Mitochondrial membrane potential and delayed graft function following kidney transplantation.

Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P = .002) and donation after cardiac death donors (75% vs 12%, P = .004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.08 1.381.78 , P = .01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.

A cost analysis of internal fixation versus nonoperative treatment in adult midshaft clavicle fractures using multiple randomized controlled trials.

BACKGROUND: To determine whether the cost of nonoperative treatment, including those who require delayed operative treatment, is less than those receiving initial operative management. METHODS: We identified 4 recent randomized controlled trials comparing operative and nonoperative treatment of displaced midshaft clavicle fractures in adults with a minimum of 1-year follow-up. A decision tree was then created from these data using reoperation for those treated with surgery or delayed operative treatment of those treated nonoperatively as end points. Actual costs estimated from 2013 Medicare reimbursement rates were applied and adjusted to better reflect private insurance rates. We then performed a 2-way sensitivity analysis to test the stability of our model. RESULTS: Based on our decision tree, the expected costs for operative and nonoperative treatment were $14,763.21 and $3112.65, respectively, producing a cost savings of $11,650.56 with nonoperative treatment. After application of a 2-way sensitivity analysis, our model remains valid until delayed operative treatment for nonoperative patients approaches 95% and reoperation after initial operative management falls below 15%. CONCLUSIONS: From the perspective of a single payer, initial nonoperative treatment of midshaft clavicle fractures followed by delayed surgery as needed is less costly than initial operative fixation. LEVEL OF EVIDENCE: Economic Level III. See Instructions for Authors for a complete description of levels of evidence.

Redesigning Organ Allocation Boundaries for Liver Transplantation in the United States.

Geographic disparities in access to and outcomes in transplantation have been a persistent problem widely discussed by transplant researchers and the transplant community. One of the alleged causes of disparities in the United States is administratively determined organ allocation boundaries that limit organ sharing across regions. This paper applies mathematical programming to construct alternative liver allocation boundaries that achieve more geographic equity in access to transplants than the current system. The performance of the optimal boundaries were evaluated and compared to that of current allocation system using discrete event simulation.

Outcomes in ethnic minority renal transplant recipients receiving everolimus versus mycophenolate: comparative risk assessment results from a pooled analysis.

BACKGROUND: Everolimus (EVR) has demonstrated good efficacy after renal transplantation. Racial disparities in clinical outcomes after de novo renal transplantation are well documented; whether the efficacy of EVR varies based on recipient ethnicity is unknown. We conducted a comparative risk assessment of EVR by ethnicity. METHODS: Data on 2004 renal transplant recipients from three EVR studies were pooled to identify the impact of ethnicity on efficacy outcomes across EVR dosing groups and control groups. Ethnic groups compared were African Americans, non-U.S. blacks, Asians, Hispanics, and Caucasians. EVR groups received either 1.5 or 3 mg per day, with either standard-dose cyclosporine or reduced-dose cyclosporine. Control groups received mycophenolic acid (MPA) with standard-dose cyclosporine. Composite efficacy failure endpoint was graft loss, death, biopsy-proven acute rejection, or lost to follow-up. Adjusted odds ratios were calculated using a logistic regression model. RESULTS: The proportion of renal transplant recipients who met the composite endpoint was African Americans (46%), non-U.S. black (35%), Caucasian (31%), Hispanic (28%), and Asian (25%). The odds of meeting the composite endpoint were significantly (P=0.0001) greater for African Americans versus Caucasians but did not differ among the other ethnic groups (ethnic groups were only compared with Caucasians). EVR and MPA were associated with similar efficacy among each of the ethnic groups. CONCLUSION: In this pooled data analysis in more than 2000 renal transplant recipients, EVR versus MPA resulted in similar composite endpoint incidence events across ethnicities. Consistent with previously published data, African Americans had poorer clinical outcomes. EVR is efficacious regardless of ethnicity.

Extracorporeal shock wave treatment of non- or delayed union of proximal metatarsal fractures.

BACKGROUND: Nonunion or delayed union of fractures in the proximal aspect of metatarsals 1 to 4 and Zone 2 of the fifth metatarsal were treated by high energy extracorporeal shock wave treatment (ESWT) to study the safety and efficacy of this method of treatment in a FDA study of the Ossatron device. MATERIALS AND METHODS: In a prospective single-arm, multi-center study, 34 fractures were treated in 32 patients (two subjects had two independent fractures) with ESWT. All fractures were at least 10 (range, 10 to 833) weeks after injury, with a median of 23 weeks. ESWT application was conducted using a protocol totaling 2,000 shocks for a total energy application of approximately 0.22 to 0.51 mJ/mm2 per treatment. The mean ESWT application time for each of the treatments was 24.6 +/- 16.6 minutes, and anesthesia time averaged 27.1 +/- 10.4 minutes. All subjects were followed for 1 year after treatment at intervals of 12 weeks, 6, 9, and 12 months. RESULTS: The overall success rate at the 12-week visit was 71% with low complications, significant pain improvement as well as improvement on the SF-36. The success/fail criteria was evaluated again at the 6- and 12-month followup, showing treatment success rates of 89% (23/26) and 90% (18/20), respectively. The most common adverse event was swelling in the foot, reported by five subjects (15.6%). CONCLUSION: High-energy ESWT appears to be effective and safe in patients for treatment of nonunion or a delayed healing of a proximal metatarsal, and in fifth metatarsal fractures in Zone 2.

Mycophenolic acid in kidney transplant patients with diabetes mellitus: does the formulation matter?

Diabetes mellitus is frequent in kidney transplant recipients and is commonly associated with gastrointestinal (GI) complications. Delayed gastric emptying affects 30% to 50% of patients with type 1 or 2 diabetes and can influence oral drug absorption. Time-to-peak concentration of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) is longer in diabetic kidney transplant patients than patients without diabetes. By retaining gut contents in the stomach for longer, this could increase local GI toxicity in diabetic recipients due to an extended duration of exposure to MPA in the stomach. The enteric-coated mycophenolate sodium (EC-MPS) formulation delays the release of MPA until pH is higher than 5.5, such that absorption takes place more distally compared with MMF. Patient-reported outcomes data have been used to assess the effect of conversion to EC-MPS in maintenance kidney transplant patients with diabetes who were experiencing MMF-related GI symptoms. Results indicated that conversion leads to improved GI symptom burden despite higher MPA exposure under the EC-MPS regimen. Improved GI tolerance using EC-MPS has permitted maintenance of optimal MPA exposure in nondiabetic populations. Comparative trials to evaluate the GI symptom burden and maximum achieved MPA dosing using the EC-MPS and MMF formulations in de novo and maintenance diabetic kidney transplant recipients are merited.

Do graft type or donor source affect acute rejection rates after liver transplant: a multivariate analysis.

We looked at acute rejection (AR) rates in adult liver transplant recipients to determine if graft type (whole liver vs. partial liver) or donor source (living vs. deceased donor) influenced the risk for AR. Between 1999 and 2005, we performed 292 whole liver transplants from a deceased donor (DD-WL) and 91 partial transplants, either from a living donor (LDLT, n = 59) or split liver from a deceased donor (DD-SL, n = 32). Pediatric recipients were not included. The groups were well matched by age and type of liver disease (p = ns), but mean model for end-stage liver disease (MELD) scores were higher in the DD-WL vs. LD recipient groups (p < 0.01). Immunosuppression was similar for all. AR rates at 12 months post-transplant were lower in the LDLT group (10.0%) vs. the DD-WL group (16.5%, p = 0.10), although this was not statistically significant. AR rates in the DD-SL transplant group (12.8%) were intermediate compared with the two other groups and not statistically different from either group (p = ns). By multivariate analysis, however, neither graft type (partial vs. whole) nor donor source (LD vs. DD) seemed to have an impact on the risk for AR. The only factor that was associated with an increased risk for AR was not using induction therapy.