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1.
Exp Clin Transplant ; 20(7): 663-667, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35924744

RESUMO

OBJECTIVES: Calcineurin inhibitors (cyclosporine and tacrolimus) are widely used in kidney transplant to prevent acute transplantrejection; however,the effects of these medications on graft sequelae after transplant remain unclear. We aimed to compare early complications, including graftrejectionandinfectionrates after kidney transplant, in childrenbetween the cyclosporine and tacrolimus immunomodulator regimens. MATERIALS AND METHODS: In this prospective cohort study, 105 pediatric patients who were candidates to receive kidney transplant in the age range of 4 to 18 years were included. There were 28 patients who received cyclosporine, and 77 patients who received tacrolimus. Participants were routinely tested for cytomegalovirus, BK virus, and bacterial infection on a monthly basis for the first 3 months and once every 3 months thereafter for the first year. The graft rejection rate was also assessed and compared between the 2 treatment regimens. RESULTS: There were no significant differences between the 2 groups receiving cyclosporine or tacrolimus in graft rejection rate (P = .719), cytomegalovirus viremia (P = .112), BK viremia (P = .278), and bacterial infection (P = .897). Graftfailure was significantly more frequent in male than in female patients (30.9% vs 8.2%; P = .004). The rates of graft failure in study patients with and without previous history of graftfailure were found to be statistically similar (16.7% vs 20.4%; P = .825). History of infection in donors did not affect the graft complications posttransplant in recipients. CONCLUSIONS: The use of either tacrolimus or cyclosporine leads to similar consequences in terms of graft rejection or posttransplant viral and bacterial infection, so either drug may be exchanged for the other if needed for tolerability.


Assuntos
Nefropatias , Transplante de Rim , Adolescente , Criança , Pré-Escolar , Ciclosporina/efeitos adversos , Feminino , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Fatores Imunológicos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Masculino , Estudos Prospectivos , Tacrolimo/efeitos adversos , Transplantados , Resultado do Tratamento , Viremia
2.
Transpl Int ; 35: 10626, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928347

RESUMO

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.


Assuntos
COVID-19 , Transplante de Rim , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Anticorpos , COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , Teste para COVID-19 , Vacinas contra COVID-19/uso terapêutico , Rejeição de Enxerto , Antígenos HLA , Humanos , Pandemias , SARS-CoV-2 , Transplantados , Vacinação
3.
Arq Bras Cardiol ; 119(2): 246-254, 2022 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-35946686

RESUMO

BACKGROUND: Cardiovascular disease is among the leading causes of death in solid organ transplant recipients with a functional graft. Although these patients could theoretically benefit from exercise-based rehabilitation (EBR) programs, their implementation is a challenge. OBJECTIVE: We present our initial experience on different delivery modes of a pilot EBR program in kidney and liver transplant recipients. METHODS: Thirty-two kidney or liver transplant recipients were invited for a 6-month EBR program delivered at the hospital gym, community gym or at home, according to the patient's preference. The significance level adopted was 5%. RESULTS: Ten patients (31%) did not complete their program. Among the 22 who did, 7 trained at the hospital gym, 7 at the community gym, and 8 at home. The overall effect was an 11.4% increase in maximum METs (Hedges' effect size g = 0.39). The hospital gym group had an increase in METs of 25.5% (g= 0.58, medium effect size) versus 10% (g= 0.25), and 6.5% (g= 0.20) for the community gym and home groups, respectively. There was a beneficial effect on systolic and diastolic blood pressures, greater for the hospital gym (g= 0.51 and 0.40) and community gym (g= 0.60 and 1.15) groups than for the patients training at home (g= 0.07 and 0.10). No significant adverse event was reported during the follow-up. CONCLUSION: EBR programs in kidney and liver transplant recipients should be encouraged, even if they are delivered outside a hospital gym, since they are safe with positive effects on exercise capacity and cardiovascular risk factors.


FUNDAMENTO: A doença cardiovascular está entre as principais causas de morte entre pacientes transplantados. Embora esses pacientes possam teoricamente se beneficiar de programas de reabilitação baseada em exercícios (RBE), sua implementação ainda é um desafio. OBJETIVO: Apresentamos nossa experiência inicial em diferentes modos de realização de um programa piloto de RBE em receptores de transplante de rim e fígado. MÉTODOS: Trinta e dois pacientes transplantados renais ou hepáticos foram convidados para um programa de RBE de 6 meses realizado na academia do hospital, na academia comunitária ou em casa, de acordo com a preferência do paciente. O nível de significância adotado foi de 5%. RESULTADOS: Dez pacientes (31%) não completaram o programa. Entre os 22 que completaram, 7 treinaram na academia do hospital, 7 na academia comunitária e 8 em casa. O efeito geral foi um aumento de 11,4% nos METs máximos (tamanho do efeito de Hedges g = 0,39). O grupo de academia hospitalar teve um aumento nos METs de 25,5% (g = 0,58, tamanho de efeito médio) versus 10% (g = 0,25) e 6,5% (g = 0,20) para os grupos de academia comunitária e em casa, respectivamente. Houve efeito benéfico nas pressões arteriais sistólica e diastólica, maior para os grupos academia hospitalar (g= 0,51 e 0,40) e academia comunitária (g= 0,60 e 1,15) do que para os pacientes treinando em casa (g= 0,07 e 0,10). Nenhum evento adverso significativo foi relatado durante o seguimento. CONCLUSÃO: Programas de RBE em receptores de transplante de rim e fígado devem ser incentivados, mesmo que sejam realizados fora da academia do hospital, pois são seguros com efeitos positivos na capacidade de exercício e nos fatores de risco cardiovascular.


Assuntos
Transplante de Fígado , Terapia por Exercício , Humanos , Rim , Projetos Piloto , Transplantados
4.
Virol J ; 19(1): 131, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941650

RESUMO

BACKGROUND AND AIMS: The John Cunningham virus (JCV) is the established etiological agent of the polyomavirus-associated nephropathy among renal transplant recipients. In the present study, we aimed to determine the probable predictive factors leading to JCV replication in renal transplant patients. MATERIAL AND METHODS: Urine and plasma samples were collected from a total of 120 consecutive renal-transplanted patients without preliminary screening from Jan 2018 to Mar 2019. After DNA extraction, the simultaneous detection and quantification of JCV and BK polyomavirus (BKV) were conducted using a Real-time quantitative PCR method. Moreover, statistical analyses were performed using the statistical software packages, SPSS version 21. RESULTS: The prevalence of JCV viruria and viremia among renal transplant recipients were 26 (21.67%) and 20 (16.67%), respectively. A significant association was observed between the JCV and two risk factors, diabetes mellitus (P = 0.002) and renal stones (P = 0.015). The prevalence of JCV viremia among recipients who were grafted near time to sampling was significantly higher (P = 0.02). There was a statistically significant coexistence between BK and JC viruses among our patients (P = 0.029). The frequency of JCV viruria in males was reported almost three times more than in females (P = 0.005). The JCV shedding in urine was significantly associated with the tropical steroids like prednisolone acetate, which have been the standard regimen (P = 0.039). Multivariable analysis revealed duration of post-transplantation (OR, 0.89; P = 0.038), diabetes mellitus (OR, 1.85; P = 0.034), and renal stone (OR 1.10; P = 0.04) as independent risk factors associated with JCV viremia post-renal transplantation. CONCLUSION: It seems that the discovery of potential risk factors, including immunological and non-immunological elements, may offer a possible preventive or therapeutic approach in the JCV disease episodes. The results of this study may also help clarify the probable clinical risk factors involving in progressive multifocal leukoencephalopathy development.


Assuntos
Vírus BK , Vírus JC , Nefropatias , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , DNA Viral/genética , Feminino , Humanos , Vírus JC/genética , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Masculino , Transplantados , Viremia/epidemiologia
6.
Transpl Int ; 35: 10375, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957939

RESUMO

Kidney transplant recipients present higher rates of pre-existing comorbidities, in particular diabetes mellitus (DM), hypertension, and cardiac disease. We aimed to verify the main risk factors related to DM that contribute to COVID-19 progression and mortality in a kidney transplant setting. From March to August 2020, we evaluated 300 kidney transplant recipients affected by COVID-19. We used propensity score matching (PSM) to estimate the impact of DM on COVID-19. After matching, all baseline characteristics were well balanced between those with and without DM (n = 100 in each group). Case fatality rate, the requirement of invasive mechanical ventilation (IMV), and acute kidney injury (AKI) were associated with previous fasting blood glucose, and C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels on admission. These findings were similar in kidney transplant patients with and without DM. Glycemia on admission and estimated glomerular filtration rate (eGFR) either on admission or basal correlated to the need of IMV and development of AKI, respectively. Poor glycaemic control, eGFR, markers of inflammation (CRP) and tissue damage (LDH) were indicative of COVID-19 burden in kidney transplant recipients and may be useful tools for risk-stratifying this population, independently of the DM status, during the pandemic.


Assuntos
Injúria Renal Aguda , COVID-19 , Diabetes Mellitus , Transplante de Rim , Injúria Renal Aguda/etiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Humanos , Transplante de Rim/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Transplantados
7.
Front Immunol ; 13: 918887, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967428

RESUMO

Emerging data suggest that costimulation blockade with belatacept effectively controls humoral alloimmune responses. However, whether this effect may be deleterious for protective anti-infectious immunity remains poorly understood. We performed a mechanistic exploratory study in 23 kidney transplant recipients receiving either the calcineurin-inhibitor tacrolimus (Tac, n=14) or belatacept (n=9) evaluating different cellular immune responses after influenza vaccination such as activated T follicular Helper (Tfh), plasmablasts and H1N1 hemagglutinin (HA)-specific memory B cells (HA+mBC) by flow-cytometry, and anti-influenza antibodies by hemagglutination inhibition test (HI), at baseline and days 10, 30 and 90 post-vaccination. The proportion of CD4+CD54RA-CXCR5+ Tfh was lower in belatacept than Tac patients at baseline (1.86%[1.25-3.03] vs 4.88%[2.40-8.27], p=0.01) and remained stable post-vaccination. At M3, HA+mBc were significantly higher in Tac-treated patients (0.56%[0.32-1.49] vs 0.27%[0.13-0.44], p=0.04) and correlated with activated Tfh numbers. When stratifying patients according to baseline HA+mBc frequencies, belatacept patients with low HA+mBC displayed significantly lower HA+mBc increases after vaccination than Tac patients (1.28[0.94-2.4] vs 2.54[1.73-5.70], p=0.04). Also, belatacept patients displayed significantly lower seroprotection rates against H1N1 at baseline than Tac-treated patients (44.4% vs 84.6%) as well as lower seroconversion rates at days 10, 30 and 90 after vaccination (50% vs 0%, 63.6% vs 0%, and 63.6% vs 0%, respectively). We show the efficacy of belatacept inhibiting T-dependent antigen-specific humoral immune responses, active immunization should be highly encouraged before starting belatacept therapy.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Transplante de Rim , Abatacepte/farmacologia , Abatacepte/uso terapêutico , Humanos , Transplante de Rim/efeitos adversos , Transplantados , Vacinação
8.
Iran J Kidney Dis ; 16(4): 269-271, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35962643

RESUMO

SARS-CoV-2 vaccines are being administered worldwide. Most of the reported side effects are mild and self-limiting with few reported cases of severe adverse reactions. Here we report a case of acute cellular rejection in a kidney transplant recipient following vaccination with an inactivated SARS-CoV-2 vaccine. fifty- one years old man with autosomal dominant polycystic kidney disease, who had received a kidney transplantation from a living related donor, 3 years ago, presented with an impaired kidney function seven days after receiving the first dose of Sinovac's COVID-19 vaccine. Kidney transplant biopsy revealed acute cellular rejection. The allograft function completely recovered after treatment with steroids. The analysis and investigation of the complications and adverse reactions induced by anti-COVID-19 vaccines, could increase our understanding of the underlying pathogenesis.  DOI: 10.52547/ijkd.6915.


Assuntos
COVID-19 , Transplante de Rim , COVID-19/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Transplante de Rim/efeitos adversos , Masculino , SARS-CoV-2 , Transplantados , Vacinação
9.
Sci Rep ; 12(1): 11614, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35803958

RESUMO

The aim of this cross-sectional study was to determine the associations between the Mediterranean diet (MeDi), nutritional status parameters, muscle strength, and periodontal status in Dalmatian kidney transplant recipients (KTRs). 89 KTRs were included in this analysis, 40 (45%) women, with a mean age of 61 years (IQR = 13) and a mean time since kidney transplantation of 5 years (IQR = 6.6). An OHIP-14 questionnaire and questionnaire-based periodontal history were obtained from all participants, a comprehensive periodontal examination was performed. Body composition data, anthropometric and clinical parameters were collected for each study participant. The Mediterranean Diet Serving Score (MDSS) was used to assess MeDi adherence, and handgrip strength was measured with a hand dynamometer. Our results showed low adherence to MeDi in KTRs (28%) and almost 50% of KTRs suffer from severe forms of periodontitis. We also found a low OHIP-14 score and poor oral hygiene habits. KTRs with a less severe form of periodontitis had higher muscle mass and handgrip strength. MDSS score was associated with a higher number of teeth, and everyday cereal intake was inversely associated with the periodontitis stage. Our results demonstrate the associations between nutritional status, muscle strength, dietary habits, and periodontal health in Dalmatian KTRs.


Assuntos
Dieta Mediterrânea , Estado Nutricional , Higiene Bucal , Periodontite , Transplantados , Idoso , Estudos Transversais , Dieta Mediterrânea/psicologia , Feminino , Hábitos , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Higiene Bucal/psicologia , Periodontite/patologia , Transplantados/psicologia , Transplantados/estatística & dados numéricos
10.
Immun Inflamm Dis ; 10(8): e673, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35894710

RESUMO

BACKGROUND: After lung transplantation (LuTX), lower respiratory tract infections (LRTI) and acute cellular rejection (ACR) are associated with changes in peripheral blood and bronchoalveolar lavage fluid mononuclear cell profile (PBMC and BALIC). PBMC is also influenced by immunosuppressive regimen and its changes with postoperative time. First-year PBMC and BALIC changes were evaluated in this study with rabbit anti-thymocyte globulin (ATG) and alemtuzumab (AL) induction therapy. METHODS: In total, 64 LuTX recipients were included, 53 of them received AL and 11 ATG as induction therapy. PBMC and BALIC were examined routinely and in cases suspicious of infection and/or rejection. A PBMC- and BALIC-based algorithm for infection and rejection prediction was also tested. RESULTS: In the AL group, peripheral blood lymphocyte and basophil cell numbers were significantly reduced, while the neutrophil cell number elevation during LRTI was significantly higher compared to the control. Early postoperative measurements showed a lower BALIC lymphocyte count. The algorithm had 17% sensitivity and 94% specificity for ACR in all patients and 33% sensitivity and 95% specificity for ACR with coexisting LRTI. CONCLUSION: BALIC is not significantly influenced by the immunosuppressive regimen. PBMC- and BALIC-based algorithm may improve the differential diagnosis of ACR.


Assuntos
Leucócitos Mononucleares , Transplantados , Alemtuzumab , Rejeição de Enxerto/diagnóstico , Humanos , Imunossupressores/uso terapêutico , Pulmão
11.
Front Immunol ; 13: 901273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844527

RESUMO

Background: Malignancy is a major cause of morbidity and mortality in transplant recipients. Identification of those at highest risk could facilitate pre-emptive intervention such as reduction of immunosuppression. Reduced circulating monocytic HLA-DR density is a marker of immune depression in the general population and associates with poorer outcome in critical illness. It has recently been used as a safety marker in adoptive cell therapy trials in renal transplantation. Despite its potential as a marker of dampened immune responses, factors that impact upon monocytic HLA-DR density and the long-term clinical sequelae of this have not been assessed in transplant recipients. Methods: A cohort study of stable long-term renal transplant recipients was undertaken. Serial circulating monocytic HLA-DR density and other leucocyte populations were quantified by flow cytometry. Gene expression of monocytes was performed using the Nanostring nCounter platform, and 13-plex cytokine bead array used to quantify serum concentrations. The primary outcome was malignancy development during one-year follow-up. Risk of malignancy was calculated by univariate and multivariate proportionate hazards modelling with and without adjustment for competing risks. Results: Monocytic HLA-DR density was stable in long-term renal transplant recipients (n=135) and similar to non-immunosuppressed controls (n=29), though was suppressed in recipients receiving prednisolone. Decreased mHLA-DRd was associated with accumulation of CD14+CD11b+CD33+HLA-DRlo monocytic myeloid-derived suppressor-like cells. Pathway analysis revealed downregulation of pathways relating to cytokine and chemokine signalling in monocytes with low HLA-DR density; however serum concentrations of major cytokines did not differ between these groups. There was an independent increase in malignancy risk during follow-up with decreased HLA-DR density. Conclusions: Dampened chemokine and cytokine signalling drives a stable reduction in monocytic HLA-DR density in long-term transplant recipients and associates with subsequent malignancy risk. This may function as a novel marker of excess immunosuppression. Further study is needed to understand the mechanism behind this association.


Assuntos
Antígenos HLA-DR , Transplante de Rim , Monócitos , Células Supressoras Mieloides , Neoplasias , Estudos de Coortes , Citocinas/imunologia , Antígenos HLA-DR/imunologia , Humanos , Monócitos/imunologia , Monócitos/patologia , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/patologia , Neoplasias/sangue , Neoplasias/imunologia , Neoplasias/patologia , Transplantados
12.
Viruses ; 14(7)2022 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-35891450

RESUMO

(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0-491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0-159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2.


Assuntos
Vacina BNT162 , ChAdOx1 nCoV-19 , Transplante de Pulmão , Transplantados , Anticorpos Antivirais , Vacina BNT162/imunologia , COVID-19/prevenção & controle , ChAdOx1 nCoV-19/imunologia , Humanos
13.
PLoS One ; 17(7): e0269990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35834500

RESUMO

INTRODUCTION: Kidney transplantation is the best therapeutical option for CKD patients. Graft loss risk factors are usually estimated with the cox method. Competing risk analysis could be useful to determine the impact of different events affecting graft survival, the occurrence of an outcome of interest can be precluded by another. We aimed to determine the risk factors for graft loss in the presence of mortality as a competing event. METHODS: A retrospective cohort of 1454 kidney transplant recipients who were transplanted between July 1, 2008, to May 31, 2019, in Colombiana de Trasplantes, were analyzed to determine risk factors of graft loss and mortality at 5 years post-transplantation. Kidney and patient survival probabilities were estimated by the competing risk analysis. The Fine and Gray method was used to fit a multivariable model for each outcome. Three variable selection methods were compared, and the bootstrapping technique was used for internal validation as split method for resample. The performance of the final model was assessed calculating the prediction error, brier score, c-index and calibration plot. RESULTS: Graft loss occurred in 169 patients (11.6%) and death in 137 (9.4%). Cumulative incidence for graft loss and death was 15.8% and 13.8% respectively. In a multivariable analysis, we found that BKV nephropathy, serum creatinine and increased number of renal biopsies were significant risk factors for graft loss. On the other hand, recipient age, acute cellular rejection, CMV disease were risk factors for death, and recipients with living donor had better survival compared to deceased-donor transplant and coronary stent. The c-index were 0.6 and 0.72 for graft loss and death model respectively. CONCLUSION: We developed two prediction models for graft loss and death 5 years post-transplantation by a unique transplant program in Colombia. Using a competing risk multivariable analysis, we were able to identify 3 significant risk factors for graft loss and 5 significant risk factors for death. This contributes to have a better understanding of risk factors for graft loss in a Latin-American population. The predictive performance of the models was mild.


Assuntos
Transplante de Rim , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Transplantados , Resultado do Tratamento
14.
BMJ Case Rep ; 15(7)2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787491

RESUMO

A man in his 50s was admitted with 4 months of myalgia, headaches, hypercalcaemia and declining renal function on a background of lung transplantation for cystic fibrosis 5 years prior. MRI confirmed myositis and a muscle biopsy revealed invasive muscular microsporidial infection. Positron emission tomography(PET)/CT revealed widespread dissemination of the infection. Albendazole was commenced and after a 1 week systemic inflammatory response syndrome, the patient made a significant recovery and was discharged home. PCR testing confirmed the species as Anncaliia algerae, which is known to infect mosquitoes, larvae and contaminate water supplies. This case highlights the need to relentlessly pursue a diagnosis and to consider atypical pathology in immune compromised patients. A tissue sample yielded highly beneficial and unexpected results. A multispecialty approach was essential given the varied infection manifestations, which included myositis, keratitis and possible central nervous system, vocal cord, parapharyngeal and renal involvement.


Assuntos
Fibrose Cística , Hipercalcemia , Ceratite , Miosite , Animais , Humanos , Hipercalcemia/etiologia , Pulmão , Masculino , Miosite/complicações , Miosite/diagnóstico , Tomografia Computadorizada por Raios X , Transplantados
15.
Immun Inflamm Dis ; 10(8): e646, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35894705

RESUMO

INTRODUCTION: Lung transplant recipients (LuTX) represent a vulnerable population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though many vaccines are already developed, more clinical data need to support effective immunological response in immunocompromised patients. METHODS: Stable LuTX recipients with no medical history of coronavirus disease (COVID-19) were enrolled. Currently available messenger RNA (mRNA) (BNT162b2-mRNA, mRNA-1273) and non-mRNA (ChAdOx1, BBIBP-CorV) vaccines were given according to availability, boosters were all mRNA-based. SARS-CoV-2 Spike1 immunoglobulin G (IgG) antibody titer was evaluated before and 2 weeks after second and third dose. Difference between mRNA versus non-mRNA vaccines was assessed. RESULTS: Forty-one patients (49% men, age 48.4 ± 13.8 years) received two doses of SARS-CoV-2 vaccines: 23 of mRNA, 18 of non-mRNA, and 24/41 (58%) received a third dose. Median 92 months passed since transplantation, and serum level of tacrolimus was median 5.5 ng/ml. Positive serology was found in 37% of all patients after the second dose, 86% had mRNA vaccine. After the third dose, 29% became positive who had no antibody before. Significantly higher level of antibody was found after the second mRNA than non-mRNA vaccines (2.2 vs. 1568.8 U/ml, respectively, p = .002). 6/23 (26%) patients received two doses of mRNA vaccine developed COVID-19 after the second injection in an average of 178 days, half of them recovered, half of them died in intensive care unit (ICU). 3/6 (50%) patients with two doses mRNA and recovered from COVID-19 had significantly higher level of antibody (average 20847.3 U/ml) than without infection. After the booster vaccine, 1/24 (4%) developed infection. CONCLUSION: Immunosuppression therapy may induce a weaker SARS-CoV-2 response in LuTX recipients; therefore, third dose is a priority in transplanted patients. The highest antibody level was measured recovering from COVID after two doses. Our data confirm that booster mRNA vaccine could increase antibody levels, even if immunization was started with non-mRNA vaccine.


Assuntos
Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Transplantados , Adulto , Anticorpos Antivirais , Vacina BNT162/efeitos adversos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinas Virais/efeitos adversos
16.
BMC Nephrol ; 23(1): 241, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799110

RESUMO

BACKGROUND: COVID-19 infection is considered to cause high mortality in kidney transplant recipients (KTR). Old age, comorbidities and acute kidney injury are known risk factors for increased mortality in KTR. Nevertheless, mortality rates have varied across different regions. Differences in age, comorbidities and varying standards of care across geographies may explain some variations. However, it is still unclear whether post-transplant duration, induction therapy, antirejection therapy and co-infections contribute to increased mortality in KTR with COVID-19. The present study assessed risk factors in a large cohort from India. METHODS: A matched case-control study was performed to analyze risk factors for death in KTR (N = 218) diagnosed with COVID-19 between April 2020 to July 2021 at the study centre. Cases were KTR who died (non-survivors, N = 30), whereas those who survived were taken as controls (survivors, N = 188). RESULTS: A high death-to-case ratio of 13.8% was observed amongst study group KTR infected with COVID-19. There was a high incidence (12.4%) of co-infections, with cytomegalovirus being the most common co-infection among non-survivors. Diarrhea, co-infection, high oxygen requirement, and need for mechanical ventilation were significantly associated with mortality on regression analyses. Antirejection therapy, lymphopenia and requirement for renal replacement therapy were associated with worse outcomes. CONCLUSIONS: The mortality was much higher in KTR who required mechanical ventilation and had co-infections. Mortality did not vary with the type of transplant, post-transplant duration and usage of depletion induction therapy. An aggressive approach has to be taken for an early diagnosis and therapeutic intervention of associated infections.


Assuntos
COVID-19 , Coinfecção , Transplante de Rim , Estudos de Casos e Controles , Coinfecção/etiologia , Humanos , Transplante de Rim/efeitos adversos , Fatores de Risco , Transplantados
17.
Transplant Rev (Orlando) ; 36(3): 100710, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35809422

RESUMO

BACKGROUND: The COVID-19 pandemic has a great impact on solid organ transplant (SOT) recipients due to their comorbidities and their maintenance immunosuppression. So far, studies about the different aspects of the impact of the pandemic on SOT recipients are limited. OBJECTIVES: This systematic review summarizes the risk factors that make SOT patients more vulnerable for severe COVID-19 disease or mortality and the impact of immunosuppressive therapy. Furthermore, their clinical outcomes, mortality risk, immunosuppression, immunity and COVID-19 vaccination efficacy are discussed. METHODS: A systematic search on PubMed was performed to select original articles on SOT recipients concerning the following four topics: (1) mortality and clinical course; (2) risk factors for mortality and composite outcomes; (3) maintenance immunosuppression; (4) immunity to COVID-19 infection and (5) vaccine immunogenicity. Relevant data were extracted, analyzed and summarized in tables. RESULTS: This systematic review includes 77 articles. Mortality was associated with advanced age. Post-transplantation time or comorbidities were variably identified as independent risk factors for mortality or severe disease. However, generally, no comorbidity was reported as a major risk factor. SOT recipients have a higher risk of acute kidney injury, but no higher rate of mortality compared to non-transplanted patients was found. Immunosuppression was individually adjusted, without leading to high rates of graft dysfunction. Generally, no association between type of immunosuppression and mortality was found. SOT patients established humoral and cellular immune responses after COVID-19 disease comparable to immunocompetent people. At last, SOT patients experience a diminished immune response after two-dose vaccination with SARS-COV-2-mRNA-vaccines. CONCLUSION: More research is needed to address the direct effect of COVID-19 disease on the graft in lung transplant recipients, as well as the factors ameliorating the immune response in SOT recipients.


Assuntos
COVID-19 , Transplante de Órgãos , Vacinas contra COVID-19 , Humanos , Transplante de Órgãos/efeitos adversos , Pandemias , SARS-CoV-2 , Transplantados
18.
Curr Opin Infect Dis ; 35(4): 288-294, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35849518

RESUMO

PURPOSE OF REVIEW: This review summarizes the impact of coronavirus disease 2019 (COVID-19) on solid organ transplantation and the most recent data pertinent to disease course and outcomes in this patient population. RECENT FINDINGS: The COVID-19 pandemic negatively impacted solid organ transplantation with decreased transplant rates in 2020 but improved in 2021, albeit not entirely to prepandemic levels. Mortality rates of COVID-19 in this patient population continued to be higher, although have improved with more available therapeutic options and vaccination. Immunosuppressed patients were found to require additional vaccine doses given blunted response and continue to be more vulnerable to the infection. Data on immunosuppression alteration when patients have COVID-19 are not available and is an area of ongoing research. Significant interaction with the metabolism of immunosuppression limits the use of some of the new antiviral therapies in patients with organ transplants. Finally, many logistical challenges continue to face the transplantation discipline, especially with pretransplant vaccine hesitancy, however acceptance of organs from donor who had COVID-19 recent infection or died from the infection is increasing. SUMMARY: Immunosuppressed solid organ transplant recipients continue to be vulnerable to COVID-19 infection with a blunted response to the available vaccines and will likely remain more susceptible to infection.


Assuntos
COVID-19 , Transplante de Órgãos , COVID-19/epidemiologia , Humanos , Transplante de Órgãos/efeitos adversos , Pandemias/prevenção & controle , SARS-CoV-2 , Transplantados
19.
Curr Opin Infect Dis ; 35(4): 302-311, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35849520

RESUMO

PURPOSE OF REVIEW: Double-stranded DNA (dsDNA) viruses remain important causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). As treatment options are limited, adoptive therapy with virus-specific T cells (VST) is promising in restoring immunity and thereby preventing and treating virus infections. Here we review current evidence and recent advances in the field of VST for dsDNA viruses in allogeneic HCT recipients. RECENT FINDINGS: Four different protocols for VST generation are currently used in clinical trials, and various products including multivirus-specific and off-the-shelf products are under investigation for prophylaxis, preemptive therapy or treatment. Data from nearly 1400 dsDNA-VST applications in allogeneic HCT patients have been published and demonstrated its safety. Although Epstein-Barr virus, cytomegalovirus, and adenovirus-specific T-cell therapy studies have predominated over the past 25 years, additional human herpes viruses were added to multivirus-specific T cells over the last decade and clinical evidence for polyomavirus-specific VST has just recently emerged. Response rates of around 70-80% have been reported, but cautious interpretation is warranted as data are predominantly from phase 1/2 studies and clinical efficacy needs to be confirmed in phase 3 studies. SUMMARY: Investigation on the 'ideal' composition of VST is ongoing. Several products recently entered phase 3 trials and may allow widespread clinical use in the near future.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Infecções por Vírus Epstein-Barr/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4 , Humanos , Hospedeiro Imunocomprometido , Transplantados
20.
Curr Opin Infect Dis ; 35(4): 312-320, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35849521

RESUMO

PURPOSE OF REVIEW: Hematopoietic stem-cell (HSCT) and solid organ transplant (SOT) recipients are particularly at risk to develop herpes zoster and its complications. A recently approved nonlive, adjuvanted recombinant zoster vaccine (aRZV) is a potential candidate to provide durable prevention of herpes zoster. This review summarizes current scientific evidence and expert recommendations for its use in these populations and offers practical clinical guidance. RECENT FINDINGS: Recent clinical trials have shown aRZV to be well tolerated and efficacious in the prevention of herpes zoster, even in the elderly. Data are emerging that this vaccine might also be effective in immunocompromised individuals, such as SOT and HSCT recipients. Evidence is sparse regarding optimal timing of vaccination and durability of responses. However, several specialized societies have already established expert-based aRZV immunization recommendations for these vulnerable populations. SUMMARY: Practical considerations, safety concerns, and timing of vaccine administration vary from one immunocompromised subpopulation to another. Initial studies show that aRZV has a favorable safety and immunogenicity profile in SOT and HSCT recipients. However, data are sparse, particularly in allogeneic HSCT, and practical recommendations are mostly based on expert opinion. Additional research is needed to offer better insight on aRZV administration in immunocompromised patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Vacina contra Herpes Zoster , Herpes Zoster , Transplante de Órgãos , Adjuvantes Imunológicos , Idoso , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Zoster/prevenção & controle , Vacina contra Herpes Zoster/efeitos adversos , Herpesvirus Humano 3 , Humanos , Transplante de Órgãos/efeitos adversos , Transplantados , Vacinas Sintéticas/efeitos adversos
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