Safety and Efficacy of Early Post-Operative Intravenous Iron Replacement In Patients With HeartMate III Left Ventricular Assist Device.

BACKGROUND: While guidelines suggest intravenous (IV) iron to improve functional status and quality of life (QoL) in patients with NYHA class II-III heart failure (HF), continuous flow left ventricular assist device (CF-LVAD) recipients were not included in early IV iron studies. Our study compared outcomes between patients who did and did not receive IV iron during the index admission following Abbott HeartMate III™ (HM 3) CF-LVAD placement. METHODS: Thirty-three adult patients with a HM3 placed at our institution who received early post-operative IV iron (n = 20) or no IV iron replacement (n = 13) were compared. The co-primary outcomes were mean change in quality of life (by the Minnesota Living with Heart Failure Questionnaire [MLHFQ]) and 6-minute walk distance (6MWD) from baseline to first >90 day clinic follow-up. RESULTS: At first clinic follow-up there was no significant difference between the IV iron and no-IV iron groups in MLHFQ (-27 ± 38 vs -21 ± 41, P = .8822) or 6MWD (360 ± 740 vs 786 ± 722, P = .208). CONCLUSION: Patients receiving IV iron during index admission following HM3 implantation did not experience an improvement in quality of life or functional capacity when compared to those who did not receive IV iron.

Pharmacotherapy of chronic lung allograft dysfunction post lung transplantation.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) remains the primary cause of death in lung transplant recipients (LTRs) despite improvements in immunosuppression management. Despite advances in knowledge regarding the pathogenesis of CLAD, treatments that are currently available are usuallyineffective and delay progression of disease at best.There are currently no evidence-based guidelines and minimal publications regarding the optimal treatment ofCLAD. OBJECTIVE: To complete a comprehensive review of the literature for the prevention and medical management of CLAD. METHODS: We identified the major domains of the medical management of CLAD and conducted a comprehensive search of PubMed and Embase databases to identify articles published from inception to December 2021 related to CLAD in LTRs. Studies published in English pertaining to the pharmacologic prevention and treatment of CLAD were included; highest priority was given to prospective, randomized, controlled trials if available. Prospective observational and retrospective controlled trials were prioritized next, followed by retrospective uncontrolled studies, case series, and finally case reports if the information was deemed to be pertinent. Reference lists of qualified publications were also reviewed to find any other publications of interest that were not found on initial search.In the absence of literature published in the aforementioned databases, additional articles were identified by reviewing abstracts presented at the International Society for Heart and Lung Transplantation and American Transplant Congress annual meetings between 2010-2021. CONCLUSION: CLAD should be identified as early as possible along with prompt intervention to optimize the possibility of stabilizing or improving lung function. More robust clinical data is needed to validate the use of all currently available and investigational treatment options for CLAD to identify the optimal pharmacotherapy management for this patient population.

Outcomes of Children with Fetal and Lactation Immunosuppression Exposure Born to Female Transplant Recipients.

Solid organ transplantation (SOT) is a lifesaving procedure for those with end-stage kidney, liver, heart, lung, and intestinal diseases, including females of childbearing age who wish to proceed with pregnancy following transplantation. While there is clear risk associated with use of mycophenolate during pregnancy, the risks associated with use of other immunosuppressant agents are less well understood, and the timing of use in pregnancy may be pertinent when considering the risk versus benefit for individual patients. In addition to overall fetal outcomes, including gestational age, birth weight, and mortality, this review summarizes published literature on additional complications that have been examined in association with maternal use during pregnancy and postpartum while breastfeeding. Compared with non-transplant pregnancies, pregnancies in transplant recipients are associated with lower birth weight and earlier gestational age. Effects associated with particular immunosuppressant agents in the infant include renal dysfunction from calcineurin inhibitors, myelosuppression from azathioprine, and decreased circulating immune cells with several agents. However, these effects are noted to primarily be transient, though the decrease in immune cells may predispose the infant to increased infectious complications in the first year of life. Utilizing relative infant dose estimations, nearly all commonly utilized immunosuppressants are likely safe during breastfeeding given the limited exposure to the infant.

Assessment of the prevalence of burnout and well-being in solid organ transplant pharmacists.

BACKGROUND: Solid organ transplant (SOT) pharmacist burnout and well-being has not been described. METHODS: A survey of SOT pharmacists was distributed to transplant pharmacy organization listservs. Burnout was assessed with the full 22 item Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-HSS-MP) and well-being was assessed with the Mayo Well-Being Index (WBI). Logistic multivariate regression was constructed to identify risk factors for a composite burnout assessment. RESULTS: In total, 230 responses were included (estimated response rate 36.2%). Survey participants were predominantly Caucasian (80.4%), female (79.1%), married/partnered (67.4%), and were within the first 5 years of practice (32.2%) as clinical pharmacist/specialists (87%). According to the MBI-HSS-MP, 63% met criteria for burnout. Comparing the groups with or without burnout, low quality of life (40.4% vs. 9.5%; P<.001), extreme fatigue (52.1% vs. 19%; P<.001), and likelihood of leaving the job for reasons other than retirement (38.5% vs. 10.7%; P<.001) were more common. The incidence of SOT pharmacists with WBI scores ≥ 5 (decreased well-being) was 26.5%. Among clinical pharmacists, risk factors for burnout included > 10 h per week of clinical duties outside of transplant (OR 2.669, P = .021) and extreme fatigue (OR 3.473, P<.001). CONCLUSIONS: Pharmacist burnout in SOT practice was similar to that reported in various pharmacy specialties (53-61%), which impacts clinical workforce retention and personal well-being.

The Clinical Conundrum of Cannabis: Current Practices and Recommendations for Transplant Clinicians: An Opinion of the Immunology/Transplantation PRN of the American College of Clinical Pharmacy.

Cannabis, or marijuana, comprises many compounds with varying effects. It has become a treatment option for chronic diseases and debilitating symptoms, and evidence suggests that it has immunomodulatory and antiinflammatory properties. Transplant centers are more frequently facing issues about cannabis, as indications and legalization expand. As of February 2020, 33 states and the District of Columbia have legalized medical cannabis, and 14 have legalized recreational cannabis. Moreover, 8 states have passed legislation prohibiting the denial of transplant listing solely based on cannabis use. Studies demonstrate the potential for significant pharmacokinetic and pharmacodynamic interactions between cannabis and immunosuppression. Additionally, safety concerns include increased risk of myocardial infarction, ischemic stroke, tachyarrhythmias, malignancy, neurocognitive deficits, psychosis, other neuropsychiatric disorders, cannabis use disorder, respiratory symptoms, and infection. A recent retrospective database study found a negative association between documented cannabis use disorder and graft survival, but little additional evidence exists evaluating this relationship. In the absence of robust clinical data, transplant centers need a clear, reasoned, and systematic approach to cannabis. The results of our national survey, unfortunately, found little consensus among institutions. As both recreational and medicinal cannabis become more ubiquitous nationwide, transplant centers will need to develop comprehensive policies to address its use.

Pharmacotherapy for durable left ventricular assist devices.

Left ventricular assist devices (LVADs) have revolutionized the care of patients with advanced heart failure, yet still require concomitant medications in order to achieve the best possible clinical outcomes. Since the outset of routine placement of durable, continuous-flow LVADs, much of the medication management of these patients to date has been based on International Society of Heart and Lung Transplantation (ISHLT) guidance, most recently published in 2013. Since 2013, numerous multidisciplinary pharmacotherapy publications have increased the LVAD community's understanding of best practices with respect to medications. We identified the major domains of LVAD medication management and conducted a comprehensive search of US National Library of Medicine MEDLINE® database using keywords chosen to identify medication-related publications of significance dated 2013 or later. Trials pertaining to the HeartMate II™ and the HeartMate™ 3 LVADs (Abbott, Chicago, IL) and the HeartWare™ HVAD™ System (Medtronic, Minneapolis, MN) were chosen for inclusion. Highest priority for inclusion was given to prospective, randomized, controlled studies. Absent these, controlled trials (retrospective or prospective observational) were given next-highest consideration, followed by retrospective uncontrolled studies, and finally case series. Reference lists of qualified publications were reviewed to find any other publications of interest that were not discovered on initial search. Case reports were generally excluded, except where the insight gained was deemed to be uniquely pertinent. This document serves to provide a comprehensive review of the current understanding of optimal medication management in patients with durable, continuous-flow LVADs.

The 2018 ISHLT/APM/AST/ICCAC/STSW Recommendations for the Psychosocial Evaluation of Adult Cardiothoracic Transplant Candidates and Candidates for Long-term Mechanical Circulatory Support.

The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients' receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs' unique needs and goals.

The 2018 ISHLT/APM/AST/ICCAC/STSW recommendations for the psychosocial evaluation of adult cardiothoracic transplant candidates and candidates for long-term mechanical circulatory support.

The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients' receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs' unique needs and goals.

The Role of mTOR Inhibitors in the Management of Viral Infections: A Review of Current Literature.

Viruses are the leading cause of infections after solid organ transplant. The antiviral properties of mammalian target of rapamycin inhibitors (mTORis) have been ascribed to a variety of mechanisms and historical data have supported their use over other immunosuppressants for a myriad of viruses. Herein, we summarize the most current data to highlight the role of mTORis in the management of viral infections after solid organ transplant. The mTORis play a clear role in the management of cytomegalovirus, and have data supporting their potential use for BK virus and human herpesvirus 8-related Kaposi sarcoma. No data definitively supports mTORis for use in Epstein-Barr virus-mediated posttransplant lymphoproliferative disorder or hepatitis C virus viral replication. Although theoretically an advantageous therapy for hepatitis C virus-related liver allograft fibrosis and human immunodeficiency virus, mTORi use specifically for these indications is less attractive with modern treatments currently available. Data surrounding mTORi efficacy in preventing rejection, and their toxicity profile must be balanced with their potential antiviral effects in combination with patient-specific factors.

Pharmacologic Considerations for Solid Organ Transplant Recipients Who Become Pregnant.

Females of childbearing age represent a large population of solid organ transplant recipients. With fertility commonly restored after transplantation, the possibility of pregnancy becomes a reality for many patients. Since the first published report of a successful pregnancy after solid organ transplantation in 1963, the number of pregnancies reported for female organ recipients has continued to increase. Despite this, information on the management of immunosuppression during pregnancy is limited, and a summary of these data is lacking in the literature. In addition to the many pharmacotherapeutic challenges in this unique patient population, physiologic changes in the peripartum period significantly affect the pharmacokinetics and pharmacodynamics of commonly used immunosuppressive agents. These changes, as well as the adverse effects and safety concerns of medications, must all be taken in to consideration to optimize outcomes for both mother and baby. In this review, we provide clinicians caring for female solid organ transplant recipients who wish to become pregnant or who are currently pregnant with a comprehensive review of maternal and fetal risks of pregnancy after transplantation. In addition, pharmacokinetic and pharmacodynamic changes of pregnancy will be discussed, and a summary of data regarding optimal immunosuppression management during pregnancy will be presented.

Assessing pharmacologic and nonpharmacologic risks in candidates for kidney transplantation.

PURPOSE: Pharmacotherapy concerns and other factors with a bearing on patient selection for kidney transplantation are discussed. SUMMARY: The process of selecting appropriate candidates for kidney transplantation involves multidisciplinary assessment to evaluate a patient's mental, social, physical, financial, and medical readiness for successful surgery and good posttransplantation outcomes. Transplantation pharmacists can play important roles in the recognition and stratification of pharmacologic and nonpharmacologic risks in prospective kidney transplant recipients and the identification of issues that require a mitigation strategy. Key pharmacotherapy-related issues and considerations during the risk assessment process include (1) anticoagulation concerns, (2) cytochrome P-450 isoenzyme-mediated drug interactions, (3) mental health-related medication use, (4) chronic pain-related medication use, (5) medication allergies, (6) use of hormonal contraception and replacement therapy, (7) prior or current use of immunosuppressants, (8) issues with drug absorption, (9) alcohol use, (10) tobacco use, (11) active use of illicit substances, and (12) use of herbal supplements. Important areas of nonpharmacologic risk include vaccine delivery, infection prophylaxis and treatment, and socially related factors such as nonadherent behavior, communication barriers, and financial, insurance, or transportation challenges that can compromise posttransplantation outcomes. CONCLUSION: Consensus opinions of practitioners in transplantation pharmacy regarding the pharmacologic and nonpharmacologic factors that should be considered in assessing candidates for kidney transplantation are presented.

Utility of procalcitonin as a biomarker for rejection and differentiation of infectious complications in lung transplant recipients.

OBJECTIVE: To evaluate the utility of procalcitonin (PCT) as a biomarker for rejection and differentiation of infectious complications in lung transplant recipients. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1966-September 2013) using the terms procalcitonin, transplantation, and lung transplantation. Additional articles were identified through a manual search of reference lists of the articles obtained. STUDY SELECTION AND DATA EXTRACTION: All articles evaluating PCT use in lung transplant recipients, including those where lung transplant patients were a subgroup of immunocompromised patients, were included. DATA SYNTHESIS: Infection and rejection are leading causes of mortality in lung transplant recipients, with similar clinical presentations; PCT could be a valuable biomarker to differentiate between these complications. Five prospective and 2 retrospective single-center observational evaluations were reviewed. Study populations were diverse, with only 3 focused solely on lung transplant recipients. PCT levels were not elevated during episodes of rejection and viral infections, whereas elevations were seen with bacterial infections. The effect of colonization or fungal infection on PCT varied. CONCLUSIONS: Current data suggest that PCT can be used to differentiate bacterial infections from rejection in lung transplant recipients, with unclear utility in colonization or fungal infection. It is reasonable to conclude that PCT values more than 8.18 ng/mL and PCT area under receiver operating curve greater than 0.97 indicate bacterial infection in this population, and PCT trends may increase predictive value. Because of the lack of randomized controlled trials, PCT should only be utilized in conjunction with standard tests for infection and rejection diagnosis.

Proliferation signal inhibitor toxicities after thoracic transplantation.

INTRODUCTION: Thoracic transplantation represents the definitive therapy for end-stage lung and heart diseases. Over the life of the allograft, upregulation of profibroproliferative mechanisms result in the advancement of chronic rejection. These take the form of bronchiolitis obliterans syndrome (BOS) in a lung recipient and cardiac allograft vasculopathy (CAV) in a heart recipient. The proliferation signal inhibitors (PSI), sirolimus and everolimus, represent a therapeutic option to downregulate this fibroproliferative effect. Additionally, these drugs may result in renal sparing and express potent anti-viral activity. However, they are fraught with substantial and complex toxicities that limit their use. AREAS COVERED: In this review, the authors first describe the mechanism of immunosuppression and pharmacokinetics of the PSIs. Subsequently, their use in thoracic transplant recipients for the purposes of renal sparing, anti-cytomegalovirus effect, and antifibroproliferative effects to prolong the onset or arrest progression of BOS and CAV are reviewed. The toxicities associated with PSI use are described, and three areas are focused on in detail: nephrotoxicities, wound healing impairment, and pulmonary toxicities. Finally, the authors summarize the patients in whom PSI use may be advantageous while minimizing potential toxicities. EXPERT OPINION: The potential benefits of PSI use in thoracic transplantation make their use attractive. Relative to alternative antiproliferatives, such as mycophenolate or azathioprine, PSI-treated patients experience significantly more serious adverse effects and discontinue treatment significantly more often. It is critical that patients be wisely selected for PSI use in an effort to minimize toxicities.