Search

Objectives: Pulmonary nocardiosis is a rare opportunistic infection that is often encountered in immunocompromised patients, in particular those with the HIV infection and in solid organ transplant recipients. As the number of immunocompromised patients increase, the number of patients with pulmonary nocardiosis is also expected to increase. This study aimed to analyse both the chest high resolution computed tomography (HRCT) findings of patients with confirmed pulmonary nocardiosis and review the imaging features of pulmonary nocardiosis in the literature. Methods: This retrospective study was conducted at The Royal Hospital, Muscat, Oman, to identify patients with a diagnosis of pulmonary nocardiosis between January 2006 and January 2019. Accordingly, nine patients with pulmonary nocardiosis were identified, but three patients were excluded as no chest HRCT images were available. Patient clinical presentation was recorded and chest HRCT images were retrospectively reviewed. Results: A total of six patients were enrolled in this study. All were male and with a mean age of 41 ± 11 years. Three patients were immunocompromised, two of whom had undergone a renal transplant. The main HRCT findings were cavitary nodules/masses, non-cavitary nodules/masses, septal thickening, centrilobular nodules, ground glass opacities, consolidation, pleural effusion, pleural thickening, enlarged lymph nodes and necrotic lymph nodes. Conclusion: Pulmonary nocardiosis shows various findings in a chest CT, the most common of which are pulmonary nodules and masses. Awareness of these findings can help radiologists with a diagnosis in the appropriate clinical settings. Keywords: Pulmonary Nocardiosis; Computed Tomography; Oman.

Antibody-mediated rejection (AMR) is a major barrier to long-term graft survival following solid organ transplantation (SOT). Major histocompatibility antigens mismatched between donor and recipient are well-recognized targets of humoral alloimmunity in SOT and thought to drive most cases of AMR. In contrast, the implication of minor histocompatibility antigens (mHAs) in AMR has not been fully investigated, and their clinical relevance remains controversial. Recent technological advances, allowing for genome-wide comparisons between donors and recipients, have uncovered novel, polymorphic mHA targets with potential influence on the graft outcome following SOT. Here, we review these latest studies relating to mHAs and discuss their clinical significance.

Resumen Antecedentes y objetivo Se han comparado la eficacia y seguridad de la profilaxis primaria estandar o prolongada de la infeccion por citomegalovirus (CMV) en el trasplante de organo solido. Materiales y metodos Estudio retrospectivo de los receptores CMV seronegativos de donante seropositivo (D+/R−) que recibieron profilaxis frente a CMV tras un trasplante de organo solido (2007-2017). Se comparo la frecuencia de infeccion por CMV en los 2 primeros anos postrasplante en los receptores que recibieron profilaxis durante mas o menos de 100 dias. Se evaluo asimismo la mielotoxicidad durante la profilaxis. Resultados Se analizaron 66 pacientes. De ellos el 43,9% (n = 29) presentaron infeccion por CMV. El 68,2% (n = 45) recibieron profilaxis prolongada, sin asociarse su uso con una menor tasa de infeccion (42,2 vs. 47,6%, p = 0,44) ni de enfermedad posprofilaxis (15,6 vs. 19%, p = 0,72). La profilaxis prolongada se asocio con una mayor frecuencia de mielotoxicidad (68,9 vs. 42,9%, p Conclusiones La prolongacion de la profilaxis primaria mas de 100 dias no aumenta su efectividad pero si la toxicidad hematologica.

Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n = 65) were matched with controls (n = 65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG antibodies against N and S antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1 month p = .007, 3 months p .001, 6 months p = .019, and 9 months p = .021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at 1 month (p = .005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls.

Introduction The Texas Children’s Hospital Lung Transplant Program undertook consideration of its first non-resident, non-citizen for lung transplantation in 2011. Methods Four referrals from the Royal Embassy of Saudi Arabia were received, and two patients were evaluated from 2011 to 2013. Results After a suitable candidate and family was identified, the program adopted a systematic approach to ensure that all the necessary elements of pre-transplant care, informed consent, and post-transplant care could be effectively delivered. Conclusion The use of hospital translation services and the development of a strong professional relationship with a well-trained pediatric respirologist in Saudi Arabia combined with an excellent early post-transplant clinical course provide lessons that may be of help to other transplant programs considering international patients as candidates for solid organ transplantation.

The diagnosis of graft-versus-host-disease (GVHD) after solid organ transplantation is made difficult by its variable clinical presentation and lack of sensitive and specific biomarkers to evaluate the immune state of transplant recipients. Emerging noninvasive diagnostic techniques like the quantification of donor-derived cell-free DNA (dd-cfDNA) for surveillance may improve the current standard-of-care. Herein, we report the use of this methodology in a patient with GVHD and corresponding levels of dd-cfDNA without any evidence of graft injury. Correlation of dd-cfDNA levels with the clinical course and its novel application here could lead to improvements in the rapid diagnosis of GVHD and in monitoring of response to treatment.

West Nile virus (WNV) is the most common domestic arbovirus in the United States. During 2018, WNV was transmitted through solid organ transplantation to 2 recipients who had neuroinvasive disease develop. Because of increased illness and death in transplant recipients, organ procurement organizations should consider screening during region-specific WNV transmission months.

Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long-term outcomes of CMV DNAemia in pediatric SOTR. We performed a single-center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue-invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High-risk (OR 6.86 [95% CI, 3.6-12.9]) and intermediate-risk (4.36 [2.3-8.2]) CMV status and lung transplantation (4.63 [2.33-9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p

Organ transplantation is a modern medical success story. However, since its inception it has been limited by the need for pharmacological immunosuppression. Regulatory cellular therapies offer an attractive solution to these challenges by controlling transplant alloresponses through multiple parallel suppressive mechanisms. A number of cell types have seen an accelerated development into human trials and are now on the threshold of a long-awaited breakthrough in personalized transplant therapeutics. Here we assess recent developments with a focus on the most likely candidates, some of which have already facilitated successful immunosuppression withdrawal in early clinical trials. We propose that this may constitute a promising approach in clinical transplantation but also evaluate outstanding issues in the field, providing cause for cautious optimism.

OBJECTIVES Pneumonia is a significant cause of morbidity and mortality in solid-organ transplant recipients. We studied the demographic characteristics, respiratory management, and outcomes of solid-organ transplant recipients with pneumonia in an intensive care unit. MATERIALS AND METHODS There have been 2857 kidney, 687 liver, and 142 heart transplants performed between October 16, 1985, and February 28, 2021, at our center. We retrospectively analyzed records for 51 of 193 recipients with pneumonia during the posttransplant period between January 1, 2016, and December 31, 2018. RESULTS Fifty-one of 193 recipients were followed in the intensive care unit. Mean age was 45.4 ± 16.6 years among 42 male (82.4%) and 9 female (17.6%) recipients. Twenty-six patients (51%) underwent kidney transplant, 14 (27.5%) liver transplant, 7 (13.7%) heart transplant, and 4 (7.8%) combined kidney and liver transplant. Most pneumonia episodes occurred 6 months after transplant (70.6%) with acute hypoxemic respiratory failure. Mean Acute Physiology and Chronic Health Evaluation System II score was 18.9 ± 7.7, and the Sequential Organ Failure Assessment score was 8.5 ± 3.9 at intensive care unit admission. Whereas 66.7% of pneumonia cases were nosocomial acquired, 33.3% were community acquired. The intensive care unit and 28-day mortality rates were 39.2% and 64.7%, respectively. CONCLUSIONS Solid-organ transplant recipients with pneumonia have been associated with poor prognosis. Our cohort followed in the intensive care unit comprised mostly patients with nosocomial pneumonia with acute hypoxemic respiratory failure, hospitalized 6 months after transplant with high Acute Physiology and Chronic Health Evaluation System II scores predictive of mortality. In this high-risk patient group, careful follow-up, early discovery of warning signs, and rapid treatment initiation could improve the outcomes in the intensive care unit.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

The number of ABO-incompatible solid organ transplantations (ABOi SOTs) has markedly increased worldwide since the early 2000s. We investigated the choice of ABO group for blood component transfusion in ABOi SOT. We conducted a survey by e-mailing a questionnaire to blood bank specialists at 77 major hospitals in Korea, among whom 34 responded to the survey. In major ABOi SOT, for red blood cells (RBCs), the recipient's type (70.6%) was the most common choice, followed by group O (29.4%); for platelets, group AB (50.0%) was the most common choice, followed by the donor type (38.2%); for plasma, group AB (55.9%) was the most common choice, followed by the donor type (32.4%). In bidirectional ABOi SOT, for RBCs, the recipient's type (55.9%) was the most common choice, followed by group O (44.1%); for platelets and plasma, group AB was the most common choice (94.1% and 97.1%, respectively). The policies for transfusion in ABOi SOT were diverse. We suggest a guideline on the choice of ABO group for transfusion in ABOi SOT to secure patient health and enable an efficient use of blood components.

Introduction Recurrent urinary tract infections remain a challenge in solid organ transplant and have a negative impact on morbidity/mortality. Project Aim The purpose of this program evaluation was to determine the impact of methenamine on recurrent urinary tract infection in kidney and liver-kidney transplant recipients. Design This retrospective review included patients > 18 years of age who received a kidney or liver-kidney transplant. Patients were divided into the following groups: (1) Methenamine therapy initiation received methenamine for ≥ 180 days or (2) Non-methenamine therapy: did not receive recurrent urinary tract infection prophylaxis. A total of 60 patients were included. Results When comparing outcomes between methenamine therapy initiation and non-methenamine therapy group, a significant reduction in the rate of recurrent urinary tract infection was reported in the methenamine therapy initiation group (0.6 vs 1.3 per 180 patient days follow-up, P = 0.0005). A significant reduction was also noted with rate of asymptomatic bacteriuria, treatment failures, bacteremia, hospitalizations due to recurrent urinary tract infection, multi-drug resistant organism isolated, and the average duration of antibiotic use. A significant difference in the time to failure of methenamine therapy initiation versus non-methenamine therapy is noted up to 180 patient-days follow-up (RR 1.56, P = 0.0019). Conclusion This evaluation supported methenamine therapy for recurrent urinary tract infection in kidney and liver-kidney transplant. The most significant impact of methenamine recurrent urinary tract infection was seen in the first 30 days after initiation.

It is well known that organ transplant recipients are prone to develop non-melanoma skin cancers, particularly cutaneous squamous cell carcinoma (cSCC). This is explained by the long-term use of immunosuppressants and thus the decrease of the immunosurveillance that protects from developing malignant tumours. Solid organ transplant recipients (SOTRs) are 65-250 times more likely to develop cSCC compared to the general population (Am J Transplant 2017; 17: 2509). Moreover, in these patients cSCCs follow a more aggressive course. Close follow-up and regular skin check-ups by a dermatologist are, therefore, crucial in the management of these patients. When detected early, cSCC can be easily and effectively treated by a simple excision. However, when advanced, outcomes are poor. Immune checkpoints inhibitors (ICIs) have been recently added to our arsenal and represent a breakthrough, having proved to be effective in achieving long-term responses. We, hereby, present two cases of difficult-to-treat cSCCs in renal transplanted patients.

Limited data exist on the use of immune checkpoint inhibitors (ICI) for the treatment of metastatic cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTR). We report a case of a SOTR who developed metastatic disease following multiple surgeries, three cycles of adjuvant radiotherapy, and minimization of immunosuppression. He was subsequently treated with pembrolizumab and achieved a complete response. However, the patient developed ICI-induced allograft rejection requiring therapy discontinuation. The allograft was salvaged following IVIg and steroids. The patient developed recurrent disease which failed rechallenge with pembrolizumab but achieved a partial response following cemiplimab administration. This case illustrates the potential to treat metastatic CSCC in a SOTR with anti-programmed death-1 therapy and preserve graft function despite allograft rejection.

Összefoglaló. Bevezetés: A gyermekkori májtranszplantációk hosszú távú kimenetelének javítása érdekében az immunológiai mechanizmusok kerültek a kutatások középpontjába. A donorspecifikus antitesteknek (DSA-k) fontos szerepük van a graft túlélésében a szervtranszplantációk után, a májtranszplantáció esetén azonban ez még vitatott. Célkitűzés: Tanulmányunk célja májtranszplantált gyermekeknél a DSA-k meghatározása, valamint a DSA-k jelenléte és a graft állapota közötti összefüggés vizsgálata volt. Módszer: A Semmelweis Egyetem I. Sz. Gyermekgyógyászati Klinikáján gondozott 54 májtranszplantált gyermek vérmintájából történt a humán leukocytaantigén (HLA) elleni antitestek meghatározása. Vizsgáltuk, hogy a laboratóriumi vérvizsgálat eredményei – szérumbilirubin (összes, direkt), alkalikus foszfatáz (ALP), transzaminázok, gamma-glutamil-transzferáz (GGT), immunglobulin-G (IgG) –, az aszpartát-aminotranszferáz/thrombocyta hányadosindex (APRI) és a 4 tényezőn alapuló fibrosisindex (FIB4) tekintetében van-e eltérés a DSA-pozitív, illetve a HLA-immunizált betegek esetén a nem immunizált csoporthoz képest. Eredmények: A vizsgált paraméterekben nem találtunk szignifikáns különbségeket a DSA-pozitív, a HLA-immunizált és a nem immunizált betegek csoportjai között. Következtetés: Bár a jelen vizsgálatban nem volt szignifikáns különbség a vizsgált paraméterek esetén, de ez a kis esetszámból is adódhat. A DSA-knak a graftfibrosis kialakulásában való szerepe tisztázására több páciens vizsgálata szükséges, ezért megkezdtük az összes páciensnél a DSA- és HLA- (donor, recipiens) meghatározást, valamint ennek a klinikai gyakorlatunkba való beépítését. Orv Hetil. 2021; 162(47): 1897–1901. Summary. Introduction: To improve the long-term survival of liver-transplanted children, immunological mechanisms became the main interest of researchers. Donor-specific antibodies (DSAs) play a significant role in graft survival after solid organ transplantation, although their role in liver transplantation is controversial. Objective: The aim of our study was to determine the presence of DSAs in liver-transplanted children and to examine their effect on graft’s condition. Method: The determination of anti-human leukocyte antigen (HLA) antibodies was performed using the blood samples of 54 liver-transplanted children. We analysed the difference between the results of the laboratory blood examination – serum bilirubin (all, direct), alkaline-phosphatase (ALP), transaminases, gamma-glutamyl transferase (GGT), immunoglobulin-G (IgG) –, aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB4) according to DSA and HLA immunization. Results: We did not find any significant difference in the examined parameters regarding DSA and HLA immunization. Conclusion: Although this study was not able to provide significant difference in the examined parameters, this can be explained with the low number of cases. To clarify the significance of DSA in graft fibrosis, we need a larger dataset. We started regular DSA and HLA (donor and recipient) determination during follow-up in liver-transplanted children. Orv Hetil. 2021; 162(47): 1897–1901.

Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades due to their potent effects on the innate immunity and tissue protective effects. But, some SOT centers are reluctant to administer GCs for long-time due to the various side effects. This review summarizes advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes cover “transplantation” and “glucocorticoids”.GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute anti-body- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells are new methods of GC usage in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects on different non-targeted organs/tissues such as bone, cardiovascular, neuromuscular, skin, and gastrointestinal tract have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

Background: The number of liver transplant recipients (LTR) is worldwide increasing and, as the survival is improving as well, there is an increasing number of patients needing total hip arthroplasty (THA). There might be increased risks for this specific group of patients and due to their comorbidities costs might be higher too. Using a big national database outcome and cost of THA should be compared between liver transplant recipients and the general population. Methods: The study was performed using a collection of Medicare, Medicaid, and private insurance claims. Length of stay (LOS), 30-day readmissions, complications rates up to 5 years, and 90-day total cost of care between liver transplant recipients and matched non-transplant patients should be compared. All primary THAs from 2010 to 2019 were identified. 513 patients with a liver transplant before their THA were matched to 10,759 patients without a history of solid organ transplant at a 1:20 ratio based on age, sex, Charlson Comorbidity Index, obesity, and diabetes status. Results: LTR had a longer average LOS (4.2 vs. 3.4 days, p Conclusions: These findings suggest that complications and costs are no major point of concern in patients with liver transplant that are operated with THA.

The COVID-19 pandemic continues to generate challenges for pediatric solid organ transplant (SOT) recipients and their families. As rates of COVID-19 fluctuate, new SARS-CoV-2 variants emerge, and adherence to and implementation of mitigation strategies vary from community to community, questions remain about the best and safest practices to prevent COVID-19 in vulnerable patients. Notably, decisions about returning to school remain difficult. We assembled a team of specialists in pediatric infectious diseases, transplant infectious diseases, public health, transplant psychology, and infection prevention and control to re-address concerns about school re-entry, as well as COVID-19 vaccines, for pediatric SOT recipients in the United States in 2021. Based on available literature and guidance from national organizations, we generated expert statements specific to pediatric SOT recipients focused on school attendance in 2021.

Purpose To summarize the journey of a tertiary and quaternary care hospital outside the United States in receiving American Society of Health-System Pharmacists (ASHP) accreditation for its pharmacy services. Summary Tertiary and quaternary care hospitals have gained their reputation owing to the high quality and advanced services that they provide. Our organization, King Faisal Hospital & Research Center (KFSH&RC), Riyadh, Saudi Arabia, is a 1300-bed capacity hospital that serves as a center of excellence in solid organ transplant, genetic and metabolic diseases, hematology and oncology, and cardiology, in addition to a diversity of medical services. Accreditation of the pharmacy services by ASHP represents an important recognition of the quality and breadth of the services performed at KFSH&RC. The process of accreditation and the accreditation standards have also continued to serve as a guide for the hospital to maintain pharmacy service standards as they evolve. Conclusion As the first internationally accredited pharmacy services, KFSH&RC now demonstrates the path forward for other international hospitals seeking to reach the same standards of practice defined by ASHP.

Abdominal pain in an immunocompromised patient represents a common clinical scenario that may have uncommon causes. Evaluation relies first on identifying the immunocompromise, whether due to congenital immunodeficiencies, malignancy, hematopoietic stem cell transplant, solid organ transplant, or human immunodeficiency virus/acquired immunodeficiency syndrome. Based on this determination, the emergency physician may then build a focused differential of pathophysiologic possibilities. Careful evaluation is necessary given the absence of classic physical examination findings, and liberal use of laboratory and cross-sectional imaging is prudent. Conservative evaluation and disposition of these high-risk patients is important to consider.

BACKGROUND AND AIM Identification of the most appropriate population pharmacokinetic model-based Bayesian estimation is required prior to its implementation in routine clinical practice to inform tacrolimus dosing decisions. This study aimed to determine the predictive performances of relevant population pharmacokinetic models of tacrolimus developed from various solid organ transplant recipient populations in adult heart transplant recipients, stratified based on concomitant azole antifungal use. Concomitant azole antifungal therapy alters tacrolimus pharmacokinetics substantially, necessitating dose adjustments. METHODS Population pharmacokinetic models of tacrolimus were selected (n = 17) for evaluation from a recent systematic review. The models were transcribed and implemented in NONMEM version 7.4.3. Data from 85 heart transplant recipients (2387 tacrolimus concentrations) administered the oral immediate-release formulation of tacrolimus (Prograf) were obtained up to 391 days post-transplant. The performance of each model was evaluated using: (i) prediction-based assessment (bias and imprecision) of the individual predicted tacrolimus concentration of the fourth dosing occasion (MAXEVAL = 0, FOCE-I) from 1-3 prior dosing occasions; and (ii) simulation-based assessment (prediction-corrected visual predictive check). Both assessments were stratified based on concomitant azole antifungal use. RESULTS Regardless of the number of prior dosing occasions (1-3) and concomitant azole antifungal use, all models demonstrated unacceptable individual predicted tacrolimus concentration of the fourth dosing occasion (n = 152). The prediction-corrected visual predictive check graphics indicated that these models inadequately predicted observed tacrolimus concentrations. CONCLUSION All models evaluated were unable to adequately describe tacrolimus pharmacokinetics in adult heart transplant recipients included in this study. Further work is required to describe tacrolimus pharmacokinetics for our heart transplant recipient cohort.

BACKGROUND Solid organ transplantation is a life-saving intervention for end-stage organ disease. Post-transplant diabetes mellitus (PTDM) is a common complication in solid organ transplant recipients, and significantly compromises long-term survival beyond a year. AIM To perform a systematic review and meta-analysis to estimate incidence of PTDM and compare the effects of the 3 major immunosuppressants on incidence of PTDM. METHODS Two hundred and six eligible studies identified 75595 patients on Tacrolimus, 51242 on Cyclosporine and 3020 on Sirolimus. Random effects meta-analyses was used to calculate incidence. RESULTS Network meta-analysis estimated the overall risk of developing PTDM was higher with tacrolimus (OR = 1.4 95%CI: 1.0–2.0) and sirolimus (OR = 1.8; 95%CI: 1.5–2.2) than with Cyclosporine. The overall incidence of PTDM at years 2-3 was 17% for kidney, 19% for liver and 22% for heart. The risk factors for PTDM most frequently identified in the primary studies were age, body mass index, hepatitis C, and African American descent. CONCLUSION Tacrolimus tends to exhibit higher diabetogenicity in the short-term (2-3 years post-transplant), whereas sirolimus exhibits higher diabetogenicity in the long-term (5-10 years post-transplant). This study will aid clinicians in recognition of risk factors for PTDM and encourage careful evaluation of the risk/benefit of different immunosuppressant regimens in transplant recipients.

Background Our objective was to determine if the addition of ultraviolet-C (UV-C) light to daily and discharge patient room cleaning reduces healthcare-associated infection rates of vancomycin-resistant enterococci (VRE) and Clostridioides difficile in immunocompromised adults. Methods We performed a cluster randomized crossover control trial in 4 cancer and 1 solid organ transplant in-patient units at the Johns Hopkins Hospital, Baltimore, Maryland. For study year 1, each unit was randomized to intervention of UV-C light plus standard environmental cleaning or control of standard environmental cleaning, followed by a 5-week washout period. In study year 2, units switched assignments. The outcomes were healthcare-associated rates of VRE or C. difficile. Statistical inference used a two-stage approach recommended for cluster-randomized trials with Results In total, 302 new VRE infections were observed during 45787 at risk patient-days. The incidence in control and intervention groups was 6.68 and 6.52 per 1000 patient-days respectively; the unadjusted incidence rate ratio (IRR) was 0.98 (95% confidence interval [CI], .78 − 1.22; P = .54). There were 84 new C. difficile infections observed during 26118 at risk patient-days. The incidence in control and intervention periods was 2.64 and 3.78 per 1000 patient-days respectively; the unadjusted IRR was 1.43 (95% CI, .93 − 2.21; P = .98). Conclusions When used daily and at post discharge in addition to standard environmental cleaning, UV-C disinfection did not reduce VRE or C. difficile infection rates in cancer and solid organ transplant units.

Purpose of review Policy development for uterus transplantation (UTx) is in its infancy. Understanding current oversight of UTx programmes can inform further development. Recent findings Currently, the United States has the most comprehensive regulations for UTx. Much of the policy outside the USA is focused on candidate selection. In the USA, UTx is categorized as, and follows policies of, a vascular composite allograft. Some considerations for UTx have not yet been addressed in policy, including the need for candidates to have a viable embryo before listing and transplantation, additional factors that may be warranted in organ allocation and the need to report data on the infant as well as the recipient. Summary Oversight of UTx falls within the governance of solid organ transplantation with unique aspects to be considered. Guidelines for multidisciplinary care, transplant-focused infrastructure and defined outcome metrics found in other solid organ transplant programmes provide a useful framework for UTx programmes.

The concept of frailty has gained considerable interest in clinical solid organ transplantation over the past decade. Frailty as a phenotypic construct to describe a patient's risk from biologic stresses, has an impact on posttransplant survival. There is keen interest in characterizing frailty in lung transplantation, both to determine which patients are suitable candidates for listing and also to prepare for their care in the aftermath of lung transplantation. Here we review the current status of research on frailty in lung transplant candidates and recipients. This review will highlight areas of uncertainty for frailty in clinical lung transplantation which are likely to impact the state-of-the-art in the field for the next decade.

The mortality rate from COVID-19 appears to be higher in solid organ transplant (SOT) recipients when compared with other populations. Vaccination is a key strategy to prevent the COVID-19 pandemic. However, it is unclear how readily SOT recipients will get vaccinated against COVID-19. We conducted an internet-based survey to investigate the vaccination willingness among Chinese SOT recipients and further explore possible influencing factors. Eight hundred and thirteen respondents participated in the survey. Overall, 46 (5.7%) recipients were vaccinated against COVID-19, while 767 (94.3%) were not. Among those not vaccinated, 175 (22.8%) intended to be vaccinated, while 592 (77.2%) were categorized as vaccine-hesitant. The most common reason for vaccination hesitancy is fear of preexisting comorbidities, followed by fear of side effects and doctors’ negative advice. Factors associated with vaccination willingness were as follows: with liver transplantation, the main source of information on COVID-19 vaccines was from medical doctors, scientists, and scientific journals, with at least college-level education, positive intention toward influenza vaccination during the current season, perceived importance of vaccination for SOT recipients, and having been vaccinated against influenza during the last season. Our survey indicated the necessity for SOT recipients to receive more comprehensive and accessible health education about vaccination and emphasized the critical role of transplantation physicians in promoting vaccine acceptance among SOT recipients. We hope that our survey results will help governments to better target communication in the ongoing COVID-19 vaccination campaign.

(COVID-19) has resulted in significant morbidity and mortality in solid organ transplant recipients. In December 2020, at the peak of the Los Angeles outbreak, our center rapidly implemented a protocol to improve outpatient management and provide bamlanivimab or casirivimab-imdevimab [COVID monoclonal antibody (mAb) therapies] to all eligible COVID-19 positive liver and kidney transplant recipients.A retrospective review of all abdominal organ transplant recipients who were COVID-19 polymerase chain reaction positive between February 2020 and February 2021 from our center was performed. Patient demographics, COVID-19 treatments, hospitalizations, and survival were reviewed. Patients were considered eligible for COVID mAb therapy if they met outpatient criteria at the time of diagnosis.In the study period, 121 patients in the kidney transplant recipients group (KG) and 105 patients in the liver or combined liver/kidney transplant recipients group (LG) were COVID-19 polymerase chain reaction positive. Hospitalization rates were similar for the KG (45%) versus LG (35%) (P = 0.20), but mortality was higher for the KG (22%) when compared to LG (10%) (P = 0.02). Our programmatic response, including outpatient COVID mAb therapies, reduced hospitalizations (P = 0.01) and deaths (P = 0.01). Ninety-four KG and 87 LG patients were identified as potentially eligible for COVID mAb therapy, and 17 KG and 17 LG patients were treated. COVID mAb therapies reduced hospitalization from 32% to 15% (P = 0.045) and eliminated mortality (13% versus 0%, P = 0.04).An aggressive approach including outpatient COVID mAb therapy in the COVID positive abdominal organ transplant recipients significantly decreased hospitalization and death. Early outpatient intervention for COVID-19 disease in transplant patients should be considered where possible.

Rotator cuff repair is the second most common soft tissue procedure performed in orthopedics. Additionally, an increasing percentage of the population has received a solid organ transplant (SOT). The chronic use of immunosuppressants as well as a high prevalence of medical comorbidities in this population are both important risk factors when considering surgical intervention. The purpose of this study is to determine the demographic profile, comorbidity profile, and perioperative complication rate of SOT patients undergoing inpatient rotator cuff repair surgery compared to nontransplanted patients.The Nationwide Inpatient Sample (NIS) database was queried from years 2002-2017 to identify all patients who underwent inpatient rotator cuff repair (n = 144,528 weighted). This group was further divided into SOT (n = 286 weighted) and nontransplant (n = 144,242 weighted) cohorts. Demographic and comorbidity analyses were performed between these groups. Additionally, a matched cohort of nontransplanted patients controlled for the year of procedure, age, sex, race, income, and hospital region was created in a 1:1 ratio to the SOT group (n = 286 each) for perioperative complication rate analysis.Compared to nontransplanted patients, SOT patients were more likely to have at least 1 significant medical comorbidity (98% vs. 69%, P.001), had a higher number of total comorbidities (3.1 vs. 1.4, P.001), and had a higher Charlson-Deyo Comorbidity Index (2.6 vs. 0.54, P.001). Compared to the matched cohort, SOT patients experienced longer hospital stays (2.9 vs. 1.8 days, P.001), higher surgery costs ($12,031 vs. $8476, P.001), and were more likely to experience a perioperative complication (24% vs. 3%, P.001) with an odds ratio of 7.7 (95% confidence interval: 3.9-15.1).Compared with nontransplanted patients, SOT patients undergoing rotator cuff repair had a significantly higher comorbidity index, longer hospital stays, costlier surgeries, and were7 times more likely to experience a perioperative complication. With nearly a quarter of all SOT patients experiencing a perioperative complication following rotator cuff repair, careful consideration for surgery as well as increased postoperative surveillance should be considered in this unique population.

Fasting in the month of Ramadan is an obligatory act for healthy adult Muslims. It requires abstinence from food and drink from dawn to sunset. Although there are exemptions from fasting, many patients are keen to fulfil what they see as a religious obligation, even if this may be against medical advice in some cases. Solid organ transplant (SOT) recipients often ask healthcare professionals for advice on fasting. Studies on the effect of fasting in transplant patients have all been done in the Middle East and North Africa where the average fasting duration is between 12 and 14 hours. In comparison, in temperate regions in the summer, fasting duration can be as long as 20 hours. Fasting when patients have to take immunosuppression 12 hours apart with little time variation poses unique challenges. In this review, current literature is reviewed, and a decision-making tool has been developed to assist clinicians in discussing the risks of fasting in transplant recipients, with consideration also given to circumstances such as the COVID-19 pandemic. Our review highlights that SOT recipients wishing to fast should undergo a thorough risk assessment, ideally 3 months before Ramadan. They may require medication changes and a plan for regular monitoring of graft function and electrolytes in order to fast safely. Recommendations have been based on risk tiers (very high risk, high risk and low/moderate risk) established by the International Diabetes Federation and the Diabetes and Ramadan International Alliance. Patients in the ‘very high risk’ and ‘high risk’ categories should be encouraged to explore alternative options to fasting such as winter fasting or Fidyah. Those in the ‘low/moderate’ category may be able to cautiously fast with guidance from their clinician. Prior to the commencement of Ramadan, all patients must receive up-to-date education on sick-day rules, instructions on when to terminate their fast or abstain from fasting.

The aim of this workis to provide basic answers to questions related to the vaccination of solid organ transplant recipients based on the latest literature sources and clinical guidelines. Vaccination of solid organ transplants and persons in constant contact with them is a mandatory measure, the provision of which is a vital measure that effectively reduces the risk of death from COVID-19. Doubts about less effectiveness in conditions of immunosuppression or the potential risk of developing adverse reactions are significantly inferior to the risk of death and the development of severe complications. Until new data become available, the vaccination regimen must strictly comply with the instructions for medical use of the drug. Before transplantation, the patient should be examined according to the screening protocol, and also consulted by the transplant doctor who supervises him. It is possible that whole virion vaccines (CoviVac) have an advantage over others when vaccinating solid organ recipients, but clinical experience in this matter has not yet been obtained.

Cytomegalovirus (CMV) is an opportunistic infection that affects immunocompromised solid organ transplant patients. Defining the imbalance between host and virus factors that predispose to its occu...

Pre‐clinical haematopoietic cell transplantation (HCT) studies in canines have proven to be invaluable for establishing HCT as a highly successful clinical option for the treatment of malignant and non‐malignant haematological diseases in humans. Additionally, studies in canines have shown that immune tolerance, established following HCT, enabled transplantation of solid organs without the need of lifelong immunosuppression. This progress has been possible due to multiple biological similarities between dog and mankind. In this review, the hurdles that were overcome and the methods that were developed in the dog HCT model which made HCT clinically possible are examined. The results of these studies justify the question whether HCT can be used in the veterinary clinical practice for more wide‐spread successful treatment of canine haematologic and non‐haematologic disorders and whether it is prudent to do so., Pre‐clinical haematopoietic cell transplantation (HCT) studies in canines were essential to the establishment of HCT as a treatment option for haematological malignant and non‐malignant diseases in man, and a proven method to induce tolerance towards solid organ transplantation. With recent advancements in mind, it is time to assess whether HCT can be applied in a more routine manner in the veterinary clinical practice for treating dogs with similardisorders.

OBJECTIVE The objective of this study was to evaluate the clinical, laboratory, imaging, and pathology findings associated with emergency department presentations of posttransplant lymphoproliferative disorder (PTLD) after solid organ transplant (SOT). METHODS Fifteen patients presenting to a single tertiary care center between 2004 and 2019 with PTLD after SOT were identified from a pathology database. Twelve patients presenting through the emergency department were included in the study. Demographic, clinical, imaging, pathology, treatment, and outcome data were reviewed. RESULTS Among this 12 patient cohort (7 men; mean age, 44.2 years), transplant history included 4 combined kidney/pancreas, 4 kidney, 2 liver, 1 cardiac, and 1 lung. Mean time from transplant to diagnosis was 7.6 years. Posttransplant lymphoproliferative disorder was identified on initial computed tomography scans in 10 of 12 patients. The most common sites for PTLD development were the gastrointestinal tract (4/12) and liver (3/12). Outcomes included resolution of PTLD in 9 of 12 patients, with 3 patients dying within 6 months of diagnosis. CONCLUSIONS Posttransplant lymphoproliferative disorder is a serious consequence of solid organ transplantation that can present in various locations and with varied symptomatology in the emergency setting. Other posttransplant complications may present similarly including chronic rejection and infection. Posttransplant lymphoproliferative disorder should be considered in SOT patients presenting with worsening abdominal pain or constitutional symptoms, even with normal laboratory workup.

Tacrolimus is an immunosuppressive drug frequently used in solid organ transplant recipients. This drug has well-documented neuropsychiatric side effects in the literature, although emergence of psychotic symptoms is rare, being only described in a very few case reports. We present a case of a renal transplant recipient with no prior psychiatric history, who developed a severe psychosis secondary to supratherapeutic tacrolimus' blood concentrations. This case highlights the importance of clinical awareness to rare but severe neuropsychiatric effects due to tacrolimus use. info:eu-repo/semantics/publishedVersion

The avoidance of antibody-mediated rejection (AMR) attributed to human leucocyte antigen (HLA) antibody incompatibility remains an essential function of clinical Histocompatibility and Immunogenetics (H&I) laboratories who are supporting solid organ transplantation. Developments in HLA antibody identification assays over the past thirty years have greatly reduced unexpected positive cellular crossmatches and improved solid organ transplant outcomes. For sensitized patients, the decision to register unacceptable HLA antigen mismatches is often heavily influenced by results from solid phase antibody assays, particularly the Luminex® Single Antigen Bead (SAB) assays, although the clinical relevance of antibodies identified solely by these assays remains unclear. As such, the identification of non-clinically relevant antibodies may proportionally increase the number of unacceptable transplant mismatches registered, with an associated increase in waiting time for a compatible organ. We reflect on the clinical relevance of antibodies identified solely by the Luminex SAB® assays and consider whether the application of additional assays and/or tools could further develop our ability to define the clinical relevance of antibodies identified in patient sera. Improvements in this area would assist equity of access to a compatible transplant for highly sensitized patients awaiting a solid organ transplant.

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1-2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6-7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.

Objective The COVID-19 pandemic and lockdown measures have had a clear psychological impact on families, and specifically those with children with chronic illnesses have reported greater overloads and exhaustion. The objective of this study was to evaluate the exposure, impact and experience of the pandemic on families of pediatric solid organ transplant (SOT) recipients compared to families of healthy children and adolescents. Methods We recruited 96 families, 48 with a pediatric SOT recipient and 48 healthy controls, matched by child age and gender. A primary caregiver from each family responded to an online sociodemographic questionnaire and the COVID-19 Exposure and Family Impact Survey (CEFIS), which explores the exposure, impact and experience of the pandemic and lockdown on families. Results Exposure to the pandemic was greater in families of healthy children and adolescents. The impact was mostly negative in both groups: caregivers reported increased anxiety (76%) and mood disturbances (71.9%) and hindered quality of sleep (64.6%) and health habits (58.3%). On the positive side, family relationships improved. Qualitatively, the SOT group positively perceived isolation and established hygienic measures as protective and destigmatizing, although they reported fear of virus transmission to their child. Conclusions The psychological impact of the pandemic has been similar in both groups, although families of transplant recipients have protected themselves more, probably because they are used to prevention measures and they see contagion as a graver risk. Additionally, SOT recipients’ families presented some idiosyncratic elements, especially a decrease in their perception of stigma associated with the medical condition.

Background Given the success of direct-acting antivirals (DAAs) in treating hepatitis C (HCV), interest is growing in utilizing solid organs from allografts with active HCV to expand donor availability. Aim To review post-transplant outcomes and patient survival in HCV-negative recipients receiving solid organ transplants (SOT) from viraemic, that is, HCV+/NAT+ (nucleic acid testing) allografts. Methods A literature search was conducted on PubMed and EMBASE from 01/01/2007 to 4/17/2021 for articles matching eligibility criteria. Two authors independently screened titles and abstracts. Disagreements were solved by a third independent reviewer. Methodological quality assessment was done using a modified Newcastle-Ottawa scale (NOS). Data synthesis was done qualitatively using median, ranges and percentages. Results Thirty-five studies were included (or 852 SOTs): 343 kidney, 233 heart, 204 liver, and 72 lung transplants from viraemic allografts. Of the recipients eligible for sustained virological response at 12 weeks (SVR12) calculation, 100% achieved cure from HCV. No deaths/graft failures were reported to be related to HCV transmission. Seven SOT recipients had viral relapse, with all seven patients treated successfully. Four patients developed fibrosing cholestatic hepatitis with complete resolution post-treatment. Conclusions Transplanting viraemic organs into uninfected individuals can become the standard of care for patients who do not have contraindications to DAAs.

Infectious complications after solid organ transplantation (SOT) are often more severe and remain a diagnostic challenge due to vague and atypical clinical presentations. Diagnostic performance of conventional diagnostic tools is frequently inadequate which may lead to delayed diagnosis with the risk of poorer outcomes. This literature review aimed to investigate the current evidence on the use of 18F-fluoro-deoxy-glucose (FDG) Positron Emission Tomography (PET)/computer tomography (CT) in infectious complications after SOT. Based on search in PubMed, Medline, and Cochrane databases, 13 articles and 46 case reports were included. For inclusion, articles were to include data on patients with infectious complications after SOT, and where FDG PET/CT was part of the work-up. Final searches were conducted on 02 September 2020. Overall, in the absence of initial diagnostic clues, FDG PET/CT should be considered as the imaging technique of choice as it may guide further investigations and eventually reveal the diagnosis in most of the patients. However, the available literature of the role of FDG PET/CT in SOT recipients with infectious complications is scarce and well-designed prospective studies including control groups are warranted to establish the role of FDG PET/C/ in SOT recipients. The main drawback of FDG PET/CT is the lack of ability to differentiate between cancer and infectious diseases which are both highly prevalent in this patient group. Accordingly, the main reasons for “false” results of FDG PET/CT is the misdiagnosis of cancer in benign inflammatory or infectious processes, information which nonetheless can be useful.

Solid organ transplantation offers life-saving treatment for patients with end-organ dysfunction. Patient survival and quality of life have improved over the past few decades as a result of pharmacological development, expansion of the donor pool, technological advances and standardization of practices related to transplantation. Still, transplantation is associated with cardiovascular complications, of which post-transplant diabetes mellitus (PTDM) is one of the most important. PTDM increases mortality, which is best documented in patients who have received kidney and heart transplants. PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus, but also from specific post-transplant risk factors such as metabolic side effects of immunosuppressive drugs, post-transplant viral infections and hypomagnesemia. Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients. However, the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited. The favourable risk/benefit ratio, which is suggested by large-scale and long-term studies on new glucose-lowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, makes studies warranted to assess the potential role of these agents in the management of PTDM.

Background Infection with multi-drug–resistant organisms (MDROs) is a life-threatening disease among abdominal solid organ transplantation recipients. Reports of donor-derived (DD) MDRO infections were few, but adverse clinical outcomes were severe, such as death or graft loss. Methods The medical records of 68 donation after citizens’ death donors with MDRO infections and 20 recipients transmitted with infections between October 1, 2015, and September 1, 2020, were reviewed according to the Declaration of Helsinki and the Declaration of Istanbul. There were no grafts from prisoners, and no donors were not coerced or paid. Results Prevalence and mortality of DD-MDRO infection among abdominal solid organ transplantation recipients were 2.3% and 18.1%, respectively. The prevalence rate of DD-MDR gram-negative bacterial infection was higher than that of gram-positive bacterial infection (1.7% vs 0.6%). Negative culture of specimens occurred in 9 of 68 donors. Recipients with DD-MDR gram-negative bacterial infections had a significantly lower survival rate compared with DD-MDR gram-positive bacterial infections (P = .046). Conclusions Donation after citizens’ death donors and recipients had high MDRO infection rates, and gram-negative bacteria were the predominant pathogens. When a possible DD-MDRO infection occurs, there may be adverse outcomes with limited choice of antibiotics. A nationwide surveillance and communication network needs to be established in China.

Solid organ transplantation has seen improvements in both surgical techniques and immunosuppression, achieving prolonged survival. Essential to graft acceptance and post-transplant recovery, immunosuppressive medications are often accompanied by a high prevalence of gastrointestinal (GI) symptoms and side effects. Apart from GI side effects, long-term exposure to immunosuppressive medications has seen an increase in drug-related morbidities such as diabetes mellitus, hyperlipidaemia, hypertension, and malignancy. Non-adherence to immunosuppression can lead to an increased risk of graft failure. Recent research has indicated that any microbial imbalances (otherwise known as gut dysbiosis or leaky gut) may be associated with cardiometabolic diseases in the long term. Current evidence suggests a link between the gut microbiome and the production of putative uraemic toxins, increased gut permeability, and transmural movement of bacteria and endotoxins and inflammation. Early observational and intervention studies have been investigating food-intake patterns, various synbiotic interventions (antibiotics, prebiotics, or probiotics), and faecal transplants to measure their effects on microbiota in treating cardiometabolic diseases. It is believed high doses of synbiotics, prebiotics and probiotics are able to modify and improve dysbiosis of gut micro-organisms by altering the population of the micro-organisms. With the right balance in the gut flora, a primary benefit is believed to be the suppression of pathogens through immunostimulation and gut barrier enhancement (less permeability of the gut).To assess the benefits and harms of synbiotics, prebiotics, and probiotics for recipients of solid organ transplantation.We searched the Cochrane Kidney and Transplant Specialised Register up to 9 March 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.We included randomised controlled trials measuring and reporting the effects of synbiotics, prebiotics, or probiotics, in any combination and any formulation given to solid organ transplant recipients (any age and setting). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.Data extraction was independently carried out by two authors using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Five studies (250 participants) were included in this review. Study participants were adults with a kidney (one study) or liver (four studies) transplant. One study compared a synbiotic to placebo, two studies compared a probiotic to placebo, and two studies compared a synbiotic to a prebiotic. Overall, the quality of the evidence is poor. Most studies were judged to have unclear (or high) risk of bias across most domains. Of the available evidence, meta-analyses undertaken were of limited data from small studies. Across all comparisons, GRADE evaluations for all outcomes were judged to be very low certainty evidence. Very low certainty evidence implies that we are very uncertain about results (not estimable due to lack of data or poor quality). Synbiotics had uncertain effects on the change in microbiota composition (total plasma p-cresol), faecal characteristics, adverse events, kidney function or albumin concentration (1 study, 34 participants) compared to placebo. Probiotics had uncertain effects on GI side effects, infection rates immediately post-transplant, liver function, blood pressure, change in fatty liver, and lipids (1 study, 30 participants) compared to placebo. Synbiotics had uncertain effects on graft health (acute liver rejection) (2 studies, 129 participants: RR 0.73, 95% CI 0.43 to 1.25; 2 studies, 129 participants; I² = 0%), the use of immunosuppression, infection (2 studies, 129 participants: RR 0.18, 95% CI 0.03 to 1.17; I² = 66%), GI function (time to first bowel movement), adverse events (2 studies, 129 participants: RR 0.79, 95% CI 0.40 to 1.59; I² = 20%), serious adverse events (2 studies, 129 participants: RR 1.49, 95% CI 0.42 to 5.36; I² = 81%), death (2 studies, 129 participants), and organ function measures (2 studies; 129 participants) compared to prebiotics.This review highlights the severe lack of high-quality RCTs testing the efficacy of synbiotics, prebiotics or probiotics in solid organ transplant recipients. We have identified significant gaps in the evidence. Despite GI symptoms and postoperative infection being the most common reasons for high antibiotic use in this patient population, along with increased morbidity and the growing antimicrobial resistance, we found very few studies that adequately tested these as alternative treatments. There is currently no evidence to support or refute the use of synbiotics, prebiotics, or probiotics in solid organ transplant recipients, and findings should be viewed with caution. We have identified an area of significant uncertainty about the efficacy of synbiotics, prebiotics, or probiotics in solid organ transplant recipients. Future research in this field requires adequately powered RCTs comparing synbiotics, prebiotics, and probiotics separately and with placebo measuring a standard set of core transplant outcomes. Six studies are currently ongoing (822 proposed participants); therefore, it is possible that findings may change with their inclusion in future updates.

Purpose of review The approach to ongoing organ transplantation and management of COVID-19 in solid organ transplant recipients (SOTR) has evolved tremendously since the pandemic’s beginning. We summarize the current literature surrounding the virology of SARS-CoV-2, epidemiology of COVID-19 in transplant recipients, review the clinical features and complications of COVID-19 in SOTR, and discuss the safety and efficacy of current therapies and candidate vaccines in this population. Recent findings Despite initial suspensions in organ transplantation during early 2020, routine donor testing and de-crowding of hospitals have allowed transplant activity to resume at pre-pandemic rates. COVID-19-associated mortality in SOTR is similar to that of the general population, and lower than that of patients with end-organ disease awaiting transplant. The optimal approach to immunosuppression in SOTR with COVID-19 is unknown and disease severity may influence management decisions. Many vaccines in development are likely to be safe for immunocompromised hosts, though post-marketing investigations will be required to determine the efficacy in the SOTR. Summary Though there are multiple unique considerations in the care of SOTR with COVID-19, immunosuppression does not appear to have a detrimental impact on overall outcome. Organ transplantation remains a lifesaving intervention and can be safely performed despite a global pandemic.

The solid organ transplant community is slow to adopt the routine practice of using direct oral anticoagulants. Rivaroxaban and apixaban share common metabolic pathways with tacrolimus. This study aimed to clarify the impact of rivaroxaban/apixaban on tacrolimus troughs. Fifty solid organ transplant recipients with concomitant use of tacrolimus and rivaroxaban/apixaban were retrospectively assessed for changes in tacrolimus troughs and dose. Average dose-adjusted tacrolimus troughs and average tacrolimus total daily doses prior to and after rivaroxaban/apixaban initiation were compared. Subgroup analyses evaluating rivaroxaban and apixaban individually were performed. Rivaroxaban was prescribed to 18 recipients, and apixaban was prescribed to 32 recipients. Transplanted organs included kidney (n = 22), lung (n = 18), liver (n = 7), simultaneous pancreas and kidney (n = 1), and simultaneous kidney and liver (n = 2). The median doseadjusted tacrolimus trough and tacrolimus total daily dose prior to rivaroxaban/apixaban initiation was 2.15 ng/mL/mg (IQR 1.17, 3.37) and 4 mg (IQR 1.88, 6.25), respectively. The median dose-adjusted tacrolimus trough and tacrolimus total daily dose after rivaroxaban/apixaban initiation was 2.16 ng/mL/mg (IQR 1.24, 4.10) and 3.55 mg (IQR 1.5, 6.35), respectively. No significant difference was found between average dose-adjusted tacrolimus troughs or tacrolimus total daily doses before and after rivaroxaban/apixaban initiation or in the individual subgroup analyses for rivaroxaban/apixaban. It is unlikely that initiating rivaroxaban/apixaban affects tacrolimus troughs or requires tacrolimus dose adjustment. This study does not elucidate if tacrolimus affects rivaroxaban/apixaban pharmacokinetics or pharmacodynamics.