Should moderate acute rejection of a cardiac transplant graft be treated?

Histologically proven, moderate acute rejection after orthotopic heart transplantation (OHT) is commonly treated with intravenous steroids. This regimen may result in severe metabolic and infectious side-effects. The purpose of this study was to assess and compare outcomes in treated (T) versus not treated (N-T) biopsy proven 3A rejection episodes in cardiac transplant recipients. METHODS: A retrospective analysis was conducted to identify all biopsy proven 3A rejection episodes that occurred over the time period 1995-2000 in patients (patients) >or= 6 months after OHT (n=48 episodes in 35 patients). Of the 48 episodes, 19 were N-T and 29 were T. Decision to treat 3A rejection was based on time after transplant, haemodynamic and/or clinical compromise and left ventricular (LV) dysfunction measured by 2D echo. Most N-T episodes received an increase in background immunotherapy. RESULTS: Time from transplant to index 3A episode in N-T patients was 4.2 versus 2.7 yr for the T patients (p=0.06). There were no differences seen between T and N-T groups for the first and second post-3A biopsy results or LV function post-3A. Presence of coronary disease or death were not different between groups. Of the 29 patients with T episodes, no differences in outcomes (death, first and second post-3A biopsy score, coronary disease, myocardial infarction, or LV function) were seen based on use of treatment with intravenous versus oral steroid. CONCLUSION: In patients more than 6 month after OHT, there were no differences in outcomes (ongoing rejection or LV function) between N-T episodes of 3A rejection and T episodes. In T patients the use of oral steroids was equally as effective for treatment of 3A episodes as intravenous steroids.     

Does endothelial chimerism correlate with renal allograft rejection?

BACKGROUND: The blood vessels of a transplanted organ are an interface between the donor and the recipient. The endothelium is believed to be a major target for graft rejection. After transplantation endothelial cells of a transplanted organ may be of recipient origin. OBJECTIVES: In this study we sought to determine whether endothelial chimerism correlates with graft rejection. METHODS: Biopsy samples from 34 renal transplants of female recipients who received kidneys from male donors were studied for the presence of endothelial cells of recipient origin. Formalin-fixed, paraffin-embedded tissue sections of renal biopsy samples were examined by fluorescence in situ hybridization (FISH) for the presence of endothelial cells containing two X chromosomes, using a biotinylated Y-chromosome probe and digoxigenin-labeled X-chromosome probe. RESULTS: The FISH methods identified endothelial cells of recipient origin. Endothelial chimerism was common, irrespective of rejection. Its presence was focal with these elements, coexisting in the biopsy. CONCLUSIONS: We observed no correlation between the percentage of recipient endothelial cells among vascular elements and the type of graft rejection (P > .05).     

Peritubular capillary C4d staining in late acute renal allograft rejection – is it relevant?

Abstract: Background: In the early post-transplant period, renal allograft rejection with diffuse peritubular capillary (PTC) C4d deposition predicts poor graft survival. In the late post-transplant setting, that is, one or more yr after transplantation, the implication of diffuse PTC C4d deposition is still a topic of debate. The purpose of our study was to see if diffuse PTC C4d deposition, in late acute rejection (LAR), occurring more than one yr post-transplant, has any impact on graft survival and function. Methods: We selected cases, both cadaveric as well as living donor renal transplant recipients, in whom acute rejection with PTC C4d deposition was first detected after the first year post-transplant. Recipients with multiple acute rejection episodes during the first year post-transplant were excluded from the study. The first biopsy diagnosed with LAR was considered the index biopsy (n = 40). We formed two groups: group 1, C4d-positive LAR (n = 20), and group 2, C4d-negative LAR (n = 20). Groups were matched for maintenance and post-rejection immunosuppressive therapy, baseline serum creatinine levels before the time of the index biopsy, time from transplant to index biopsy, as well as chronic allograft damage index (CADI) score in the index biopsies. We compared the rate of graft loss, and the graft function of the surviving grafts at the end of the study period, as well as histologic parameters in the index biopsy specimens between the two groups. The mean follow-up period was 20 months. Results: No significant differences in the rate of graft loss or graft function were found between groups 1 and 2 at the end of the follow-up period. Histologically, PTC margination and transplant glomerulopathy were more common in the C4d-positive group, and this difference was statistically significant. There was no statistically significant difference in the degree of plasma cell infiltrates. Conclusions: Unlike in the acute setting, the presence or absence of PTC C4d staining in renal allografts with LAR may not have a predictive value regarding graft outcome.     

Do cardiovascular risk factors influence cardiac allograft vasculopathy?

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of heart transplant failure after the first year. The etiological factors involved are currently a controversial matter. Intravascular ultrasound (IVUS) is considered the diagnostic procedure of choice. We assessed the relationship of cardiovascular risk factors with CAV. MATERIALS: We analyzed prospectively 22 patients. We conducted a first study with coronary angiography and IVUS at 36 +/- 3 days and a second at 598 +/- 49 days. We performed an average of 5.6 clinical revisions per patient, assessing the effect of the classic cardiovascular risk factors, the cause of heart failure, and the age of the patient and donor. The statistics used were chi(2), Fisher exact test, and Student t test. RESULTS: CAV was found in 10 subjects (45.5%). Univariate analysis showed statistically significant differences in the assessment of the presence of diabetes and dyslipidemia posttransplantation, but not pretransplantation. Among the patients with CAV there was a higher percentage of diabetics (32.8% vs 12%, P < .01). The patients with CAV also had higher levels of total cholesterol (211 +/- 40 mg/dL vs 195 +/- 35 mg/dL, P = .02), triglycerides (172 +/- 108 mg/dL vs 136 +/- 66 mg/dL, P = .03), low-density lipoprotein (133 +/- 35 mg/dL vs 117 +/- 30 mg/dL, P = .01), and lower high-density lipoprotein levels (46 +/- 15 mg/dL vs 52 +/- 12 mg/dL, P = .03). CONCLUSIONS: Only the diabetes and dyslipidemia present in the posttransplantation period were associated with CAV, which highlights the fact that it is a condition that both shares and has different features with atherosclerosis and probably requires a different diagnostic-therapeutic approach.     

Update on medical and surgical options for patients with acute severe ulcerative colitis: What is new?

Acute severe ulcerative colitis(UC) is a highly morbid con dition that requires both medical and surgical managementhrough the collaboration of gastroenterologists and colorectal surgeons. First line treatment for patients presenting with acute severe UC consists of intravenous steroids, but those who do not respond require escalation of therapy or emergent colectomy. The mortality of emergent colectomy has declined significantly in recent decades, but due to the morbidity of this procedure, second line agents such as cyclosporine and infliximab have been used as salvage therapy in an attempt to avoid emergent surgery. Unfortunately, protracted medical therapy has led to patients presenting for surgery in a poorer state of health leading to poorer post-operative outcomes. In this era of multiple medical modalities available in the treatment of acute severe UC, physicians must consider the advantages and disadvantages of prolonged medical therapy in an attempt to avoid surgery. Colectomy remains a mainstay in the treatment of severe ulcerative colitis not responsive to corticosteroids and rescue therapy, and timely referral for surgery allows for improved post-operative outcomes with lower risk of sepsis and improved patient survival. Options for reconstructive surgery include three-stage ileal pouchanal anastomosis or a modified two-stage procedure that can be performed either open or laparoscopically. The numerous avenues of medical and surgical therapy have allowed for great advances in the treatment of patients with UC. In this era of options, it is important to maintain a global view, utilize biologic therapy when indicated, and then maintain an appropriate threshold for surgery. The purpose of this review is to summarize the growing number of medical and surgical options available in the treatment of acute, severe UC.     

Pregnancy and cardiac interventions: What are the optimal management options?

Cardiac disease is the leading cause of maternal mortality in the United Kingdom. Major causes of cardiac death in pregnant women include cardiomyopathies, myocardial infarction, ischemic heart disease, and aortic dissection. Uncorrected congenital heart disease and women who have had corrective or palliative surgery may have complicated pregnancies as well. Some women with significant cardiac disease are unable to meet the increased physiological demands of pregnancy. Of these, those who do not respond to medical treatment may require surgical correction such as coronary artery bypass grafting. The risk of cardiac operations for pregnant women is similar to that for nonpregnant women but the fetal mortality rate remains high. Contributing factors to high fetal mortality rates include timing, urgency of operation, and the fetal/fetoplacental response to cardiopulmonary bypass. The aim of this review is to summarize current evidence in utilizing the different management approaches of cardiac issues during pregnancy.     

Renal allograft rejection with normal renal function in simultaneous kidney/pancreas recipients: does dissynchronous rejection really exist?

BACKGROUND: Between July 1, 1994 and December 1, 1998, 147 simultaneous kidney/pancreas transplantations were performed at our center. Of 95 patients who experienced at least one acute renal allograft rejection episode after transplantation, 7 (7.4%) developed rejection in the presence of stable and normal or near-normal renal function. METHODS: The indication for renal allograft biopsy was a rising serum lipase, i.e., suspected pancreatic rejection. All seven patients were treated with steroids and augmentation of the tacrolimus dose, with a fall in the serum lipase and no change in the serum creatinine. RESULTS: The serum creatinine levels just before, at the time of, 1 week after the biopsy, and at most recent follow-up were 1.4+/-0.4, 1.3+/-0.3, 1.2+/-0.2, and 1.2+/-0.2 mg/dl. The serum lipase levels just before, at the time of, 1 week after the biopsy, and at most recent follow-up were 1022+/-1157 mg/dl, 874+/-996 mg/dl, 243+/-260 mg/dl, and 94+/-75 mg/dl. The tacrolimus dosages and levels at the time of the biopsy and 1 week later were 14.9+/-5.0 mg/day and 15.0+/-4.0 ng/ml, and 16.4+/-6.3 mg/day and 15.1+/-6.8 ng/ml. CONCLUSIONS: These findings suggest that, in patients undergoing simultaneous kidney/pancreas transplantation, the entity of dissynchronous pancreatic allograft rejection without renal allograft rejection may not really exist. These data also make an additional fundamental point that acute rejection may occur in patients with normal and stable renal function.     

Cardiac allograft vasculopathy after cardiac transplantation and hormone therapy: positive effects?

BACKGROUND: There is a great deal of controversy surrounding the issue of hormone replacement therapy after transplantation. The question whether or not this therapy has effects in cardiac allograft vasculopathy (CAV), the Achilles heel of cardiac transplantation or other unique aspects of allograft function is still unknown. METHODS: We investigated the long-term effect of 17beta-estradiol as well as phytoestrogen Coumestrol, a synthetically produced phytoestrogen, on the development of CAV and the degree of fibrosis in an ovariectomized female heterotopic chronic allograft model (LEW-F344). RESULTS: We found that, 150 days after transplantation, no significant effect of estrogen application on intimal thickening of coronary arteries was observed. 17beta-estradiol and phytoestrogen Coumestrol did significantly reduce the perivascular immune reaction. However, the immune effect had no consequence on the intensity of CAV. Although neither 17beta-estradiol nor phytoestrogen Coumestrol revealed a positive effect on CAV, the group of animals treated with 17beta-estradiol showed the highest decline in heart function and the most distinct fibrosis. CONCLUSIONS: 17beta-estradiol does not affect CAV positively, but worsens cardiac allograft function and leads to increased fibrosis. This is the first study showing a negative effect of 17-beta-estradiol after heart transplantation in the long term.     

Corticosteroid administration for acute respiratory distress syndrome : therapeutic option?

Despite a number of clinical trials there is still controversy about the role of corticosteroid therapy in acute respiratory distress syndrome (ARDS). In addition recent meta-analyses differed markedly in the conclusions. This review is intended to provide a short practical guide for the clinician. Based on the available literature, high-dose and pre-emptive administration of corticosteroids is hazardous and not indicated. A low-dose corticosteroid regime given for 4 weeks may potentially be helpful and can be considered in acute or unresolved ARDS in less than 14 days after onset of ARDS, if a close infection surveillance program is available, if neuromuscular blockade can be avoided and if a stepwise dose reduction of corticosteroids is performed. The total daily dose at the beginning of treatment should not exceed 2?mg/kg body weight (BW) methylprednisolone.