Impact of immunosuppression on the incidence of early subclinical renal allograft rejection: implications for protocol biopsy policy.

In order to determine the impact of immunosuppression (IS) on the incidence of early subclinical rejection (SCR), we studied two groups of patients receiving different immunosuppressive regimens. Patients received cyclosporin (CsA), azathioprine and prednisolone (group 1; n = 304) or IS according to immunological risk (group 2; n = 150). The highest-risk patients received basiliximab induction, tacrolimus, mycophenolate mofetil (MMF) and prednisolone; medium-risk patients CsA, MMF and prednisolone; low-risk CsA, azathioprine and prednisolone. Protocol biopsies were performed in all patients, irrespective of graft function, on days 7 and 28 post-transplantation. Only patients with good stable function at the time of biopsy were included for assessment of SCR. Group 2 patients showed significant reductions in total rejection frequency (32.6% vs. 57.2%, P = <0.0001) and SCR frequency in day 7 protocol biopsies (2% vs. 13%, P = <0.05). In group 2 patients, all SCRs, but not borderline changes, were treated. Untreated borderline changes did not have an adverse impact on graft function at 1 year post-transplantation. New immunosuppressive regimens may reduce subclinical in addition to clinical rejection-frequency, suggesting that the relative benefit of early protocol biopsies in detecting SCR is also reduced.

Risk factors for delayed graft function defined as need for dialysis or failure of creatinine to fall by 10% in the first 24 hours after transplant.

OBJECTIVES: Delayed graft function after deceased-donor transplant remains a significant clinical problem. The conventional definition of delayed graft function is the requirement of dialysis within the first week after transplant, but this criterion has many problems that have led to many controversies including those of incidence and significance. Therefore, we sought to identify the possible risk factors of delayed graft function and to investigate their effect on short-term graft survival, according to a composite criterion. MATERIALS AND METHODS: We reviewed the records of 94 renal transplants obtained from heart-beating deceased donors done at our center during a 2-year period. Variables related to the donor, recipient, and graft were retrospectively collected. Follow-up was 12 months. Delayed graft function was defined as the need for dialysis or the failure of the creatinine level to fall by 10% during the first 24 hours after transplant. To confirm suspected rejection, protocol biopsies were done, irrespective of graft function, on the seventh and 28th days after transplant, or when indicated to confirm suspected rejection. RESULTS: The overall incidence of delayed graft function was 31.9%. Multivariate analysis showed donor age as a significant independent predictor of delayed graft function (OR=1.05, P = .03, 95% CI: 1.01-1.09), whereas donor hypotension was the only independent risk factor associated with a worse 1-year graft survival rate (OR=4.6, P = .021, 95% CI: 1.3-16.5). No association could be established between delayed graft function, acute rejection, and graft survival. CONCLUSIONS: Advanced donor age is a predictor of delayed graft function defined as the need for dialysis or the failure of creatinine to fall by 10% during the first 24 hours after transplant. Preventing hemodynamic instability should be an important aspect of donor care.

Do ward round stickers improve surgical ward round? A quality improvement project in a high-volume general surgery department.

INTRODUCTION: Increasing pressure and limitations on the NHS necessitate simple and effective ways for maintaining standards of patient care. This quality improvement project aims to design and implement user-friendly and clear ward round stickers as an adjunct to surgical ward rounds to evidence standardised care. PROJECT DESIGN AND STRATEGY: Baseline performance was measured against the recommended standards by the Royal College of Physicians, General Medical Council and a study performed at the Imperial College London. A total of 16 items were studied. All members of staff in surgery department were informed that an audit on ward round entries would be implemented but exact dates and times were not revealed. In the first cycle, ward round sticker was implemented and results collected across three random days for use and non-use of sticker. Feedback was collected through the use of questionnaires. In the second cycle, the ward round sticker was redesigned based on feedback and results collected for use and non-use of sticker. RESULTS: Baseline performance noted in 109 ward round entries showed that checking of drug chart, intravenous fluid chart, analgesia, antiemetic, enoxaparin, thromboembolic deterrents ranged from 0% to 6%. With the introduction of ward round stickers in both cycles, there was noticeable improvement from baseline in all items; in ward round entries where stickers were not used, performance was similar to baseline. CONCLUSION: This quality improvement project showed that the use of stickers as an adjunct to surgical ward round is a simple and effective way of evidencing good practice against recommended standards. Constant efforts need to be made to promote compliance and sustainability. Commitment from all levels of staff are paramount in ensuring standardised patient care without overlooking basic aspects.

Recipient memory-like lymphocytes remain unresponsive to graft antigens after CAMPATH-1H induction with reduced maintenance immunosuppression.

BACKGROUND: Treatment with CAMPATH-1H at the time of transplantation allows reduced maintenance immunosuppression. We hypothesized that CAMPATH-1H induction would modulate the response of repopulating leukocytes to donor alloantigens. METHODS: The phenotype, proliferative and stimulatory capacity of peripheral blood leukocytes from 14 renal transplant recipients treated with CAMPATH-1H and reduced immunosuppression with mycophenolate mofetil and tacrolimus were investigated for the first six months after transplantation. The impact of immunosuppressive drugs on leukocytes that escape depletion was also evaluated in vitro. RESULTS: CAMPATH-1H therapy caused a significant decrease in the number of B and T cells, with CD4 T central memory cells being the most resistant to depletion. The recovery of CD8 T cells was faster than that of CD4 T cells. Lymphopenia correlated with a decrease in both proliferative and effector responses, however, the recipient T cells remained responsive to third-party antigens. Dendritic cells (DC) were also depleted but to a lesser extent than lymphocytes; lymphoid DC were more resistant than myeloid DC; these changes correlated with decreased allostimulatory capacity. One of the patients experienced rejection that was treated successfully. The rejection was associated with a high proportion of CD4 T effector memory cells and myeloid DC, increased proliferation and enhanced effector activity to donor antigens. In vitro studies confirmed that the reduced dose of immunosuppressive drugs used could prevent activated T cells from switching to the effector compartment, suppressing both their proliferation and effector activity. CONCLUSIONS: CAMPATH-1H induction combined with reduced maintenance immunosuppression is sufficient to control the effector phase of immune response to donor antigens.

Fournier's gangrene secondary to an acutely inflamed appendix herniating into the deep inguinal ring.

Fournier's gangrene (FG) requires prompt recognition and management. We report the case of a 68-year-old man who presented with extensive pain and purple discolouration from the right iliac fossa to perineum. Computed tomography demonstrated gas within the right hemiscrotum extending into the inguinal canal and right buttock, with a right pelvic fluid and air collection. At debridement necrotic fluid was arising from the superficial inguinal ring so laparotomy was performed, revealing a grossly inflamed appendix herniating into the inguinal canal; a right hemicolectomy was performed. Unfortunately, the patient went into cardiac arrest and passed away on the operating table. Histological analysis demonstrated acute-on-chronic inflammation involving the appendix. The condition where appendicitis is implicated in FG is usually due to retroperitoneal rupture and tracking into the perineal spaces. This is the first case reported of an inflamed appendix herniating into the inguinal canal and thus causing FG.

Hepatic steatosis and normothermic perfusion-preliminary experiments in a porcine model.

BACKGROUND: Steatotic livers are increasingly common in the donor population. Cold storage of steatotic livers exacerbates ischemia-reperfuson injury and risks primary nonfunction and recipient death. Normothermic preservation avoids prolonged cooling of the organ and may be well suited to the preservation and resuscitation of damaged livers. By ex vivo normothermic perfusion, it may be possible to preserve and improve steatotic livers, so that transplantation is a viable option. METHODS: In a porcine model, streptozotocin was used to induce a hyperglycemic, ketotic state that, together with a high fat diet, resulted in mild hepatic steatosis at 5 weeks. A blood-based oxygenated ex vivo normothermic preservation system was then used to compare extended preservation of normal and mildly steatotic porcine livers at physiological pressures and flows. Serial liver biopsies were stained with Oil Red O, a specialist triglyceride stain, and were analyzed using custom-designed image analysis to quantify the degree of lipid deposition. RESULTS: Steatotic livers were capable of correcting the perfusate base excess and maintaining factor V and bile production and showed markers of liver injury comparable with normal livers. Steatotic livers had a significantly higher urea production and required no glucose support. Preliminary results suggest that prolonged normothermic perfusion results in a reduction in steatosis. CONCLUSIONS: This study suggests that steatotic livers can be successfully preserved using normothermic preservation for prolonged periods and that normothermic preservation facilitates a reduction in hepatic steatosis. Further studies are now needed including transplantation of steatotic livers after normothermic preservation.

Non-heart-beating donor porcine livers: the adverse effect of cooling.

Normothermic preservation has been shown to be advantageous in an experimental model of preservation of non-heart-beating donor (NHBD) livers, which have undergone significant warm ischemic injury. The logistics of clinical organ retrieval might dictate a period of cold preservation prior to warm perfusion. We have investigated the effects of a brief period of cold preservation on NHBD livers prior to normothermic preservation. Porcine livers were subjected to 60 minutes of warm ischaemia and then assigned to following groups: Group W (n = 5), normothermic preservation for 24 hours; and Group C (n = 6), cold preservation in University of Wisconsin solution for 1 hour followed by normothermic preservation for 23 hours (total preservation time, 24 hours). Synthetic function (bile production and factor V production) and cellular damage were compared on the ex vivo circuit during preservation. There was no significant difference in the synthetic function of the livers (bile production and factor V production). Markers of hepatocellular damage (alanine aminotransferase and aspartate aminotransferase release), sinusoidal endothelial cell dysfunction (hyaluronic acid), and Kupffer cell injury (beta-galactosidase) were significantly higher in Group C. The histology of the livers at the end of perfusion was similar. In conclusion, a brief-period cold preservation prior to normothermic perfusion maintains the synthetic function and metabolic activity but results in significant hepatocellular damage, sinusoidal endothelial cell dysfunction, and Kupffer cell injury. Transplant studies are required to establish whether livers treated in this way are viable for transplantation.

Liver transplantation from non-heart-beating donors: current status and future prospects.

Liver transplantation is the treatment of choice for many patients with acute and chronic liver failure, but its application is limited by a shortage of donor organs. Donor organ shortage is the principal cause of increasing waiting lists, and a number of patients die while awaiting transplantation. Non-heart-beating donor (NHBD) livers are a potential means of expanding the donor pool. This is not a new concept. Prior to the recognition of brainstem death, organs were retrieved from deceased donors only after cardiac arrest. Given the preservation techniques available at that time, this restricted the use of extrarenal organs for transplantation. In conclusion, after establishment of brain death criteria, deceased donor organs were almost exclusively from heart-beating donors (HBDs). To increase organ availability, there is now a resurgence of interest in NHBD liver transplantation. This review explores the basis for this and considers some of the published results.