Randomized trial of mycophenolate mofetil versus enteric-coated mycophenolate sodium in primary renal transplant recipients given tacrolimus and daclizumab/thymoglobulin: one year follow-up

BACKGROUND: It was of interest to compare enteric-coated mycophenolate sodium (EC-MPS) versus mycophenolate mofetil (MMF) among renal transplant recipients receiving a tacrolimus-based immunosuppressive regimen. METHODS: Between December 2004 and February 2006, a single-center, open-label randomized trial of MMF (group A, n=75) versus EC-MPS (group B, n=75) was performed in primary renal transplant recipients receiving combined thymoglobulin/daclizumab induction along with reduced tacrolimus dosing and elimination of corticosteroids 1 week postoperatively. The primary endpoint was the incidence rate of acute rejection (AR) during the first 12 months posttransplant; secondary aims were to compare graft and patient survival, renal function, drug dosing and monitoring, gastrointestinal side effects, and other adverse events at 12 months of follow-up. RESULTS: Patient/graft survival in groups A and B were 100%/96% versus 99%/96%, respectively (N.S.). At 12 months, a total of nine patients (6%) experienced biopsy-proven AR, 3% (2/75) vs. 9% (7/75) in the MMF and EC-MPS arms, respectively (N.S.). At 12 months, the geometric mean*/SE serum creatinine concentration and arithmetic mean+/-SE calculated glomerular filtration rate in groups A and B, respectively, were 1.30*/1.03 and 61.4+/-2.0 vs. 1.26*/1.03 and 66.0+/-2.1 (N.S.). Incidence of new onset diabetes mellitus (11% vs. 11%), infections requiring hospitalization (13% vs. 15%), and gastrointestinal side effects (36% vs. 32%) appeared equivalent (N.S.). CONCLUSIONS: Early efficacy and toxicity were equivalent between the two study arms. Optimizing either MMF or EC-MPS along with a combined thymoglobulin/daclizumab induction, low tacrolimus dosing and steroid avoidance resulted in a low AR rate and an acceptably high renal function at 12 months.     

Characterizing TUNA ablative treatments of the prostate for benign hyperplasia with gadolinium-enhanced magnetic resonance imaging

BACKGROUND AND PURPOSE: Transurethral Needle Ablation of the prostate TUNA has been accepted as an office-based treatment for benign prostatic hyperplasia (BPH) for many years. Clinical outcomes have been reported, but the amount and location of the necrosis produced have yet to be characterized. The necrosis caused by TUNA was evaluated by gadolinium-enhanced magnetic resonance imaging (MRI) of the pelvis. PATIENTS AND METHODS: Twelve patients with BPH/lower urinary-tract symptoms underwent standard TUNA, and MRI scans with gadolinium enhancement were performed before and 1 week after treatment. The images were studied using Analyze software to quantify the amount of necrosis compared with the prostatic volume. Transverse, coronal, and sagittal images were obtained to identify the location of the necrosis. RESULTS: New gadolinium defects were seen in all patients after TUNA. The lesions coalesced into continuous areas of necrosis and correlated with the site of needle placement. The mean volume of necrosis was 6.84 cc and equated to 8.6% of the prostate volume. No lesions were found near the apex, urethra, or rectum; and none extended beyond the prostate capsule. CONCLUSIONS: Gadolinium-enhanced MRI demonstrates new vascular defects representing necrosis caused by TUNA of the prostate. This therapy for BPH produces necrotic lesions that can be placed strategically by the surgeon. The standard protocol produces lesions that coalesce to create larger lesions. This MRI study has characterized, for the first time, the heating pattern and intraprostatic necrosis of a complete TUNA procedure.     

Perioperative cardiac arrests in children between 1988 and 2005 at a tertiary referral center: a study of 92,881 patients

BACKGROUND: The objective of this study was to determine the incidence and outcome of perioperative cardiac arrest (CA) in children younger than 18 yr undergoing anesthesia for noncardiac and cardiac procedures at a tertiary care center. METHODS: After institutional review board approval (Mayo Clinic, Rochester, Minnesota), all patients younger than 18 yr who had perioperative CA between November 1, 1988, and June 30, 2005, were identified. Perioperative CA was defined as a need for cardiopulmonary resuscitation or death during anesthesia care. A cardiac procedure was defined as a surgical procedure involving the heart or great vessels requiring an incision. RESULTS: A total of 92,881 anesthetics were administered during the study period, of which 4,242 (5%) were for the repair of congenital heart malformations. The incidence of perioperative CA during noncardiac procedures was 2.9 per 10,000, and the incidence during cardiac procedures was 127 per 10,000. The incidence of perioperative CA attributable to anesthesia was 0.65 per 10,000 anesthetics, representing 7.5% of the 80 perioperative CAs. Both CA incidence and mortality were highest among neonates (0-30 days of life) undergoing cardiac procedures (incidence: 435 per 10,000; mortality: 389 per 10,000). Regardless of procedure type, most patients who experienced perioperative CA (88%) had congenital heart disease. CONCLUSION: The majority of perioperative CAs were caused by factors not attributed to anesthesia, in distinction to some recent reports. The incidence of perioperative CA is many-fold higher in children undergoing cardiac procedures, suggesting that definition of case mix is necessary to accurately interpret epidemiologic studies of perioperative CA in children.     

Quantification of Basal and Stimulated ROS Levels as Predictors of Islet Potency and Function

We have developed a luminol-based assay using intact islets, which allows for quantification of reactive oxygen species (ROS). In addition, an index capable of characterizing metabolic and mitochondrial integrity prior to transplantation was created based on the capacity of islets to respond to high glucose and rotenone (mitochondrial respiratory chain complex I inhibitor) by production of ROS. To validate this assay, lipid peroxidation and antioxidative defense capacity were evaluated by detection of malondialdehyde (MDA) levels and glutathione peroxidase activity (GPx), respectively. Also, flow cytometric analyses of ROS (dihydroethidine), apoptosis (Annexin V, active caspases), necrosis (Topro3), and mitochondrial membrane potential (JC-1) were done in parallel to correlate with changes in luminol-measured ROS. ATP/ADP ratios were quantified by HPLC and the predictive value of ROS measurement on islet functional potency was correlated with capacity to reverse diabetes in a streptozotocin-induced diabetic NOD.scid mouse model as well as in human transplant recipients. Our data demonstrate that levels of ROS in islets correlate with the percentage of apoptotic cells and their functional potency in vivo. The ROS indices following glucose and rotenone exposure are indicative of metabolic potency and mitochondrial integrity and can be used as surrogate markers to evaluate the quality of islets prior to transplantation.     

Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content (BMC) and density (BMD) and determined the contribution of inflammatory markers to 1-yr changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss project who were randomly assigned to 1 of 3 treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy X-ray absorptiometry and the 4% distal tibia by peripheral quantitative computed tomography. Serum inflammatory markers (C-reactive protein, interleukin [IL]-1β, IL-6, tumor necrosis factor-alpha [TNF-α], and white blood cell count [WBC]) were measured at baseline, 6, and 12 mo. Because of attrition or missing values, data analysis at 12 mo includes only 235 women. Significant associations among IL-6, TNF-α, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1–6.1% of the variance to the observed 12-mo changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss.     

The impact of simultaneous pancreas-kidney transplantation on long-term patient survival

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) ameliorates the progression of microvascular diabetic complications but the procedure is associated with excess initial morbidity and an uncertain effect on patient survival when compared with solitary cadaveric or living donor renal transplantation. We evaluated mortality risks associated with SPK, solitary renal transplantation, and dialysis treatment in a national cohort of type 1 diabetics with end-stage nephropathy. METHODS: A total of 13,467 adult-type 1 diabetics enrolled on the renal and renal-pancreas transplant waiting list between 10/01/88 and 06/30/97 were followed until 06/30/98. Time-dependent mortality risks and life expectancy were calculated according to the treatment received subsequent to wait-list registration: SPK; cadaveric kidney only (CAD); living donor kidney only (LKD) transplantation; and dialysis [wait-listed, maintenance dialysis treatment (WLD)]. RESULTS: Adjusted 10-year patient survival was 67% for SPK vs. 65% for LKD recipients (P=0.19) and 46% for CAD recipients (P<0.001). The excess initial mortality normally associated with renal transplantation and the risk of early infectious death was 2-fold higher in SPK recipients. The time to achieve equal proportion of survivors as the WLD patients was 170, 95, and 72 days for SPK, CAD, and LKD recipients, respectively (P<0.001). However, the adjusted 5-year morality risk (RR) using WLD as the reference and the expected remaining life years were 0.40, 0.45, and 0.75 and 23.4, 20.9, and 12.6 years for SPK, LKD, and CAD, respectively. There was no survival benefit in SPK recipients > or =50 years old (RR=1.38, P=0.81). CONCLUSIONS: Among patients with type 1 DM with end-stage nephropathy, SPK transplantation before the age of 50 years was associated with long-term improvement in survival compared to solitary cadaveric renal transplantation or dialysis.