Infections and Organ Transplantation

Grossi, Paolo; Costa, Alessandro Nanni; Fehily, Deirdre; Blumberg, Emily A.; Kuehnert, Matthew J.; Fishman, Jay A.; Ison, Michael G.; Lattes, R.; Kotton, Camille N.; Lilleri, Daniele; Kabanova, Anna; Lanzavecchia, Antonio; Gerna, Giuseppe; Razonable, Raymund R.; Comoli, Patrizia; Zecca, Marco; Basso, Sabrina; Ginevri, Fabrizio; Grossi, A.; Schena, Francesco Paolo; Rimola, Antoni; Burra, Patrizia; E, Martín; Rodríguez–Castro, Kryssia Isabel; Fagiuoli, Stefano; Pasulo, L.; Bruno, Raffaele; Andreone, Pietro; Loggi, Elisabetta; Arena, Fabio; Rossolini, Gian María; Sganga, Gabriele; Cozza, Valerio

doi:10.1097/tp.0b013e3182481347

Cited by 27 publications

(7 citation statements)

References 254 publications

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“…The main absolute contraindication to donation is a high risk of transmission of infectious or neoplastic diseases with a poorer prognosis or progression than maintenance of renal replacement therapy - see question 19 (B) . ( 187 )…”

Section: Part 4: Organ-specific Contraindicationsmentioning

confidence: 99%

Guidelines for the assessment and acceptance of potential brain-dead organ donors

Westphal¹,

Garcı́a²,

Souza³

et al. 2016

Revista Brasileira De Terapia Intensiva

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Organ transplantation is the only alternative for many patients with terminal diseases. The increasing disproportion between the high demand for organ transplants and the low rate of transplants actually performed is worrisome. Some of the causes of this disproportion are errors in the identification of potential organ donors and in the determination of contraindications by the attending staff. Therefore, the aim of the present document is to provide guidelines for intensive care multi-professional staffs for the recognition, assessment and acceptance of potential organ donors.

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Section: Part 4: Organ-specific Contraindicationsmentioning

confidence: 99%

Guidelines for the assessment and acceptance of potential brain-dead organ donors

Westphal¹,

Garcı́a²,

Souza³

et al. 2016

Revista Brasileira De Terapia Intensiva

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“…CMV can trigger direct and indirect morbidities such as chronic allograft rejection or in the case of kidney transplantation (KTx) chronic nephropathy (2, 3). Therapeutic control of CMV may be hampered by the development of anti-viral drug resistance (4). Moreover, after discontinuation of anti-viral prophylaxis, late-onset CMV disease frequently occurs and overall mortality is significantly higher in CMV-infected compared to uninfected KTx patients (1).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Characterization of a Next-Generation Antiviral T-Cell Product and Feasibility for Application in Immunosuppressed Transplant Patients

et al. 2019

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Viral infections have a major impact on morbidity and mortality of immunosuppressed solid organ transplant (SOT) patients because of missing or failure of adequate pharmacologic antiviral treatment. Adoptive antiviral T-cell therapy (AVTT), regenerating disturbed endogenous T-cell immunity, emerged as an attractive alternative approach to combat severe viral complications in immunocompromised patients. AVTT is successful in patients after hematopoietic stem cell transplantation where T-cell products (TCPs) are manufactured from healthy donors. In contrast, in the SOT setting TCPs are derived from/applied back to immunosuppressed patients. We and others demonstrated feasibility of TCP generation from SOT patients and first clinical proof-of-concept trials revealing promising data. However, the initial efficacy is frequently lost long-term, because of limited survival of transferred short-lived T-cells indicating a need for next-generation TCPs. Our recent data suggest that Rapamycin treatment during TCP manufacture, conferring partial inhibition of mTOR, might improve its composition. The aim of this study was to confirm these promising observations in a setting closer to clinical challenges and to deeply characterize the next-generation TCPs. Using cytomegalovirus (CMV) as model, our next-generation Rapamycin-treated (Rapa-)TCP showed consistently increased proportions of CD4 + T-cells as well as CD4 + and CD8 + central-memory T-cells (T CM ). In addition, Rapamycin sustained T-cell function despite withdrawal of Rapamycin, showed superior T-cell viability and resistance to apoptosis, stable metabolism upon activation, preferential expansion of T CM , partial conversion of other memory T-cell subsets to T CM and increased clonal diversity. On transcriptome level, we observed a gene expression profile denoting long-lived early memory T-cells with potent effector functions. Furthermore, we successfully applied the novel protocol for the generation of Rapa-TCPs to 19/19 SOT patients in a comparative study, irrespective of their history of CMV reactivation. Moreover, comparison of paired TCPs generated before/after transplantation did not reveal inferiority of the latter despite exposition to maintenance immunosuppression post -SOT. Our data imply that the Rapa-TCPs, exhibiting longevity and sustained T-cell memory, are a reasonable treatment option for SOT patients. Based on our success to manufacture Rapa-TCPs from SOT patients under maintenance immunosuppression, now, we seek ultimate clinical proof of efficacy in a clinical study.

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“…Transplant rejection rates decreased with improved immunosuppression and quality of life increased with better post-transplant care. Donor- and recipient- derived, opportunistic, nosocomial or community acquired infections including newly emerging infectious diseases and malignancies remain a problem, however [1], [2]. Most infections in SOT recipients are associated with high morbidity and mortality compared to immunocompetent individuals.…”

Section: Introductionmentioning

confidence: 99%

Serologic Vaccination Response after Solid Organ Transplantation: A Systematic Review

et al. 2013

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BackgroundInfectious diseases after solid organ transplantation (SOT) are one of the major complications in transplantation medicine. Vaccination-based prevention is desirable, but data on the response to active vaccination after SOT are conflicting.MethodsIn this systematic review, we identify the serologic response rate of SOT recipients to post-transplantation vaccination against tetanus, diphtheria, polio, hepatitis A and B, influenza, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitides, tick-borne encephalitis, rabies, varicella, mumps, measles, and rubella.ResultsOf the 2478 papers initially identified, 72 were included in the final review. The most important findings are that (1) most clinical trials conducted and published over more than 30 years have all been small and highly heterogeneous regarding trial design, patient cohorts selected, patient inclusion criteria, dosing and vaccination schemes, follow up periods and outcomes assessed, (2) the individual vaccines investigated have been studied predominately only in one group of SOT recipients, i.e. tetanus, diphtheria and polio in RTX recipients, hepatitis A exclusively in adult LTX recipients and mumps, measles and rubella in paediatric LTX recipients, (3) SOT recipients mount an immune response which is for most vaccines lower than in healthy controls. The degree to which this response is impaired varies with the type of vaccine, age and organ transplanted and (4) for some vaccines antibodies decline rapidly.ConclusionVaccine-based prevention of infectious diseases is far from satisfactory in SOT recipients. Despite the large number of vaccination studies preformed over the past decades, knowledge on vaccination response is still limited. Even though the protection, which can be achieved in SOT recipients through vaccination, appears encouraging on the basis of available data, current vaccination guidelines and recommendations for post-SOT recipients remain poorly supported by evidence. There is an urgent need to conduct appropriately powered vaccination trials in well-defined SOT recipient cohorts.

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Infections and Organ Transplantation

Cited by 27 publications

References 254 publications

Guidelines for the assessment and acceptance of potential brain-dead organ donors

Guidelines for the assessment and acceptance of potential brain-dead organ donors

Comprehensive Characterization of a Next-Generation Antiviral T-Cell Product and Feasibility for Application in Immunosuppressed Transplant Patients

Serologic Vaccination Response after Solid Organ Transplantation: A Systematic Review

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