Solid Organ Transplant Patients Research Articles

The use of once-daily LCP-Tacrolimus with adolescent and young adult solid organ transplant recipients.

Adolescent and young adult (AYA) solid organ transplant (SOT) recipients experience increased rates of rejection and graft loss surrounding the time of health care transition, in part due to poor medication adherence. This study aims to examine the impact of a once-daily formulation of tacrolimus, LCP-tacrolimus (LCPT), on medication adherence for AYA SOT patients. A retrospective descriptive analysis was performed for all patients who underwent SOT and were prescribed LCPT after the age of 12 at our single-center pediatric hospital. Medication adherence was assessed via provider documentation and the medication level variability index (MLVI). Twenty-nine patients were prescribed LCPT as part of their immunosuppression regimen. Twenty patients were converted to LCPT from immediate-acting (IR) tacrolimus; six patients were initiated immediately following transplant, and three patients were unable to receive LCPT due to insurance denial. There was a numeric improvement in medication adherence for converted patients when measured by provider assessment (45.0% vs. 68.4%, p = .140) and MLVI (40.0% vs. 71.4%, p = .276), though these did not reach statistical significance. There were no differences in episodes of rejection or adverse effects. LCPT prescription was not associated with decreased medication burden, and two patients transitioned back to IR tacrolimus due to increased cost. LCPT use did not significantly improve patient adherence; however, it resulted in numerically higher perceived and measured adherence rates. LCPT appears to be safe and effective in the management of SOT recipients; however, it may not affect pill burden and may result in a higher financial burden. Use may be considered for a select group of AYA SOT recipients.

Focus on Pneumonia After Organ Transplantation: Is There a Need for Specific Medical Care in the Emergency Department?

Pneumonia is a major cause of hospitalization and has a substantial impact on health care costs. Diagnosis and treatment of pneumonia in solid organ transplant (SOT) patients remain a challenge for clinicians in the emergency department. This study aimed to evaluate demographic features, clinical patterns, history of hospitalization, and diagnosis of adult patients after organ(s) transplantation (liver, kidney, pancreas) with severe pneumonia requiring hospitalization. The aim is to determine whether patients undergoing SOT receive or require specific care and whether they need to be prioritized. This was a single-center observational study of adult patients after SOT with severe pneumonia requiring hospitalization. The data set for the analysis included only patients with pneumonia as the main reason for hospitalization. The diagnosis of pneumonia was suspected based on the American Thoracic Society criteria. The study revealed that the standard of care for patients with a history of SOT did not significantly differ from care provided to the non-SOT patients with pneumonia admitted to the same hospital during a 94-week period. There were notable differences, such as post-transplant patients being transferred more quickly to the hospital ward, having longer hospital stays, and receiving antibiotics earlier than the non-SOT group.

Real-life use of letermovir prophylaxis for cytomegalovirus in heart transplant recipients.

Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high-risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR). In this observational, retrospective, single-center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen. The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor-positive, recipient-negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3-12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir. This real-life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post-treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted.

Clinical Application of Frailty in the Evaluation of Solid Organ Transplant Patients

Clinical Application of Frailty in the Evaluation of Solid Organ Transplant Patients

Use of biologics for psoriasis in solid organ transplant recipients.

Biologics have significantly advanced the treatment of inflammatory disorders, including psoriasis. However, their use in immunosuppressed patients, such as those with solid-organ transplants, is less understood. These patients often face dermatological issues, but inflammatory skin diseases are rare due to their immunosuppressive treatments. Our study aims to assess biologics' effectiveness in such immunocompromised patients. We report a case from our institution of a 29-year-old man with a history of psoriasis, who underwent a kidney transplant and later developed erythroderma. He did not respond to traditional treatments and was successfully treated with adalimumab, leading to the discontinuation of MMF. We also reviewed literature in solid organ transplant patients with psoriasis. Our findings, based on 10 articles, indicate a cautious approach to using biologics in this group, with further research needed for efficacy and safety.

Sexual and reproductive health screening and counseling in adolescent and young adult transplant recipients.

Adolescents and young adults with and without chronic illnesses partake in risk-taking behavior. Clinicians in transplant clinics should be aware of the prevalence of risk-taking behavior in their adolescent and young adult solid organ transplant patients in order to provide complete care. Creating an environment where teens and young adults feel comfortable discussing risky behavior is important and includes creating a privacy policy and increasing comfort of the healthcare provider in asking sensitive questions. This review is intended to help the providers in the transplant clinic screen for and counsel about risk-taking behaviors with their adolescent and young adult patients, specifically around sexual and reproductive health.

Patients Who Have Prior Solid Organ Transplants Have Increased Risk Of 10-Year Periprosthetic Joint Infection Revision Following Primary Total Knee Arthroplasty: A Propensity Matched Analysis

Total knee arthroplasty (TKA) for solid organ transplant (SOT) patients is becoming more prominent as life expectancy in this population increases. However, data on long-term (10 year) implant survivorship in this cohort is sparse. The purpose of this study was to compare 90-day, 2-year, 5-year, and 10-year implant survivability following primary TKA in patients who did and did not have prior SOT. The PearlDiver database was utilized to query patients who underwent unilateral elective TKA with at least 2 years of active follow-up. These patients were stratified into those who had a SOT before TKA and those who did not. The SOT cohort was propensity-matched to control patients based on age, sex, Charlson Comorbidity Index, and obesity in a 1:2 ratio. Cumulative incidence (CI) rates and hazard ratios (HR) were compared between the SOT, matched, and unmatched cohorts. No difference was observed in 10-year CI and risk of all-cause revision surgery in TKA patients with prior SOT when compared to matched and unmatched controls. Compared to the matched control, the SOT cohort had no difference in the risk of revision when stratified by indication and timing. However, when compared to the unmatched control, patients who had prior SOT had a higher risk for revision due to periprosthetic joint infection (PJI) at 10 years (HR: 1.80; 95% Confidence Interval: 1.17 to 2.76) as well as all-cause revision within 90 days after TKA (HR: 1.93; 95% Confidence Interval: 1.10 to 3.36). Prior SOT patients have higher rates of all-cause revision within 90 days and PJI within 10 years when compared to the general population, likely associated with the elevated number of comorbidities in SOT patients and not the transplant itself. Therefore, these patients should be monitored in the preoperative and early postoperative settings to optimize their known comorbidities.

Impact of varied immunosuppressive agents and post-transplant diabetes mellitus on prognosis among diverse transplant recipients (experimental studies).

The success of solid organ transplantation (SOT) and the use of immunosuppressive agents offer hope to patients with end-stage diseases. However, the impact of post-transplant diabetes mellitus (PTDM) on SOT patients has become increasingly evident. In our study, we utilized the Scientific Registry of Transplant Recipients (SRTR) database to investigate the association between PTDM and patient survival in various types of organ transplantations, including liver, kidney, intestinal, heart, lung, and combined heart-lung transplantations (all P <0.001). Our findings revealed a negative effect of PTDM on the survival of these patients. Furthermore, we examined the effects of both generic and innovator immunosuppressive agents on the development of PTDM and the overall survival of different SOT populations. Interestingly, the results were inconsistent, indicating that the impact of these agents may vary depending on the specific type of transplantation and patient population. Overall, our study provides a comprehensive and systematic assessment of the effects of different immunosuppressive agents on prognosis, as well as the impact of PTDM on the survival of patients undergoing various types of SOT. These findings emphasize the need for further research and highlight the importance of optimizing immunosuppressive regimens and managing PTDM in SOT patients to improve their long-term outcomes.

Updates in Skin Cancer in Transplant Recipients and Immunosuppressed Patients: Review of the 2022-2023 Scientific Symposium of the International Immunosuppression and Transplant Skin Cancer Collaborative.

The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) and its European counterpart, Skin Care in Organ Transplant Patients-Europe (SCOPE) are comprised of physicians, surgeons, and scientist who perform integrative collaborative research focused on cutaneous malignancies that arise in solid organ transplant recipients (SOTR) and patients with other forms of long-term immunosuppression. In October 2022, ITSCC held its biennial 4-day scientific symposium in Essex, Massachusetts. This meeting was attended by members of both ITSCC and SCOPE and consisted of specialists including Mohs micrographic and dermatologic oncology surgeons, medical dermatologists, transplant dermatologists, transplant surgeons, and transplant physicians. During this symposium scientific workshop groups focusing on consensus standards for case reporting of retrospective series for invasive squamous cell carcinoma (SCC), defining immunosuppressed patient status for cohort reporting, development of multi-institutional registry for reporting rare tumors, and development of a KERACON clinical trial of interventions after a SOTRs' first cutaneous SCC were developed. The majority of the symposium focused on presentation of the most up to date research in cutaneous malignancy in SOTR and immunosuppressed patients with specific focus on chemoprevention, immunosuppression regimens, immunotherapy in SOTRs, spatial transcriptomics, and the development of cutaneous tumor registries. Here, we present a summary of the most impactful scientific updates presented at the 2022 ITSCC symposium.

The Influence of Solid Organ Transplant on Inpatient Complications, Length of Stay, and Hospital Costs in Reverse Shoulder Arthroplasty Patients.

With innovations in transplant medicine and longer life expectancies in solid organ transplant (SOT) recipients, the incidence of shoulder arthroplasty is predictably rising in this population. Reverse shoulder arthroplasty (RSA) has become increasingly popular due to advances in prosthetic design with expanded indications. While previous studies have examined shoulder arthroplasty in SOT patients, information specifically related to RSA patients is largely unexplored. We aim to analyze the demographics and characteristics of SOT patients who have undergone RSA while assessing inpatient complication rates, length of stay (LOS), and hospital costs in these patients compared to a matched cohort of non-transplant patients. The National Inpatient Sample (NIS) Database was utilized to identify all patients undergoing RSA from 2016 to 2019. We generated propensity-matched groups based on pre-operative variables (diabetes, tobacco use, sex, age, and obesity) to compare complications, LOS, and inpatient costs between the SOT and control groups. T-tests and Chi-squared tests were performed where appropriate and odds ratios were calculated. We identified 59925 patients who underwent RSA. Among those, 59769 patients (99.7%) did not have a SOT and 156 patients (0.26%) had a history of SOT. Patients in the SOT group were younger than the control group (67.0 versus 71.4 years, p<0.001). The SOT group were more likely males compared to the control group (53.8% versus 39.3%, p<0.001). Following 1:1 matching, there were 156 patients in each group. The SOT group had a higher risk of acute renal failure (ARF) compared to the control group (OR 9.41, 95% CI (2.13-41.49), p<0.001). The LOS (p<0.001) and inpatient costs (p<0.001) were higher in the SOT group. For RSA, SOT patients are younger and more likely male compared to those without SOT. Inpatient medical and surgical complications are similar between SOT and non-SOT patients, except SOT patients have a higher risk of ARF. SOT patients tend to have longer LOS and higher inpatient costs than non-SOT patients.

Therapy of Mycobacterium abscessus Infections in Solid Organ Transplant Patients.

Mycobacterium abscessus complex (MABC), a rapidly growing Mycobacterium, is one of the most common causes of non-tuberculous mycobacteria (NTM) infections in the United States of America, and it has been associated with a wide spectrum of infections in immunocompetent and immunosuppressed individuals. Eradicating MABC is very challenging, even with prolonged combination therapies. The management of MABC infections in solid organ transplant (SOT) patients is usually complex given their net state of immunosuppression, associated comorbidities, and potential drug-drug interactions, among other things. In this manuscript, we discussed the antimicrobial management of pulmonary and extrapulmonary MABC infections. In addition, we reviewed promising novel therapies such as clofazimine, omadacycline, bedaquiline, and inhaled tigecycline that could join the existing antimicrobial armamentarium to fight this infection associated with significant morbidity and mortality. However, further studies are needed, especially among the immunocompromised host.

A comprehensive evaluation of risk factors for mortality, infection and colonization associated with CRGNB in adult solid organ transplant recipients: a systematic review and meta-analysis

Background The burden of carbapenem-resistant gram-negative bacteria (CRGNB) among solid organ transplant (SOT) recipients has not been systematically explored. Here, we discern the risk factors associated with CRGNB infection and colonization in SOT recipients. Methods This study included observational studies conducted among CRGNB-infected SOT patients, which reported risk factors associated with mortality, infection or colonization. Relevant records will be searched in PubMed, Embase and Web of Science for the period from the time of database construction to 1 March 2023. Results A total of 23 studies with 13,511 participants were included, enabling the assessment of 27 potential risk factors. The pooled prevalence of 1-year mortality among SOT recipients with CRGNB was 44.5%. Prolonged mechanical ventilation, combined transplantation, reoperation and pre-transplantation CRGNB colonization are salient contributors to the occurrence of CRGNB infections in SOT recipients. Renal replacement therapy, post-LT CRGNB colonization, pre-LT liver disease and model for end-stage liver disease score increased the risk of infection. Re-transplantation, carbapenem use before transplantation and ureteral stent utilization increaesd risk of CRGNB colonization. Conclusion Our study demonstrated that SOT recipients with CRGNB infections had a higher mortality risk. Invasive procedure may be the main factor contribute to CRGNB infection.

Seroprevalence of SARS-CoV-2 IgG in people with cystic fibrosis

BackgroundWhen the first known US case of COVID-19 (Coronavirus Disease 2019) was reported in early 2020, little was known about the impact of this novel virus on the cystic fibrosis community. As the majority of individuals with CF have chronic lung disease, this population was initially considered to be at high risk for severe disease as infection with a multitude of viruses has proven to cause pulmonary exacerbation. SARS-CoV-2 virus has proven challenging to study given the multiple disease manifestations, range of severity, and wave-like phenomenon that varies geographically. People with CF who become infected with COVID-19 can be asymptomatic or have symptoms ranging from mild cough and congestion to full respiratory failure, similar to the manifestations seen in non-CF individuals. By studying the seroprevalence, clinical course, and antibody durability due to COVID-19 and vaccinations, we will be better equipped to provide appropriate and informed care to people with CF. MethodsBetween July 2020 and April 2021 we enrolled 123 people with CF (pwCF) who receive care at the MN CF Center. We monitored their serology every 6 months for SARS-CoV-2 immunoglobulins (nucleocapsid and spike IgG) for evidence of natural and induced immunity. Medication use, pulmonary function, exacerbation history, and hospitalizations were extracted via electronic medical record (EMR). Results84% (101/120) of enrolled participants were vaccinated against SARS-CoV-2 during the study. Eighty three percent of the cohort showed evidence of either natural or induced “immunity.” The average duration of antibody from induced immunity in participants was 6.1 months and from natural immunity was 7.4 months with an overall average duration of antibody of 6.8 months. Earliest antibody detected was 12 days after a single dose of the BNT162b2 vaccine and antibody was detectable across a span of 13 months. Eleven percent of vaccinated individuals did not have measurable IgG. 36% of non-responders (NRs) were solid organ transplant patients on chronic immunosuppressive therapy. Only 3 people within this cohort were hospitalized due to COVID pneumonia and all three survived. ConclusionTo our knowledge, this is the first report on the seroprevalence and longevity of SARS-CoV-2 IgG to 1 year in adults with CF after the widespread availability of SARS-CoV-2 vaccinations. These data show that pwCF respond to the COVID vaccination and produce long-lasting antibodies similar to the general population.

Features of cryptococcosis among 652 HIV-seronegative individuals in France: a cross-sectional observational study (2005-2020)

ObjectivesWe aimed to describe features and outcomes of cryptococcosis among HIV-seronegative individuals in a large surveillance network for cryptococcosis in France. MethodsWe included incident cases of cryptococcosis in HIV-seronegative individuals from 2005 to 2020. We compared patient characteristics, disease presentations, cryptococcal antigen (CrAg) results, and induction antifungal treatments according to underlying disease. We examined factors associated with 90-day mortality. Among patients with disseminated infections, we investigated whether receipt of flucytosine and polyene combination was associated with lower mortality. ResultsAmong 652 individuals, 209 (32.1%) had malignancy, 130 (19.9%) were solid-organ transplant (SOT) recipients, 204 (31.3%) had other immunocompromising conditions, and 109 (16.7%) had no reported underlying factor. The commonest presentations were disseminated infections (63.3%, 413/652) and isolated pulmonary infections (25.3%, 165/652). SOT patients were most likely to have disseminated infections and a positive serum CrAg result. Patients with malignancy were older and less likely to receive a flucytosine-containing regimen for disseminated infections than others (58.7%, 78/133 vs. 73.2%, 194/265, p=0.029). The crude 90-day case-fatality ratio was 27.2% (95%CI: 23.5%-31.1%). Age ≥60 years (aOR: 2.75 [1.78-4.26], p<0.001), meningitis/fungaemia (aOR: 4.79 [1.80-12.7], p=0.002), and malignancy (aOR: 2.4 [1.14-5.07], p=0.02) were associated with higher 90-day mortality. Receipt of flucytosine and polyene combination was associated with lower 90-day mortality (aOR: 0.40 [0.23-0.71], p=0.002) in multivariable analysis and inverse probability of treatment weighted analysis (aOR: 0.45 [0.25-0.80], p=0.006). ConclusionsHIV-seronegative individuals with cryptococcosis comprise a wide range of underlying conditions with different presentations and outcomes, requiring a tailored approach to diagnosis and management.

Early pandemic in-hospital outcomes and mortality risk factors in COVID-19 solid organ transplant patients

Background Solid organ transplant (SOT) recipients with COVID-19 have a higher risk of mortality than those without COVID-19. However, it is unclear how SOT patient outcomes compare to the general population without SOT who contract COVID-19. Methods We used the National Inpatient Sample from January to December 2020 to investigate inpatient outcomes seen in SOT recipients after contracting COVID-19 compared to nontransplant patients. We identified our study sample using ICD-10 CM and excluded those <18 years of age and those with dual organ transplants. Inpatient outcomes were compared in SOT and non-SOT COVID cohorts, and we further evaluated predictors of mortality in the SOT with COVID population. Results Out of the 1,416,445 COVID-19 admissions included in the study, 8315 (0.59%) were single SOT recipients. Our analysis that adjusted for multiple baseline characteristics and comorbidities demonstrated that COVID-19 in SOT patients was associated with higher rates of acute kidney injury (adjusted odds ratio [aOR] 2.34, 95% confidence interval [CI] 1.81–3.02, P < 0.01), lower rates of acute respiratory distress syndrome (aOR 0.68, 95% CI 0.54–0.85, P < 0.01), and similar rates of cardiac arrest, pulmonary embolism, circulatory shock, cerebrovascular events, and in-hospital mortality. Age >65 was associated with mortality in SOT patients. Conclusion In this nationally representative sample, SOT patients presenting with COVID-19 experienced similar rates of mortality compared to those without SOT. SOT patients were more likely to develop acute kidney injury. Further research is needed to understand the complex relationship between transplant patient outcomes and COVID-19.

Postoperative Care and Outcomes in Solid Organ Transplant Patients undergoing Lower Extremity Fracture Treatment.

Determine the postoperative outcomes in solid-organ transplant (SOT) patients undergoing operative treatment of lower extremity fractures. Design: Retrospective comparative study. Academic Level 1 Trauma center. Patients who underwent SOT and operative treatment for lower extremity fracture from 2013-2021 were identified, excluding pathologic fractures.Outcome Measures and Comparisons: postoperative complications, length of stay, time to death, 90-day and 1-year readmission rates, readmission causes, discharge location, and immunosuppressive regiments. 61 patients with an average age of 67 (range 29-88) were included. The mortality rate was 37.7%. The average follow-up was 15.2 months (range of 2 weeks to 10 years). The majority of patients (42.6%) had received a liver transplant, and femoral neck fractures constituted the largest fracture group (39.4%). The average length of stay was 10 days, with the shortest being one day and the longest being 126 days (SD 18). The majority of patients were not discharged home (56.6%). Only two suffered from a postoperative complication requiring another procedure: hardware removal and liner exchange for periprosthetic joint infection, respectively. There was a 27.9% 90-day readmission rate with two deaths within that period with the most common being altered mental status (29.4%), genitourinary infections (17.6%), repeat falls (11.8%), and low hemoglobin requiring transfusion (11.8%). The longest average time to death analyzed by transplant type was found among lung transplant patients (1076 days, 62.5% mortality), followed by liver transplant patients (949 days 35.0% mortality), then kidney transplant patients (834 days, 38.9% mortality). The shortest time to death was 71 days from index procedure. Family members of solid-organ transplant patients undergoing operative treatment of lower extremity fractures should be made aware of the high risk for 90-day readmission postoperatively (27.9%) and overall mortality (12.5%). Providers should be aware of the need for multidisciplinary involvement for inpatient care, monitoring postoperative complications and facilitating discharge planning. Level IV. See Instructions for Authors for a complete description of levels of evidence.

Tacrolimus-Induced Neurotoxicity After Transplant: A Literature Review.

Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used globally to prevent rejection after organ transplantation. Although it significantly improves outcomes for solid organ transplant patients, it is associated with various side effects such as nephrotoxicity and neurotoxicity. Tacrolimus-induced neurotoxicity is frequently encountered in clinical practice and can present with a variety of symptoms that may occur even at therapeutic levels. Although tacrolimus-induced neurotoxicity is well documented, there is limited literature available on pharmacologic management. Twenty-eight case reports of tacrolimus-induced neurotoxicity were identified and analyzed in addition to other literature including reviews, retrospective studies, and animal model studies. The severity of cases of tacrolimus-induced neurotoxicity reported ranged from mild symptoms that could be managed with symptomatic treatment to conditions such as posterior reversible encephalopathy syndrome and chronic inflammatory demyelinating polyradiculoneuropathy that may require more immediate intervention. This information was utilized in addition to clinical experience to compile potential management options for prevention and treatment of neurotoxic adverse events. This review is limited by the utilization of primarily retrospective studies and case reports. The available literature on the subject is largely narrative and there are no guidelines on treatment of tacrolimus-induced neurotoxicity at the time of this research. This comprehensive review may guide further studies to investigate the pathophysiology of tacrolimus-induced neurotoxicity and to define patient-specific strategies for mitigation or minimization of neurotoxicity. This is especially important given that management of tacrolimus-induced neurotoxicity can include changes to immunosuppression that can result in an increased risk of rejection.

Viral meningoencephalitis in pediatric solid organ or hematopoietic cell transplant recipients: a diagnostic and therapeutic approach.

Neurologic complications, both infectious and non-infectious, are frequent among hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. Up to 46% of HCT and 50% of SOT recipients experience a neurological complication, including cerebrovascular accidents, drug toxicities, as well as infections. Defects in innate, adaptive, and humoral immune function among transplant recipients predispose to opportunistic infections, including central nervous system (CNS) disease. CNS infections remain uncommon overall amongst HCT and SOT recipients, compromising approximately 1% of total cases among adult patients. Given the relatively lower number of pediatric transplant recipients, the incidence of CNS disease amongst in this population remains unknown. Although infections comprise a small percentage of the neurological complications that occur post-transplant, the associated morbidity and mortality in an immunosuppressed state makes it imperative to promptly evaluate and aggressively treat a pediatric transplant patient with suspicion for viral meningoencephalitis. This manuscript guides the reader through a broad infectious and non-infectious diagnostic differential in a transplant recipient presenting with altered mentation and fever and thereafter, elaborates on diagnostics and management of viral meningoencephalitis. Hypothetical SOT and HCT patient cases have also been constructed to illustrate the diagnostic and management process in select viral etiologies. Given the unique risk for various opportunistic viral infections resulting in CNS disease among transplant recipients, the manuscript will provide a contemporary review of the epidemiology, risk factors, diagnosis, and management of viral meningoencephalitis in these patients.

Mycophenolate mofetil inhibits Merkel cell carcinoma growth.

The direct antitumour effects of mTOR inhibitors against cutaneous squamous cell carcinoma (SCC) have prompted a paradigm shift towards using sirolimus for allograft rejection prophylaxis in patients with high-risk SCC who have had a solid organ transplant (SOT). Patients who have had an SOT are at higher risk for Merkel cell carcinoma (MCC), yet there is little evidence concerning potential antitumour effects of immunosuppressive drugs against MCC. Screening seven immunosuppressive drugs in six MCC cell lines revealed that mycophenolate mofetil (MMF) had strong antitumour activity (surpassing mTOR inhibitors) and higher potency in MCC vs. other cancer types. MMF also inhibited MCC tumour growth in mice. Our preclinical findings strongly suggest the utility of MMF in patients with MCC who require immunosuppression.

Risk Index Predicts Pediatric Heart Allograft Non-Utilization.

Children listed for heart transplantation face the highest waitlist mortality among all solid organ transplant patients (14%). Attempts at decreasing donor allograft non-utilization (41.5%) could potentially decrease waitlist mortality for pediatric heart transplant patients. Our aim was to quantify the non-utilization risk of pediatric donor heart allografts at the time of initial offering. Using the United Network of Organ Sharing (UNOS) database, we retrospectively analyzed 8823 deceased donors (≤18 years old) data through univariable and multivariable analysis and logistic regression models. These factors were divided into a training (n = 5882) and validation set (n = 2941). Donor clinical characteristics and laboratory values were used to predict non-utilization of donor hearts. The multivariable analysis used factors that were significant from the univariable analysis (p-value < .05), and the pediatric non-utilization risk index (pDRSI) included significant factors from the multivariable analysis, producing an overall risk score for non-utilization. With these data, we created a non-utilization risk index to predict likelihood of donor allograft non-utilization. From the 24 potential factors that were identified from univariable analysis, 17 were significant predictors (p < .05) of pediatric heart non-utilization in the multivariable analysis. Low left ventricular ejection fraction (odds ratio (OR)-35.3), hepatitis C positive donor (OR-23.3), high left ventricular ejection fraction (OR-3.29), and hepatitis B positive donor (OR-3.27) were the most significant risk factors. The phDSRI has a C-statistic of 0.80 for the training set and 0.80 for the validation set. Using over 8000 donors, the phDSRI uses 17 significant risk factors to predict risk of pediatric heart donor allograft non-utilization.