C.T. Doligalski

Epidemiology of invasive mold infections in lung transplant recipients.

Invasive mold infections (IMIs) are a major source of morbidity and mortality among lung transplant recipients (LTRs), yet information regarding the epidemiology of IMI in this population is limited. From 2001 to 2006, multicenter prospective surveillance for IMIs among LTR was conducted by the Transplant‐Associated Infection Surveillance Network. The epidemiology of IMI among all LTRs in the cohort is reported. Twelve percent (143/1173) of LTRs under surveillance at 15 US centers developed IMI infections. The 12‐month cumulative incidence of IMIs was 5.5%; 3‐month all‐cause mortality was 21.7%. Aspergillus caused the majority (72.7%)of IMIs; non‐Aspergillus infections (39, 27.3%) included Scedosporium (5, 3.5%), mucormycosis (3, 2.1%) and “unspecified” or “other” mold infections (31, 21.7%). Late‐onset IMI was common: 52% occurred within 1 year posttransplant (median 11 months, range 0–162 months). IMIs are common late‐onset complications with substantial mortality in LTRs. LTRs should be monitored for late‐onset IMIs and prophylactic agents should be optimized based on likely pathogen.

Incidence and Risk Factor Analysis for Gastrointestinal Bleeding and Pump Thrombosis in Left Ventricular Assist Device Recipients.

Left ventricular assist devices (LVADs) are associated with hemostatic complications. We describe the incidence and risk factors for gastrointestinal bleeding (GIB) and pump thrombosis (PT) to optimize patient selection/management. An IRB-approved retrospective review of first LVAD implants between October 1, 2011 and September 30, 2013 at a single center was conducted. Endpoints included epidemiological and risk factor analyses for GIB and PT. Descriptive statistics, chi-squared, and t-tests were used. Sixty-four patients received continuous-flow LVADs. The 12-month incidence of GIB and PT was 23.4% and 12.5%. Time to first GIB was 72.6 days (9-160). The 1-, 3-, and 6-month rate of PT was 1.6%, 6.25%, and 12.5%, respectively. All PT required pump exchange. Females (50% vs. 16%, P = 0.026) and patients without antiplatelet therapy (12.5% vs. 50%, P = 0.046) were at increased risk of PT. No pre-implant comorbidities were associated with PT. Infection was not identified as a risk factor in our cohort (25% vs. 51.8%, P = 0.156). Mean INR preceding event was not different from nonevent patients (2.1 vs. 2.24, P = 0.24). Regarding biomarkers preceding event, elevated plasma free hemoglobin (pfHg) did not reach significance (75% vs. 58%, P = 0.383) while lactate dehydrogenase was elevated significantly (744 vs. 298, P < 0.001). Receiver operating characteristic (ROC) analysis demonstrated that an LDH of >500 was highly sensitive and specific for PT. No pre-implant factors were associated with GIB. Post-implant risk factors for GIB included infection (80% vs. 38.8%, P = 0.005) and infrequent elevations in pfHg (13.3% vs. 63.3%, P < 0.001). Increased pump speed as a GIB risk factor was confirmed (HeartMate II 9560 rpm vs. 9490 rpm, P < 0.001; HeartWare 2949 rpm vs. 2710 rpm, P < 0.001). Anticoagulation/antiplatelet therapy did not affect GIB: mean INR preceding event was not different from nonevent patients (2.21 vs. 2.27, P = 0.67) and antiplatelet use was not different (46.7% vs. 46.9%, P = 0.985). LVADs are associated with early hemostatic-related morbidity. Few pre-implantation risk factors were elucidated; however, post-implantation factors including antiplatelet therapy, infection, and pump speed were identified.

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.

Device-Related Thrombosis in Continuous-Flow Left Ventricular Assist Device Support.

Advanced heart failure therapy has been revolutionized with the advent of continuous-flow ventricular assist devices (CF-LVADs) which have improved both survival and quality of life. Despite this, support with CF-LVADs is frequently complicated, with 70% of recipients experiencing a major complication in the first year of durable support. The most concerning of these complications to emerge is device-related thrombosis, which is associated with increased morbidity and mortality. Pathophysiology and diagnosis are multifaceted and complex, with pump-specific and patient-specific factors to be considered. Incidence estimates are evolving with increases seen in the past 2 years compared with earlier implant data. Evidence for treatment is limited to case series and reports, which are subject to significant publication bias. Finally, appropriate primary and secondary prophylaxis is imprecise with multiple antiplatelet and antithrombotic strategies described. This review seeks to summarize the current literature surrounding the pathophysiology, diagnosis, and management of thrombosis in CF-LVAD recipients.

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.

Sublingual Administration of Tacrolimus: Current Trends and Available Evidence

Widespread anecdotal use of sublingual tacrolimus administration has arisen, although little literature exists to guide practice. Given the paucity of data, we conducted a survey to evaluate the practice of sublingual tacrolimus administration at transplant centers across the United States and evaluated the literature that is currently available. A 10‐question online survey assessing the current state of sublingual tacrolimus use was distributed to pharmacists at transplant centers that each performed more than 100 solid organ transplantations in 2013. In addition, a literature review was performed by searching the PubMed database to identify available evidence for the sublingual administration of tacrolimus. The online survey was completed by 59 (65.6%) of the 90 targeted transplant centers, representing 51.3% of all solid organ transplantations performed in 2013. Sublingual administration of tacrolimus was used in all solid organ transplant populations, with ~67% of lung transplant centers using this route for tacrolimus. The most common dose conversion was 2 mg oral to 1 mg sublingual, with 92% of centers opening oral capsules and administering the contents sublingually. Home use of sublingual administration and use in the pediatric population was uncommon. Seven peer‐reviewed reports and one abstract were identified in the literature review. Seven of the eight publications reported favorably on sublingual administration, although no consistent dose conversion or method of administration was elucidated. The majority of the transplant centers surveyed found sublingual tacrolimus a viable alternative when oral administration is unavailable. A large robust prospective evaluation of sublingual administration of tacrolimus is imperative to provide the most effective care to solid organ transplant recipients and to ensure optimal safety for both patients and providers who administer the drug.

Practice Management Training in the PGY1 Residency Year: Best Practices from Two Nationwide Surveys:

Purpose The development of future pharmacy leaders is vital to the advancement of our profession. Postgraduate year 1 (PGY1) residency training requires residents to exercise leadership and practice management skills. Two national surveys were conducted to describe the current state of practice management experiences and elucidate best practice recommendations. Methods The surveys, online multiple choice and free response, queried American Society of Health-System Pharmacists (ASHP)–accredited residency program practice management preceptors (survey 1) and PGY1 residents (survey 2) and were distributed via the ASHP residency program directors’ listserv. Responses were reviewed and analyzed by members of the University HealthSystem Consortium Pharmacy Council Strategic Initiatives and Programming Committee. Results Survey 1, completed by 240 institutions, identified that a combination of concentrated and longitudinal practice management experiences were used most frequently (47%), followed by concentrated alone (33%). Universally noted activities included meeting attendance (98%), projects (94%), and committee involvement (92%). Sixty-seven percent of the programs changed the experience in the previous 3 years, with 43% planning changes in the coming year. Survey 2 was completed by 58 PGY1 residents from 42 programs. Most (80%) residents stated they had enough time with their preceptors, and 55% rated their enjoyment of the rotation as 4 or 5 on a 1 to 5 scale (5 = most enjoyed) Conclusion Our findings suggest that there is not a best practice for the structure or content of the PGY1 practice management experience. These results highlight key recommendations, including the need for practice management-specific preceptor development, incorporation of longitudinal experiences, and more practice management and leadership activities.

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.

621 Treatment of HCV Recurrence After Liver Transplant: A Review of Early Virologic Responses Using Telaprevir, A Single Center Experience of 24 Patients

two groups were compared using independent-samples t-test. Survival analysis and the distributions were calculated using Kaplan-Meier method and Mantel-Cox log-rank test. Results: Out of total 43 combined liver-kidney transplants, 30 SLK cases (24 post-MELD and 6 pre-MELD) were included. Proportions of age, gender, ethnicity, pre-transplant MELD score; pre-transplant renal replacement therapy requirement, hypertension, diabetes mellitus and follow-up period were similar in two groups. Median follow up period was 30 months. Both overall and kidney-graft survival in pre-MELD era were 50%, but improved to 91.7% in post-MELD era (p=0.02). When compared according to HCV diagnosis, there was no statistical significance in overall and kidney-graft survival between 9 HCV and 15 non-HCV groups in post-MELD era (p=0.67 and p=0.4, respectively). Conclusion: Literature suggests lower risk of liver graft loss in SLK compared to LTA, but not much information is available regarding the specific diagnosis of the underlying liver disease, HCV vs non-HCV.Our study demonstrated that overall and kidney graft survival has significantly improved post-MELD as compared to pre-MELD era. Additionally, our study showed that there was no statistical difference in overall and kidney-graft survival between HCV and non-HCV groups. This observation needs to be further studied and verified in larger cohort to fully identify the impact of Hepatitis C infection on liver and kidney grafts, post transplantation.

Postoperative Transplant Immunosuppression in the Critical Care Unit

S organ transplant is a growing treatment option for many end-stage diseases. Kidney, liver, pancreas, small bowel, heart, and lung organs are all transplanted in the United States, and a registry is maintained through the United Network for Organ Sharing ( http://www.unos.org ). The type of organ transplanted determines postoperative care of the patient and requirement for immediate care in a critical care setting. In most transplant centers, recipients of kidney transplants will receive postoperative care in an acute care floor, unless hemodynamic compromise during surgery is a concern or high acuity nursing care is unavailable in a step-down unit. All other transplant recipients will receive postoperative care in an intensive care unit (ICU) as a standard of care, which accommodates invasive monitoring strategies, the use of medication drips, intensive nursing care, and hemodynamic support. Patients undergoing solid organ transplant require immediate suppression of their immune system to prevent rejection of the newly grafted organ or allograft. 1 – 3