Associations of demographic and behavioural factors with glycaemic control in young adults with type 1 diabetes mellitus.

BACKGROUND: Despite recognised benefits of optimal glycaemic control in patients with type 1 diabetes mellitus (T1DM), good control is still difficult to achieve, particularly for adolescents and young adults. Recognition of factors that may assist early optimisation of glycaemic control is therefore important. AIMS: We explored associations of demographic, social and behavioural factors with glycosylated haemoglobin (HbA1c) levels in participants with T1DM aged 18-25 years. METHODS: A cross-sectional analysis was performed on young adults attending a dedicated multidisciplinary clinic at Fremantle Hospital, Western Australia from January to August 2014. RESULTS: Data from 93 participants were analysed. Mean age was 21.4 ± 2.3 years, and 39.8% of the cohort were female. Longer duration of diabetes was associated with higher HbA1c (r = 0.25, P = 0.04). Men had lower HbA1c than women (8.2 ± 1.6 vs 9.2 ± 2.0%, P = 0.01). Increased frequency of clinic attendance was associated with lower HbA1c (r = -0.27, P = 0.02). Those engaged in work or study had better HbA1c compared with those who were not (8.9 ± 2.1 vs 10.5 ± 2.1%, P = 0.03). Socioeconomic disadvantage, risk-taking behaviour, insulin pump use and distance travelled to clinic were not associated with differences in HbA1c. CONCLUSION: In young adults with T1DM, geographical separation, socioeconomic disadvantage and risk-taking behaviours did not influence glycaemic control. Longer duration of diabetes identifies young adults at higher risk of poor control, while attendance at a multidisciplinary clinic and engagement in work or study was associated with better glycaemic control. Additional studies are warranted to clarify the role of behavioural interventions to improve diabetes management in young adults.

Cryptic B cell response to renal transplantation.

Transplantation reliably evokes allo-specific B cell and T cell responses in mice. Yet, human recipients of kidney transplants with normal function usually exhibit little or no antibody specific for the transplant donor during the early weeks and months after transplantation. Indeed, the absence of antidonor antibodies is taken to reflect effective immunosuppressive therapy and to predict a favorable outcome. Whether the absence of donor-specific antibodies reflects absence of a B cell response to the donor, tolerance to the donor or immunity masked by binding of donor-specific antibodies to the graft is not known. To distinguish between these possibilities, we devised a novel ELISPOT, using cultured donor, recipient and third-party fibroblasts as targets. We enumerated donor-specific antibody-secreting cells in the blood of nine renal allograft recipients with normal kidney function before and after transplantation. Although none of the nine subjects had detectable donor-specific antibodies before or after transplantation, all exhibited increases in the frequency of donor-specific antibody-secreting cells eight weeks after transplantation. The responses were directed against the donor HLA-class I antigens. The increase in frequency of donor-specific antibody-secreting cells after renal transplantation indicates that B cells respond specifically to the transplant donor more often than previously thought.

Extracorporeal support: improves donor renal graft function after cardiac death.

Donors after cardiac death (DCD) could increase the organ pool. Data supports good long-term renal graft survival. However, DCDs are <10% of deceased donors in the United States, due to delayed graft function, and primary nonfunction. These complications are minimized by extracorporeal support after cardiac death (ECS-DCD). This study assesses immediate and acute renal function from different donor types. DCDs kidneys were recovered by conventional rapid recovery or by ECS, and transplanted into nephrectomized healthy swine. Warm ischemia of 10 and 30 min were evaluated. Swine living donors were controls (LVD). ECS-DCDs were treated with 90 min of perfusion until organ recovery. After procurement, kidneys were cold storage 4-6 h. Renal vascular resistance (RVR), urine output (UO), urine protein concentration (UrPr) and creatinine clearance (CrCl), were collected during 4 h posttransplantation. All grafts functioned with adequate renal blood flow for 4 h. RVR at 4 h posttransplant returned to baseline only in the LVD group (0.36 mmHg/mL/min +/- 0.03). RVR was higher in all DCDs (0.66 mmHg/mL/min +/- 0.13), without differences between them. UO was >50 mL/h in all DCDs, except in DCD-30 (6.8 mL/h +/- 1.7). DCD-30 had lower CrCl (0.9 mL/min +/- 0.2) and higher UrPr >200 mg/dL, compared to other DCDs >10 mL/min and <160 mg/dL, respectively. Normothermic ECS can resuscitate kidneys to transplantable status after 30 min of cardiac arrest/WI.

The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients.

Late-onset cytomegalovirus (CMV) disease is a significant problem with a standard 3-month prophylaxis regimen. This multicentre, double-blind, randomized controlled trial compared the efficacy and safety of 200 days' versus 100 days' valganciclovir prophylaxis (900 mg once daily) in 326 high-risk (D+/R-) kidney allograft recipients. Significantly fewer patients in the 200-day group versus the 100-day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200-day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy-proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild-to-moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days' prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5.

Should heart, lung, and liver transplant recipients receive immunosuppression induction for kidney transplantation?

As the outcomes of heart, liver, and lung transplantation continue to improve, more patients will present for subsequent renal transplantation. It remains unclear whether these patients benefit from induction immunosuppression. We retrospectively reviewed induction on solid organ graft recipients who underwent renal transplant at our center from January 1, 1995 to March 30, 2007. Induction and the non-induction groups were compared by univariate and Kaplan-Meier analyses. There were 21 patients in each group, with mean follow-up of 4.5-6.0 years. Forty-seven percent of patients receiving induction had a severe post-operative infection, compared with 28.6% in the non-induction group (p = NS). The one yr rejection rate in the induction group was 9.5% compared with 14.3% for non-induction (p = NS). One-yr graft survival was 81.0% and 95.2% in the induction and non-induction group (p = NS). In summary, there is a trend toward lower patient and graft survival among patients undergoing induction. These trends could relate to selection bias in the decision to prescribe induction immunosuppression, but further study is needed to better define the risks and benefits of antibody-induction regimens in this population.

Improving organ procurement practices in Michigan.

Travel to procure deceased donor organs is associated with risk to transplant personnel. In many instances, multiple teams are present for a given operation. We studied our statewide experience to determine how much excess travel this redundancy entails, and generated alternate models for organ recovery. We reviewed our organ procurement organization's experience with deceased donor operations between 2002 and 2008. Travel was expressed as cumulative person-miles between procurement team origin and donor hospital. A model of minimal travel was created, using thoracic and abdominal teams from the closest in-state center. A second model involved transporting donors to a dedicated procurement facility. Travel distance was recalculated using these models, and mode and cost of travel extrapolated from current practices. In 654 thoracic and 1469 abdominal donors studied, the mean travel for thoracic teams was 1066 person-miles and for abdominal teams was 550 person-miles. The mean distance traveled by thoracic and abdominal organs was 223 miles and 142 miles, respectively. Both hypothetical models showed reductions in team travel and reliance on air transport, with favorable costs and organ transport times compared to historical data. In summary, we found significant inefficiency in current practice, which may be alleviated using new paradigms for donor procurement.

The effects of donor and recipient practices on transplant center finances.

Over the past several years we have noted a marked decrease in this profitability of our kidney transplant program. Our hypothesis is that this reduction in kidney transplant institutional profitability is related to aggressive donor and recipient practices. The study population included all adults with Medicare insurance who received a kidney transplant at our center between 1999 and 2005. Adopting the hospital perspective, multi-variate linear regression models to determine the independent effects of donor and recipient characteristics and era effects on total reimbursements and total hospital margin. We note statistically significant decreased medical center incremental margins in cases with ECDs (-$5887) and in cases of DGF (-4937). We also note an annual change in the medical center margin is independently associated with year and changes at a rate of -$5278 per year, related to both increasing costs and decreasing Medicare reimbursements. The financial loss associated with patient DGF and the use of ECD kidneys may resonate with other centers, and could hinder efforts to expand kidney transplantation within the United States. The Centers for Medicare and Medicaid Services (CMS) should consider risk-adjusted reimbursement for kidney transplantation.

Organ donation and utilization in the United States, 1996-2005.

The success of clinical transplantation as a therapy for end-stage organ failure is limited by the availability of suitable organs for transplant. This article discusses continued efforts by the transplant community to collaboratively improve the organ supply. There were 7593 deceased organ donors in 2005. This represents an all-time high and a 6% increase over 2004. Increases were noted in deceased organ donation of all types of organs; notable is the increase in lung donation, which occurred in 17% of all deceased donors. The percentage of deceased donations that occurred following cardiac death has also reached a new high at 7%. The number of living donors decreased by 2%, from 7003 in 2004 to 6895 in 2005. This article discusses the continued efforts of the Organ Donation Breakthrough Collaborative and the Organ Transplantation Breakthrough Collaborative to support organ recovery and use and to encourage the expectation that for every deceased donor, all organs will be placed and transplanted.

Risk factors for urinary complications after renal transplantation.

Urinary complications are common following renal transplantation. The aim of this study is to evaluate the risk factors associated with renal transplant urinary complications. We collected data on 1698 consecutive renal transplants patients. The association of donor, transplant and recipient characteristics with urinary complications was assessed by univariable and multivariable Cox proportional hazards models, fitted to analyze time-to-event outcomes of urinary complications and graft failure. Urinary complications were observed in 105 (6.2%) recipients, with a 2.8% ureteral stricture rate, a 1.7% rate of leak and stricture, and a 1.6% rate of urine leaks. Seventy percent of these complications were definitively managed with a percutaneous intervention. Independent risk factors for a urinary complication included: male recipient, African American recipient, and the "U"-stitch technique. Ureteral stricture was an independent risk factor for graft loss, while urinary leak was not. Laparoscopic donor technique (compared to open living donor nephrectomy) was not associated with more urinary complications. Our data suggest that several patient characteristics are associated with an increased risk of a urinary complication. The U-stitch technique should not be used for the ureteral anastomosis.

Financial implications of pancreas transplant complications: a business case for quality improvement.

We quantified the financial implications of surgical complications following pancreas transplantation. We reviewed medical and financial records of 49 pancreas transplant recipients at the University of Michigan Health System (UMHS) between 1/6/2002 and 11/22/2004. The association of donor, transplant recipient and financial variables was assessed. The median costs to UMHS of procedures and follow-up were $92,917 for recipients without surgical complications versus $108,431 when a surgical complication occurred, a difference of $15,514 (p = 0.03). Median reimbursement by the payer was $17,363 higher in patients with a surgical complication (p = 0.001). Similar trends (higher insurer costs) were noted when stratifying by payer (public and private) and specific procedure (SPK and PAK). All parties (patient, physician, payer and medical center) should benefit from quality improvement, with payers having a financial interest in pancreas transplant surgical quality initiatives.

Characteristics associated with liver graft failure: the concept of a donor risk index.

Transplant physicians and candidates have become increasingly aware that donor characteristics significantly impact liver transplantation outcomes. Although the qualitative effect of individual donor variables are understood, the quantitative risk associated with combinations of characteristics are unclear. Using national data from 1998 to 2002, we developed a quantitative donor risk index. Cox regression models identified seven donor characteristics that independently predicted significantly increased risk of graft failure. Donor age over 40 years (and particularly over 60 years), donation after cardiac death (DCD), and split/partial grafts were strongly associated with graft failure, while African-American race, less height, cerebrovascular accident and 'other' causes of brain death were more modestly but still significantly associated with graft failure. Grafts with an increased donor risk index have been preferentially transplanted into older candidates (>50 years of age) with moderate disease severity (nonstatus 1 with lower model for end-stage liver disease (MELD) scores) and without hepatitis C. Quantitative assessment of the risk of donor liver graft failure using a donor risk index is useful to inform the process of organ acceptance.

Who pays for biliary complications following liver transplant? A business case for quality improvement.

We use biliary complication following liver transplantation to quantify the financial implications of surgical complications and make a case for surgical improvement initiatives as a sound financial investment. We reviewed the medical and financial records of all liver transplant patients at the UMHS between July 1, 2002 and June 30, 2005 (N = 256). The association of donor, transplant, recipient and financial data points was assessed using both univariable (Student's t-test, a chi-square and logistic regression) and multivariable (logistic regression) methods. UMHS made a profit of $6822 +/- 39087 on patients without a biliary complication while taking a loss of $5742 +/- 58242 on patients with a biliary complication (p = 0.04). Reimbursement by the payer was $5562 higher in patients with a biliary complication compared to patients without a biliary complication (p = 0.001). Using multivariable logistic regression analysis, the two independent risk factors for a negative margin included private insurance (compared to public) (OR 1.88, CI 1.10-3.24, p = 0.022) and biliary leak (OR = 2.09, CI 1.06-4.13, p = 0.034). These findings underscore the important impact of surgical complications on transplant finances. Medical centers have a financial interest in transplant surgical quality improvement, but payers have the most to gain with improved surgical outcomes.

Preliminary analysis of early outcomes of a prospective, randomized trial of complete steroid avoidance in liver transplantation.

Steroids are a mainstay in liver transplantation for induction and maintenance immunosuppression but are associated with significant adverse effects. While prior studies have successfully limited the use of steroids, whether complete steroid avoidance will improve outcomes remains unclear. To further evaluate the need for steroids, consenting patients who underwent liver transplantation between June 2002 and May 2004 were entered into a prospective, randomized trial to receive either standard therapy (tacrolimus, mycophenolate mofetil, steroid induction/maintenance) or complete steroid avoidance (standard therapy without steroid induction/maintenance). Clinically suspected rejection was confirmed by biopsy and treated with pulse steroid therapy. Outcomes were compared on an intention to treat basis. Of the 72 patients enrolled, 36 (50%) were randomized to the steroid avoidance group with a mean follow up of 412 +/- 41 days. Donor and recipient characteristics were similar between groups. The steroid avoidance group was more likely to have significant infections (52% vs 28%, P = .03). There was a trend toward an increased rate of acute rejection (25% vs 14%, P = .23). Twelve of 36 recipients (33%) enrolled in the steroid avoidance group later received steroids. The incidence of recurrent hepatitis C was similar between groups. The 1-year patient (90% vs 83%, P = .44) and graft survivals (90% vs 81%, P = .27) were similar between groups. These data suggest complete steroid avoidance in liver transplantation results in acceptable patient and graft survival. However, the potential long-term benefits of steroid avoidance, including a decrease in severity of recurrent hepatitis C, remain under investigation.

Successful surgical salvage of partial pancreatic allograft thrombosis.

BACKGROUND: Venous thrombosis remains an important cause of pancreatic graft loss. Nevertheless, reports are scarce of treatment alternatives to complete graft removal. We describe a case of surgical salvage of a partial pancreatic graft thrombosis. METHODS: We used descriptive retrospective analysis. RESULTS: A 36-year-old patient with juvenile-onset diabetes mellitus and previous living related renal transplant received a cadaveric pancreas transplant in the right iliac fossa with enteric exocrine drainage and standard vascular anastomosis. Two days after discharge from the hospital, he presented with severe right upper quadrant pain, nausea, vomiting, fever, and leukocytosis. He was taken to the operating room for exploration. The tail of the pancreas, which was kinked under the gallbladder, was necrotic and excised. The remainder of the pancreas looked normal. The patient recovered well from surgery and was discharged home 7 days later. CONCLUSIONS: Partial pancreatectomy is an acceptable surgical alternative for incomplete graft thrombosis.

Results of a phase I trial evaluating a liver support device utilizing albumin dialysis.

BACKGROUND: We have previously reported the clearance of protein-bound and water-soluble hepatic toxins, in vitro and in an animal model, using albumin dialysis as an extracorporeal hepatic support (ECHS) device. OBJECTIVE: The objective of this study was to evaluate albumin dialysis through a phase I clinical trial. We hypothesized that albumin dialysis would (1) decrease elevated levels of hepatic toxins, (2) increase the Fischer ratio, and (3) decrease hepatic encephalopathy (HES) and intracranial pressure (ICP), while (4) maintaining stable hemodynamics. METHODS: Patients with acute liver failure were treated with an ECHS device utilizing continuous hemodiafiltration with continuous albumin dialysis. Mean arterial blood pressure (MAP), heart rate (HR), systemic venous oxygen saturation (Svo(2)), ICP, and HES were recorded. Blood samples were evaluated for hepatic toxins and factor VII levels. RESULTS: Nine patients were enrolled (status I, n = 5; status IIA, n = 4). There was no significant change in MAP, HR, or Svo(2) (MAP: Pre = 81 +/- 5.6 mm Hg, Post = 79 +/- 5.9 mm Hg, P =.70; HR: Pre = 104 +/- 5.2 bpm, Post = 107 +/- 6.2 bpm, P =.62; Svo(2): Pre = 72 +/- 3.5, Post = 71 +/- 1.7, P =.77). There was a decrease in the ammonia and total bilirubin levels (NH(3): Pre = 129.8 +/- 23.8 mg/dL, Post = 63.9 +/- 16.1 mg/dL, P =.01; total bilirubin: Pre = 20.3 +/- 2.5 mg/dL, Post = 17.6 +/- 2.7 mg/dL, P =.4). There was a significant increase of the Fischer ratio and factor VII levels (Fischer ratio: Pre = 0.98 +/- 0.2, Post = 2.17 +/- 0.5, P =.038; factor VII: Pre = 13.9 +/- 4.9, Post = 23.2 +/- 4.8, P =.015). There was a significant decrease in the HES and ICP (HES: Pre = 3.8 +/- 0.1, Post = 2 +/- 0.7, P =.02; ICP: Pre = 37 +/- 3.9, Post = 13.3 +/- 2.8, P =.048). Of 5 status I patients, 1 recovered native hepatic function and 3 were bridged to transplantation. CONCLUSIONS: This phase I study suggests that albumin dialysis as a liver support device is safe and effective in clearing hepatic toxins, with an associated decrease in the HES and ICP. This encouraging efficacy data warrant further investigation with a phase II/III trial.