Impact of early corticosteroid withdrawal on simultaneous pancreas-kidney transplant long-term outcomes: Single center experience and comparison to the International Pancreas Transplant Registry.

BACKGROUND: There remains a paucity of modern data comparing early steroid withdrawal (ESW) versus chronic corticosteroid (CCS) immunosuppression in simultaneous pancreas kidney (SPK) transplant recipients with long-term follow-up. Therefore, the purpose of this study is to assess the effectiveness and tolerability of ESW compared to CCS post-SPK. METHODS: This was a retrospective single-center matched comparison with the International Pancreas Transplant Registry (IPTR). Patients from University of Illinois Hospital (UIH) represented the ESW group and were compared to those matched CCS patients from the IPTR. Included patients were adult recipients of a primary SPK transplant between 2003 and 2018 within the US receiving rabbit anti-thymocyte globulin induction. Patients were excluded if they had early technical failures, missing IPTR data, graft thrombosis, re-transplant, or positive crossmatch SPK. RESULTS: A total of 156 patients were matched and included in the analysis. Patients were predominantly African American (46.15%) males (64.1%) with Type 1 diabetes etiology (92.31%). Overall pancreas allograft survival (hazard ratio [HR] = .89, 95% confidence interval [CI] .34-2.30, p = .81) and kidney allograft survival (HR = .80, 95%CI .32-2.03, p = .64) were similar between the two groups. Immunologic pancreas allograft loss was statistically similar at 1-year (ESW 1.3% vs. CCS 0%, p = .16), 5-year (ESW 1.3% vs. CCS 7.7%, p = .16), and 10-year (ESW 11.0% vs. CCS 7.7%, p = .99). The 1-year (ESW 2.6% vs. CCS 0%, p > .05), 5-year (ESW 8.3% vs. CCS 7.0%, p > .05), and 10-year (ESW 22.7% vs. CCS 9.9%, p = .2575) immunologic kidney allograft loss were also statistically similar. There was no difference in 10-year overall patient survival (ESW 76.2% vs. CCS 65.6%, p = .63). CONCLUSIONS: No differences were found between allograft or patient survival post-SPK when comparing an ESW or CCS protocol. Future assessment is needed to determine differences in metabolic outcomes.

The use of non-transplant biologics in solid organ transplant recipients: A practical review for the frontline clinician.

Biologics have become the forefront of medicine for management of autoimmune conditions, leading to improved quality of life. Many autoimmune conditions occur in solid organ transplant (SOT) recipients and persist following transplant. However, the use of biologics in this patient population is not well studied, and questions arise related to risk of infection and adjustments to induction and maintenance immunosuppression. Guidelines have been published highlighting management strategies of biologics around the time of elective surgical procedures, but this is not always feasible in urgent situations, especially with deceased donor transplantation. The aim of this review is to summarize the current literature regarding the use of these agents in solid organ transplant recipients, and specifically address induction and maintenance immunosuppression, as well as the need for alternative infective prevention strategies to create a practical reference for the frontline clinician, when faced with this complex clinical scenario.

Effects of angiotensin II in the management of perioperative hypotension in kidney transplant recipients.

BACKGROUND: Due to the mechanisms of action of conventional catecholamine vasopressors, there is increased risk of renal allograft injury and adverse events in transplant recipients with fluid-refractory distributive shock during the perioperative period. As such, mechanistically alternative vasopressors like angiotensin II (ATII) may avoid these complications, but there is an absence of data supporting use in this population. METHODS: This was a single-center, single-arm, open-label, phase 4 study conducted as a 1-year pilot of 20 adult renal transplant recipients receiving ATII as their first continuous infusion vasopressor in the perioperative period. The study aim was to systematically assess the safety and hemodynamic effects of ATII. Safety was assessed based on the incidence of adverse events. Hemodynamic effect was assessed by the achievement of per protocol hemodynamic goals (i.e., SBP ≥120 mmHg) and the need for adjunct vasopressors. RESULTS: Most cases involved deceased donors (70%), with a corresponding mean (SD) cold ischemia time of 14.7 (8.6) h. Over a surgery duration of 5.3 (1.2) h, subjects received 3.2 (2.0) L of total volume resuscitation prior to ATII initiation. No adverse events were directly related to ATII administration. Throughout this period, ATII was utilized for a median of 1.0 (IQR, 1.5) h intraoperatively (N = 7), 26.5 (IQR, 84.8) h postoperatively (N = 4), and 63.8 (IQR, 57.8) h in subjects who required ATII both intra- and postoperatively (N = 9). Only one of the 20 patients needed adjunct continuous infusion vasopressors in addition to ATII. CONCLUSIONS: Based on the observations of this pilot study, ATII is a safe and effective vasopressor option for renal transplant recipients requiring perioperative hypotension reversal.

Entrustable professional activities for pharmacy students: A primer for solid organ transplant preceptors.

DISCLAIMER: In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The role of a solid organ transplant pharmacist is multifaceted and translates to diverse experiential and elective learning experiences that can be provided to pharmacy learners. Here we provide a guide to integrating pharmacy students into patient care and other pharmacist activities in solid organ transplantation. SUMMARY: Thoughtful incorporation of learners into clinical practice and clinical research creates a positive learning environment for pharmacy students that can foster the development of core skills necessary for students to become "practice-ready" and "team-ready" pharmacy graduates and can equip them with valuable skills to incorporate into the specialty practice areas and careers they pursue. To help develop these educational experiences, attention to the list of core entrustable professional activities (EPAs) established by the American Association of Colleges of Pharmacy can help create a rich environment of learning with carefully cultivated tasks. Furthermore, learners can serve as transplant pharmacist extenders to assist in overall patient care and multidisciplinary involvement on the transplant team. This article serves as a "how-to" guide for applying the EPA framework to integrating pharmacy students in patient care and other pharmacist activities in solid organ transplantation and other specialty practice areas. CONCLUSION: As pharmacy preceptors design and operationalize their teaching to incorporate EPAs, they can benefit from recommendations tailored to specialty practice areas such as solid organ transplantation. Students may start and finish these experiences at different EPA levels, but continuance of training will allow them to achieve the final EPA level across the 6 EPA domains.

Clinical Implications of Tacrolimus Time in Therapeutic Range and Intrapatient Variability in Urban Renal Transplant Recipients Undergoing Early Corticosteroid Withdrawal.

Tacrolimus demonstrates wide intrapatient and interpatient variability requiring therapeutic drug monitoring. The utility of tacrolimus time in therapeutic range (TTR) after renal transplantation (RT) under an early corticosteroid withdrawal (ECSWD) protocol is unknown. The purpose of this study is to assess the impact of tacrolimus TTR in an ECSWD RT population. MATERIALS: A retrospective analysis of adult RT recipients maintained on tacrolimus was conducted. Patients were excluded if they were on nonstandard protocol immunosuppression agents <12 months post-RT. Tacrolimus TTR was calculated using the Rosendaal method. Patients were divided into high (TTR-H) and low (TTR-L) TTR groups based on cohort median. The primary outcome was to compare the incidence of acute rejection 12 months post-RT. Secondary outcomes included comparing rejection subtypes, incidence of donor-specific antibody (DSA) and de novo DSA (dnDSA), risk factors for acute rejection and dnDSA development, and allograft function (serum creatinine and estimated glomerular filtration rate). RESULTS: A total of 193 patients were analyzed (TTR-H = 98 and TTR-L = 95). There was no difference in the incidence of acute rejection (TTR-H 20.4% versus TTR-L 20.0%; P = 0.944). Positive DSA posttransplant (odds ratio [OR], 3.62; 95% confidence interval [CI], 1.41-9.26; P = 0.007) was associated with a higher acute rejection at 12 months posttransplant. Mycophenolate dose reduction (OR, 2.82; 95% CI, 1.13-6.97; P = 0.025) and acute rejection (OR, 2.99; 95% CI, 1.09-8.18; P = 0.032) were associated with dnDSA formation. No difference in serum creatinine or estimated glomerular filtration rate was observed (P > 0.05). CONCLUSIONS: Tacrolimus TTR was not significantly different with regards to acute rejection in an ECSWD population. Future studies are still needed to determine tacrolimus TTR thresholds post-RT and identify populations that may benefit from this intrapatient variability monitoring parameter.

Factors Influencing Emergency Department Utilization and Hospital Re-Admissions in a Predominantly Obese, Racially Diverse Urban Renal Transplant Population.

INTRODUCTION: Early emergency department and hospital re-admissions are common in renal transplant recipients, but data are lacking in unique populations. Study Aim: The purpose of this study was to identify patient risk factors for multiple acute care utilization events within the first year of renal transplantation. DESIGN: This was a single-center, retrospective cohort study of adult renal transplant recipients between 9/2013-9/2016. Patients were compared across number of emergency department visits and by hospital re-admissions. Diagnoses were categorized. Univariate and multivariate logistic regression was used to assess risk for multiple acute care utilization events within the first 12 months post-transplant. RESULTS: A total of 216 patients were analyzed and were on average 50.5 (SD 13.9) years old, redominantly Black (49.77%) with an average body mass index of 33.33 (9.8) and were recipients of deceased donor renal transplants (61.11%). A total of 105 (48.6%) patients visited the emergency epartment and 119 (55.1%) patients had a hospital readmission. Patients having a body mass index >35 kg/m2 did not differ across emergency department visit or hospitalization groups. Delayed graft function (OR 2.86, 95% CI 1.07-7.65) and previous renal transplant (OR 2.77, 95% CI 1.04-7.39) were significantly associated with multiple acute care utilizations. DISCUSSION: Acute care utilization following renal transplantation was similar to previously reported experiences. Obesity did not impact use of acute care resources or patient outcomes. Strategies addressing potential preventable emergency visits and hospital re-dmissions should be promoted.

Utilization of direct-acting oral anticoagulation in solid organ transplant patients: A national survey of institutional practices.

The safety and efficacy of direct-acting oral anticoagulants (DOACs) and reversal strategies are not well established in the solid organ transplant population. This was a survey of pharmacists to assess DOAC and urgent reversal practices among adult transplant programs in the United States. A 27-question survey was distributed to members of transplant pharmacy organization listservs between 5/28/19 and 6/30/19. A total of 115 responses were received from kidney (43.5%), heart (20.0%), lung (18.3%), liver (13.9%), and pancreas (4.4%) transplant programs. DOAC use prior to transplant was mostly prohibited in thoracic programs (77.3%) but more permissive in kidney transplant programs (64.0%). If permitted, apixaban (57.8%) was most preferred. At transplant surgery, reversal of DOAC was performed "as needed" (20.9%) or was not routine (18.3%). DOAC use post-transplant was more permissive (94.3%). A majority of responders follow FDA recommended dosing in the setting of drug-drug interactions (51.1%). Major factors influencing DOAC prescribing decisions included renal function, drug-drug interactions, and insurance. High clinical practice variability exists regarding DOAC utilization and urgent reversal strategies in pre-, peri-, and post-transplant stages. While more research is needed to refine the clinical landscape, many institutions are using DOAC therapy under the perception that they pose a similar risk of bleeding compared to a non-transplant population.

Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract.

The increased proliferation of cancer cells is directly dependent on the increased activity of the endoplasmic reticulum (ER) machinery which is responsible for protein folding, assembly, and transport. In fact, it is so critical that perturbations in the endoplasmic reticulum can lead to apoptosis. This carefully regulated organelle represents a unique target of cancer cells while sparing healthy cells. In this study, a standardized mangosteen fruit extract (MFE) was evaluated for modulating ER stress proteins in prostate cancer. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells (PrECs) procured from two patients undergoing radical prostatectomy were treated with MFE. Flow cytometry, MTT, BrdU and Western blot were used to evaluate cell apoptosis, viability, proliferation and ER stress. Next, we evaluated MFE for microsomal stability and anti-cancer activity in nude mice. MFE induced apoptosis, decreased viability and proliferation in prostate cancer cells. MFE increased the expression of ER stress proteins. Interestingly, MFE selectively promotes ER stress in prostate cancer cells while sparing PrECs. MFE suppressed tumor growth in a xenograft tumor model without obvious toxicity. Mangosteen fruit extract selectively promotes endoplasmic reticulum stress in cancer cells while sparing non-tumorigenic prostate epithelial cells. Furthermore, in an in vivo setting mangosteen fruit extract significantly reduces xenograft tumor formation.