Benefit of Neoral C2 monitoring in de novo cardiac transplant recipients receiving basiliximab induction

BACKGROUND: For cyclosporine (CsA), 2-hr postdose level (C2) is the best single time point predictor of the area under the curve and a critical measure for effective dosing. The therapeutic CsA microemulsion (Neoral) C2 range in de novo heart transplant patients remains to be determined. PURPOSE: The purpose of this study was to determine the efficacy of CsA C2 monitoring in de novo heart transplant patients receiving basiliximab induction. METHODS: This prospective, multicenter, randomized study enrolled 87 adult heart transplant recipients stratified according to 4 to 6 hrs posttransplant serum creatinine less than or equal to 170 micromol/L (cohort A) or more than 170 micromol/L (cohort B). Patients in cohort A were randomized into three C2 ranges (A1: "high" n=25, 1600-1800 ng/mL; A2: "intermediate" n=27, 1400-1600 ng/mL; and A3: "low" n=24, 1200-1400 ng/mL). Patients in cohort B were randomized into intermediate (n=5) and low C2 (n=6). Target ranges were progressively lowered after 1 month. Immunosuppression included basiliximab, Neoral, mycophenolate mofetil, and corticosteroids. Endpoints were acute rejection and renal function. RESULTS: The incidence of acute rejection at 12 months was 44% in group A1, 41% in group A2, 33% in group A3, and 27% in cohort B. Pretransplant and 12-month creatinine clearance (mL/min) were group A1, 72+/-25 and 64+/-24; group A2, 81+/-32 and 68+/-25; group A3, 91+/-28 and 86+/-26; and cohort B, 62+/-28 and 79+/-37. CONCLUSION: These results suggest that C2 monitoring is safe in de novo heart transplant patients. A low Neoral C2 range in combination with basiliximab induction resulted in preserved renal function without increased risk of acute rejection.     

Post-transplant Lymphoproliferative Syndrome in the Pediatric Liver Transplant Population

Post-transplant lymphoproliferative disease remains a complication with a high morbidity and mortality. The present study examined 291 pediatric liver transplants performed in 263 children from October 1984 to December 1999. Post-transplant lymphoproliferative disease has an overall incidence of 12%. Tacrolimus and cyclosporine had a similar incidence of post-transplant lymphoproliferative disease. Fifty-six per cent of patients who developed post-transplant lymphoproliferative disease were Epstein-Barr virus negative at the time of transplantation. Mean time of conversion to Epstein-Barr virus positivity was 1.1 years after liver transplantation. Ten per cent of those who developed post-transplant lymphoproliferative disease never had Epstein-Barr virus detected. Mean time from Epstein-Barr virus positivity to detection of post-transplant lymphoproliferative disease was 2.68 years, and 3.13 years from liver transplantation (OLTx) to post-transplant lymphoproliferative disease. There was a 35% incidence of mortality. Deaths occurred a mean of 0.76 years after diagnosis of post-transplant lymphoproliferative disease. Most cases of post-transplant lymphoproliferative disease had extranodal location. There was one recurrence in 10% of patients, and two in 3%. All recurrent cases were seen in recipients who became Epstein-Barr virus positive after transplantation. There has been a decrease in the incidence of post-transplant lymphoproliferative disease from 15% to 9% to 4%. Post-transplant lymphoproliferative disease should be diagnosed promptly and treated aggressively. The best treatment, however, seems to be prevention, starting in the immediate postoperative period. Survivors should be monitored for both recurrence of post-transplant lymphoproliferative disease and acute cellular rejection.     

Predictive model for estimating risk of crush syndrome: a data mining approach

BACKGROUND: There is no standard triage method for earthquake victims with crush injuries because of a scarcity of epidemiologic and quantitative data. We conducted a retrospective cohort study to develop predictive models based on clinical data for crush injury in the Kobe earthquake. METHODS: The medical records of 372 patients with crush injuries from the Kobe earthquake were retrospectively analyzed. Twenty-one risk factors were assessed with logistic regression analysis for three outcomes relating to crush syndrome. Two types of predictive triage models--initial evaluation in the field and secondary assessment at the hospital--were developed using logistic regression analysis. Classification accuracy, Brier score and area under the receiver operating characteristic curve (AUC) were used to evaluate the model. RESULTS: The initial triage model, which includes pulse rate, delayed rescue, and abnormal urine color, has an AUC of 0.73. The secondary model, which includes WBC, tachycardia, abnormal urine color, and hyperkalemia, shows an AUC of 0.76. CONCLUSIONS: These triage models may be especially useful to nondisaster experts for distinguishing earthquake victims at high risk of severe crush syndrome from those at lower risk. Application of the model may allow relief workers to better utilize limited medical and transportation resources in the aftermath of a disaster.     

Successful treatment of complex traumatic and surgical wounds with a foetal bovine dermal matrix

A foetal bovine dermal repair scaffold (PriMatrix, TEI Biosciences) was used to treat complex surgical or traumatic wounds where the clinical need was to avoid skin flaps and to build new tissue in the wound that could be reepithelialised from the wound margins or closed with a subsequent application of a split‐thickness skin graft (STSG). Forty‐three consecutive cases were reviewed having an average size of 79·3 cm², 50% of which had exposed tendon and/or bone. In a subset of wounds (44·7%), the implantation of the foetal dermal collagen scaffold was also augmented with negative pressure wound therapy (NPWT). Complete wound healing was documented in over 80% of the wounds treated, whether the wound was treated with the foetal bovine dermal scaffold alone (95·2%) or when supplemented with NPWT (82·4%). The scaffold successfully incorporated into wounds with exposed tendon and/or bone to build vascularised, dermal‐like tissue. The new tissue in the wound supported STSGs however, in the majority of the cases (88·3%); wound closure was achieved through reepithelialisation of the incorporated dermal scaffold by endogenous wound keratinocytes. The foetal bovine dermal repair scaffold was found to offer an effective alternative treatment strategy for definitive closure of challenging traumatic or surgical wounds on patients who were not suitable candidates for tissue flaps.     

Morphologic expression of the left coronary artery in pigs. An approach in relation to human heart

Introduction

In spite of its importance as an experimental model, the information on the left coronary artery in pigs is sparse.

Objective

To determine the morphologic features of the left coronary artery in pigs.

Methods

We evaluated 158 pig hearts. The left coronary artery was perfused with synthetic resin after their ostia had been catheterized. Diameters and courses of the vascular beds were measured with an electronic caliper (Mitutoyo^®).

Results

The diameter of left coronary artery was 6.98 ± 1.56 mm and its length was 3.51±0.99 mm. It was found to end up by bifurcating itself into the anterior interventricular artery and the circumflex artery in 79% of the cases, and by trifurcating in 21% of the cases, with the presence of the diagonal artery. The anterior interventricular artery ended up at the apex in 79.7% of the cases, and the circumflex artery at the posterior aspect of the left ventricle in 64% of the case, this artery never reached the posterior interventricular sulcus. An anastomosis between the terminal branches of the anterior interventricular artery and the posterior interventricular artery was found in 7.6% of the specimens. The antero-superior branch of the anterior interventricular artery occurred in 89.9% of the hearts. A left marginal branch was observed in 87.9% of the cases with a diameter of 2.25±0.55 mm.

Conclusion

Compared with humans, pigs have shorter left coronary artery trunks and branches; even the circumflex artery never reaches the posterior interventricular sulcus. Our findings are useful for the design of experimental hemodynamic and procedural models.     

Effect of low-level laser therapy on types I and III collagen and inflammatory cells in rats with induced third-degree burns

Low-level laser therapy (LLLT) has been increasingly used to accelerate wound healing in third-degree burns. This study investigated the effects of lasers on the tissue repair process of third-degree burns. Burns were produced on the backs of male Wistar rats. The animals were divided into four groups (n?=?12): control, injury, LLLT 3 J/cm², and LLLT 4 J/cm². Each group was further divided into two subgroups; the rats in one subgroup were killed on day 8 and those in the other, on day 16 after injury. The animals in LLLT 3 J/cm² and LLLT 4 J/cm² were irradiated 1 h after injury, and irradiation was repeated every 48 h. Laser (660 nm, 35 mW) treatment at fluences of 3 and 4 J/cm² were used. After killing the rats, tissue fragments from the burnt area were removed for histological analysis. The LLLT-treated groups showed a significant decrease (p <0.05) in the number of inflammatory cells and increased collagen deposition compared to the injury group. Laser irradiation (both 3 and 4 J/cm²) resulted in reduction in the inflammatory process and improved collagen deposition, thereby ameliorating the healing of third-degree burns.     

Absence of donor CD40 protects renal allograft epithelium and preserves renal function

Blocking the CD40‐CD154 pathway prevents allograft rejection and induces donor‐specific tolerance in various experimental models. However, the translation to clinical studies has been hampered by unexpected thromboembolic complications of CD154‐blocking antibodies. Thus, blocking CD40 instead is now considered as an alternative strategy. Here, we evaluated the role of donor CD40 in allospecific T‐cell responses in vitro and in an in vivo model for renal transplantation. Fully MHC‐mismatched allografts from CD40‐deficient donors displayed better renal function than wild type. These functional data correlated with a lower level of apoptosis in renal tubular epithelial cells and higher expression of PD‐L1, which is most probably because of a reduced Th17 response in recipients of a CD40‐deficient donor. This hypothesis was supported in vitro, where donor CD40 expression was important for the induction of direct allospecific T‐cell responses. Especially the induction of Th17 cells was critically dependent on donor CD40. IL‐17A in conjunction with interferon‐γ in turn rendered renal tubular epithelial cells to a more costimulatory state by upregulating CD40 and downregulating PD‐L1 expression. In conclusion, CD40 blockade not only reduces the allospecific T‐cell responses, but might also lead to protection of tubular epithelium from apoptosis and thereby preserve kidney allograft function.     

Giant cell tumor and Paget's disease of bone in one family: geographic clustering

Giant cell tumor is a rare complication of Paget's disease of bone. Typically, this tumor occurs in the case of polyostotic disease and only in pagetic bones. This tumor rarely has been seen in multiple family members who have Paget's disease, although Paget's bone disease clearly has a hereditary component. Our report documents four cases of polyostotic Paget's bone disease complicated by benign giant cell tumor. In two patients, the giant cell tumor also was multifocal. All patients were from one family. They were born in Avellino and reside in Campania, a Southern Italian region. The ancestors of the patients with familial giant cell tumor in Paget's bone disease were born in the same geographic area. These data suggest that a combination of environmental and genetic factors could be responsible for linkage of the patients born in Avellino with this neoplasm that is highly unusual in patients with Paget's disease of bone.     

Implementation of a successful endovascular surgical program in a non-teaching tertiary-care centre in Ontario.

Endovascular surgical techniques have become an accepted standard of care for high-risk patients with abdominal aortic aneurysms and for certain patients with thoracic aortic pathology and peripheral arterial aneurysms. In Canada, endovascular surgery has been concentrated in tertiary-care academic teaching institutions. As the technology evolves and as expertise advances, the applicability of endovascular techniques will expand. With time, and as the demand for endovascular techniques rises, this expertise will increasingly need to be delivered by dedicated vascular surgical services in nonteaching institutions. The dissemination of endovascular surgical capabilities represent a unique challenge. We report the successful implementation of an endovascular surgical program in a tertiary-care nonteaching institution using a carefully planned preceptorship model. We review our initial 49 cases and discuss 6 factors important to the successful establishment of an endovascular surgical service: education, teamwork, strict selection of patients, use of a single stent-graft manufacturer, industry support and endovascular preceptorship. Our experience may be used as a model by other institutions in Canada.