Clinical Outcomes of Perioperative Desensitization in Heart Transplant Recipients.

BACKGROUND: Sensitization remains a barrier to heart transplantation (HT). Perioperative desensitization strategies have been described; however, a paucity of evidence exists to demonstrate efficacy and safety in HT. METHODS: This single-center, retrospective study consisted of adults who received an HT. Perioperative desensitization was initiated if virtual crossmatch or flow-cytometry crossmatch was positive. Therapy consisted of plasmapheresis, intravenous immunoglobulin, and rabbit antithymocyte globulin. Historical controls received standard immunosuppression or induction. The primary endpoint was survival at 12 mo. Secondary endpoints included freedom from acute rejection, cardiac allograft vasculopathy (CAV), and infectious complications. RESULTS: Of the 104 patients included, 48 received no induction, 46 received induction, and 10 underwent perioperative desensitization. No differences were observed in the primary endpoint at 12 mo (90.0% versus 97.9%, P = 0.25 for desensitization versus no-induction; 90.0% versus 100%, P = 0.72 for desensitization versus induction). Rates of acute rejection were lower with induction and desensitization compared with no-induction. There were no significant differences in CAV between the groups. Infectious complications were also similar among the groups (10.0% versus 16.7%, P = 0.62 for desensitization versus no-induction; 10.0% versus 30.4%, P = 0.34 for desensitization versus induction). CONCLUSIONS: This study suggests that a perioperative desensitization strategy triggered by positive virtual crossmatch or flow-cytometry crossmatch allows for successful transplantation of sensitized HT recipients and results in acceptable rates of survival, rejection, CAV, and infection at 12 mo.

Alternatives to immediate release tacrolimus in solid organ transplant recipients: When the gold standard is in short supply.

Given the current climate of drug shortages in the United States, this review summarizes available comparative literature on the use of alternative immunosuppressive agents in adult solid organ transplant recipients including kidney, pancreas, liver, lung, and heart, when immediate-release tacrolimus (IR-TAC) is not available. Alternative options explored include extended-release tacrolimus (ER-TAC) formulations, cyclosporine, belatacept, mammalian target of rapamycin inhibitors, and novel uses of induction therapy for maintenance immunosuppression. Of available alternatives, only ER-TAC formulations are of non-inferior efficacy compared to IR-TAC when used de novo or after conversion in stable kidney transplant recipients (KTRs). All other alternatives were associated with higher rates of biopsy-proven rejection, but improved tolerance from classic adverse effects of IR-TAC including nephrotoxicity and development of diabetes. While most alternative therapies are approved in KTRs, access via third-party payors is an obstacle in non-KTRs. In the setting of IR-TAC shortage, alternate therapeutic options may be plausible depending on the organ population and individual patient situation to ensure appropriate, effective immunosuppression for each patient.

Pharmacophore development, drug-likeness analysis, molecular docking, and molecular dynamics simulations for identification of new CK2 inhibitors.

Protein kinase 2 (CK2), an essential serine/threonine casein kinase, is considered an interesting target for cancer treatments. Different molecular modeling approaches such as pharmacophore modeling, molecular docking, and molecular dynamics simulations have been used to develop new CK2 inhibitors. This study presents a pharmacophore model that was generated by combining and merging the structure-based and ligand-based pharmacophore features and validated using receiver operating characteristic (ROC). Based on validation results revealing good predictive ability, this pharmacophore model was used as a three-dimensional query in a virtual screening simulation. Several compounds with different chemical scaffolds were retrieved as hits, which were further analyzed and refined using several molecular property filters. The obtained compounds were then filtered and compared to the crystallographic ligand on the basis of their predicted docking energies, binding mode, and interactions with CK2 active site residues. This step resulted in a compound with a high pharmacophore fit value and better docking energy. Molecular dynamics simulation indicated stable binding of the predicted compound to CK2 protein, characterized by root mean square deviation (RMSD) and root mean square fluctuation (RMSF) and hydrogen bond. Graphical abstract.

Using technology to enhance medication regimen education after solid organ transplantation.

PURPOSE: The design and implementation of a tool that combines clinical teaching with cutting-edge, simplified technology for providing medication education to solid organ transplant (SOT) recipients are described. METHODS: In a retrospective study of adults who received kidney transplants from February 2015 through May 2017, patients were educated about their medications using a tablet computer application, Medication Regimen Education (MRxEd), that presented concise videos describing the name, indication, dose, adverse effects, and associated interactions of all medications received, as well as special considerations applicable to each agent. Assessment questions were used to reinforce key concepts and identify knowledge gaps. RESULTS: The digital educational intervention was provided to 282 kidney transplant recipients. Patients were predominantly white (48%) and/or male (63%), with a median age of 51 years (interquartile range, 37-61 years). Patients came from a variety of education backgrounds. Most patients (81%) were educated on dual maintenance immunosuppression (with tacrolimus and mycophenolate) and 3 infection prophylaxis agents (nystatin, sulfamethoxazole-trimethoprim, and valganciclovir). Most patients (90%) correctly answered questions related to medication indications, dosing, and special rules, but many (61%) had difficulty correctly answering questions about adverse effects. CONCLUSION: An innovative approach for interactive and engaging medication teaching with the MRxEd application enhanced the education process for SOT recipients.