Post-transplant Complications Research Articles

Effect of pregnancy-specific β1-glycoprotein on the expression of arginase-1 and indolamine-2,3-dioxygenase by myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSC) - a population of immature cells of myeloid origin with inhibitory functions, mainly related to T lymphocytes. Normally, MDSC account for less than 1% of leukocytes in peripheral blood. The number of these cells increases during healthy pregnancy. However, MDSC have been shown to play a critical role in the maintenance of tumor growth and in autoimmune diseases.
 Because MDSC are now considered important regulators of immunity, finding ways to manipulate their functions is important for the development of therapies for malignant and autoimmune diseases, as well as for pregnancy pathologies and post-transplant complications. The immunosuppressive mechanisms of these cells are mediated by their expression of the surface molecules CD73, ADAM17, PD -L1, the enzymes arginase 1 (Arg 1), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO), reactive oxygen species, and the production of the anti-inflammatory cytokines IL -10 and TGF-1.
 Pregnancy-specific 1-glycoprotein (PSG) is a pregnancy glycoprotein that has immunomodulatory effects on natural (dendritic cells and macrophages) and adaptive (T cells) immunity cells. At the same time, the effect of PSG on MDSC has not been investigated so far. Since this glycoprotein has promising pharmacological applications, it is necessary to study not only the native variant of PSG but also its recombinant form.
 Since the main function of MDSC is immunosuppression, the aim of our work was to evaluate one of its mechanisms, namely the intracellular expression of amino acid degradation enzymes Arg1 and IDO under the influence of native and recombinant PSG in vitro.
 MDSC differentiation was performed from CD11b+ cells isolated from peripheral blood of healthy volunteers. Cells were cultured for 7 days with stepwise addition of GM-CSF, IL -1, and LPS. Native (n) (1, 10, and 100 g/mL) and recombinant (r) (1 and 10 g/mL) PSG was added to the cultures three days before the end of incubation. The percentage of MDSCs (Lin- HLA-DR -CD11b+CD33+) intracellularly expressing Arg1 and IDO was determined by flow cytometry.
 It was found that nPSG and rPSG did not alter the amount of Arg1-expressing MDSCs at all concentrations examined. However, at a concentration of 10 g/mL, both types of proteins caused a statistically significant increase in the percentage of cells expressing IDO.
 We have already established that nPSG and rPSG affect MDSC differentiation by increasing the proportion of these cells belonging to the monocytic subpopulation. However, now we can say that PSG, in addition, enhances the suppressive function of the studied cells.
 The obtained data are novel and open perspectives for targeting myeloid suppressor cells to improve cellular technologies in science and medicine.

Heart transplantation and human immunodeficiency virus–navigating drug-drug interactions: a case report

BackgroundAntiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions.Case presentationA 58-year-old man with HIV-1 developed ischemic cardiomyopathy, progressed to end-stage HF and underwent orthotopic HT. To avoid DDIs with planned immunosuppressive therapies, the ART regimen was modified to consist of lamivudine, tenofovir disoproxil fumarate, rilpivirine, and raltegravir. Following HT, the patient’s immunosuppression consisted of tacrolimus and mycophenolate mofetil. He has had normal cardiac function and no opportunistic infections and was subsequently switched to tenofovir alafenamide, emtricitabine, and bictegravir in combination for convenience. Serial HIV-1 RNA blood levels were constantly below the limit of quantification, and his CD4 count remained above 200 cells/mm3 (30–35%). Several DDIs were identified and addressed; however, his long-term post-HT complications included one episode of asymptomatic acute cellular rejection, adenocarcinoma of the prostate, basal cell carcinoma, cardiac allograft vasculopathy, and peripheral neuropathy.ConclusionThe clinical outcome of this case supports the conclusion of previously published reports, summarized here within, demonstrating that HIV-1 positive status should not preclude HT in carefully selected individuals. Both addressing potential DDIs prior to HT and long-term monitoring for routine post-transplant complications and secondary and incidental malignancies are imperative.

The role of von Willebrand factor in thrombotic post-transplantation complications

The role of von Willebrand factor in thrombotic post-transplantation complications

Psychological Changes in Post Kidney Transplant Recipients: Phenomenology Study

Aims: Kidney transplantation can have a big impact on recipients, so they must be able to adapt to many changes, including psychological changes. Psychological changes are the most complained about by post- kidney transplant recipients. Psychological changes including feelings of anxiety and worry after kidney transplantation, these feelings arise due to post-transplant complications, feelings of guilt and fear of rejection, treatment regimens and uncertainty about the future. Therefore, recipients must be able to deal with psychological changes after kidney transplantation. Objective: To explore the psychological changes of post-kidney transplant recipients. Methods: A qualitative study using a phenomenological approach. This study was conducted on 6 participants who were undergone kidney transplantation. Purosive sampling was performed and data was collected through 35 to 60 min. Data collection in this study was carried out through in-depth interviews, audio recording and field notes. The data analysis technique uses the Collaizi method (1978). Result: This study obtained results including: psychological adaptation transitions and post-transplant anxiety control strategies. Conclusion: Kidney transplant provide better psychological changes if the recipients can implement strategies to control emotions. Therefore, it is important to have family, social and nurses support in controlling the psychological changes of post-kidney transplant recipients.

Successful allogeneic hematopoietic stem cell transplantation in a patient with type I CD36 deficiency: a case study and literature review.

CD36-deficient individuals may produce anti-CD36 antibodies through antigenic exposure to CD36, in situations including blood transfusions. Therefore, allogeneic hematopoietic stem cell transplantation (HSCT) from CD36-positive donors to CD36-negative patients remains a challenge. A 64-year-old man with acute myeloid leukemia became refractory to platelet transfusions during chemotherapy. Anti-CD36 antibodies without anti-HLA antibodies were detected in serum, and the absence of CD36 expression on platelets and monocytes confirmed type I CD36 deficiency. The patient achieved complete remission, and received maintenance therapy with CD36-negative platelet transfusions. However, he relapsed soon afterward, and thus underwent peripheral blood stem cell transplantation (PBSCT) from a CD36-positive unrelated donor. The anti-CD36 antibody titer had decreased before the transplant, and the PBSCT-course was uneventful. The patient has been well without any complications associated with CD36 status mismatch. The few reports of allogeneic HSCT in patients with CD36 deficiency have suggested that anti-CD36 antibodies could be involved in several post-transplant complications, such as delayed platelet recovery, transfusion refractoriness, and transfusion-related acute lung injury. Our present case confirmed that stem cell transplantation from CD36-positive donors to negative patients is feasible, when it includes careful prior assessment of anti-CD36 antibody titers and interventions to attenuate them.

Improved waitlist and comparable post-transplant outcomes in simultaneous heart-kidney transplantation under the 2018 heart allocation system

ObjectiveThis study aimed to investigate the clinical trends and the impact of the 2018 heart allocation policy change on both waitlist and post-transplant outcomes in simultaneous heart-kidney transplantation in the United States. MethodsThe United Network for Organ Sharing registry was queried to compare adult patients before and after the allocation policy change. This study included 2 separate analyses evaluating the waitlist and post-transplant outcomes. Multivariable analyses were performed to determine the 2018 allocation system's risk-adjusted hazards for 1-year waitlist and post-transplant mortality. ResultsThe initial analysis investigating the waitlist outcomes included 1779 patients listed for simultaneous heart-kidney transplantation. Of these, 1075 patients (60.4%) were listed after the 2018 allocation policy change. After the policy change, the waitlist outcomes significantly improved with a shorter waitlist time, lower likelihood of de-listing, and higher likelihood of transplantation. In the subsequent analysis investigating the post-transplant outcomes, 1130 simultaneous heart-kidney transplant recipients were included, where 738 patients (65.3%) underwent simultaneous heart-kidney transplantation after the policy change. The 90-day, 6-month, and 1-year post-transplant survival and complication rates were comparable before and after the policy change. Multivariable analyses demonstrated that the 2018 allocation system positively impacted risk-adjusted 1-year waitlist mortality (sub-hazard ratio, 0.66, 95% CI, 0.51-0.85, P < .001), but it did not significantly impact risk-adjusted 1-year post-transplant mortality (hazard ratio, 1.03; 95% CI, 0.72-1.47, P = .876). ConclusionsThis study demonstrates increased rates of simultaneous heart-kidney transplantation with a shorter waitlist time after the 2018 allocation policy change. Furthermore, there were improved waitlist outcomes and comparable early post-transplant survival after simultaneous heart-kidney transplantation under the 2018 allocation system.

Diagnostic and therapeutic potential of transforming growth factor beta 1 in solid organ transplantation: recent research findings

Federation Clinical outcomes of solid organ transplantation depend on many factors. One of the main factors is the risk of post-transplant complications, which affect allograft and recipient survival. Multifactorial organ damage in post-transplant complications and the search for diagnostic and prognostic indicators of the condition have contributed to the study and selection of a wide range of proteomic and molecular genetic biomarkers, which have shown to be effective in solid organ transplantation. The use of biomarkers opens up additional possibilities for assessing the risk of complications and their early diagnosis. This potentially reduces the frequency of invasive diagnostic procedures. Transforming growth factor beta 1 (TGF-β1) regulates many biological processes, has anti-inflammatory and immunosuppressive effects, participates in immune response, and plays a key role in extracellular matrix (ECM) protein synthesis. ECM dysregulation leads to fibroblast hyperproliferation and increased collagen synthesis and, consequently, tissue fibrosis. The variability of the diagnostic and prognostic potential of TGF-β1 has been demonstrated in studies on recipients of various solid organs. The objective of this review is to analyze recent evidence on the role of TGF-β1 in the development of post-transplant complications and to assess its prospects as a marker of graft pathology or as a target for therapy.

Waiting time dictates impact of frailty: A Spanish multicenter prospective study

Frailty is prevalent in liver transplant (LT) candidates. It is considered an independent predictor of adverse outcomes pre- and post-transplant according to data obtained in the United States. We aimed to externally validate the liver frailty index (LFI) in a multicenter cohort of LT candidates. Outpatients with cirrhosis were prospectively recruited from five Spanish centers (2018-2020). Patients were defined as "frail" by an optimal cut-off of LFI ≥4.5. Patients were followed for at least 6 months to study associations of pre-LT frailty with pre- and post-transplant mortality, length of hospital and intensive care unit (ICU) stays, risk of early (<30 days) and late (30-90 days) post-transplant complications, retransplantation and cardiovascular events. Of 212 patients included, 45 patients (21%) were frail pre-LT, and the median LFI was 3.9 (IQR 3.5-4.4). After a median waiting time of 78 days, 2% died or were delisted for clinical worsening. The LFI at baseline was not predictive of mortality/delisting in LT candidates in univariable or multivariable analyses after adjusting for age and MELD-Na score (hazard ratio 1.48; p= 0.586). In contrast, compared to non-frail patients, frail LT candidates had a significantly higher length of hospital stay (9 vs. 13 days; p= 0.001) and rate of early (<30 days) post-transplant complications (55% vs. 100%; p= 0.021). In the context of a short LT waiting time, frailty does not impact pretransplant mortality and/or delisting. In contrast, LT frailty is predictive of higher post-transplant complication rates and length of hospital stay. Whether strategies aimed at pre- and/or re-habilitation are beneficial in settings with short waiting times needs to be confirmed in prospective studies. Literature is scarce on the actual impact of physical frailty on adverse outcomes in the liver transplant scenario outside North America. Evidence-based justification to extend the use of objective frailty tools in the decision-making processes in other liver transplant settings is needed. This study is the first to evaluate the predictive value of the liver frailty index in outpatients in the European liver transplant setting, showing that in a low MELD, high access system, frailty does not impact pretransplant mortality and/or delisting but is predictive of higher complication rates and longer post-transplant length of stay. In practical ways, physicians should consider physical frailty as a vital sign to be measured systematically and routinely during clinic visits; researchers are encouraged to initiate prospective studies to evaluate the benefit of applying strategies aimed at pre- and or re-habilitation in liver transplant settings with short waiting times.

The European Society for Blood and Marrow Transplantation (EBMT) roadmap and perspectives to improve nutritional care in patients undergoing hematopoietic stem cell transplantation on behalf of the Cellular Therapy and Immunobiology Working Party (CTIWP) and the Nurses Group (NG) of the EBMT.

Malnutrition is the most common comorbidity during the continuum of hematopoietic stem cell transplant (HSCT) and negatively impacts clinical outcomes, response to therapy, quality of life, and costs. The intensive conditioning regimen administered before transplant causes inflammatory damages to the gastrointestinal system, which themselves contribute to trigger graft versus host disease (GvHD) in the allogeneic setting. GvHD and other post-transplant complications such as infections adversely affect food intake and gut absorption of nutrients. Consequently, patients exhibit signs of malnutrition such as weight loss and muscle wasting, thus triggering a "vicious circle" that favours additional complications. Among HSCT centres, there is marked variability in nutritional care, from screening for malnutrition to nutritional intervention. The present paper, elaborated by the Cellular Therapy and Immunobiology Working Party and the Nurses Group of the European Society for Blood and Marrow Transplantation, aims at defining a roadmap that identifies the main nutritional critical issues in the field of HSCT. This document will be propaedeutic to the development of clinical algorithms to counteract risk factors of malnutrition, based on scientific evidence and shared among HSCT centres, and thus maximize transplant outcomes.

Portal vein thrombosis: Before, during, and after liver transplant.

Portal vein thrombosis: Before, during, and after liver transplant.

Impella 5.5 as a bridge to heart transplantation: Waitlist outcomes in the United States.

The 2018 United Network for Organ Sharing allocation policy change has led to a significant increase in the use of mechanical circulatory support devices in patients listed for orthotopic heart transplantation. However, there has been a paucity of data regarding the newest generation Impella 5.5, which received FDA approval in 2019. The United Network for Organ Sharing registry was queried for all adults awaiting orthotopic heart transplantation who received Impella 5.5 support during their listing period. Waitlist, device, and early post-transplant outcomes were assessed. A total of 464 patients received Impella 5.5 support during their listing period with a median waitlist time of 19 days. Among them, 402 (87%) patients were ultimately transplanted, with 378 (81%) being directly bridged to transplant with the device. Waitlist death (7%) and clinical deterioration (5%) were the most common reasons for waitlist removal. Device complications and failure were uncommon (<5%). The most common post-transplant complication was acute kidney injury requiring dialysis (16%). Survival at 1-year post-transplant survival was 89.5%. Since its approval, the Impella 5.5 has been increasingly used as a bridge to transplant. This analysis demonstrates robust waitlist and post-transplant outcomes with minimal device-related and postoperative complications.

Lung transplant recipients with telomere-mediated pulmonary fibrosis have increased risk for hematologic complications

Idiopathic pulmonary fibrosis lung transplant recipients (IPF-LTRs) are enriched for short telomere length (TL) and telomere gene rare variants. A subset of patients with nontransplant short-TL are at increased risk for bone marrow (BM) dysfunction. We hypothesized that IPF-LTRs with short-TL and/or rare variants would be at increased risk for posttransplant hematologic complications. Data were extracted from a retrospective cohort of 72 IPF-LTRs and 72 age-matched non-IPF-LTR controls. Genetic assessment was done using whole genome sequencing or targeted sequence panel. TL was measured using flow cytometry and fluorescence in-situ hybridization (FlowFISH) and TelSeq software. The majority of the IPF-LTR cohort had short-TL, and 26% of IPF-LTRs had rare variants. Compared to non-IPF controls, short-TL IPF-LTRs were more likely to have immunosuppression agents discontinued due to cytopenias (P = .0375), and BM dysfunction requiring BM biopsy was more prevalent (29% vs 4%, P = .0003). IPF-LTRs with short-TL and rare variants had increased requirements for transfusion and growth factor support. Multivariable logistic regression demonstrated that short-TL, rare variants, and lower pretransplant platelet counts were associated with BM dysfunction. Pretransplant TL measurement and genetic testing for rare telomere gene variants identified IPF-LTRs at increased risk for hematologic complications. Our findings support stratification for telomere-mediated pulmonary fibrosis in lung transplant candidates.

Correlation of Model for End Stage Liver Disease (MELD), MELD-Sodium (MELD-Na), and Child-Turcotte-Pugh (CTP) Score With Frailty in Patients With Hepatitis C Virus (HCV) Related Cirrhosis.

The model for end stage liver disease (MELD), model for end stage liver disease-sodium (MELD Na), and Child-Turcotte-Pugh (CTP) score are independent predictors of mortality in cirrhotic patients.Approximately 43% of cirrhotic patients with advanced disease are frail and can have detrimental effects on the disease prognosis and survival including delisting from the transplant list and increased risk of post-transplant complications. Therefore, our aim was to determine the correlation of MELD, MELD-Na, and CTP score with frailty in patients with hepatitis C virus (HCV) related cirrhosis. This cross-sectional study was conducted at the Department of Hepato-gastroenterology, Sindh Institute of Urology and Transplantation from 1stJanuary 2022 to 30thJune 2022. All the patients of either gender aged between 18 and 70 years with serological evidence of HCV and features of cirrhosis on ultrasound abdomen were included in the study. Patients with conditions over estimating frailty were excluded from the study. Liver Frailty Index (LFI) was calculated using grip strength measured in kilograms, timed chair stands, and balance testing. CTP and MELD-Na scores for each patient were also recorded. All the data were analyzed using SPSS version 22.0 (IBM Corp., Armonk, NY). The correlation of MELD, MELD-Na, and CTP with LFI was analyzed using the Pearson correlation coefficient and a p-value < 0.05 was considered statistically significant. A total of 274 patients were included in the study. Out of them, 185 (67.5%) were males. The mean CTP score was 8.1 + 2.1, MELD score of 13.6 + 7.1, MELD-Na score of 15 + 6.6, and LFI of 4.1 + 0.83. LFI was found to be weakly correlated with MELD (r = 0.278) (p < 0.001), MELD-Na score (r = 0.41) (p < 0.001), and CTP score (r = 0.325) (p < 0.001). Weak correlation was noted between LFI, CTP, MELD, and MELD-Na scores in HCV-associated chronic liver disease. Therefore, frailty along with MELD, MELD-Na, and CTP must be assessed before considering the patients for liver transplantation.

#5999 GRADES II-III INTRA-ABDOMINAL HYPERTENSION INCREASE THE RISK OF GRAFT LOSS OR DEATH AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Intra-abdominal hypertension (IAH) is common among post-surgical, critically ill and kidney transplant patients, and is associated with acute kidney injury and increased morbidity and mortality. We aimed to describe the medium-term effect of IAH on graft and patient survival after deceased-donor kidney transplantation. Method 192 consecutive patients who received a cadaveric renal allograft transplant at our hospital were included in this study. IAP was measured every 8h for at least the first 72h after surgery using the urinary bladder technique, and an average value was obtained. Patients were followed up for 24 months or until a composite outcome (defined as graft loss or recipient death) occurred. Clinical, anthropometric, and analytical data was extracted from our hospital's database. Statistical analysis was performed using IBM SPSS Statistics 22. The study was approved by the local ethics committee. Results 192 patients were included. Relevant clinical and anthropometric data are summarized in Table 1. Patients with grades II or III IAH were more frequently male, had longer dialysis vintage, received more frequently hemodialysis as renal replacement therapy and suffered delayed graft function, graft loss or death more repeatedly. In Kaplan-Meier analysis, grade II IAH or higher were associated with lower composite-outcome free survival (Log-Rank: 8.053; p = 0.018) (Figure 1). Conclusion Grade II-III IAH appear to be a risk factor for graft loss or recipient death in our sample of deceased donor kidney transplant recipients. Monitoring of intra-abdominal hypertension could provide useful information to identify patients at higher risk of post-transplant complications.

Secondary Acute Myeloid Leukemia in Myelodysplastic Syndrome Patients Aged Over 60 Years.

In myelodysplastic syndrome (MDS), neoplastic cells originate in hematopoietic stem cells of the bone marrow, causing dysplasia in multiple cell lines. This may ultimately lead to cytopenia and anemia. MDS generally occurs in patients aged over 60 years, and if left unchecked, it can lead to secondary acute myeloid leukemia (AML), which has a worse prognosis than de novo AML. Hence, it is important to find methods to treat and manage MDS and prevent secondary AML. This review tries to point out the best methods to find out the best possible treatment for MDS, which can lead to its remission or possibly cure and prevent it from progressing into AML. In order to do this, the pathogenesis of MDS is taken into account, and it is clear that the various molecular mutations that lead to the hematologic neoplasms directly affect the different chemotherapy agents that can be used. The different common mutations leading to MDS and secondary AML have been reviewed along with the drugs best inclined to target them. Some mutations lead to a worse prognosis than others, and ongoing mutations can lead to drug-resistant neoplasms. Thus, drugs targeting the mutations need to be used. The feasibility of an allogeneic stem cell transplant is also taken into account, as this can lead to a total cure of MDS. Methods of decreasing post-transplant recovery time and complications have been looked into, and more studies need to be done on the matter. Currently, it is clear that a more personalized approach to each individual case with its own set of drug combinations is the best approach to treating MDS and secondary leukemia and increasing the overall survival (OS).

Impact of bacterial infections prior to liver transplantation on post-transplant outcomes in patients with cirrhosis

Bacterial infections are frequent in patients with cirrhosis and increase the risk of death and drop-out from liver transplant (LT) waiting list. In patients with bacterial infections, LT is frequently delayed because of the fear of poor outcomes. We evaluated the impact of pre-LT infections on post-LT complications and survival. From 2012 to 2018, consecutive patients transplanted at the Hospital of Padua were identified and classified in two groups: patients surviving an episode of bacterial infection within 3 months before LT (study group) and patients without infections before LT (control group). Post-LT outcomes (complications, new infections, survival) were collected. A total of 466 LT recipients were identified (study group n= 108; control group n= 358). After LT, the study group had a higher incidence of new bacterial (57% vs. 20%, p <0.001) and fungal infections (14% vs. 5%, p= 0.001) and of septic shock (8% vs. 2%, p= 0.004) than the control group. Along with the model for end-stage liver disease (MELD) score and alcohol-related cirrhosis, bacterial infection pre-LT was an independent predictor of post-LT infections (odds ratio= 3.92; p <0.001). Nevertheless, no significant difference was found in 1-year (88% vs. 89%, p= 0.579) and 5-year survival rates (76% vs. 75%, p= 0.829) between the study group and control group. Within the study group, no association was found between the time elapsed from infection improvement/resolution to LT and post-LT outcomes. Patients with pre-LT infections have a higher risk of new bacterial and fungal infections and of septic shock after LT. However, post-LT survival is excellent. Therefore, as soon as the bacterial infection is improving/resolving, transplant should not be delayed, but patients with pre-transplant bacterial infections require active surveillance for infections after LT. Bacterial infections increase mortality and delay transplant in patients with cirrhosis awaiting liver transplantation (LT). Little is known about the impact of adequately treated infections before LT on post-transplant complications and outcomes. The study highlights that pre-LT infections increase the risk of post-LT infections, but post-LT survival rates are excellent despite the risk. These findings suggest that physicians should not delay LT because of concerns about pre-LT infections, but instead should actively monitor these patients for infections after surgery.

The impact of NKG2A and NKG2D receptors and HLA-E and MICA ligands polymorphisms on post-transplant complications after paediatric allogeneic HSCT: a single-centre experience.

Introduction: Natural Killer cells are the first subpopulation of lymphocytes that reconstitute after allogeneic haematopoietic stem cell transplantation (HSCT). Their activity is regulated by various receptor-ligand interactions, including stimulation of the activating NKG2D receptor by the MICA molecule, and inhibitory NKG2A receptor interacting with the HLA-E. In this study the research effort focused on the effect of selected NKG2A and NKG2D receptors and their ligands (HLA-E and MICA molecules) polymorphisms that may affect the pathomechanisms of post-transplant complications after HSCT in children. Methods: One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions (NKG2A rs7301582; NKG2D rs1049174, rs1154831; HLA-E rs1264457; MICA rs1051792, rs1063635) were genotyped, and the influence of polymorphisms was analysed on acute and chronic graft-versus-host disease (GvHD), cytomegalovirus (CMV) infection incidence, disease relapse and survival. Results: The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of HLA-E rs1264457 polymorphism in patients' HLA-E*01:01 allele, which was associated with increased risk of CMV infection (p = 0.050), especially in children positive for CMV IgG before transplantation (p = 0.001). Furthermore, the effect of HLA-E*01:01 allele on CMV infections was more evident in children above the age of 7 years (p = 0.031). Strong tendencies (0.05 < p < 0.10) towards association with the risk of acute GvHD were also observed for the NKG2A or MICA polymorphisms of the recipients. In addition, NKG2D rs1154831 AA and MICA rs1063635 GG might play a protective role as they were not present in any recipient who died after transplantation. Conclusion: In summary, there is emerging evidence that genotyping results of NKG2 receptors and their ligands, may have prognostic value for the outcome of paediatric allogeneic HSCT, but more extensive studies performed on larger groups of donors and transplant recipients are required to confirm these observations.

Clinical Utility of 18Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) in Multivisceral Transplant Patients.

Multivisceral transplant (MVTx) refers to a composite graft from a cadaveric donor, which often includes the liver, the pancreaticoduodenal complex, and small intestine transplanted en bloc. It remains rare and is performed in specialist centres. Post-transplant complications are reported at a higher rate in multivisceral transplants because of the high levels of immunosuppression used to prevent rejection of the highly immunogenic intestine. In this study, we analyzed the clinical utility of 28 18F-FDG PET/CT scans in 20 multivisceral transplant recipients in whom previous non-functional imaging was deemed clinically inconclusive. The results were compared with histopathological and clinical follow-up data. In our study, the accuracy of 18F-FDG PET/CT was determined as 66.7%, where a final diagnosis was confirmed clinically or via pathology. Of the 28 scans, 24 scans (85.7%) directly affected patient management, of which 9 were related to starting of new treatments and 6 resulted in an ongoing treatment or planned surgery being stopped. This study demonstrates that 18F-FDG PET/CT is a promising technique in identifying life-threatening pathologies in this complex group of patients. It would appear that 18F-FDG PET/CT has a good level of accuracy, including for those MVTx patients suffering from infection, post-transplant lymphoproliferative disease, and malignancy.

Regulation of gut microbiota: a novel pretreatment for complications in patients who have undergone kidney transplantation.

Kidney transplantation is an effective method to improve the condition of patients with end-stage renal disease. The gut microbiota significantly affects the immune system and can be used as an influencing factor to change the prognoses of patients who have undergone kidney transplantation. Recipients after kidney transplantation showed a lower abundance of Firmicutes and Faecalibacterium prausnitzii and a higher proportion of Bacteroidetes and Proteobacteria. After using prebiotics, synbiotics, and fecal microbiota transplantation to regulate the microbial community, the prognoses of patients who underwent kidney transplantation evidently improved. We aimed to determine the relationship between gut microbiota and various postoperative complications inpatients who have undergone kidney transplantation in recent years and to explore how gut microecology affects post-transplant complications. An in-depth understanding of the specific functions of gut microbiota and identification of the actual pathogenic flora during complications in patients undergoing kidney transplantation can help physicians develop strategies to restore the normal intestinal microbiome of transplant patients to maximize their survival and improve their quality of life.

Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that primarily suppress T lymphocytes in healthy pregnancies and pathologies. MDSCs are one of the key regulators of immune responses. Finding ways to control them is important for the treatment of cancer, autoimmune diseases, miscarriage, and post-transplant complications. The mechanisms of immune suppression by MDSC are: expression of CD73, ADAM17, PD -L1, production of Arg 1, iNOS, IDO, IL -10 and TGF-b1.Pregnancy-specific b1-glycoprotein (PSG) has modulatory effects on dendritic cells and macrophages that mediate the shift of T cell phenotypes toward Th2 and Treg. We have previously shown that native PSG suppresses Th17 differentiation and cytokine production, stimulates the production of IDO by monocytes and the differentiation of Tregs.Considering the immunomodulatory properties of PSG and the key role of MDSCs in pathologies, the aim of our work was to investigate the effect of native and recombinant PSG on the differentiation of MDSCs in vitro.MDSCs were differentiated from CD11b+ peripheral blood cells. Cells were cultured for 7 days and received stepwise GM-CSF, IL-1b, and LPS. Native (n) (1; 10 and 100 mg/mL) and recombinant (r) (1 and 10 mg/mL) PSG were introduced into the cultures three days before the end of incubation. Flow cytometry was used to determine the percentage of MDSC among the cells in culture and the percentage of M-, PMN-, and e-MDSC among the total number of MDSCs.It was found that rPSG (1 mg/mL) increased the percentage of MDSCs in culture. Both nPSG (1 and 10 mg/mL) and rPSG (10 mg/mL) increased the proportion of M-MDSC, whereas rPSG (10 mg/mL) decreased the number of PMN-MDSC.Thus, the cytokine background in CD11b+ cell cultures favored the differentiation of predominantly M-MDSC, similar to the tumor microenvironment, whereas native and recombinant PSG enhanced this effect. Thus, nPSG and rPSG are able to modulate the differentiation of MDSCs by increasing their number, mainly due to the monocytic subpopulation. This fact opens perspectives for new research on targeted manipulation of MDSCs.