Browsing by Author "Mangus, Richard"

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    Challenges with Intestine and Multivisceral Re-Transplantation: Importance of Timing of Re-Transplantation and Optimal Immunosuppression
    (Springer, 2018-02-06) Kubal, Chandrashekhar A.; Pennington, Catherine; Fridell, Jonathan; Ekser, Burcin; Muhaylov, Plamen; Mangus, Richard; Surgery, School of Medicine
    BACKGROUND Patients undergoing re-transplantation often receive high doses of immunosuppression, which may lead to an immunocompromised status of the recipient. This study investigates the outcomes after intestine/multivisceral re-transplantation. MATERIAL AND METHODS Clinical outcomes of 23 patients undergoing 24 re-transplantations at a single intestine transplant center were reviewed. Bone marrow suppression was used as a surrogate marker of immunocompromised status, and was defined as platelet count <50 k/mm3 and absolute lymphocyte count <200/mm³. RESULTS All re-transplants except one were liver inclusive. Fifteen of 23 patients died at a median time of 12 months (range 0.2-75) after re-transplantation. Of the 15 deaths, nine (60%) resulted from complications associated with a compromised host immune status: graft versus host disease (GVHD) affecting bone marrow (three cases), persistent viral infection (three cases), post-transplant lymphoproliferative disorder (PTLD (one case), metastatic cancer (one case), multi-drug resistant polymicrobial sepsis (one case). Four deaths (27%) resulted from severe rejection. Non-survivors were more likely to have received alemtuzumab, and had higher incidence of bone marrow suppression. In addition to immunocompromised status and rejection, the use of alemtuzumab was associated with mortality after intestinal/multivisceral re-transplantation. CONCLUSIONS High mortality was associated with intestine/multivisceral re-transplantation. To improve clinical outcomes of intestine and multivisceral transplantation, it is important to allow reconstitution of host immunity. Longer interval between the two transplantations, and strategies such as allograft specific immunosuppression, may spare the host from the devastating effects of potent immunosuppression currently used.
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    Expanding the Donor Pool with Utilization of Extended Criteria DCD Livers
    (AASLD, 2019) Mihaylov, Plamen; Mangus, Richard; Ekser, Burcin; Cabrales, Arianna; Timsina, Lava; Fridell, Jonathan; Lacerda, Marco; Ghabril, Marwan; Nephew, Lauren; Chalasani, Naga; Kubal, Chandrashekhar A.; Pediatrics, School of Medicine
    Utilization of donation after circulatory death donor (DCD) livers for transplantation has remained cautious in the U.S. The aim of this study was to demonstrate the expansion of DCD liver transplant (LT) program with the use of extended criteria DCD livers. After institutional review board approval, 135 consecutive DCD LTs were retrospectively studied. ECD DCD livers were defined as those with one of the followings: 1) donor age >50 years, 2) donor BMI >35 kg/m2, 3) donor functional warm ischemia time (fWIT) >30 minutes, and 4) donor liver macrosteatosis >30%. An optimization protocol was introduced in July 2011 to improve outcomes of DCD LT, which included thrombolytic donor flush, and efforts to minimize ischemic times. The impact of this protocol on outcomes was evaluated in terms of graft loss, ischemic cholangiopathy (IC) and change in DCD LT volume. Of 135 consecutive DCD LT, 62 were ECD DCDs. 24 ECD DCD LT were performed before (Era I) and 38 after the institution of optimization protocol (Era II), accounting for an increase in the use of ECD DCD livers from 39% to 52%. Overall outcomes of ECD DCD LT improved in Era II, with a significantly lower incidence of IC (5% vs. 17% in Era I; P = 0.03) and better 1‐year graft survival (93% vs. 75% in Era I, P = 0.07). Survival outcomes for ECD DCD LT in Era II were comparable to matched deceased donor (DBD) LT. With the expansion of the DCD donor pool, the number of DCD LT performed at our center gradually increased in Era II to account for > 20% of the center's LT volume. In conclusion, with the optimization of perioperative conditions, ECD DCD livers can be successfully transplanted to expand the donor pool for LT.
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    Prognostic Impact of Peritransplant Serum Sodium Concentrations in Liver Transplantation
    (International Scientific Information, 2019-07-16) Mihaylov, Plamen; Nagai, Shunji; Ekser, Burcin; Mangus, Richard; Fridell, Jonathan; Kubal, Chandrashekhar; Surgery, School of Medicine
    BACKGROUND Serum sodium (Na) is considered to reflect the severity of liver cirrhosis. In the last few years, much effort has been made to integrate this association into prognostic models after liver transplantation. The aim of this study was to investigate the associations between peritransplant Na and neurological complications, as well as short-term survival, after liver transplantation. MATERIAL AND METHODS A total of 306 liver transplantations between 2012 and 2015 were evaluated. Pre- and posttransplant sodium concentrations were investigated with regard to 3-month survival and incidence of posttransplant neurological complications, along with other factors present in the operative side of the recipient and donor. RESULTS The 3-month survival rate was 94%. Neither hyponatremia (<130 mEq/L) nor hypernatremia (>145 mEq/L) at pretransplantion predicted 3-month survival. A large amount of intraoperative blood transfusion and a large delta Na showed a significant association with poor outcomes at 3 months. On multivariate analysis, the requirement of blood transfusion and warm ischemia time remained independent prognostic factors for 3-month mortality. Hyponatremia and a large delta Na tended to lead to the frequent development of neurological complications. These complications, secondary to rapid Na correction, were concerning and potentially led to a prolonged hospital stay and early mortality. CONCLUSIONS Rapid change in the sodium level might be caused by large amounts of blood transfusion products. This leads to a diminished short-term survival, as well as a higher rate of neurological complications.
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    Steroid Free Three Drug Maintenance Regimen for Pancreas Transplant Alone: Comparison of Induction with Rabbit Antithymocyte Globulin +/- Rituximab
    (Wiley, 2018) Fridell, Jonathan; Mangus, Richard; Chen, Jeanne; Taber, Tim; Cabrales, Arianna E.; Sharfuddin, Asif; Yaqub, Muhammad; Powelson, John; Surgery, School of Medicine
    Graft survival following pancreas transplant alone (PTA) is inferior to other pancreas transplants. Steroid elimination is appealing, but a two drug maintenance strategy may be inadequate. Additionally, recipients tend to have diabetic nephropathy and do not tolerate nephrotoxic medications. A three‐drug maintenance strategy permits immunosuppression through different mechanisms as well as an opportunity to use lower doses of the individual medications. Induction consisted of five doses of rabbit antithymocyte globulin (1 mg/kg/dose). As of October 2007, a single dose of rituximab (150 mg/m2) was added. Maintenance consisted of tacrolimus, sirolimus and mycophenolate mofetil. From 2004 to 2017, 166 PTA were performed. Graft loss at 7‐ and 90‐ days were 4% and 5%, and one year patient and graft survival were 97% and 91%. Comparing induction without and with rituximab, there was no significant difference in 7 or 90 day graft loss, 1 year patient or graft survival or in the rate of rejection or infection. Rabbit antithymocyte globulin induction and steroid withdrawal followed by a three drug immunosuppression regimen is an excellent strategy for PTA recipients.