Organ Transplant Patients Research Articles

Abstract 4134309: From Heartache to Headache: Cryptococcal Meningitis Post-Heart Transplant in a Chronic Hepatitis B and Sarcoidosis Patient

Introduction: We report the case of a heart transplant patient on chronic immunosuppression diagnosed with cryptococcal meningitis. Up to 5% of solid organ transplant patients develop cryptococcosis, carrying a 50% mortality rate in central nervous system involvement. Case Presentation: This is a 57-year-old male with a past medical history of heart failure with reduced ejection fraction (HFrEF) status post orthotopic heart transplantation (on prednisone 7.5 mg daily, mycophenolate, tacrolimus and sirolimus), pulmonary sarcoid, and chronic hepatitis B (on tenofovir and entecavir) who presented with headache, nausea, vomiting and seizure-like activity. The patient’s heart rate was 129 beats per minute, blood pressure 188/92 mmHg, but was afebrile. He eventually underwent a lumbar puncture with the cerebrospinal fluid (CSF) positive for cryptococcal antigen (1:2560). The patient was started on liposomal amphotericin B and flucytosine. Mycophenolate and sirolimus were held in the setting of his infection. The patient’s hospital course was complicated by acute kidney injury likely secondary to elevated tacrolimus levels while on fluconazole. He was ultimately discharged with plans to repeat CSF studies as an outpatient. Discussion: Here we report a case of cryptococcal meningitis in a heart transplant patient in the context of pulmonary sarcoidosis, chronic hepatitis B and quadruple immunosuppression. Of note, as part of rejection surveillance, the patient undertook serial AlloSure and AlloMap testing. Sirolimus was added to his regimen due to persistently elevated AlloSure scores. Indeed, immunosuppressive agents are the leading risk factor for cryptococcosis in organ transplant patients. Our patient also has two important risk factors for cryptococcal infection. Firstly, sarcoidosis is associated with T-cell dysregulation, compromising cell-mediated immunity. Additionally, hepatitis B carriers have an increased predisposition for cryptococcal infections, notwithstanding that our patient had been on dual antiviral therapy. Conclusion: Quadruple immunosuppression in heart transplant patients, especially in the context of risk factors such as sarcoidosis and hepatitis B infection, can result in cryptococcal meningitis and should be considered in patients with suggestive symptoms. Effective prophylactic regimens for such higher risk patients may be a potential area for further investigation.

Central nervous system infection with Hantavirus in a solid organ transplant patient

Central nervous system infection with Hantavirus in a solid organ transplant patient

Pathologists Providing Direct Patient Care in Thoracic Transplant: Same Objective, Different Scope

Context.— Cardiac and pulmonary allograft recipients represent a unique population, frequently interacting with support groups and exhibiting intense curiosity about their pathology. Like other solid organ transplant patients, they have enduring and frequent interaction with the laboratory for routine allograft surveillance. Objective.— To address patient requests to understand what happens to their explanted organ and to better understand their disease while simultaneously improving awareness of pathologists’ role in their continuing care. Design.— At routine follow-up appointments, transplant nurse coordinators offer each allograft recipient the opportunity to interact with a pathologist in our “On My Path” program. Organ viewing occurs in a private setting, in a specialized room. Relevant pathology is discussed, and questions are answered, with documentation in the medical record. The patient is subsequently gifted a 3-dimensional model of their explanted organ. Transplant coordinators were surveyed for their feedback on the experience. Results.— One hundred fifty-eight interactions have been documented (2017–2022), including patients who underwent cardiac transplant (96, 61%), single or bilateral lung transplant (54, 34%), or combination lung and heart transplant (8, 5%). Transplant coordinators reported an increase in patient understanding of their disease and emotional closure related to the disease through the On My Path program. Conclusions.— Pathologists providing direct patient care is a feasible model that addresses currently unmet desires of the transplant population to better understand their pathology. Providing a 3-dimensional model helps to empower patients and drives satisfaction. These interactions also improve awareness about pathology as a discipline and its importance in the continued care of transplant recipients.

Lung transplantation for alpha-1-antitrypsin deficiency and Behçet's disease: A case report

INTRODUCTIONAlpha-1-Antitrypsin deficiency (A1ATD) is a genetically determined anti-proteinase deficiency which predisposes to early onset emphysema and liver disease. Lung transplantation (LTx) is the final therapeutic option. Behçet's disease (BD) is a rare autoimmune disease characterized by oral and genital ulcers, deep venous thrombosis associated with large and small-vessel vasculitis and aneurysms. The association of A1ATD and BD is unknown. We aim to describe a rare case of concomitant presentation of these pathologies in a patient submitted to LTx. CASE REPORTA 31-years-old female presented with oral and genital ulcers associated with cavernous sinus thrombosis in 2012, being diagnosed with BD. In 2018 debuted with progressive respiratory symptoms. CT-scan revealed extensive pulmonary emphysema associated with decreased pulmonary function. A1ATD was identified with a heterozygous “MZ” allelic combination. She was referred to LTx center in 2021. After additional investigation, the patient was considered to LTx. She underwent standard bilateral LTx in July of 2022. During post-operative time, special attention was given to the risk of vascular complications, and pos-operative angio-CT was performed actively searching for this possible outcome. Nevertheless, no major events occurred. After 1 year, she is fully functional with no signs of BD activity. CONCLUSIONTo our knowledge, this is the first description of LTx for A1ATD in a patient with BD, proving its feasibility in a highly selected patient at an experienced and specialized center. Nonetheless, solid organ transplantation in patients with BD remains a high risk procedure and should be indicated with caution.

Outcomes and inflammation changes in different types of immunocompromised patients with critically ill COVID-19 admitted to ICU: a national multicenter study

BackgroundImmunocompromised patients face higher risks of Severe Acute Respiratory Syndrome Coronavirus 2 infection and co-infections, leading to a possibility of high disease severity and poor outcomes. Conversely, immunosuppression can mitigate the excessive inflammatory response induced by the virus, potentially reducing disease severity. This study aims to investigate the prognostic differences and early inflammatory response characteristics in various types of immunocompromised patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU), summarize their clinical features, and explore potential mechanisms.MethodsA retrospective analysis was conducted on critically ill COVID-19 patients admitted to the ICU of 59 medical centers in mainland China during the Omicron outbreak from November 2022 to February 2023. Patients were categorized into two groups based on their immunosuppression status: immunocompromised and immunocompetent. Immunocompromised patients were further subdivided by etiology into cancer patients, solid organ transplant (SOT) patients, and other immunocompromised groups, with immunocompetent patients serving as controls. The mortality rates, respiratory support, complications, and early inflammatory cytokine dynamics upon ICU admission among different populations were analyzed.ResultsA total of 2030 critically ill COVID-19 patients admitted to ICU were included, with 242 in the immunocompromised group and 1788 in the immunocompetent group. Cancer patients had a higher median age of 69 years (IQR 59, 77), while SOT patients were generally younger and had less severe illness upon ICU admission, with a median APACHE II score of 12.0 (IQR 8.0, 20.0). Cancer patients had a twofold increased risk of death (OR = 2.02, 95% CI 1.18–3.46, P = 0.010) compared to immunocompetent patients. SOT and cancer patients exhibited higher C-reactive protein and serum ferritin levels than the immunocompetent group in their early days of ICU admission. The CD8+ T cells dynamics were inversely correlated in cancer and SOT patients, with Interleukin-6 levels consistently lower in the SOT group compared to both immunocompetent and cancer patients.ConclusionCritically ill COVID-19 patients admitted to the ICU exhibit distinct clinical outcomes based on their immunosuppression status, with cancer patients facing the highest mortality rate due to variations in inflammatory responses linked to their immunosuppression mechanisms. Monitoring dynamic changes in inflammatory markers and immune cells, particularly CD8+ T lymphocytes and IL-6, may offer valuable prognostic insights for these patients.

Proceedings of the Conference “CMV Vaccine Development—How Close Are We?” (27–28 September 2023)

Congenital cytomegalovirus (cCMV) is the most common infectious cause of disability in children, including sensorineural hearing loss. There is interest in developing a pre-conception vaccine that could confer protective immunity on a woman of child-bearing age, hence resulting in a reduced cCMV disease burden. Other populations, including solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients, could also benefit from CMV vaccination. To review and discuss vaccines that are in clinical development, a workshop, sponsored by the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID), was empaneled. At this workshop, correlates of protective immunity against CMV, epidemiologic features of CMV transmission, and vaccine platforms in development were reviewed. Representatives from academia, pharma, and the NIH engaged in discussion on the current state-of-the-art in CMV vaccinology. A summary of the presentations from this is provided in this report.

Beyond Awareness: Hope for a CMV Vaccine! An Introduction to the Conference, “CMV Vaccine Development—How Close Are We?” (27–28 September 2023)

Congenital cytomegalovirus (cCMV) is the most common infectious cause of disability in children. The major theme of this National Institute of Allergy and Infectious Diseases (NIAID) workshop, “CMV Vaccine Development—How Close Are We?”, was to report progress on the development of a pre-conception vaccine that could confer protective immunity for women of child-bearing age. Such a vaccine could result in a reduced cCMV disease burden, although other populations, including solid organ transplant and hematopoietic stem cell transplant patients, could benefit as well. To frame the compelling need for a cCMV vaccine, a keynote lecture by Dr. Megan Pesch, immediate past-president of the National CMV Foundation and a leading cCMV researcher from the University of Michigan, was given. This manuscript provides a summary of Dr. Pesch’s presentation from this workshop, which was written as the introductory conference report for the meeting.

Draft genomes of the bile duct microbiome strains Klebsiella pneumoniae and Enterococcus lactis isolated from bilioenteric drainages with biofilm-forming abilities.

We describe the genetic properties of two strains isolated from the elusive bile duct microbiome from solid organ transplant patients. Bacterial strains Enterococcus lactis (MS-STENT-08-E-001) and Klebsiella pneumoniae (MS-STENT-01-M-001) were isolated from the biofilms of bile duct catheters.

CYP3A4*1B but Not CYP3A5*3 as Determinant of Long-Term Tacrolimus Dose Requirements in Spanish Solid Organ Transplant Patients.

Tacrolimus (TAC) is a commonly used immunosuppressive drug in solid organ transplantation. Pharmacogenetics has been demonstrated before to be decisive in TAC pharmacotherapy. The CYP3A5*3 variant has been reported to be the main determinant of TAC dose requirements; however, other polymorphisms have also proven to be influential, especially in CYP3A5 non-expressor patients. The aim of this study is to evaluate the influence of genetic polymorphisms in TAC therapy in a cohort of Spanish transplant recipients. Genetic analysis including ten polymorphic variants was performed, and demographic and clinical data and pharmacotherapy of 26 patients were analyzed. No significant differences were found in weight-adjusted dose between CYP3A5 expressors and non-expressors (0.047 mg/kg vs. 0.044 mg/kg), while they were found for carriers of the CYP3A4*1B allele (0.101 mg/kg; p < 0.05). The results showed that patients with at least one CYP3A4*1B allele had a higher TAC dose and lower blood concentration. Dose-adjusted TAC blood levels were also lower in CYP3A4*1B carriers compared to non-carriers (0.72 ng/mL/mg vs. 2.88 ng/mL/mg). These results support the independence of CYP3A5*3 and CYP3A4*1B variants as determinants of dose requirements despite the linkage disequilibrium present between the two. The variability in genotype frequency between ethnicities may be responsible for the discrepancy found between studies.

Maribavir use in pediatric immunocompromised hosts: A case series to talk about real-world experience

Abstract Background Cytomegalovirus (CMV) is a common infection affecting pediatric immunocompromised hosts. The treatment of CMV in solid organ (SOT) or hematopoietic stem cell transplant (HSCT) patients is challenged by the toxicities associated with antiviral therapies (myelosuppression with valganciclovir, ganciclovir and cidofovir; nephrotoxicity with foscarnet and cidofovir) and the prevalence of resistant/refractory CMV. Maribavir, a novel benzimidazole, competitively inhibits CMV UL97 protein kinase to inhibit DNA synthesis and block nuclear exit of viral particles from CMV-infected cells. It is FDA approved for use in patients at least 12 years of age and weighing at least 35 kg. The use of maribavir in pediatric patients is of interest due to its availability as an oral dosage formulation and improved side effect profile. To date, there are no pediatric case series or studies describing the use of maribavir for CMV treatment. Methods This study is a retrospective case series compiling the findings the first pediatric patients at Children’s National Hospital, DC that received maribavir. We included children who received maribavir from 01/2017 – 10/2023. Patients were included if they were on maribavir monotherapy, or combination therapy with additional anti-CMV agent(s). The medical records were reviewed for indication of medication use, viral response to therapy and side effects. Side-effects review specifically evaluated for increased LFTs, increased serum creatinine, and decreased absolute neutrophil count or factors that may contribute to early discontinuation of maribavir. Results (table) Maribavir was used in three male patients with varied conditions – including solid organ transplant (SOT), hematopoietic stem cell transplant (HSCT) and Severe Combined Immunodeficiency (SCID) s/p HSCT. Two cases had signs of CMV disease, and one had CMV viremia. All cases included documented CMV resistance (n=2) or refractory CMV (n=1) and had previously been receiving at least one antiviral with CMV activity for at least 14 days and had increasing CMV DNA-emia in the blood. None of the patients had side effects such as nephrotoxicity, liver toxicity or myelosuppression that aggravated after starting maribavir. Dosing of 400mg BID (range 12mg/kg/day to 55mg/kg/day) was used. Once started, maribavir was continued until CMV quantitative levels were undetectable for two weeks. Clearance of CMV and was achieved in all the patients on maribavir or combination of maribavir with other drugs (n=1). Duration of maribavir treatment ranged from 4.2 to 6.2 weeks. Conclusion This is the first case series describing use of maribavir in a pediatric population. In this small cohort maribavir is effective and well tolerated. Further studies are needed to better CMV care in children with immunocompromised conditions.

Immunosuppressive medication adherence and affecting factors in solid organ transplantation patients: a mixed-methods study

Objectives: Transplantation is a form of treatment that requires long-term pharmacotherapy. After transplantation, patients may have difficulty adapting to medication use for various reasons, and this may result in rejection. The aim of this study is to determine participants’ medication compliance and the factors affecting it. Methods: The research was conducted with a sequential explanatory mixed method. In the study, quantitative data were collected using the Turkish Immunosuppressive Medication Adherence Scale, and qualitative data were collected using the In-Depth Individual Interview Guide. Quantitative data were analyzed using statistical methods, and qualitative data were examined according to Braun and Clarke's thematic analysis framework. Results: In this study, 62.3% of the participants were male, 37.0% were 50 years old and over, 71.3% lived with their spouse, 54.0% had primary and secondary school education, and 42.0% could not work due to their current health condition. From a clinical perspective, it was determined that 78% of the transplants were kidney transplants, and 41.3% were more than 4 years after transplantation. 74.3% of the transplants were from living donors. The mean score of the immunosuppressive medication compliance scale was determined to be 40.91±4.09. In the qualitative data analysis of the study, factors affecting medication adherence were examined and the themes of "individual factors", "complexity of the regimen" and "social support resources" were obtained. The sub-themes of the individual factors theme are reluctance, hopelessness and addiction; Sub-themes of the complexity of the regimen theme are drug side effects and polypharmacy; The sub-themes of the social support resources theme are loneliness and family pressure. Conclusions: The factors influencing medication adherence among organ transplant recipients have been investigated, revealing that adherence levels vary significantly depending on various factors. These findings underscore the importance of tailored care strategies and individualized support approaches.

Layered double hydroxide nanozyme (LDHzyme)-assisted high-performance electrochemical analysis of organ transplant therapeutic drug concentration

The variability in mycophenolic acid (MPA) exposure levels among organ transplant patients is substantial and directly influences the drug’s therapeutic efficacy. Therefore, precise monitoring of MPA blood concentrations is imperative to devise personalized diagnostic and treatment plans tailored to individual patient profiles. In this study, we developed a screen-printed carbon electrode (SPCE) incorporating Layered Double Hydroxide-based nanozymes (LDHzymes) and multi-walled carbon nanotubes (MWCNT) to achieve high-sensitivity and stable determination of MPA in blood samples. We synthesized three distinct LDHzymes via a straightforward co-precipitation method, selecting CuMn-LDHzyme for its superior electrochemical properties and laccase activity in the context of MPA detection. The sensor’s performance was enhanced by the amalgamation of CuMn-LDHzyme with MWCNT, leveraging the laccase-like activity of CuMn-LDHzyme and the exceptional conductivity of MWCNT to amplify the oxidation current response to MPA. This integration significantly bolstered the sensor’s detection capabilities. The developed electrochemical sensor exhibited remarkable characteristics, including high selectivity, stability, repeatability, and reproducibility. It demonstrated a notable sensitivity with a detection range of 0.5 µM to 200 µM for MPA, and a detection limit of 0.1 µM, effectively detecting MPA in mouse blood samples. These attributes underscore the sensors as promising tool for clinical drug detection, ensuring fast and precise monitoring of MPA levels in organ transplant patients. This innovative approach holds significant promise for advancing personalized medical care and improving therapeutic outcomes.

Infective endocarditis with metastatic infections in a renal transplant recipient: a case report

BackgroundInfective endocarditis is an uncommon but well-known post-transplant complication with significant morbidity and mortality. It has been observed to be about 171 times more common in solid organ transplant patients than in the general population. With the increasing rate of end-stage kidney disease, the higher demand for kidney transplantation with better graft survival, and life expectancy rates, more transplant recipients may develop infective endocarditis as a late post-transplant complication. Prompt diagnosis of infective endocarditis is therefore necessary to avert graft loss and other life-threatening outcomes.Case presentationWe present a case of a 52-year-old African patient who had a live donor kidney transplant 18 months prior to presentation and had been on oral tacrolimus 5 mg every morning/4.5 mg every evening, mycophenolic acid (MPA) 720 mg twice daily, and oral prednisolone 10 mg daily as maintenance immunosuppressive medications. Regarding the above immunosuppressive medications, he had been in good health and had a functioning transplant graft. He presented with a resolving right thigh swelling, recurrence of fever, new onset left hemiplegia, and seizures. Enterococcus faecalis infective endocarditis was diagnosed with metastatic brain abscesses, which was treated with intravenous vancomycin and gentamycin for 5 weeks. There are very few reported cases of infective endocarditis due to Enterococcus faecalis, and this case is unique because the initial presentation was pyomyositis.ConclusionInfective endocarditis with septic embolization to the brain should be considered in kidney transplant recipients with pyomyositis and multiple rim-enhancing lesions, especially in the late post-transplant period with Enterococcal spp. as an emerging cause of infective endocarditis in kidney transplant recipients. Clinicians will need to have a high index of suspicion to aid early diagnosis with appropriate treatment to prevent adverse outcomes.

SIGNET: protocol for a multicentre, single-blind prospective, group sequential, randomised controlled trial to evaluate the benefits of a single dose of simvastatin given to potential organ donors declared dead by neurological criteria on outcomes in organ recipients

IntroductionSuccessful organ transplantation in patients with end-stage organ failure improves long-term survival, improves quality of life and reduces costs to the NHS. Despite an increase in the number of deceased...

302.6: Atypical cervical cytology in solid organ transplantation patients: 20 years of experience in a single center.

302.6: Atypical cervical cytology in solid organ transplantation patients: 20 years of experience in a single center.

P.152: Respiratory multiplex PCR could predict morbidity and mortality in solid organ transplant patients.

P.152: Respiratory multiplex PCR could predict morbidity and mortality in solid organ transplant patients.

P.054: CMV colitis in solid organ transplant patients.

P.054: CMV colitis in solid organ transplant patients.

The Major Role of T Regulatory Cells in the Efficiency of Vaccination in General and Immunocompromised Populations: A Review.

Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including the recent COVID-19 outbreak. Insightful studies have uncovered the complexities of different functional networks of CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 T cells (T cytotoxic; Tc), as well as B cell (BIgM, BIgG, BIgA and BIgE) subsets, during the response to vaccination. Both T and B cell subsets form central, peripheral, and tissue-resident subsets during vaccination. It has also become apparent that each vaccination forms a network of T regulatory subsets, namely CD4+ CD25+ Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+ Foxp3- T regulatory 1 (Tr1), as well as many others, which shape the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on considering how the pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work has revealed that Treg/Tr1 involvement evokes different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response, such as increasing the dose, changing the delivery route, and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Rα chain) or anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAb) to decrease the Tregs and boost the T/B cell immune response. All of these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals, as well as organ transplant patients.

Risk Factors and Outcomes Associated With the Development of Persistent Acute Kidney Injury in Non-Renal Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

Persistent acute kidney injury (pAKI), compared with acute kidney injury (AKI) that resolves in <72h, is associated with worse prognosis in critically ill patients. Definitions and prognosis of pAKI are not well characterized in solid organ transplant patients. Our aims were to investigate (a) definitions and incidence of pAKI; (b) association with clinical outcomes; and (c) risk factors for pAKI among heart, lung, and liver transplant recipients. We systematically reviewed the literature including PubMed, Embase, Web of Science, and Cochrane from inception to 8/1/2023 for human prospective and retrospective studies reporting on the development of pAKI in heart, lung, or liver transplant recipients. We assessed heterogeneity using Cochran's Q and I2. We identified 25 studies including 6330 patients. AKI (8%-71.6%) and pAKI (2.7%-55.1%) varied widely. Definitions of pAKI included 48-72h (six studies), 7days (three studies), 14days (four studies), or more (12 studies). Risk factors included age, body mass index (BMI), diabetes, preoperative chronic kidney disease (CKD), intraoperative vasopressor use, and intraoperative circulatory support. pAKI was associated with new onset of CKD (odds ratio [OR] 1.41-11.2), graft dysfunction (OR 1.81-8.51), and long-term mortality (OR 3.01-13.96), although significant heterogeneity limited certainty of CKD and graft dysfunction outcome analyses. pAKI is common and is associated with worse mortality among liver and lung transplant recipients. Standardization of the nomenclature of AKI will be important in future studies (PROSPERO CRD42022371952).

Combined Organ Transplantation in Patients with Advanced Liver Disease.

Transplantation of the liver in combination with other organs is an increasingly performed procedure. Over the years, continuous improvement in survival could be realized through careful patient selection and refined organ preservation techniques, in spite of the challenges posed by aging recipients and donors, as well as the increased use of steatotic liver grafts. Herein, we revisit the epidemiology, allocation policies in different transplant zones, indications, and outcomes with regard to simultaneous organ transplants involving the liver, that is combined heart-liver, liver-lung, liver-kidney, and multivisceral transplantation. We address challenges surrounding combined organ transplantation such as equity, utility, and logistics of dual organ implantation, but also advantages that come along with combined transplantation, thereby focusing on molecular mechanisms underlying immunoprotection provided by the liver to the other allografts. In addition, the current standing and knowledge of machine perfusion in combined organ transplantation, mostly based on center experience, will be reviewed. Notwithstanding all the technical advances, shortage of organs, and the lack of universal eligibility criteria for certain multi-organ combinations are hurdles that need to be tackled in the future.