Complications In Transplant Patients Research Articles

Risk Factors for the Occurrence of Early Postoperative Urological and Surgical Complications after Kidney Transplantation from a Living and Cadaveric Donor

This study is based on a retrospective analysis of the medical history of 35 patients who underwent kidney transplantation at the Clinic of Urology of the “Alexandrovska” University Hospital, Sofia for the period from February 2018 to December 2019. Early postoperative complications were detected in 46% of the observed transplant patients. All possible early surgical and urological complications were followed up, including symptomatic and asymptomatic manifestations that did not require active invasive treatment.
 In our group of patients, possible factors, influencing the occurrence of early complications such as age and BMI of the recipient, age of the donor, preoperative hemodialysis and preoperative recipient residual diuresis, time of cold ischemia, creatinine levels at admission and discharge, hospital stay were studied. Our results show that the incidence of early postoperative urological and surgical complications correspond to the literature data from other transplant centres. We believe that higher preoperative residual diuresis is a good prognostic factor for lower rate of early postoperative complications. Prolonged time of cold ischemia does not affect the frequency of postoperative complications and allows better organization of operative activity. Obesity of the recipient is a risk factor for the occurrence of postoperative complications in transplant patients. In the studied group there is only a hint of the influence of the age of the recipient on the occurrence of complications without it reaching significant values. In our study, there was no relationship between the age of the donor and the occurrence of complications. Our opinion is that the age of the recipient and the donor does not in itself play a significant role, and it is much more important to increase the cardiovascular risk with age and against the background of emerging comorbidities. Serum creatinine levels at admission do not significantly affect the occurrence of early postoperative complications, but only suggest that quality of dialysis treatment plays an important role in the success of kidney transplantation. According to the values of serum creatinine at discharge, postoperative complications have a negative impact on the function of the transplanted kidney and their timely and adequate treatment is necessary to prolong the survival of the graft. The average length of hospital stay in the Clinic of Urology of “Alexandrovska” University Hospital for transplanted patients may be extended due to the specifics of the structure and organization of healthcare in the country.

Duodenal graft perforation after 9 years from simultaneous pancreas-kidney transplantation

Transplantation is a natural replacement therapy for kidney and pancreatic failures. Transplant complications should be treated in hub centers; however, it is also true that some acute complications must be treated by emergency surgeons. Simultaneous pancreas-kidney transplantation (SPK) is a standardized surgical procedure; however, it is associated with complications, some of which can lead to graft loss. We report the case of a 41-year-old woman with duodenal graft perforation nine years after undergoing SPK. The patient was referred with an acute abdomen secondary to small-bowel obstruction. The finding of an adhesive band near the cecal valve during surgery led us to understand the cause of this complication. This case report demonstrates the need for rapid treatment of the most dangerous complications in transplant patients. The intestinal obstruction and duodenal graft perforation were treated in the emergency surgery department.

Critical Role for the Human Cytomegalovirus Major Immediate Early Proteins in Recruitment of RNA Polymerase II and H3K27Ac To an Enhancer-Like Element in OriLyt.

Human cytomegalovirus (HCMV) is an opportunistic pathogen that infects most of the population. The complex 236 kbp genome encodes more than 170 open reading frames, whose expression is temporally regulated by both viral transcriptional regulators and cellular factors that control chromatin and transcription. Here, we have used state of the art genomic technologies to investigate the viral transcriptome in conjunction with 2 key transcriptional regulators: Pol II and H3K27Ac. Although it is well known that the major immediate early (IE) proteins activate early gene expression through both direct and indirect interactions, and that histone modifications play an important role in regulating viral gene expression, the role of the IE proteins in modulating viral chromatin is not fully understood. To address this question, we have used a virus engineered for conditional expression of the IE proteins combined with RNA and Chromatin immunoprecipitation (ChIP) analyses to assess the role of these proteins in modulating both viral chromatin and gene expression. Our results show that (i) there is an enhancer-like element in OriLyt that is extraordinarily enriched in H3K27Ac; (ii) in addition to activation of viral gene expression, the IE proteins play a critical role in recruitment of Pol II and H3K27Ac to this element. IMPORTANCE HCMV is an important human pathogen associated with complications in transplant patients and birth defects. The complex program of viral gene expression is regulated by both viral proteins and host factors. Here, we have investigated the role of the immediate early proteins in regulating the viral epigenome. Our results show that the viral immediate early proteins bring about an enormous enrichment of H3K27Ac marks at the OriLyt RNA4.9 promoter, concomitant with an increase in RNA4.9 expression. This epigenetic characteristic adds importantly to the view that OriLyt has structural and functional characteristics of a strong enhancer that, we now discover, is regulated by IE proteins.

CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation.

Reactivation of human cytomegalovirus (HCMV) is a life-threatening complication in transplant patients. Natural Killer (NK) cells are the first lymphocyte lineage to reconstitute following an allogeneic hematopoietic stem cell transplant (HSCT). Amongst them, NK cell Group 2 isoform C/Killer cell lectin-like receptor subfamily C, member 2 (NKG2C)-expressing NK cells contribute significantly to patient protection upon HCMV reactivation. NKG2C+ NK cells are capable of immunological memory, albeit NK cell memory is not restricted to them. Hepatic C-X-C Motif Chemokine Receptor 6 (CXCR6)-expressing NK cells also mediate memory responses in mice and humans. Small numbers of them circulate and can thus be studied in peripheral blood samples. We hypothesize that NKG2C+ and CXCR6+ NK cell subsets are distinct. To test our hypothesis, we used multi-parametric flow cytometry to determine the phenotypes and effector functions of CD56bright vs. CD56dim and NKG2C+ vs. CXCR6+ human NK cell subsets in the peripheral blood (PB) of pediatric transplant recipients monthly while monitoring patients for HCMV reactivation. Interestingly, we did not find any NKG2C+CXCR6+ NK cells in the transplant recipients’ peripheral blood, suggesting that NKG2C+ and CXCR6+ NK cells are distinct. Also, NKG2C–CXCR6– NK cells, rather than NKG2C+ NK cells, made up most NK cells post-transplant, even in transplant recipients with HCMV viremia. In contrast to NKG2C+ NK cells, CXCR6+ NK cells appeared phenotypically less differentiated but were highly proliferative and produced IFN-γ and TNF α . Our findings contribute to our understanding of post-transplant NK cell development and its implications for human health.

A unique case of Miller Fisher-Guillain-Barr\xe9 overlap syndrome in a liver transplant recipient

Guillain-Barré syndrome (GBS) is an ascending demyelinating polyneuropathy often associated with recent infection. Miller Fisher syndrome represents a variant with predominant facial and cranial nerve involvement, although Miller Fisher and Guillain-Barré overlap syndromes can occur. Guillain-Barré spectrum syndromes have been thought to be rare among solid organ transplant recipients. We describe an immunocompromised patient with a liver transplant who presented with ophthalmoplegia and bulbar deficits. His symptoms rapidly progressed to a state of descending paralysis involving the diaphragm; he then developed acute respiratory failure and eventually developed quadriparesis. Electromyography and a nerve conduction study demonstrated a severe sensorimotor axonal polyneuropathy consistent with Miller Fisher variant Guillain-Barré syndrome. Despite several negative nasopharyngeal swabs for COVID-19 polymerase chain reaction, a serology for SARS-CoV-2 IgG was positive. He was diagnosed with Miller Fisher-Guillain-Barré overlap syndrome with rapid recovery following treatment with plasma exchange. Although Guillain-Barré is a rare complication in solid organ transplant recipients, this case highlights the importance of rapid diagnosis and treatment of neurologic complications in transplant patients. Furthermore, it demonstrates a possible case of neurological complications from COVID-19 infection.

Pre-existing immunity to cytomegalovirus in macaques influences human CMV vaccine responses in preclinical models

Development of a human cytomegalovirus (HCMV) vaccine is a Tier 1 priority by the National Institutes of Medicine, as HCMV is the most common congenital infection globally and most frequent infectious complication in transplant patients. Relevant preclinical non-human primate models used for testing HCMV vaccine immunogenicity are rhesus and cynomolgous monkeys. However, a complication in using these models is that species-specific CMV variants are endemic in non-human primate breeding colonies. We hypothesize that natural immunity to species-specific CMV in rhesus and cynomolgous monkeys impacts HCMV vaccine immunogenicity and may interfere with our ability to fully interpret vaccine immunogenicity. A modified mRNA vaccine encoding HCMV glycoprotein (gB) and the pentameric complex (PC) packaged in lipid nanoparticles (LNP) was delivered intramuscularly to groups of cynomolgous (n = 16, CyCMV-seropositive) and rhesus macaques (n = 24, RhCMV-seropositive). High pre-vaccination IgG binding responses to HCMV gB were present in both species, but pre-vaccination binding responses to PC were mostly present in rhesus macaques. Yet, at least a log increase in both PC and gB-specific plasma IgG levels was detected post-second HCMV mRNA vaccination in both species. Both species responded with high epithelial cell neutralizing antibody responses at 4 weeks post second HCMV mRNA vaccination, but limited fibroblast neutralizing antibodies. HCMV gB + PC mRNA/LNP vaccine also elicited IgG binding responses to cell-associated gB, an identified immune correlate of protection, in both species after the second vaccination, and there was a moderately strong direct correlation between this pre- and post-vaccination response in rhesus macaques. Based on the correlation between pre-existing and post-vaccine gB-specific binding responses in rhesus macaques, we conclude that species-specific CMV variant-specific antibody responses contribute to antibody responses to HCMV vaccination in primate models, indicating that pre-existing immunity must be taken into account in non-human primate preclinical models and will impact immunogenicity of HCMV vaccines seropositive human vaccinees.

Transplant Tourism and Organ Trafficking: Current Practices, Controversies and Solutions

The controversial subject of transplant tourism has been neglected in the travel medicine literature. According to the Declaration of Istanbul, travel for transplantation can be regarded as transplant tourism if it involves organ trafficking and/or commercialised transplantation activities. While no registry of transplant tourism activities exists, published case series point to significant negative clinical outcomes. Adverse outcomes among donors include postoperative depression and anxiety, deterioration in health status, poor surgical wound care, and negative financial effects. Poor perioperative management, inadequate immunosuppression, blood transfusion-associated infections, antibiotic-resistant bacterial infections and invasive fungal infections, are among the most commonly reported complications in transplanted patients. Iran operates a legal and ethically regulated system of rewarded altruistic kidney donation. Travel medicine practitioners have a role to play in protecting the health of intending transplant tourists through targeted pre-travel health counselling and vaccination.

POS-556 VASCULAR MORBIDITY ASSOCIATED WITH TUNNELIZED CATHETERS FOR HEMODIALYSIS IN THE POST-TRANSPLANT PERIOD

One of the most determining factors of morbidity and mortality of hemodialysis patients is the presence of jugular vein tunnelized catheter (JTC) as vascular access (VA). Our purpose was to determine the effect of vascular complications related to JTC during HD period and their consequences after kidney transplant. We analyzed the presence of vascular complications related to JTC in 196 consecutive kidney transplant patients realized in our center during 2010-2020. 6 transplanted patients (5 males) present VA complications, mean age was 69.17±8.68 ys. CKD etiologies were diabetic nephropathy (n=4), nephroangiosclerosis (n=1) and IgAN (n=1). All of them were hypertensive and 3 had peripheral vascular disease. During their HD period, 4 patients presented complications related to JTC: dysfunction (n=3) and stenosis of subclavian vein (n=1). In 4 patients these complications occurred in the first three months after JTC implantation. Endovascular treatment performed was JTC replacement (n=3) and angioplasty (n=1). Prior to transplantation, the VA of all patients was the AVF and none had YTC.In the post-transplant, the entire sample studied presented vascular complications related to VA: stenosis of subclavian vein (n=3), secondary heart failure (n=1), partial AVF occlusion (n=1), and complete jugulo-subclavian occlusion (n=1). The 50% of the complications appeared 3 months after transplantation and the rest, from the first year. Initial treatment in all cases it was balloon angioplasty ± stent and antiplatelet therapy. In a period of less than 3 months, there was a close of 70% of relapses, thus deciding the closure of the AVF.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The presence of vascular complications in transplant patients is related to JTC as vascular access during HD period. These complications could increase the morbidity and affect graft function due in part to the interventional procedures needed to solve them. We propose strategies to identify those transplant patients at risk in order to prevent these complications.

GUT MICROBIOME DYNAMICS OVER A COURSE OF KIDNEY TRANSPLANTATION: PRELIMINARY RESULTS OF A PILOT STUDY

Minsk Study Group for Infections in Hematology, Transplantation and Cancer (MSTH). Background: Earlier studies have shown the protective effect of diverse gut microbiota against development of infectious complications in hematological patients after hematopoietic stem cell transplantation, including protection against highly antibiotic-resistant bacteria. Other publications have underlined the effect of butyrate-producing gut bacteria on risk of viral complications in kidney transplantation, and aspects of tacrolimus dosing based on microbiome composition. The aim of this pilot study was to assess the dynamics of gut microbiome composition during the first 10 days after kidney transplantation, looking for possible associations with clinical outcomes at a second stage of the study. Materials and Methods: In this observational cohort study we characterized the dynamics of gut microbiota composition in kidney transplant recipients during the early post-transplant period within 10 days after surgery. Participants were enrolled in a fecal collection protocol with at least three sequenced fecal samples during the kidney transplantation hospitalization with one sample collected at baseline. DNA was extracted and purified from each fecal sample, and the V3 to V4 region of the 16S rRNA gene was PCR-amplified using modified universal bacterial primers. Purified products were sequenced using the MiSeq Illumina platform. Results: In this pilot study we have sequenced 18 fecal specimens collected from 6 kidney allograft recipients. All of the kidney transplant recipients had a baseline fecal sample collected and sequenced before the transplantation. Other samples were collected during the 10 day period after the transplantation. Among the significant alterations in the gut microbiota following kidney transplantation were: major loss of diversity (Shannon index) during the first 10 days post-transplant and an increase in Proteobacteria phylum abundance. Clinical associations between the gut microbiome dynamical characteristics are planned to be studied in the second part of this ongoing study. Conclusion: Loss of gut microbiome bacterial diversity during the early post-transplant course in kidney transplant recipients may have associations with clinical outcomes. As it was shown earlier, highly diverse microbiome composition may have a protective effect against various infectious complications in transplant patients. Clinical associations should be studied in a second stage of this pilot study. Solodkaia Olga. Sergey Korotkov. Andrey Babenko.

Effects of the influenza vaccine on pediatric kidney transplant outcomes.

The influenza vaccine is critical for preventing influenza-related complications in transplant patients. Previous studies demonstrated de novo donor-specific antibody formation and rejection following the influenza vaccination. This risk has not been adequately assessed in the pediatric population. We performed a single-center retrospective analysis of 187 unique pediatric kidney transplant recipients, transplanted from January 1, 2006, to December 31, 2015, assessing for an association of the influenza vaccination with various transplant outcomes. The influenza vaccine was received by 125 of 187 patients within the first year post-transplant. Using log-rank tests and Kaplan-Meier curves, vaccinated patients had a significantly lower risk of mortality (P=0.048). There were no differences in death-censored graft survival (P=0.253), graft survival (P=0.098), or rejection (P=0.195) between vaccinated and unvaccinated groups. To address the problem of multiple exposures for a yearly vaccine, Cox proportional hazards regression was utilized with post-transplant vaccination status considered as a time-dependent covariate; analyses were performed using both a 360- and 180-day vaccination period following any post-transplant influenza vaccination. In this model, being vaccinated did not result in a significant difference in mortality (HR 0.90 [0.16, 5.15], P=0.91), death-censored graft survival (HR 0.70 [0.31, 1.58], P=0.39), graft survival (HR 0.69 [0.32, 1.49], P=0.34), or rejection (HR 0.67 [0.37, 1.19], P=0.17). Eight patients developed de novo donor-specific antibodies following the first post-transplant influenza vaccination; three then developed biopsy-proven rejection. These results suggest influenza vaccination is safe in pediatric kidney transplant recipients, and larger prospective studies are required to conclusively confirm our findings.

Analysis of neoplastic skin complications in transplant patients: experience of an Italian multidisciplinary transplant unit.

Transplant patients need to be strictly followed, since the immunosuppressive therapies they usually receive can increase the risk of skin complications. This study aims to evaluate the prevalence of neoplastic skin complications in transplant patients. We analyzed 256 liver or kidney transplant patients. The follow-up mean period was 7±3.5 years. It was also evaluated the prevalence of cutaneous neoplastic complications according to the immunosuppressive regimen received by patients as follows: cyclosporine, tacrolimus, steroids, mycophenolate mofetil or everolimus, in single, double or triple therapy. The 18.36% of patients developed neoplastic complications, among these 9.37% actinic keratoses, 8.20% non-melanoma skin cancer, and 0.78% cutaneous melanoma. Among patients who developed non melanoma skin cancer, 61.90% had basal cell carcinoma, 23.81% squamous cell carcinoma, 52% Kaposi's sarcoma and 4.76%, Malherbe's epithelioma. This study demonstrated the increased risk of skin cancer in transplant patients during the first 7 years of follow-up and made the dermatologists aware about the need of a regular cutaneous follow-up for this subset of patients.

MTOR Inhibitors Maintain Low Levels of Immune Activation, Immune Senescence and EBV Load in Kidney Transplant Patients

Introduction Post-transplant lymphoproliferative disorders (PTLD) represent a severe complication in transplant patients. Epstein-Barr Virus (EBV) is the main driver of PTLD, particularly of those occurring early after transplantation. Immune activation/inflammation, immune senescence, reactivation of EBV and expansion of EBV-positive B cells, which play a pivotal role in the onset of PTLD, may be modulated by immunosuppressive strategies. The aim of this study was to assess the impact of mTOR inhibitor (mTORi) on viral and host cofactors involved in the PTLD’s pathogenesis. Materials and Methods Sixty-two kidney transplant patients were enrolled in the study: 33 were treated with mycophenolic acid (MPA) and 29 with mTORi, both in combination with tacrolimus and steroids. Thymoglobulin was the induction in all cases. All patients were assessed at the time of transplant and after 1 year of follow-up. Markers of T-cell activation(CD3+CD8+CD38+), exhaustion(CD3+CD8+PD-1+), senescence (CD3+CD8+CD28-CD57+), and B-cell activation (CD19+CD10-CD21lowCD27+) were evaluated by flow cytometry. Plasma levels of PAMPs(microbial translocation marker 16s ribosomal(r)DNA) and DAMPs(mitochondrial(mt)DNA) were quantified by real-time PCR. Inflammatory cytokines (IL-6 and TNF-alpha) were quantified by Luminex platform. EBV was typed and quantified by multiplex real-time PCR, and telomere lengths in peripheral blood cells (PBMC) were estimated by telomere/single copy gene ratio (T/S), using multiplex real-time PCR. Results After 1 year of follow-up, plasma levels of 16s rDNA increased in MPA-treated patients (p=0.029), while remained stable in the mTORi group. Levels of mtDNA and pro- inflammatory cytokines tended to decrease in mTORi-treated patients (mtDNA, p=0.034; IL-6, p=0.08; TNF-alpha, p<0.001), while no significant changes were observed in the MPA group. Percentages of activated, exhausted and senescent T cells significantly increased in the MPA-treated patients (4.6[2.2-9.1] vs 17.8[12.1-23.3],p<0.001; 4.8[3.0-6.9] vs 11.6[8.7-16.8],p<0.001; and 7.9[4.4-14.5] vs 14.5[8.5-27.7],p=0.005), but remained stable in the mTORi group (2.4[1.8-6.1] vs 4.1[2.4-6.3], p=0.161; 6.4[4.9-12.1] vs 7.1[4.3-12.7],p=0.888; and 9.7[5.2-13.8]vs 10.8[5.6-16.2],p=0.460). The increase in immunosenescent cells in the MPA group was supported by telomere shortening, higher in MPA than in mTORi-treated patients (ΔT/S=-0.449 vs ΔT/S=-0.219). Percentages of activated B cells and levels of EBV-DNA significantly increased in the MPA group (10.3[6.4-16.9] vs 18.3[11.6-28.4],p=0.002, and 1[1-17] vs 27[1-118] EBV-DNA copies/105 PBMC, p=0.004), while remained stable in the mTORi group (12.8[6.8-18.8]vs 13.0[9.2-18.0], p=0.836, and 1[1-7]vs 6[1-26] EBV-DNA copies/105 PBMC, p=0.128). Conclusions mTORi maintained low levels of pro-inflammatory cytokines, immune activation and senescence, thus constraining EBV reactivation and expansion of EBV-positive B cells. Overall, these findings suggest that mTORi may reduce the risk of EBV-related malignancies in kidney transplant patients. AIRC grant IG2016 Id 19112.

Research progress of de novo colorectal cancer in solid organ transplant cecipients

Solid organ transplantation (SOT) is an effective treatment for organ failure in clinic. At present, the survival time of organ transplant recipients is significantly prolonged. The high incidence of a disease and mortality of new malignancies after transplantation has become a common long-term complication in transplant patients. Colorectal cancer (CRC) in the new malignant patients is increasing. This article summarizes the domestic and foreign related research of de novo CRC in SOT patients to provide a theoretical basis for clinical treatment of de novo CRC after transplantation. Key words: Organ transplantation/AE; Colorectal neoplasms/CO; Review

Chitinase 3-Like-1-Deficient Splenocytes Deteriorated the Pathogenesis of Acute Graft-Versus-Host Disease via Regulating Differentiation of Tfh Cells.

Acute graft-versus-host disease (aGVHD) is an intractable complication in transplant patients, limiting the efficacy of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family that lacks chitinase activity, plays a critical role in a variety of inflammatory diseases. Here, we investigated the in vitro and in vivo effects of CHI3L1 on the development of aGVHD. In this study, mixed lymphocyte reactions (MLR) in vitro showed that CHI3L1 deficiency in CD4+ T cell promoted the production of interferon (IFN)-γ and T follicular helper (Tfh)-related cytokines such as interleukin-6 (IL-6) and interleukin-21 (IL-21). Meanwhile, the inducible Tfh cell population increased remarkably in CHI3L1-KO CD4+ T cells' induction group, compared with WT group. Then, in the murine acute GVHD model, we found that CHI3L1 deficiency in donor splenocytes dramatically increased the severity of aGVHD through enhancing Tfh cell differentiation. Moreover, at mRNA and protein levels, we defined several molecules that may account for the enhanced ability of CHI3L1-KO splenocytes to migrate into target organs and produce IFN-γ and Tfh-related cytokines and chemokines, such as IL-6, IL-21, and CXCL13. Expression of inducible co-stimulator (ICOS) and B cell lymphoma 6 (Bcl6) increased in the skin, the intestine, the lung, and the liver from CHI3L1-KO splenocyte-treated aGVHD mice. Therefore, these results strongly imply that CHI3L1 levels in donor cells may be related to the risk of aGVHD and targeting CHI3L1 represents a novel therapeutic strategy for controlling aGVHD progression.

Results of Biliary Reconstruction Using a Polytetrafluoroethylene Graft in Liver Transplant Patients.

Biliary complications after liver transplant are a major concern with their high incidence, the need for repeated and long-term treatment, and their potential effects on graft and patient survival. We report our experience with biliary anastomosis using a spiral polytetrafluoroethylene graft. Between December 8, 1988, and July 2016, we performed 538 liver transplant procedures. We used a spiral polytetrafluoroethylene graft for biliary anastomosis in 10 patients: for biliary stricture reconstruction after liver transplant in 4 patients and during the primary liver transplant in 6 patients. Four patients who underwent biliary stricture reconstruction are doing well, with normal liver function. Of the 6 patients who received the graft during primary liver transplant, 2 died from sepsis, although they maintained normal liver function. Of the 4 living patients, 1 had a biliary complication that was reconstructed surgically. The 4 living patients are currently doing well, with normal liver function. Our small series of patients shows that the use of a spiral polytetrafluoroethylene graft is effective at reducing biliary complications in transplant patients.

Involvement of Recipient Transplant Coordinators in Transplant Outpatient Clinics in Japan.

Transplant recipients require long-term immunosuppressive therapy, so continued medical follow-up is necessary for long-term survival. To investigate the current role of recipient transplant coordinators (RTCs) in the outpatient care of organ transplant recipients in Japan. We sent a questionnaire survey to doctors in transplant facilities affiliated with the Japan Society for Transplantation probing attitudes on the role of RTCs in outpatient clinics. The questionnaire assessed responses using an ordinal scale of 5 ranks. In total, 139 responses were obtained from 233 transplant facilities. Respondents were divided into 2 groups, doctors currently working with RTCs (group A) and doctors not currently working with RTCs (group B). Differences in response rates between groups were analyzed using the Mann-Whitney U test. The overall attendance rate of RTCs in outpatient clinics was only 45%. Of all items on transplant outpatient clinics, group A exhibited a significantly higher response rate of "strongly agree" for "The involvement of an RTC in outpatient work can be expected to help prevent complications in transplant patients" ( P < .01) and "The involvement of an RTC in outpatient work can be expected to help prevent or reduce drug-related side effects in transplant patients" ( P < .01). Those with the highest rate of "strongly agree" were "It is necessary for RTCs to provide outpatient follow-up for transplant patients alongside doctors" (82.1% vs 67.3%, P < .07). We suggest that Japanese RTCs must participate more frequently in posttransplant outpatient care.

Influence of Body Mass Index on Venous Thrombotic Complications of Liver Transplants

ObjectiveTo analyze venous thrombotic complications in transplanted patients as a function of their body mass index (BMI). Materials and MethodsThis single-center, observational retrospective study of individuals undergoing liver transplantation between January 2008 and December 2014 analyzed the frequency of pretransplant portal thrombosis, post-transplant venous complications (early and late portal thrombosis), deep vein thrombosis, pulmonary thromboembolism and the survival outcomes as a function of World Health Organization BMI class. ResultsLiver transplantation was performed in 208 patients during the study period. No statistically significant differences in study variables were found as a function of BMI in bivariate analyses (P < .05), and Kaplan-Meier survival analysis results were also nonsignificant. ConclusionNo differences in the rate of venous thrombotic complications or survival were found as a function of the BMI class of these liver transplant recipients. These findings are in line with previous reports that complication rates are not higher in obese patients and support the proposal that obesity should not be considered a contraindication for liver transplantation based on the risk of venous complications.

Uso de leflunomida en infección de citomegalovirus resistente: a propósito de un caso

Background and objectivecytomegalovirus (CMV) infection is one of the most common complications in transplant patients, which can lead to multiple organ failure. The 80-90% of patients are cured with intravenous treatment standard (ganciclovir), or its oral prodrug (valganciclovir). In case there is no answer, we have alternatively another antiviral, foscarnet. A small number of patients do not respond to this, having a bad prognosis.The aim is to describe the case of a double lung transplant for cystic fibrosis, and recurrent CMV infection in which the use of leflunomide gets lower and even reach undetectable viral load. Description of casewoman, 22 year old, double lung transplant for cystic fibrosis in March 2014. The CMV serology performed was positive in the donor and negative in the recipient. Controls viral load during prophylaxis with valganciclovir were negative in the receiver until the 6th month after transplantation, at which viral load was detected in controls (2 090 IU/ml). The patient was admitted to our hospital to receive intravenous treatment with ganciclovir, after one month with intravenous therapy viral load persisted positive (42 400 IU/ml). One study of resistance showed that was resistant to ganciclovir, so began treatment with intravenous foscarnet. This drug achieved negativizar viral load, so the treatment was discontinued, continuing with fortnightly controls viral load. After two months without treatment, viral load increased to 13 665 IU/ml, why was requested to Pharmacy Service the off-label use of leflunomide, with the intention that use oral therapy, instead of intravenous therapy. The patient was treated with valganciclovir until have the authorization of use of leflunomide, although unanswered, since in March 2015, at the start of leflunomide treatment the patient had a viral load of 17 344 IU/ml.The initial regimen was 100 mg of leflunomide daily for the first five days, followed by 20 mg every 12 hours. After fifteen days of treatment viral load had fallen to 531 IU/ml, becoming undetectable in one month. After four months of treatment the patient remains with undetectable viral load without having any adverse effect associated with it. Conclusionour case is an example where the use of leflunomide in CMV infection resistant to other therapies is an effective and convenient alternative for patients because it keeps unde-tectable viral load with an oral therapy without having to enter the hospital for intravenous treatment.

Noninvasive diagnosis of dysfunctions in patients after organ transplantation by monitoring the redox potential of blood serum.

The problem of noninvasive diagnosis of transplant dysfunction in patients is one of the most complex problems in transplantology at the present time. Because transplanted organs can be ischemic, the measurement of redox potential (RP) in blood serum reflects the prooxidant-antioxidant balance in the organism. It was hypothesized that certain dysfunctions and postoperative complications in transplant patients may be accompanied by a change in the RP of blood plasma. Monitoring of the RP in the blood serum of patients was performed as a noninvasive method of diagnosis of transplant dysfunctions. The RP values were measured in blood serum of 63 apparently healthy subjects. Monitoring of blood serum RP was performed in 64 liver transplant patients, 59 kidney allotransplantation patients and six lung transplant patients. A total of 1,759 measurements were performed in 192 total subjects. Statistical analysis of RP values was performed using the Statistica 6.0 software package. The proposed method is based on the electrochemical measurement of the open-circuit potential of the platinum electrode immersed in blood serum because the measured value reflects the state of equilibrium between prooxidant and antioxidant systems of the organism. Shifts in values of the RPs (open circuit potentials) observed in the course of monitoring are significantly different in patients with transplant dysfunction compared to patients with unremarkable recoveries. The analysis of monitoring allows for the development of certain diagnostic and prognostic criteria of transplant dysfunction. It is important that the proposed method is noninvasive, simple, and inexpensive.

All-trans retinoic acid favors the development and function of regulatory T cells from liver transplant patients

Graft-versus-host disease (GVHD) is an intractable complication in transplant patients. Regulatory T cells (Tregs) have the ability to prevent GVHD and consist of two subsets: natural Tregs (nTregs) and induced Tregs (iTregs). In comparison to nTregs, iTregs originate in the periphery under certain conditions and show improved proliferative and suppressive abilities in an inflammatory milieu. All-trans retinoic acid (atRA) favors Treg expansion and FoxP3 expression in human Tregs. However, whether atRA can affect the function of iTregs from transplant patients remains inconclusive. Therefore, we sorted naïve T cells from liver transplant patients and cultured them in vitro. Further analyses were performed to assess the suppressive function of iTregs in vitro and in vivo. atRA favored expansion and forkhead box P3 expression in iTregs from transplant patients. In comparison to iTregs from healthy donors, iTregs from transplant patients showed decent suppressive abilities in vitro and in vivo. Our findings suggest that atRA can potentially improve the development and function of iTregs from transplant patients. Furthermore, our results provide novel insights into Treg therapy in GVHD clinical trials.