RESUMO
BACKGROUND: Pneumocystis pneumonia (PCP) is associated with morbidity and mortality in solid organ transplant (SOT) recipients. In this case-control study, we determined the association between posttransplant PCP and 3 variables: cytomegalovirus (CMV) infection, allograft rejection, and prophylaxis. METHODS: Eight transplant centers participated. For each case (SOT recipient with PCP), 3-5 controls (SOT recipients without PCP) were included. Controls were matched to the cases based on transplant center, type of allograft, and date of transplantation (±6 months). RESULTS: We enrolled 53 cases and 209 controls. Transplant types included kidney (n = 198), heart (n = 30), liver (n = 15), kidney-pancreas (n = 14), and lung (n = 5). PCP occurred beyond 12 months after transplantation in 43 (81.1%) cases. Thirty-four cases (64.1%) required admission to the intensive care unit, and 28 (52.8%) had mechanical ventilation. Allograft failure occurred in 20 (37.7%) cases, and 14 (26.9%) died. No patient developed PCP prophylaxis breakthrough. The proportion of female sex (P = .009), kidney dysfunction (P = .001), cardiac diseases (P = .005), diabetes mellitus (P = .03), allograft rejection (P = .001), CMV infection (P = .001), and severe lymphopenia (P = .001) were significantly higher in cases. In the logistic regression model, CMV infection (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 2.0-10.5]) and allograft rejection (aOR, 3.0 [95% CI, 1.5-6.1]) significantly increased the likelihood of PCP. CONCLUSIONS: PCP was mostly a late-onset disease occurring after complete course of prophylaxis, particularly among patients with CMV infection or allograft rejection. PCP is associated with significant allograft loss. Extended prophylaxis targeting recipients with allograft rejection or CMV infection may reduce the risk of PCP.
Assuntos
Infecções por Citomegalovirus/imunologia , Rejeição de Enxerto/imunologia , Pneumonia por Pneumocystis/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Transplantados , Transplante HomólogoRESUMO
Influenza vaccine is known to have suboptimal immunogenicity in transplant recipients. Despite this, influenza vaccine may have the added benefit of inducing a cross-reactive immune response to viral strains not found in the vaccine. This is termed "heterologous immunity" and has not been assessed previously in transplant patients. Pre- and postvaccination sera from kidney transplant recipients (n = 60) immunized with the 2012-2013 adjuvanted or nonadjuvanted influenza vaccine underwent testing by hemagglutination inhibition assay for strains not present in vaccine: A/New Caledonia/20/99 (H1N1), A/Texas/50/2012 (H3N2) and B/Brisbane/60/2008. The geometric mean titer of antibody to heterologous strains increased after vaccine (H1N1: 80.0 to 136.1, p < 0.001; H3N2: 23.3 to 77.3, p < 0.001; B: 13.3 to 19.5, p < 0.001). Seroconversion rates were 16.7%, 41.7%, and 13.3%, respectively. No differences in heterologous response were seen in the adjuvanted versus nonadjuvanted groups. Patients were more likely to seroconvert for a cross-reactive antigen if they seroconverted for the specific vaccine antigen. Seroconversion to heterologous A/H3N2, for example, was 84.0% for homologous H3N2 seroconverters versus 11.4% for nonseroconverters (p < 0.001). This study provides novel evidence that transplant recipients are able to mount significant cross-protective responses to influenza vaccine that may be an additional, previously unknown benefit of immunization.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/uso terapêutico , Influenza Humana/imunologia , Falência Renal Crônica/imunologia , Transplante de Rim , Adulto , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Estudos de Coortes , Reações Cruzadas , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Testes de Inibição da Hemaglutinação , Humanos , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Falência Renal Crônica/cirurgia , Falência Renal Crônica/virologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Transplantados , Vacinação , Adulto JovemRESUMO
Cell-mediated immune responses predict clinical cytomegalovirus (CMV) events but have not been adopted into routine practice due to lack of interventional studies. Our objective was to demonstrate the safety and feasibility of early discontinuation of antivirals based on the real-time measurement of CMV-specific cell-mediated immunity (CMI) in patients with CMV viremia. Transplant patients were enrolled at the onset of CMV viremia requiring antiviral therapy. CD8 T cell responses were determined using the Quantiferon-CMV assay, and results were used to guide subsequent management. A total of 27 patients (median viral load at onset 10 900 International Units/mL) were treated until viral load negative. At end of treatment, 14/27 (51.9%) had a positive CMV-CMI response and had antivirals discontinued. The remaining 13/27 (48.1%) patients had a negative CMV-CMI response and received 2 months of secondary antiviral prophylaxis. In those with a positive CMI and early discontinuation of antivirals, only a single patient experienced a low-level asymptomatic recurrence. In contrast, recurrence was observed in 69.2% of CMI-negative patients despite more prolonged antivirals (p = 0.001). In conclusion, this is the first study to demonstrate the feasibility and safety of real-time CMV-specific CMI assessment to guide changes to the management of CMV infection.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Imunidade Celular/imunologia , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Transplante de Pulmão/efeitos adversos , Medicina de Precisão , Adulto , Idoso , Idoso de 80 Anos ou mais , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/patologia , DNA Viral/genética , Intervenção Médica Precoce , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Linfócitos T/imunologia , Carga ViralRESUMO
Due to the enduring organ shortage, living donor liver transplantation has been a valuable treatment strategy for advanced liver disease patients for over 20 years. A variety of reviews have summarized the extensive data now available on medical and psychosocial risks to living donors in the aftermath of donation. However, evidence on donor medical and psychosocial outcomes beyond the first year postdonation has not been synthesized in any previous review. The evidence base on such "long-term" outcomes has been growing in recent years. A review of this evidence would therefore be timely and could serve as an important resource to assist transplant centers in their efforts to fully educate prospective donors and gain informed consent, as well as develop appropriate postdonation clinical care and surveillance plans. We reviewed recent literature on long-term donor outcomes, considering (a) medical outcomes, including mortality risk, rates of complications, abnormalities detected in laboratory testing, and the progress of liver regeneration; and (b) donor-reported psychosocial outcomes reflecting physical, emotional, and interpersonal/socioeconomic well-being, as well as overall health-related quality of life. We summarize limitations and gaps in available evidence, and we provide recommendations for future research and clinical care activities focused on long-term outcomes in liver donors.
Assuntos
Regeneração Hepática/fisiologia , Transplante de Fígado/psicologia , Doadores Vivos/psicologia , Qualidade de Vida , Humanos , Fatores de TempoRESUMO
The role of antiviral prophylaxis for the prevention of posttransplant lymphoproliferative disease (PTLD) remains controversial for solid organ transplantation (SOT) recipients who are seronegative for Epstein-Barr virus (EBV) but who received organs from seropositive donors. We performed a systematic review and meta-analysis to address this issue. Two independent assessors extracted data from studies after determining patient eligibility and completing quality assessments. Overall, 31 studies were identified and included in the quantitative synthesis. Nine studies were included in the direct comparisons (total 2366 participants), and 22 were included in the indirect analysis. There was no significant difference in the rate of EBV-associated PTLD in SOT recipients among those who received prophylaxis (acyclovir, valacyclovir, ganciclovir, valganciclovir) compared with those who did not receive prophylaxis (nine studies; risk ratio 0.95, 95% confidence interval 0.58-1.54). No significant differences were noted across all types of organ transplants, age groups, or antiviral use as prophylaxis or preemptive therapy. There was no significant heterogeneity in the effect of antiviral prophylaxis on the incidence of PTLD. In conclusion, the use of antiviral prophylaxis in high-risk EBV-naive patients has no effect on the incidence of PTLD in SOT recipients.
Assuntos
Antivirais/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/patogenicidade , Transtornos Linfoproliferativos/prevenção & controle , Transplante de Órgãos/métodos , Pré-Medicação/métodos , Infecções por Vírus Epstein-Barr/virologia , Humanos , Transtornos Linfoproliferativos/etiologia , PrognósticoRESUMO
Lung transplantation using RNA+ hepatitis C (HCV+) donors to seronegative recipients is not currently performed due to the very high risk of transmission. Previous reports have shown poor survival when this practice was applied. The emergence of new direct-acting antiviral drugs (DAA) suggests a high chance of sustained virologic response in immunocompetent patients. We report here successful transplantation of lungs from HCV+ donor to HCV- recipient. The recipient was an HCV- patient with chronic lung allograft dysfunction. Viral transmission occurred early posttransplant but excellent clinical outcomes were observed including elimination of HCV after 12 weeks of treatment using DAAs.
Assuntos
Sobrevivência de Enxerto , Hepatite C/prevenção & controle , Transplante de Pulmão/métodos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Transplantados , Adulto , Hepacivirus/fisiologia , Hepatite C/transmissão , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg preloaded with cell membrane vesicles from allogeneic peripheral blood mononuclear cells induce T cell hyporesponsiveness to donor alloantigen (alloAg) in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 × 106 /kg) were administered intravenously, 1 day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 immunoglobulin [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n = 6 historical controls) and 29 days with control unpulsed DCreg (n = 2), to 56 days with donor Ag-pulsed DCreg (n = 5) was associated with evidence of modulated host CD4+ and CD8+ T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4 Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days posttransplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen.
Assuntos
Células Dendríticas/imunologia , Sobrevivência de Enxerto/imunologia , Isoantígenos/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Linfócitos T/imunologia , Doadores de Tecidos , Animais , Leucócitos Mononucleares , Macaca mulatta , Masculino , Tolerância ao Transplante , Transplante HomólogoRESUMO
In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.
Assuntos
Doadores Vivos , Transplante de Órgãos , Sistema de Registros , Obtenção de Tecidos e Órgãos , Atenção à Saúde , HumanosRESUMO
Human (Homo sapiens) micro-RNAs (hsa-miRNAs) regulate virus and host-gene translation, but the biological impact in patients with human cytomegalovirus (hCMV) infection is not well defined in a clinically relevant model. First, we compared hsa-miRNA expression profiles in peripheral blood mononuclear cells from 35 transplant recipients with and without CMV viremia by using a microarray chip covering 847 hsa-miRNAs. This approach demonstrated a set of 142 differentially expressed hsa-miRNAs. Next, we examined the effect of each of these miRNAs on viral growth by using human fibroblasts (human foreskin fibroblast-1) infected with the hCMV Towne strain, identifying a subset of proviral and antiviral hsa-miRNAs. miRNA-target prediction software indicated potential binding sites within the hCMV genome (e.g., hCMV-UL52 and -UL100 [UL = unique long]) and host-genes (e.g., interleukin-1 receptor, IRF1). Luciferase-expressing plasmid constructs and immunoblotting confirmed several predicted miRNA targets. Finally, we determined the expression of selected proviral and antiviral hsa-miRNAs in 242 transplant recipients with hCMV-viremia. We measured hsa-miRNAs before and after antiviral therapy and correlated hsa-miRNA expression levels to hCMV-replication dynamics. One of six antiviral hsa-miRNAs showed a significant increase during treatment, concurrent with viral decline. In contrast, six of eight proviral hsa-miRNAs showed a decrease during viral decline. Our results indicate that a complex and multitargeted hsa-miRNA response occurs during CMV replication in immunosuppressed patients. This study provides mechanistic insight and potential novel biomarkers for CMV replication.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/etiologia , Rejeição de Enxerto/etiologia , MicroRNAs/genética , Transplante de Órgãos/efeitos adversos , Viremia/etiologia , Replicação Viral/genética , Western Blotting , Estudos de Casos e Controles , Células Cultivadas , Estudos de Coortes , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto , Interações Hospedeiro-Patógeno , Humanos , Complicações Pós-Operatórias , Prognóstico , RNA Mensageiro/genética , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Viremia/diagnóstico , Viremia/tratamento farmacológico , Replicação Viral/efeitos dos fármacosRESUMO
Monitoring of cytomegalovirus cell-mediated immunity is a promising tool for the refinement of preventative and therapeutic strategies posttransplantation. Typically, the interferon-γ response to T cell stimulation is measured. We evaluated a broad range of cytokine and chemokines to better characterize the ex vivo host-response to CMV peptide stimulation. In a cohort of CMV viremic organ transplant recipients, chemokine expression-specifically CCL8 (AUC 0.849 95% CI 0.721-0.978; p = 0.003) and CXCL10 (AUC 0.841, 95% CI 0.707-0.974; p = 0.004)-was associated with control of viral replication. In a second cohort of transplant recipients at high-risk for CMV, the presence of a polymorphism in the CCL8 promoter conferred an increased risk of viral replication after discontinuation of antiviral prophylaxis (logrank hazard ratio 3.6; 95% CI 2.077-51.88). Using cell-sorting experiments, we determined that the primary cell type producing CCL8 in response to CMV peptide stimulation was the monocyte fraction. Finally, in vitro experiments using standard immunosuppressive agents demonstrated a dose-dependent reduction in CCL8 production. Chemokines appear to be important elements of the cell-mediated response to CMV infection posttransplant, as here suggested for CCL8, and translation of this knowledge may allow for the tailoring and improvement of preventative strategies.
Assuntos
Quimiocina CCL8/metabolismo , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/isolamento & purificação , Transplante de Órgãos , Fragmentos de Peptídeos/farmacologia , Complicações Pós-Operatórias , Viremia/imunologia , Antivirais/uso terapêutico , Estudos de Casos e Controles , Quimiocina CCL8/genética , Estudos de Coortes , Citocinas/genética , Citocinas/metabolismo , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/metabolismo , Seguimentos , Genes MHC Classe I/imunologia , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunidade Celular , Terapia de Imunossupressão , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Regiões Promotoras Genéticas , Fatores de Risco , Taxa de Sobrevida , Linfócitos T/imunologia , Transplantados , Viremia/epidemiologia , Viremia/mortalidade , Replicação ViralRESUMO
Cytomegalovirus (CMV) encodes multiple microRNAs. While these have been partially characterized in vitro, their relevance to clinical CMV infection has not been evaluated. We analyzed samples from a cohort of solid organ transplant patients with CMV disease (n = 245) for viral microRNA expression. Several CMV microRNAs were readily detectable in patients with CMV disease in variable relative abundance. Expression level generally correlated with DNA viral load and the absence of viral microRNA was associated with faster viral clearance. Detection of hcmv-miR-UL22A-5p at baseline independently predicted the recurrence of CMV viremia upon discontinuation of antiviral therapy (OR 3.024, 95% CI: 1.35-6.8; p = 0.007). A combination of direct mRNA targeting by the microRNA and indirect modulation of gene expression involving isoforms of the transcriptional regulator C-MYC may be responsible for the broad effects seen in the association of gene transcripts with the RNA-induced silencing complex and in global protein expression upon hcmv-miR-UL22A-5p transfection. This novel study of in vivo viral microRNA expression profiles provides unique insight into the complexity of clinical CMV infection following transplantation. We provide evidence that viral microRNAs may have complex effects on gene expression and be associated with specific virologic and clinical outcomes, and thus could be further evaluated as biomarkers.
Assuntos
Infecções por Citomegalovirus/genética , Citomegalovirus/genética , Perfilação da Expressão Gênica , Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , MicroRNAs/genética , Transplante de Órgãos , Biomarcadores , Western Blotting , Estudos de Coortes , Biologia Computacional , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/virologia , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoprecipitação , MicroRNAs/sangue , Prognóstico , RNA Viral/sangue , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Recidiva , Fatores de Risco , Replicação ViralRESUMO
Guidelines recommend targeted antifungal prophylaxis for liver transplant (LT) recipients based on tiers of risk, rather than universal prophylaxis. The feasibility and efficacy of tiered, targeted prophylaxis is not well established. We performed a retrospective study of LT recipients who received targeted prophylaxis (n = 145; voriconazole [VORI; 54%], fluconazole [8%], no antifungal [38%]) versus universal VORI prophylaxis (n = 237). Median durations of targeted and universal prophylaxis were 11 and 6 days, respectively (p < 0.0001). The incidence of invasive fungal infections (IFIs) in targeted and universal groups was 6.9% and 4.2% (p = 0.34). Overall, intra-abdominal candidiasis (73%) was the most common IFI. Posttransplant bile leaks (p = 0.001) and living donor transplants (p = 0.04) were independent risk factors for IFI. IFIs occurred in 6% of high-risk transplants who received prophylaxis and 4% of low-risk transplants who did not receive prophylaxis (p = 1.0). Mortality rates (100 days) were 10% (targeted) and 7% (universal) (p = 0.26); attributable mortality due to IFI was 10%. Compliance with prophylaxis recommendations was 97%. Prophylaxis was discontinued for toxicity in 2% of patients. Targeted antifungal prophylaxis in LT recipients was feasible and safe, effectively prevented IFIs and reduced the number of patients exposed to antifungals. Bile leaks and living donor transplants should be considered high-risk indications for prophylaxis.
Assuntos
Antifúngicos/uso terapêutico , Rejeição de Enxerto/epidemiologia , Hepatopatias/complicações , Transplante de Fígado/efeitos adversos , Micoses/prevenção & controle , Transplantados , Adulto , Idoso , Algoritmos , Feminino , Seguimentos , Rejeição de Enxerto/microbiologia , Sobrevivência de Enxerto , Humanos , Hospedeiro Imunocomprometido , Hepatopatias/microbiologia , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Micoses/epidemiologia , Micoses/microbiologia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Lung transplant (LT) recipients are at high risk for infection owing to lifelong immunosuppression and direct communication of the graft with the environment. Guidelines have been established for safe-living strategies after transplantation. We conducted a survey of LT patients to determine compliance with these strategies. METHODS: Adult LT outpatients completed a survey consisting of questions on a 5-point Likert scale with the following categories: hand washing, gardening, respiratory infections, food and water safety, animal contact, travel, and occupation. RESULTS: A total of 194 LT recipients completed the survey (age 54.4 ± 13.3 years; time post transplant 4.76 ± 3.5 years). Regular hand washing was practiced usually or always by 87.6%. Of those who worked with soil/gardened, 70/99 (70.7%) never wore a mask and 15.7% never wore gloves. Pet ownership was common (52%), but most patients used specific precautions during handling. Over one-third of patients continued employment after transplant but, of these, 56% had modified their occupation often because of perceived infectious risks. Most patients were fully compliant with influenza vaccination (92.3%). Patients <40 years of age were less likely to wear long-sleeved clothing in mosquito season (P = 0.002), more likely to handle pet feces (P = 0.005), and less likely to wear a mask with sick contacts (P = 0.021). CONCLUSIONS: We provide important insight into safe-living practices following lung transplantation and identify specific areas and subgroups of patients that could be targeted for enhanced education, with potential significant clinical benefit.
Assuntos
Rejeição de Enxerto/prevenção & controle , Desinfecção das Mãos , Comportamentos Relacionados com a Saúde , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Transplante de Pulmão , Máscaras/estatística & dados numéricos , Animais de Estimação , Adolescente , Adulto , Idoso , Água Potável , Feminino , Inocuidade dos Alimentos , Jardinagem/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/estatística & dados numéricos , Inquéritos e Questionários , Transplantados , Viagem/estatística & dados numéricos , Adulto JovemRESUMO
We evaluated secreted wingless (Wnt) modulators during cytomegalovirus (CMV) infection in solid organ transplant recipients (SOTr). The major findings were: (i) Plasma levels of Dickkopf-1 (DKK-1) were significantly lower in patients with CMV DNAemia above lower level of quantification at baseline. (ii) Receiver operating characteristic analysis indicated that low DKK-1 and increased secreted frizzled related protein-3 levels were predictors of poor virological outcomes during follow-up. Our findings demonstrate an imbalanced pattern of circulating secreted Wnt modulators in SOTr with poor virological outcomes following treatment for CMV disease, and may suggest a role for dysregulated Wnt signaling on viral pathogenesis during CMV infection.
Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Transplante de Órgãos , Proteínas/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Adulto , Infecções por Citomegalovirus/sangue , DNA Viral/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Via de Sinalização Wnt/fisiologiaRESUMO
INTRODUCTION: Bacterial infections are major causes of early morbidity and mortality after liver transplantation. Selective digestive decontamination (SDD) can be used pre-operatively for living-donor liver transplant (LD-LT), but its role in this setting remains controversial. METHODS: To evaluate this strategy, we retrospectively analyzed a cohort of consecutive LD-LTs performed in our center from March 2007 to February 2011 and compared the incidence and nature of early infectious complications, length of intensive care unit stay and hospitalization, antibiotic use, and emergence of resistant bacteria in patients with or without SDD prophylaxis. RESULTS: Of 148 LD-LTs in the study period, 111 received SDD prophylaxis while 37 did not. In a multivariate model, the independent factors associated with an increased risk of early post-transplant infections were length of postoperative mechanical ventilation (for every additional day odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.4-4.0; P = 0.002), and choledochojejunostomy (OR = 4.5, 95% CI 1.95-10.5; P < 0.001). Use of SDD did not affect the rate or distribution of infectious complications, duration of hospitalization, antibiotic use, or acquisition of resistant bacteria (OR = 3.52, 95% CI 0.43-15.17; P = 0.376). CONCLUSION: In conclusion, the use of SDD prophylaxis in LD-LT was not beneficial and should be avoided, as it offers no advantage and could potentiate the emergence of multidrug-resistant organisms.
Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/prevenção & controle , Descontaminação/métodos , Sistema Digestório/microbiologia , Transplante de Fígado/métodos , Doadores Vivos , Adulto , Antibacterianos/administração & dosagem , Colistina/administração & dosagem , Colistina/uso terapêutico , Quimioterapia Combinada , Feminino , Gentamicinas/administração & dosagem , Gentamicinas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Adulto JovemRESUMO
Fungal respiratory infections in patients with CF are a significant concern both pre- and post-lung transplantation (LTx). Fungal infection is associated with increased mortality post-LTx, and in the past decade, the prevalence of fungal colonization in Canadian pediatric patients with CF has increased. The emergence of novel fungal pathogens is particularly challenging to the transplant community, as little is known regarding their virulence and optimal management. We present a case of a successful double-lung transplant in a pediatric patient with CF who was infected pretransplantation with a novel yeast, Blastobotrys rhaffinosifermentans. This patient was treated successfully with aggressive antifungal therapy post-transplantation, followed by extended fungal prophylaxis. The significance of fungal colonization and infection in children with CF pre- and post-LTx is reviewed.
Assuntos
Fibrose Cística/terapia , Transplante de Pulmão , Micoses/terapia , Antifúngicos/uso terapêutico , Ascomicetos , Broncoscopia , Canadá , Criança , Fibrose Cística/complicações , Volume Expiratório Forçado , Humanos , Inflamação , Pulmão/microbiologia , Pulmão/patologia , Masculino , Testes de Sensibilidade Microbiana , Micoses/complicações , Complicações Pós-Operatórias , Resultado do TratamentoRESUMO
Innovative and exciting advances in the clinical sciences in organ transplantation were presented at the American Transplant Congress 2012. The full spectrum of transplantation was covered with important advancements in many topics. Key areas covered by presentations included living donor outcomes, organ preservation, optimal allocation of deceased donors, new immunosuppression regimens, antibody mediated rejection and the regulatory environment. This review will highlight some of the most interesting and innovative clinical presentations from the meeting.
Assuntos
Transplante/métodos , Boston , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Transplante de Fígado/métodos , Doadores Vivos , Preservação de Órgãos , Transplante de Pâncreas/métodos , Obtenção de Tecidos e Órgãos/organização & administração , Transplante/tendências , Resultado do Tratamento , Estados UnidosRESUMO
Solid organ transplant recipients are at risk of morbidity from human papillomavirus (HPV)-related diseases. Quadrivalent HPV vaccine is recommended for posttransplant patients but there are no data on vaccine immunogenicity. We determined the immunogenicity of HPV vaccine in a cohort of young adult transplant patients. Patients were immunized with three doses of quadrivalent HPV vaccine containing viral types 6, 11, 16 and 18. Immunogenicity was determined by type-specific viral-like protein ELISA. Four weeks after the last dose of vaccine, a vaccine response was seen in 63.2%, 68.4%, 63.2% and 52.6% for HPV 6, 11, 16 and 18, respectively. Factors that led to reduced immunogenicity were vaccination early after transplant (p = 0.019), having a lung transplant (p = 0.007) and having higher tacrolimus levels (p = 0.048). At 12 months, there were significant declines in antibody titer for all HPV types although the number of patients who remained seropositive did not significantly differ. The vaccine was safe and well tolerated. We show suboptimal immunogenicity of HPV vaccine in transplant patients. This is important for counseling patients who choose to receive this vaccine. Further studies are needed to determine an optimal HPV vaccine type and schedule for this population.
Assuntos
Transplante de Rim , Transplante de Fígado , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Humanos , Masculino , Vacinas contra Papillomavirus/uso terapêutico , Estudos Prospectivos , Vacinação , Adulto JovemRESUMO
As the disparity between the number of candidates listed for transplant and the number of donors continues to grow, marginal organ donors are increasingly utilized. This includes bacteremic donors which may carry an increased risk of transmission of infection. It is recommended that recipients of organs from bacteremic donors receive antibiotic prophylaxis based on the susceptibilities of the donor isolate to prevent transmission. Here, we present four cases of donor-derived bacteremia, despite appropriate antimicrobial prophylaxis, in four liver transplant recipients. Transmitted pathogens included Staphylococcus aureus in two cases, and Escherichia coli and Group B Streptococcus each in one case. Interestingly, none of the nonhepatic organs (n=10) utilized from these bacteremic donors resulted in transmissions. These cases highlight the fact that risk of transmission from bacteremic donors is not eliminated with antimicrobial therapy in the donor and recipient. As no transmissions occurred in recipients of nonhepatic organs from these donors, these cases also suggest that liver recipients may be at higher risk of donor transmitted bacteremia.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Doadores de Tecidos , Adulto , Idoso , Antibioticoprofilaxia/métodos , Bacteriemia/etiologia , Escherichia coli , Feminino , Humanos , Lactente , Fígado/microbiologia , Falência Hepática/complicações , Falência Hepática/microbiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Staphylococcus aureus , Streptococcus agalactiaeRESUMO
The immunogenicity of standard intramuscular (IM) influenza vaccine is suboptimal in transplant recipients. Also, recent studies suggest that alloantibody may be upregulated due to vaccination. We evaluated a novel high-dose intradermal (ID) vaccine strategy. In conjunction, we assessed alloimmunity. Transplant recipients were randomized to receive IM or high-dose ID vaccine. Strain-specific serology and HLA alloantibody production was determined pre- and postimmunization. In 212 evaluable patients (105 IM, 107 ID), seroprotection to H1N1, H3N2 and B strains was 70.5%, 63.8% and 52.4% in the IM group, and 71.0%, 70.1%, 63.6% in the ID group (p=ns). Seroconversion to ≥1 antigen was 46.7% and 51.4% in the IM and ID groups respectively (p=0.49). Response was more likely in those≥6 months posttransplant (53.2% vs. 19.2%; p=0.001). Use of mycophenolate mofetil was inversely associated with vaccine response in a dose-dependent manner (p<0.001). Certain organ subgroups had higher response rates for influenza B in the ID vaccine group. Differences in anti-HLA antibody production were detected in only 3/212(1.4%) patients with no clinical consequences. High-dose intradermal vaccine is an alternative to standard vaccine and has potential enhanced immunogenicity in certain subgroups. In this large cohort, we also show that seasonal influenza does not result in significant alloantibody production.