Diagnosis of morbid obesity may not impact healthcare utilization for orthotopic liver transplantation: A propensity matched study.

AIM: To study mortality, length of stay, and total charges in morbidly obese adults during index hospitalization for orthotopic liver transplantation. METHODS: The Nationwide Inpatient Sample was queried to obtain demographics, healthcare utilization, post orthotopic liver transplantation (OLT) complications, and short term outcomes of OLT performed from 2003 to 2011 (n = 46509). We divided patients into those with [body mass index (BMI) ≥ 40] and without (BMI < 40) morbid obesity. Multivariable logistic regression analysis was performed to characterize differences in in-hospital mortality, length of stay (LOS), and charges for OLT between patients with and without morbid obesity after adjusting for significant confounders. Additionally, propensity matching was performed to further validate the results. RESULTS: Of the 46509 patients who underwent OLT during the study period, 818 (1.8%) were morbidly obese. Morbidly obese recipients were more likely to be female (46.8% vs 33.4%, P = 0.002), Caucasian (75.2% vs 67.8%, P = 0.002), in the low national income quartile (32.3% vs 22.5%, P = 0.04), and have ≥ 3 comorbidities (modified Elixhauser index; 83.9% vs 45.0%, P < 0.001). Morbidly obese patient also had an increase in procedure related hemorrhage (P = 0.028) and respiratory complications (P = 0.043). Multivariate and propensity matched analysis showed no difference in mortality (OR: 0.70; 95%CI: 0.27-1.84, P = 0.47), LOS (ß: -4.44; 95%CI: -9.93, 1.05, P = 0.11) and charges for transplantation (ß: $15693; 95%CI: -51622-83008, P = 0.64) between the two groups. Morbidly obese patients were more likely to have transplants on weekdays (81.7%) as compared to those without morbid obesity (75.4%, P = 0.029). CONCLUSION: Morbid obesity may not impact in-hospital mortality and health care utilization in OLT recipients. However, morbidly obese patients may be selected after careful assessment of co-morbidities.

Early immunosuppression treatment correlates with later de novo donor-specific antibody development after kidney and pancreas transplantation.

BACKGROUND: De novo donor-specific antibodies (dnDSA) post-transplant correlate with a higher risk of immunologic graft injury and loss following kidney and pancreas transplantation. Post-transplant dnDSA can occur within the first post-transplant year. METHODS: In this study, 817 of 1290 kidney and simultaneous kidney/pancreas recipients were tested for dnDSA post-transplant. Recipient immunosuppressive treatment at one, three, six, and 12 months post-transplant was correlated with dnDSA incidence by univariate and multivariate analyses. RESULTS: The overall incidence of dnDSA was 21.3% detected a median of 3.5 yr post-transplant. By univariate analysis, the immunosuppressive treatment at all time points correlated with dnDSA (p < 0.01). Month 6 treatment correlated best in multivariable analysis (p = 0.004). At six months, recipients receiving rapamune/mycophenolic acid (Rapa/MPA) had the highest dnDSA incidence at five yr (25.3%) and last follow-up (30.7%), those treated with cyclosporine/rapamune (CNI/Rapa) had the lowest incidence at five yr (10.8%) and last follow-up (18.6%), and cyclosporine/mycophenolic acid (CNI/MPA) treatment had an intermediate incidence at five yr (16.7%) and last follow-up (20.4%) (p < 0.01). Six-month CNI/MPA and Rapa/MPA treatment significantly correlated with dnDSA (hazard ratios of 2.36 and 1.80, respectively) by Cox proportional hazards regression modeling. CONCLUSION: The risk of post-transplant dnDSA development correlates with early immunosuppressive management.

Preservation solutions used during abdominal transplantation: Current status and outcomes.

Organ preservation remains an important contributing factor to graft and patient outcomes. During donor organ procurement and transportation, cellular injury is mitigated through the use of preservation solutions in conjunction with hypothermia. Various preservation solutions and protocols exist with widespread variability among transplant centers. In this review of abdominal organ preservation solutions, evolution of transplantation and graft preservation are discussed followed by classification of preservation solutions according to the composition of electrolytes, impermeants, buffers, antioxidants, and energy precursors. Lastly, pertinent clinical studies in the setting of hepatic, renal, pancreas, and intestinal transplantation are reviewed for patient and graft survival as well as financial considerations. In liver transplants there may be some benefit with the use of histidine-tryptophan-ketoglutarate (HTK) over University of Wisconsin solution in terms of biliary complications and potential cost savings. Renal grafts may experience increased initial graft dysfunction with the use of Euro-Collins thereby dissuading its use in support of HTK which can lead to substantial cost savings. University of Wisconsin solution and Celsior are favored in pancreas transplants given the concern for pancreatitis and graft thrombosis associated with HTK. No difference was observed with preservation solutions with respect to graft and patient survival in liver, renal, and pancreas transplants. Studies involving intestinal transplants are sparse but University of Wisconsin solution infused intraluminally in combination with an intra-vascular washout is a reasonable option until further evidence can be generated. Available literature can be used to ameliorate extensive variation across centers while potentially minimizing graft dysfunction and improving associated costs.

Passenger lymphocyte syndrome: a forgotten cause of postliver transplant jaundice and anemia.

A 48-year-old man with cirrhosis secondary to nonalcoholic steatohepatitis and chronic hepatitis C infection underwent a successful orthotopic liver transplant from a B+ donor without intraoperative complications. His postoperative course was complicated by hemolytic anemia, and he was ultimately diagnosed as having passenger lymphocyte syndrome. Passenger lymphocyte syndrome is a complication of both solid-organ and stem cell transplants. It is caused by donor B lymphocyte production of antibodies causing a primary or secondary immune response to recipient erythrocytes. Most commonly, it is in the setting of minor ABO mismatches, such as with a group B liver transplanted into a group AB recipient. Typically, passenger lymphocyte syndrome presents as a mild, self-limiting hemolytic anemia. Laboratory findings are consistent with other forms of hemolytic anemia including decreased hemoglobin and haptoglobin, elevated reticulocyte count, and indirect hyperbilirubinemia There is no definitive treatment for passenger lymphocyte syndrome or strong evidence to favor a particular treatment regimen. Passenger lymphocyte syndrome has been successfully treated with supportive care and blood transfusions matched to the liver donor. It is prudent that physicians caring for patients who receive ABO mismatched organs have a high index of clinical suspicion for passenger lymphocyte syndrome during the early postoperative period when posttransplant patients present with jaundice and anemia.

Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients.

The natural vitamin E family is composed of 8 members equally divided into 2 classes: tocopherols (TCP) and tocotrienols (TE). A growing body of evidence suggests TE possess potent biological activity not shared by TCP. The primary objective of this work was to determine the concentrations of TE (200 mg mixed TE, b.i.d.) and TCP [200 mg α-TCP, b.i.d.)] in vital tissues and organs of adults receiving oral supplementation. Eighty participants were studied. Skin and blood vitamin E concentrations were determined from healthy participants following 12 wk of oral supplementation of TE or TCP. Vital organ vitamin E levels were determined by HPLC in adipose, brain, cardiac muscle, and liver of surgical patients following oral TE or TCP supplementation (mean duration, 20 wk; range, 1-96 wk). Oral supplementation of TE significantly increased the TE tissue concentrations in blood, skin, adipose, brain, cardiac muscle, and liver over time. α-TE was delivered to human brain at a concentration reported to be neuroprotective in experimental models of stroke. In prospective liver transplantation patients, oral TE lowered the model for end-stage liver disease (MELD) score in 50% of patients supplemented, whereas only 20% of TCP-supplemented patients demonstrated a reduction in MELD score. This work provides, to our knowledge, the first evidence demonstrating that orally supplemented TE are transported to vital organs of adult humans. The findings of this study, in the context of the current literature, lay the foundation for Phase II clinical trials testing the efficacy of TE against stroke and end-stage liver disease in humans.

Steroid-free maintenance immunosuppression with rapamune and low-dose neoral in pancreas transplant recipients.

BACKGROUND: Steroid-free immunosuppression is an attractive option because it avoids the many side effects of chronic corticosteroid use. It is especially attractive in pancreas recipients because it avoids the diabetogenic effects of steroids. METHODS: We evaluated the outcome of a steroid-free maintenance immunosuppressive protocol in pancreas transplant recipients. Between August 2003 and May 2006, a total of 97 pancreas transplant recipients received steroid-free maintenance immunosuppression, consisting of induction with thymoglobulin and prednisone for the first 5 days. Patients were maintained on sirolimus adjusted to a target rapamycin trough level and reduced-dose cyclosporine adjusted to target C2 levels. All pancreas transplants (n=124) performed in the previous 3 years and maintained on a steroid-based immunosuppressive protocol with cyclosporine and mycophenolate mofetil were used for comparison. RESULTS: One-year patient and death censored pancreas graft survival were 93.8% and 94.8% for the steroid free group versus 95.2% and 87.9% for the comparator group, respectively. The incidence of acute rejection was 9.3% in the steroid-free group versus 28.3% in the comparator group (P<0.01). No pancreas loss in the steroid-free group was caused by acute rejection, whereas seven (5.6%) patients in the comparator group lost their pancreases because of acute rejection (P<0.05). At 1 year after transplant, the mean serum glucose and creatinine levels were not different between the two groups. CONCLUSION: We conclude that excellent graft survival with a significantly lower incidence of acute rejection can be achieved using a steroid-free maintenance immunosuppressive protocol consisting of sirolimus and cyclosporine.

Hand-assisted laparoscopic versus open nephrectomies in living donors.

UNLABELLED: Shortages of cadaveric kidneys for transplant into rising numbers of patients with end-stage renal failure have increased the demand for kidneys from live donors. The morbidity associated with traditional open donor nephrectomies (ODN) may discourage many candidates. The newer laparoscopic technique has been promoted as having less morbidity. OBJECTIVES: To evaluate outcomes of hand-assisted laparoscopic nephrectomies (HALN) and prospectively compare HALN and ODN. METHODS: After retrospectively reviewing donor and recipient outcomes in 33 HALN (December through August, 2000), we prospectively compared another 47 with 30 ODN performed from September 2000 through April 2001. RESULTS: All 80 HALN were successful, with no requirement to convert to an open procedure. Four donors experienced surgery-related complications: wound infection, retroperitoneal hematoma, prolonged ileus and early small-bowel obstruction, respectively. Two recipients had ureteral complications (1 stricture, 1 leak); 5 experienced delayed graft function, 2 requiring dialysis; and 2 kidneys were lost from infarction. The prospective comparison showed the operative time for HALN (mean 184 min, standard deviation [SD] 39 min) was significantly longer (143 [SD 27] min, p < 0.01), but resulted in less blood loss (p < 0.05). Lengths of time to warm ischemia/early graft function, resumption of oral intake/first bowel movement, and hospital discharge were similar. The abdominal-wall laxity and loss of cutaneous sensation from the flank incision experienced by many ODN patients after was uncommon in the HALN group. Three months after nephrectomy, donor complaints of incisional pain were less common after HALN (p < 0.01). CONCLUSIONS: HALN had good outcomes for donors and recipients, with quicker, more complete recoveries 3 months afterward.

Evolution of immunosuppression in kidney transplantation: the Ohio State University experience.

The goals and outcomes of immunosuppression in renal transplantation have changed significantly over the last 30 years. When graft survival rates were relatively low and acute rejection was a frequent occurrence in the early era of transplantation, the goal of immunosuppression was to improve survival and reduce the rate of acute rejection. Today, with excellent graft survival rates and a low incidence of acute rejection, the goal of immunosuppression has shifted toward not only eliminating acute rejection, but also toward reducing the side effects of medications, and maintaining long-term graft function by decreasing chronic nephropathy. Between September 1982-December 2004, 3,211 primary kidney transplant procedures were performed at The Ohio State University. We excluded from analysis all combined transplants as well as patients who were involved in clinical research protocols. Our immunosuppressive protocol changed substantially over this 24-year period, which can be divided into 5 eras in time. Each era is defined by a distinct immunosuppressive protocol that resulted in an incremental improvement in outcomes of patient and graft survival rates. In the present study, the outcomes of each era in patients with previous kidney transplant only are compared and future directions are discussed. The incidence of acute rejection episodes and graft survival from each era are compared and demonstrate the substantial improvement in results that have been achieved over the past 24 years.

Magnetic resonance cholangiography with mangafodipir trisodium (Teslascan) to evaluate bile duct leaks after T-tube removal in liver transplantation.

Liver transplant patients who present with abdominal pain after removal of the T-tube can be initially evaluated by contrast-enhanced magnetic resonance cholangiography (CEMRC) instead of abdominal computed tomography and hepatobiliary scintigraphy. In this article, 3 liver transplant patients who were evaluated by CEMRC after removal of the T-tube. CEMRC successfully identified the presence, location and extent of bile duct leaks, and can be performed as a diagnostic study in patients with suspected bile duct leaks.

Twenty years of renal transplantation at Ohio State University: the results of five eras of immunosuppression.

Over the past 20 years, more than 4,000 patients have undergone an abdominal solid organ transplant at Ohio State University. The 20-year period can be divided into five eras, each defined by an immunosuppressive protocol used during that period. With each successful era came a new immunosuppressive protocol that produced an incremental improvement in outcomes of patients and graft survival resulting from the application of the newest and most sophisticated combination of immunosuppressive drugs. The incidence of acute rejection episodes and graft survival from each era are compared and demonstrate the substantial improvement in results that has been achieved over the past 20 years.

The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) has proven to be a very effective drug for the prevention of acute rejection following renal transplantation when dosed as prescribed at 2 or 3 g/d. However, circumstances arise in clinical transplantation where the dose must be lowered, either to avoid drug toxicity or because of concurrent infection. The impact on the incidence of acute rejection and graft survival when the MMF dose must be lowered has not previously been investigated. METHODS: In this study, a cohort of 721 kidney transplant recipients who received immunosuppression using MMF in conjunction with cyclosporine and prednisone and OKT3 (n = 425) or Simulect (n = 296) induction were evaluated. Clinical outcomes were compared and contrasted between patients with and without MMF dose changes within the first year post-transplantation. RESULTS: The majority of patients (70.3%, n = 507) had at least one dose change within the first post-transplant year. Compared with the 214 patients who did not have a dose change, these patients had a much higher incidence of acute rejection within the first post-transplant year (23.3% vs. 3.7%, p < 0.001). This resulted in a significantly decreased 3-yr death-censored graft survival (76.3% vs. 88.3%, p = 0.003). The incidence of acute rejection for patients who had a dose change was highest if the dose change occurred within the first post-transplant month (34.4%). The incidence of acute rejection for the dose change patients was influenced by recipient ethnicity (African-American vs. Caucasian) and the type of induction agent used (OKT3 vs. Simulect). CONCLUSION: Altering the dose of MMF within the first post-transplant year correlated with a significantly worse clinical outcome in this cohort of renal transplant recipients. These data suggest that avoidance of MMF dose changes within the first year after renal transplantation would result in improved graft survival.

Simultaneous pancreas-kidney transplantation at a single center.

Simultaneous pancreas-kidney transplantation (SPKT) is the procedure of choice in our program to treat type I diabetic patients with end-stage renal disease. Its value in type II diabetic patients remains to be carefully evaluated. With the improvements in the technical results and immunosuppression medications, the procedures have become safer than those performed in the previous decade. However, the diabetic host is a high-risk individual. Careful evaluation and selection is prudent to maintain excellent results with this scarce organ. As we have seen in this series, death is the number one cause of graft loss and improved pre-operative evaluation will continue to be of significant value to lower the mortality rate of SPKT. The success of SPKT has led to wider application of this procedure to less than ideal recipients. Due to the shortage of organs, there is a trend to use more marginal donors. The use of marginal donors and marginal recipients requires careful evaluation to maintain safety and cost effectiveness. At our center, long-term patient and graft survival rates have been acceptable. We will continue to use SPKT as the procedure of choice for acceptable candidates. There has been a trend to change our philosophy to use living donors for the kidney transplant followed by a sequential pancreas transplant in order to overcome the shortage of organs. The issue of primary enteric drainage has not been addressed in this report due to our success with bladder drainage, as we feel that it is a safer procedure and are comfortable that patient education and outpatient therapy has minimized the problems with its use. Despite the lower threshold for enteric conversion, fewer than 10% of our patients undergo conversion when they are at low risk for complications.