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1.
Exp Clin Transplant ; 22(4): 267-269, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742316

RESUMO

OBJECTIVES: BK virus is a major cause of chronic renal allograft failure.Transplant ureteral stent use has been reported as a risk factorfor BK virus infection. Recently, the use of a new type of ureteral stent (Magnetic Black Star) was reported in kidney transplant recipients. The aim ofthis preliminary report was to compare BK virus viremia and viruria occurrence depending on the type of double-J stent (standard versus Magnetic Black Star). MATERIALS AND METHODS: We included all kidney transplants performed in our center from January to December 2022. Each case had double-J stent placement. Indwelling stents were either a 6- or 7-Fr standard double-J stent or a 6-Fr Magnetic Black Star double-J stent. The type of double-J stent was chosen according to the surgeon's preference. A standard BK virus screening protocol was followed during the study period, which consisted of routine polymerase chain reaction examination of plasma and urine samples during monthly follow-ups. RESULTS: We assessed 120 patients without missing data: 92 patients received standard double-J stents and 28 patients received Magnetic Black Star stents. Patients were mostly male in the standard group (70.7%) versus the Magnetic Black Star group (42.9%) (P = .01). ABO- and HLA-incompatible transplant rates were similar in both groups. BK viremia occurrence and BK viruria occurrence were similar between groups at 1 month, 3 months, and 6 months. CONCLUSIONS: This preliminary study showed no differences concerning BKvirus infection depending on the type of double-J stents used during kidney transplant.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Desenho de Prótese , Stents , Infecções Tumorais por Vírus , Viremia , Humanos , Transplante de Rim/efeitos adversos , Vírus BK/patogenicidade , Vírus BK/imunologia , Masculino , Viremia/diagnóstico , Viremia/virologia , Feminino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/urina , Fatores de Risco , Resultado do Tratamento , Adulto , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/urina , Fatores de Tempo , Dados Preliminares , Estudos Retrospectivos
2.
Am J Transplant ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461883

RESUMO

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.

3.
Transpl Infect Dis ; 26(2): e14260, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38547002

RESUMO

INTRODUCTION: As there is no specific antiviral treatment currently available for BK polyomavirus associated nephropathy (BKVAN), its management relies on immunosuppression reduction in kidney transplant patients. Data on efficacy of steroid pulses in this indication are lacking. METHODS: We performed a retrospective monocenter study on 64 patients diagnosed with biopsy-proven BKVAN. Patients within the "pulse group" (n = 37) received IV methylprednisolone 10 mg/kg 3 days consecutively. In the "low dose" steroid group (n = 27), patients were continued oral prednisone 5 mg daily. RESULTS: Mean follow up was 78 months in the steroid pulse group and 56 months in the low dose group (p = 0.15). Mean eGFR values at diagnosis were comparable, as well as other demographic characteristics. Mean BK plasma viral load was higher in "pulse" than in "low dose" steroid group. Pulse group had higher inflammation and tubulitis (p < 0.05). Graft loss reached 57% in the "pulse" group versus 41% in the "low dose" group, p = 0.20. Rejection events were similar. No major adverse event was statistically associated with steroid pulse, including infections, cancer, and de novo diabetes. CONCLUSION: No significant differences were found in the evolution of both groups of patients, despite patients receiving "pulse" steroids were identified as the most severe sharing higher BK viral load and more frequent active lesions on histology.


Assuntos
Vírus BK , Nefropatias , Nefrite Intersticial , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Estudos Retrospectivos , Nefrite Intersticial/patologia , Aloenxertos/patologia , Inflamação , Esteroides/uso terapêutico , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Rejeição de Enxerto/tratamento farmacológico
5.
Am J Transplant ; 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38097016

RESUMO

The intricate association between histologic lesions and circulating antihuman leucocyte antigen donor-specific antibodies (DSA) in liver transplantation (LT) requires further clarification. We conducted a probabilistic, unsupervised approach in a comprehensively well-annotated LT cohort to identify clinically relevant archetypes. We evaluated 490 pairs of LT biopsies with DSA testing from 325 recipients transplanted between 2010 and 2020 across 3 French centers and an external cohort of 202 biopsies from 128 recipients. Unsupervised archetypal analysis integrated all clinico-immuno-histologic parameters of each biopsy to identify biopsy archetypes. The median time after LT was 1.17 (interquartile range, 0.38-2.38) years. We identified 7 archetypes distinguished by clinico-immuno-histologic parameters: archetype #1: severe T cell-mediated rejection (15.9%); #2: chronic rejection with ductopenia (1.8%); #3: architectural and microvascular damages (3.5%); #4: (sub)normal (55.9%); #5: mild T cell-mediated rejection (4.9%); #6: acute antibody-mediated rejection (6.5%); and #7: chronic rejection with DSA (11.4%). Cell infiltrates vary in the archetype. These archetypes were associated with distinct liver biological markers and allograft outcomes. These findings remained consistent when stratified using the patient's age or indications for LT, with good performance in the external cohort (mean highest probability assignment = 0.58, standard deviation ± 0.17). In conclusion, we have identified clinically meaningful archetypes, providing valuable insights into the intricate DSA-histology association, which may help standardize liver allograft pathology classification.

6.
Biology (Basel) ; 12(10)2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37887068

RESUMO

Allogenic graft acceptance is only achieved by life-long immunosuppression, which comes at the cost of significant toxicity. Clinicians face the challenge of adapting the patients' treatments over long periods to lower the risks associated with these toxicities, permanently leveraging the risk of excessive versus insufficient immunosuppression. A major goal and challenge in the field of solid organ transplantation (SOT) is to attain a state of stable immune tolerance specifically towards the grafted organ. The immune system is equipped with a set of inhibitory co-receptors known as immune checkpoints (ICs), which physiologically regulate numerous effector functions. Insufficient regulation through these ICs can lead to autoimmunity and/or immune-mediated toxicity, while excessive expression of ICs induces stable hypo-responsiveness, especially in T cells, a state sometimes referred to as exhaustion. IC blockade has emerged in the last decade as a powerful therapeutic tool against cancer. The opposite action, i.e., subverting IC for the benefit of establishing a state of specific hypo-responsiveness against auto- or allo-antigens, is still in its infancy. In this review, we will summarize the available literature on the role of ICs in SOT and the relevance of ICs with graft acceptance. We will also discuss the possible influence of current immunosuppressive medications on IC functions.

7.
JHEP Rep ; 5(10): 100832, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37681206

RESUMO

Background & Aims: Liver transplantation (LT) is a last resort treatment for patients at high risk of mortality from end-stage liver disease. Over the past years, alcohol-associated liver disease has become the most frequent indication for LT in the world. The outcomes of LT for alcohol-associated liver disease are good, but return to alcohol use is detrimental for medium-term survival because of cancer development, cardiovascular events, and recurrent alcohol-associated cirrhosis. Several strategies have been developed to prevent return to alcohol use during the pre- or post-LT period, but there are no specific recommendations. Therefore, the main objective of this study was to investigate if the integration of an addiction team in a LT unit affected the rate of severe alcohol relapse after LT. The secondary objectives were to assess the effects of addiction follow up on cardiovascular events, cancer, and overall survival. Methods: This study was a retrospective comparison between centres with or without addiction monitoring. Results: The study included 611 patients of which 79.4% were male with a mean age of 55.4 years at the time of LT, 190 were managed by an integrated addiction team. The overall alcohol relapse rate was 28.9% and the rate of severe relapse was 13.0%. Patients with addiction follow-up had significantly less frequent severe alcohol relapse than those in the control group (p = 0.0218). Addiction follow up (odds ratio = 0.19; p = 0.001) and age at LT (odds ratio = 1.23; p = 0.02) remained significantly associated with post-LT cardiovascular events. Conclusions: Our study confirms the benefits of integrating an addiction team to reduce return to alcohol use after LT. Clinical Trials registration: This study is registered at ClinicalTrials.gov (NCT04964687). Impact and implications: The main indication for liver transplantation is alcohol-associated cirrhosis. There are currently no specific recommendations on the addiction monitoring of transplant candidates, although severe return to alcohol use after liver transplantation has a negative impact on long-term survival of patients. In this study, we explored the impact of a systematic addiction intervention on the return to alcohol use rates. In our transplantation centre, we demonstrated the interest of an addiction follow up to limit the severe alcohol relapses rate. This information should be further investigated in prospective studies to validate these data.

8.
Kidney Int ; 103(6): 1167-1179, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36990211

RESUMO

We previously established a six-gene-based blood score associated with operational tolerance in kidney transplantation which was decreased in patients developing anti-HLA donor-specific antibodies (DSA). Herein, we aimed to confirm that this score is associated with immunological events and risk of rejection. We measured this using quantitative PCR (qPCR) and NanoString methods from an independent multicenter cohort of 588 kidney transplant recipients with paired blood samples and biopsies at one year after transplantation validating its association with pre-existing and de novo DSA. From 441 patients with protocol biopsy, there was a significant decrease of the score of tolerance in 45 patients with biopsy-proven subclinical rejection (SCR), a major threat associated with pejorative allograft outcomes that prompted an SCR score refinement. This refinement used only two genes, AKR1C3 and TCL1A, and four clinical parameters (previous experience of rejection, previous transplantation, sex of recipient and tacrolimus uptake). This refined SCR score was able to identify patients unlikely to develop SCR with a C-statistic of 0.864 and a negative predictive value of 98.3%. The SCR score was validated in an external laboratory, with two methods (qPCR and NanoString), and on 447 patients from an independent and multicenter cohort. Moreover, this score allowed reclassifying patients with discrepancies between the DSA presence and the histological diagnosis of antibody mediated rejection unlike kidney function. Thus, our refined SCR score could improve detection of SCR for closer and noninvasive monitoring, allowing early treatment of SCR lesions notably for patients DSA-positive and during lowering of immunosuppressive treatment.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Imunossupressores/uso terapêutico , Anticorpos , Tacrolimo/uso terapêutico , Soro Antilinfocitário , Expressão Gênica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/genética , Isoanticorpos , Estudos Retrospectivos
10.
Ann Neurol ; 93(2): 257-270, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36151879

RESUMO

OBJECTIVE: Our aim was to assess the real-world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML). METHODS: We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care. One-year follow-up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1-year survival. RESULTS: Predisposing conditions included hematological malignancy (n = 38, 48.1%), primary immunodeficiency (n = 14, 17.7%), human immunodeficiency virus/acquired immunodeficiency syndrome (n = 12, 15.2%), inflammatory disease (n = 8, 10.1%), neoplasm (n = 5, 6.3%), and transplantation (n = 2, 2.5%). Pembrolizumab was most commonly used (n = 53, 67.1%). One-year survival was 51.9% (41/79). PML-immune reconstitution inflammatory syndrome (IRIS) was reported in 15 of 79 patients (19%). Pretreatment expression of programmed cell death-1 on circulating T cells did not differ between survivors and nonsurvivors. Development of contrast enhancement on follow-up magnetic resonance imaging at least once during follow-up (OR = 3.16, 95% confidence interval = 1.20-8.72, p = 0.02) was associated with 1-year survival. Cerebrospinal fluid JC polyomavirus DNA load decreased significantly by 1-month follow-up in survivors compared to nonsurvivors (p < 0.0001). Thirty-two adverse events occurred among 24 of 79 patients (30.4%), and led to treatment discontinuation in 7 of 24 patients (29.1%). INTERPRETATION: In this noncontrolled retrospective study of patients with PML who were treated with immune checkpoint inhibitors, mortality remains high. Development of inflammatory features or overt PML-IRIS was commonly observed. This study highlights that use of immune checkpoint inhibitors should be strictly personalized toward characteristics of the individual PML patient. ANN NEUROL 2023;93:257-270.


Assuntos
Síndrome Inflamatória da Reconstituição Imune , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Humanos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico
11.
J Transl Autoimmun ; 7: 100223, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38162455

RESUMO

Bacterial recombinant cysteine protease Ides (imlifidase, Idefirix®, Hansa Biopharma) is used to prevent humoral transplant rejection in highly HLA-sensitized recipients, and to control IgG-mediated autoimmune diseases. We report the case of a 51 years old woman suffering from lupus nephritis with end stage kidney disease, grafted for the second time and pre-treated with imlifidase. The patient was HLA-hypersensitized (calculated Panel Reactive Antibodies [Abs], cPRA>99 %) and has three preformed Donor Specific Antibodies (DSA). Circulating immunoglobulins were monitored at initiation (0, 6, 36, 72 and 96 h), and at Ab recovery one and two months following imlifidase injection. From baseline, the higher depletion was reported after 36h for total IgG (-75 %) and IgG subclasses (-87 % for IgG1, IgG2 and IgG3, -78 % for IgG4), while no significant impact on IgA and IgM was observed. Anti-SSA 60 kDa and anti-SSB auto-Abs quickly decreased after imlifidase injection (-96 % for both after 36 h) as well as post-vaccinal specific IgG (-95 % for tetanus toxoid, -97 % for pneumococcus and -91 % for Haemophilus influenzae Abs after 36 h). At the Ab recovery phase, total IgG and anti-SSA60/SSB Abs reached their initial level at two months. Regarding alloreactive Abs, anti-HLA Abs including the three DSA showed a dramatic decrease after injection with 100 % depletion from baseline after 36 h as assessed by multiplex single bead antigen assay, leading to negative crossmatches using both lymphocytotoxicity (LCT) and flow cell techniques. DSA rebound at recovery was absent and remained under the positivity threshold (MFI = 1000) after 6 months. The findings from this case report are that imlifidase exerts an early depleting effect on all circulating IgG, while IgG recovery may depend in part from imlifidase's capacity to target memory B cells.

12.
J Clin Med ; 11(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35160055

RESUMO

Large granular T-cell leukemia is a clonal hematological condition often associated with autoimmune disorders. Whether small-sized T-cell clones that are otherwise asymptomatic can promote immune kidney disorders remains elusive. In this monocentric retrospective cohort in a tertiary referral center in France, we reviewed characteristics of 29 patients with T-cell clone proliferation and autoimmune kidney disorders. Next-generation sequencing of the T-cell receptor of circulating T-cells was performed in a subset of patients. The T-cell clones were detected owing to systematic screening (mean count 0.32 × 109/L, range 0.13-3.7). Strikingly, a common phenotype of acute interstitial nephropathy was observed in 22 patients (median estimated glomerular filtration rate at presentation of 22 mL/min/1.73 m2 (range 0-56)). Kidney biopsies showed polymorphic inflammatory cell infiltration (predominantly CD3+ T-cells, most of them demonstrating positive phospho-STAT3 staining) and non-necrotic granuloma in six cases. Immune-mediated glomerulopathy only or in combination with acute interstitial nephropathy was identified in eight patients. Next-generation sequencing (n = 13) identified a major T-cell clone representing more than 1% of the T-cell population in all but two patients. None had a mutation of STAT3. Twenty patients (69%) had two or more extra-kidney autoimmune diseases. Acute interstitial nephropathies were controlled with corticosteroids, cyclosporin A, or tofacitinib. Thus, we showed that small-sized T-cell clones (i.e., without lymphocytosis) undetectable without specific screening are associated with various immune kidney disorders, including a previously unrecognized phenotype characterized by severe inflammatory kidney fibrosis and lymphocytic JAK/STAT activation.

13.
Liver Int ; 42(5): 1132-1143, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35184373

RESUMO

BACKGROUND & AIMS: Low calcineurin inhibitor (CNI) levels expose liver transplant recipients to rejection episodes and potentially to antibody-mediated rejection. There are little data on the impact of CNI-free immunosuppression on de novo donor-specific HLA antibody (dnDSA) development. Here we evaluated the prevalence of dnDSA in liver transplant recipients on CNI-free maintenance regimens and their associations with histopathological abnormalities of allografts. METHODS: Seven hundred and twenty-seven liver transplant recipients underwent a first liver transplant between 2000 and 2018 in three French transplant centres and had protocolized follow-up with dnDSA screening and allograft biopsy 1, 5 and 10 years after transplantation. RESULTS: CNIs were withdrawn in 166 (22.8%) patients with or without conversion to mammalian target of rapamycin inhibitors and/or maintenance with mycophenolic acid. DSA were present after withdrawal in 30.1% (50/166) patients on CNI-free immunosuppression compared with 16% (90/561) on CNI maintenance therapy (p < 0.001). The cumulative incidence of dnDSA 10 years after transplant was 20% in the CNI group versus 28% in the CNI-free group (p < 0.01). dnDSAs were associated with histological graft abnormalities (significant allograft fibrosis or rejection) (HR 2.24, 95% CI 1.2-4.1; p = 0.01). In univariate Cox regression analysis, being on a CNI-free regimen did not impact graft histology. CONCLUSIONS: Patients on a CNI-free IS regimen have a higher prevalence of dnDSA than patients on a standard IS regimen. dnDSAs but not CNI-free immunosuppression were associated with abnormal allograft histology.


Assuntos
Rejeição de Enxerto , Transplante de Fígado , Formação de Anticorpos , Inibidores de Calcineurina/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Transplantados
14.
Clin Microbiol Infect ; 28(1): 139.e5-139.e8, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34537363

RESUMO

OBJECTIVES: To evaluate the impact of neutralizing monoclonal antibody (mAb) treatment and to determine whether the selective pressure of mAbs could facilitate the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with spike protein mutations that might attenuate mAb effectiveness. PATIENTS AND METHODS: We evaluated the impact of mAbs on the nasopharyngeal (NP) viral load and virus quasispecies of mAb-treated patients using single-molecule real-time sequencing. The mAbs used were: Bamlanivimab alone (four patients), Bamlanivimab/Etesevimab (23 patients) and Casirivimab/Imdevimab (five patients). RESULTS: The NP SARS-CoV-2 viral load of mAb-treated patients decreased from 8.2 log10 copies/mL before administration to 4.3 log10 copies/mL 7 days after administration. Five immunocompromised patients given Bamlanivimab/Etesevimab were found to have mAb activity-reducing spike mutations. Two patients harboured SARS-CoV-2 variants with a Q493R spike mutation 7 days after administration, as did a third patient 14 days after administration. The fourth patient harboured a variant with a Q493K spike mutation 7 days post-treatment, and the fifth patient had a variant with a E484K spike mutation on day 21. The emergence of the spike mutation was accompanied by stabilization or rebound of the NP viral load in three of five patients. CONCLUSION: Two-mAb therapy can drive the selection of resistant SARS-CoV-2 variants in immunocompromised patients. Patients given mAbs should be closely monitored and measures to limit virus spread should be reinforced.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos , COVID-19 , Evolução Molecular , SARS-CoV-2/genética , Carga Viral , Anticorpos Monoclonais Humanizados , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais , Antineoplásicos Imunológicos/uso terapêutico , COVID-19/terapia , Humanos , Mutação , Quase-Espécies , Seleção Genética
15.
Clin Res Hepatol Gastroenterol ; 46(1): 101774, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34332131

RESUMO

The field of liver transplantation directly or indirectly embodies all liver diseases, in addition to specific ones related to organ rejection (cellular and humoral). The recommended non-invasive methods for determining the indication for liver transplantation are the Model for End-stage Liver Disease score, and the alpha-foetoprotein score in case of hepatocellular carcinoma. Radiological methods are the cornerstones for the diagnosis of vascular and biliary complications after liver transplantation. The possible diseases of the liver graft after transplantation are multiple and often intertwined. Non-invasive diagnostic methods have been poorly evaluated in this context, apart from the recurrence of hepatitis C. Liver biopsy remains the gold standard for evaluating graft lesions in the majority of cases, especially graft rejection.


Assuntos
Carcinoma Hepatocelular , Doença Hepática Terminal , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Seguimentos , Rejeição de Enxerto/diagnóstico , Humanos , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Recidiva Local de Neoplasia/patologia , Recidiva , Índice de Gravidade de Doença
16.
Crit Care Med ; 49(9): 1513-1523, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33900216

RESUMO

RATIONALE: There is an unmet need to improve the description of the state of T-cell exhaustion in patients with sepsis, its reproducibility and correlation with the outcomes before including immunotherapy (like recombinant interleukin-7 or immune checkpoint inhibitors) in the therapeutic armamentarium against sepsis. DESIGN: Observational prospective study. SETTING: Two ICUs in a teaching hospital (France). PATIENTS: Eighty patients with sepsis admitted to the ICU. INTERVENTIONS: Quantification of CD4+ and CD8+ T-cell exhaustion at days 1 and 3. Quantification of the exhaustion markers (programmed death [PD]-1, 2B4, and cluster of differentiation [CD] 160) on T cells, the number of CD4+ regulatory T cells (CD3+ CD4+ CD25hi CD127Lo cells), and the phorbol myristate acetate/ionomycin/ionomycin-induced cytokines production (tumor necrosis factor-α, interleukin-2, and interferon-γ). MEASUREMENTS AND MAIN RESULTS: Using unsupervised clustering analysis, patients could be split in three clusters according to their dominant pattern expression of exhaustion markers on CD8+ T cells (i.e., 2B4lowPD-1lowCD160low, 2B4hiPD-1hiCD160low, and 2B4hiPD-1lowCD160hi) regardless of their underlying morbidities. Only 2B4hiPD-1hiCD160low CD8+ T cells had cytokine production defect, whereas 2B4hi PD-1lowCD160hi pattern correlated with cytokine overproduction. Patients with a predominant "highly activated" 2B4hiPD-1lowCD160hi pattern did not develop secondary bacterial infections. By multivariate analysis, Simplified Acute Physiology Score 2 gravity score at day 1 (p = 0.003) and patterns of exhaustion markers on CD8+ T cells (p = 0.03) were associated with the risk of death. Neither the level of CD4+ regulatory T cells nor the CD4+ exhaustion patterns were associated with the outcomes. CONCLUSIONS: Easy-to-use multicolor flow cytometry assessing 2B4, PD-1, and CD160 expression on CD8+ T cells at day 1 identifies septic patients with poor outcome and discriminates patient subsets in who immunomodulatory drugs should be tested.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Sepse/complicações , Idoso , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD8-Positivos/fisiologia , Feminino , França , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Estudos Prospectivos , Reprodutibilidade dos Testes , Sepse/metabolismo , Índice de Gravidade de Doença
17.
World J Urol ; 39(4): 1287-1298, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32562044

RESUMO

PURPOSE: The main objective was to compare minor (Clavien I-II) and major (Clavien ≥ III) intra- and postoperative complications of living donor robotic assisted kidney transplantation (RAKT) in obese (≥ 30 kg/m2 BMI), overweight (< 30/ ≥ 25 kg/m2 BMI) and non-overweight recipients (< 25 kg/m2 BMI). METHODS: For the present retrospective study, we reviewed the multi-institutional ERUS-RAKT database to select consecutive living donor RAKT recipients. Functional outcomes, intra- and postoperative complications were compared between obese, overweight and non-overweight recipients. RESULTS: 169 living donor RAKTs were performed, by 10 surgeons, from July 2015 to September 2018 in the 8 European centers. 32 (18.9%) recipients were obese, 66 (39.1%) were overweight and 71 (42.0%) were non-overweight. Mean follow-up was 1.2 years. There were no major intra-operative complications in either study group. Conversion to open surgery occurred in 1 obese recipient, in 2 overweight recipients and no conversion occurred in non-overweight recipients (p = 0.3). Minor and major postoperative complications rates were similar in the 3 groups. At one-year of follow-up, median eGFR was similar in all groups [54 (45-60) versus 57 (46-70) versus 63 (49-78) ml/min/1.73 m2 in obese, overweight and non-overweight recipient groups, respectively, p = 0.5]. Delayed graft function rate was similar in the 3 groups. Only the number of arteries was an independent predictive factor of suboptimal renal function at post-operative day 30 in the multivariate analysis. CONCLUSION: RAKT in obese recipients is safe, compared to non-overweight recipients and yields very good function, when it performed at high-volume referral centers by highly trained transplant teams.


Assuntos
Transplante de Rim/métodos , Obesidade/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Robóticos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Clin Transplant ; 35(3): e14207, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33369772

RESUMO

After kidney transplantation, withdrawal of calcineurin inhibitors (CNI) and conversion to sirolimus (SRL) may reduce the occurrence of new non-melanoma skin cancer (NMSC). Conversely, a reduced CNI exposure with everolimus (EVR) is an alternative strategy that has not been thoroughly evaluated. We retrospectively compared the occurrence of newly diagnosed NMSCs in two cohorts of kidney transplant recipients (KTR) with at least one NMSC: 35 patients were converted to EVR with reduced CNI exposure (CNI/EVR group), whereas 46 patients were converted to SRL in association with mycophenolic acid (MPA) (SRL/MPA group). Two years after conversion, survival free of new NMSC was similar between the two cohorts (p = .37), with 19 KTR (54.3%) in the CNI/EVR group and 22 (47.8%) in the SRL/MPA group being diagnosed of at least one new NMSC. Half of the KTR from both groups showed adverse events, leading to mTORi discontinuation for 37.1% of KTR in the CNI/EVR group and 21.7% in the SRL/MPA group (p = .09). The incidence of rejections was similar between the two groups. In a retrospective cohort of KTR with at least one post-transplant NMSC, the outcome of the patients converted to a CNI/EVR regimen was not different from those converted to a SRL/MPA regimen.


Assuntos
Transplante de Rim , Neoplasias Cutâneas , Inibidores de Calcineurina , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Ácido Micofenólico , Projetos Piloto , Estudos Retrospectivos , Prevenção Secundária , Sirolimo/uso terapêutico , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Serina-Treonina Quinases TOR
20.
Front Surg ; 7: 49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850946

RESUMO

Objective: The objective of this preliminary study was to report and compare the peri-operative and functional results of ABO-incompatible (ABOi) living-donor robotic-assisted kidney transplantation (RAKT), ABO-compatible (ABOc) living-donor RAKT, and ABOi living-donor open kidney transplantation (OKT). Materials and Methods: For the present retrospective study, we analyzed data of consecutive patients who underwent ABOi or ABOc-RAKT and ABOi-OKT, from January 2015 to December 2019, in one French academic center. Patients' baseline characteristics, operative, and functional outcomes were compared between ABOi-RAKT, ABOc-RAKT, and ABOi-OKT. Results: 29 RAKT, including 7 ABOi-RAKT, and 56 ABOi-OKT were performed in our center. Median follow-up was 2.0 years. Median recipient age, pre-emptive kidney transplantation rate, sex ratio and desensitization procedures were similar in ABOi-RAKT, ABOc-RAKT, and ABOi-OKT groups. Recipient BMI at transplantation was statistically higher in ABOi and ABOc-RAKT groups compared to ABOi-OKT. The surgical site complication (principally infection-related) rate was lower in ABOi-RAKT, without statistical differences (0 vs. 8.9%, respectively, in ABOi-RAKT and ABOi-OKT, p = 0.7). The delayed graft function rate was 0% in ABOi-RAKT, 13.6% in ABOc-RAKT, and 10.7% in ABOi-OKT (p = 0.6). The post-transplantation blood transfusion rate was statistically higher in the ABOi-OKT group (14.3 vs. 13.6 vs. 57.1% in ABOi-RAKT, ABOc-RAKT, and ABOi-OKT, respectively, p = 0.001). The kidney graft survival at 1 month and at last follow-up was not different between ABOi-RAKT and ABOi-OKT. Conclusion: Our data support the use of ABOi-RAKT to restore accessibility to kidney transplantation for obese patients to the greatest extent possible. Large series are required to confirm these encouraging data from a single center.

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