acute rejection>or=grade 3A was observed in only 1 patient (7.7%), who was in the SE group. There were no acute rejection episodes associated with hemodynamic compromise. The incidences of adverse events in each group were similar. CONCLUSIONS: Concentration-controlled EVL (C0 target 3-8 ng/mL) in combination with reduced CsA exposure of one-half the usual concentration achieved good efficacy and safety over 6 months. The renal function at 6 months among the RE group showed a trend toward improvement, suggesting a benefit of halving the target CsA blood level after heart transplantation.

Combined sirolimus-calcineurin inhibitor immunosuppressive therapy in simultaneous heart and kidney transplantation: a retrospective analysis of a single hospital's experience.

Simultaneous heart and kidney transplantation (SHKT) has become an accepted therapeutic option for patients with end-stage heart failure associated with end-stage renal disease. The immunosuppressive therapy is usually based upon a heart transplantation protocol using a calcineurin inhibitor (CNI). Sirolimus (SRL) is a potent nonnephrotoxic immunosuppressant with antiproliferative activity in nonimmune cells. Its use has recently been reported to show less nephrotoxicity among both heart and kidney transplants. However, the data for the SHKT are limited. We retrospectively examined the causes of 5 patients who received combined SRL-CNI immunosuppressive therapy with reduced CNI doses from 2003 to 2009. There was no mortality during follow-up. Two of the 3 patients who received a conversion regimen recovered renal function. One who suffered severe proteinuria after transplantation proceeded to hemodialysis at 3 years after conversion. Both of the patients who received the combined regimen de novo remained stable regarding their renal function. Cardiac function was stable in these patients; there was neither allograft rejection nor allograft coronary vasculopathy. We observed that patients without dyslipidemia or hyperuricemia before SHKT were less likely to develop these disorders under the combined regimen. Early medical intervention after close follow-up of lipid and uric acid values by dose adjustments resulted in a stable status of our patients.

The survival of heart transplant recipients using cyclosporine and everolimus is not inferior to that using cyclosporine and mycophenolate.

INTRODUCTION: Heart transplantation has become the best available therapy for patients with refractory end-stage heart failure. Cyclosporine (CsA) and mycophenolate mofetil (MMF) are the 2 FDA-approved drugs to prevent posttransplant acute rejection episodes. The purpose of this study was to evaluate the result of heart transplantation treated with CsA and everolimus (EVL), compared with that of patients treated with CsA and MMF. MATERIALS AND METHODS: From 2000 to 2009 heart transplantation was performed in 239 patients among whom we enrolled 93 patients with a serum creatinine values