Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
Mais filtros

País/Região como assunto
Intervalo de ano de publicação
1.
Am J Transplant ; 21(1): 258-271, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32812351

RESUMO

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Citomegalovirus/genética , DNA Viral/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos
2.
Transpl Infect Dis ; 23(4): e13627, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33908148

RESUMO

The potential role of active CMV infection in promoting acute Graft-versus-Host Disease (aGvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. We further addressed this issue conducting a retrospective, observational, multicenter study of 632 patients subjected to allogeneic peripheral blood HSCT at 20 Spanish centers. Monitoring of CMV DNA load in plasma or whole blood was performed by real-time PCR assays. Cumulative incidence of CMV DNAemia was 48.9% (95% CI, 45%-52.9%), of any grade aGvHD, 45.6; 95% (CI, 41.3%-50.1%), and of grade II-IV aGvHD, 30.7 (95% CI, 24.9%-36.4%). Overall, development of CMV DNAemia at any level resulted in an increased risk of subsequent all grade (HR, 1.38; 95% CI, 1.08 - 1.76; P = .009) or grade II-IV (HR, 1.58; 95% CI, 1.22 - 2.06; P = .001) aGvHD. The increased risk of aGvHD linked to prior occurrence of CMV DNAemia was similar to the above when only clinically significant episodes were considered for the analyses (HR for all grade aGvHD, 1.48; 95% CI, 1.13 - 1.91; P = .041, and HR for grade II-IV aGvHD, 1.53; 95% CI. 1.13-1.81; P = .04). The CMV DNA doubling time in blood was comparable overall in episodes of CMV DNAemia whether followed by aGvHD or not. Whether CMV replication is a surrogate risk marker of aGvHD or it is causally involved is an important question to be addressed in future experimental research.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Citomegalovirus/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos
3.
Clin Exp Rheumatol ; 38 Suppl 124(2): 112-119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32441643

RESUMO

OBJECTIVES: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice. METHODS: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week). RESULTS: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice. CONCLUSIONS: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Arterite de Células Gigantes/terapia , Humanos , Resultado do Tratamento
4.
Xenotransplantation ; 26(3): e12507, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30963648

RESUMO

INTRODUCTION: Recent immunological and transgenic advances are a promising alternative using limited materials of human origin for transplantation. However, it is essential to achieve social acceptance of this therapy. OBJECTIVE: To analyze the attitude of nursing students from Spanish universities toward organ xenotransplantation (XTx) and to determine the factors affecting their attitude. MATERIALS AND METHODS: Type of study: A sociological, multicentre, and observational study. STUDY POPULATION: Nursing students enrolled in Spain (n = 28,000). SAMPLE SIZE: A sample of 10 566 students estimating a proportion of 76% (99% confidence and precision of ±1%), stratified by geographical area and year of study. Instrument of measurement: A validated questionnaire (PCID-XenoTx-RIOS) was handed out to every student in a compulsory session. This survey was self-administered and self-completed voluntarily and anonymously by each student in a period of 5-10 min. STATISTICAL ANALYSIS: descriptive analysis, Student's t test, the chi-square test, and a logistic regression analysis. RESULTS: A completion rate: 84% (n = 8913) was obtained. If the results of XTx were as good as in human donation, 74% (n = 6564) would be in favor and 22% (n = 1946) would have doubts. The following variables affected this attitude: age (P < 0.001); sex (P < 0.001); geographical location (P < 0.001); academic year of study (P < 0.001); attitude toward organ donation (P < 0.001); belief in the possibility of needing a transplant (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); and the opinion of one's partner (P < 0.001). The following variables persisted in the multivariate analysis: being a male (OR = 1.436; P < 0.001); geographical location (OR = 1.937; P < 0.001); an attitude in favor of donation (OR = 1.519; P < 0.001); belief in the possibility of needing a transplant (OR = 1.497; P = 0.036); and having spoken about the issue with family (OR = 1.351; P < 0.001) or friends (OR = 1.240; P = 0.001). CONCLUSIONS: The attitude of nursing students toward organ XTx is favorable and is associated with factors of general knowledge about organ donation and transplantation and social interaction.


Assuntos
Atitude , Transplante de Órgãos , Estudantes de Enfermagem/estatística & dados numéricos , Transplante Heterólogo , Feminino , Xenoenxertos/imunologia , Humanos , Doadores Vivos , Masculino , Transplante de Órgãos/métodos , Estudantes de Medicina , Obtenção de Tecidos e Órgãos/métodos
5.
Vet Res ; 49(1): 106, 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30333061

RESUMO

Endogenous transplacental transmission, which occurs during pregnancy as the result of reactivation of a latent infection in the dam, is the main mechanism of propagation of Neospora caninum within cattle herds. However, the importance of this propagation mechanism has not yet been evaluated in relation to ovine neosporosis. In this study, involving three generations of ewes naturally infected by N. caninum, we demonstrated that endogenous transplacental transmission may also be highly efficient in the ovine host since transmission of infection occurred in 96.6% of gestations and the congenital infection rate ranged between 66.7 and 93%. Nevertheless, parasite burdens decreased gradually in consecutive generations. Reactivation of latent infections had a strong impact on the pregnancy outcome, with high mortality rates recorded in the offspring of the two first generations of ewes (21.4-46.1%). Histological examination of the brain revealed that all aborted foetuses had characteristic lesions of neosporosis (necrotic glial foci) and a few parasite cysts, whereas most stillborn and newborn lambs that died shortly after birth had non-specific lesions (mild glial foci without necrosis) and parasite cysts were more frequent. Microsatellite analysis revealed scarce genetic variability in the N. caninum population, in accordance with a scenario in which infections were of a single origin and were exclusively maintained by clonal propagation through endogenous transplacental transmission.


Assuntos
Coccidiose/veterinária , Transmissão Vertical de Doenças Infecciosas/veterinária , Neospora , Complicações Parasitárias na Gravidez/veterinária , Doenças dos Ovinos/parasitologia , Animais , Anticorpos Antiprotozoários/sangue , Feminino , Imunoglobulina G/sangue , Placenta , Gravidez , Ovinos
6.
Rev Enferm ; 40(3): 57-65, 2017 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-30277695

RESUMO

Nowadays, social and health representatives are putting the focus on emerging need: promote intergenerational programs and practices to generate spaces of encounter and collaboration between people of different ages. According to it, the purpose of intergenerational practices should be to achieve as aim for a society for all ages, regardless of age, an expression proposed by United Nations, not only to integrate all ages but to respond to their needs and provide them a higher quality of life.


Assuntos
Relação entre Gerações , Dinâmica Populacional , Humanos
7.
Rev Enferm ; 39(10): 40-4, 2016 10.
Artigo em Espanhol | MEDLINE | ID: mdl-30253085

RESUMO

The attention deficit hyperactivity disorder (ADHD) is the most prevalent chronic neuropsychiatric illness in childhood. It interferes with normal development of children. Its impact transcends childhood to appear in adolescence and adulthood. Diagnosis would be developed if the child shows the main symptoms of inattention and/or hyperactivity-impulsivity, with consequences in different aspects of daily life, such as academic achievements, family life or social interactions with other children. These symptoms will come up along life in different ways. When the child is young, hyperactivity and impulsivity prevail, but as he/she grows, the dispersion and difficulty to remember things and facts will become more evident. The aim of the study was to assess with the Vanderbilt scale, based on DSM-IV diagnostic criteria, the differences of the impact of ADHD among parents, in comparison to the medical diagnosis. A retrospective study was carried out by using this questionnaire, which completed by both parents individually. A total of 78 children took part in this study, all of them diagnosed with ages ranging from 6 to 16 years old, who attended to Neuropedriatics at VAlle del Nalón Hospital(Asturias), between October 2011 and March 2013. Regarding attention deficit, the average responses given by mothers (7.38 ± 1.81) was higher than that offered by fathers (647 ± 2/46). The same is true for hyperactivity/impulsivity, with average scores of mothers (5.80 ± 2.90) which were one positive response higher than those given by male patients (4.74 ± 3.04). Mothers show a higher percentage of agreement with the medical diagnosis (86.3%) when the child was a girl and 66% with boys, whereas for fathers the percentage of agreement was less than 50% female children and 44.6% for male children.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Pessoal de Saúde , Pais , Adolescente , Criança , Feminino , Humanos , Masculino , Fatores Sexuais
8.
J Pediatr Gastroenterol Nutr ; 59(4): 522-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24886992

RESUMO

OBJECTIVES: The aim of this study was to assess the incidence and clinical pattern of celiac disease (CD) presently diagnosed in Spanish children. METHODS: A prospective, multicenter, nationwide registry of new cases of CD in children <15 years was conducted from June 1, 2006 to May 31, 2007. The parameters studied were age at diagnosis, sex, clinical symptoms, associated diseases, nutritional status, CD serology, histological lesions, and HLA-DQ2/-DQ8. The crude incidence rate of CD was calculated as new cases per 1000 live births and as new cases per 100,000 person-years <15 years of age. RESULTS: A total of 974 new cases of CD were included. The median age at diagnosis was 2.3 years; 39.5% of CD diagnoses occurred in the first 2 years, 42% between 2 and 6, and 18.4% from 6 to 15. Total number of cases in each age group was 385, 409, and 180, respectively. Regarding clinical presentation 70.9% showed classical symptoms, 21.9% were nonclassical, and 7% were asymptomatic. A total of 95.7% of 931, 94.7% of 611, and 86.7% of 651 children tested positive, respectively, for immunoglobulin A (IgA) anti-transglutaminase type 2 antibodies, IgA endomysial antibodies, and IgA anti-gliadin antibodies. Villous atrophy was observed in 92.4% and increased intraepithelial lymphocytes with crypt hyperplasia in 3.3%. Of the children, 55% had normal growth, and 3.4% were overweight. The HLA phenotype was DQ2: 88.3%, DQ2/DQ8: 8.4%, and DQ8: 2.3%. The incidence rate was 7.9 cases of CD per 1000 live births and 54 cases per 100,000 person-years. CONCLUSIONS: In Spain, the most frequent clinical presentation of CD is the classical form, mainly diagnosed during the first 2 years of life. The observed incidence of CD in Spanish children is much higher than the present CD incidence rates observed in other European countries.


Assuntos
Anticorpos/sangue , Doença Celíaca/epidemiologia , Mucosa Intestinal , Linfócitos/metabolismo , Peso Corporal , Doença Celíaca/sangue , Doença Celíaca/complicações , Doença Celíaca/patologia , Criança , Pré-Escolar , Feminino , Antígenos HLA-DQ/sangue , Humanos , Incidência , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Fenótipo , Sistema de Registros , Espanha/epidemiologia
9.
J Drugs Dermatol ; 13(10): 1240-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25607559

RESUMO

BACKGROUND: Cardiovascular morbidity and mortality have been demonstrated to be greater in psoriasis patients than in the general population. Our study aimed to assess the 10-year cardiovascular risk in patients with moderate to severe psoriasis compared with those suffering from other dermatological diseases, using the calibrated Framingham risk score and the Systematic Coronary Risk Evaluation (SCORE) risk charts. METHODS: A cross-sectional, multicentre study was made of 477 patients, of whom 238 had moderate to severe psoriasis (cases) and 239 were diagnosed with another dermatological disease (controls). RESULTS: The proportion of patients with intermediate to high 10-year cardiovascular risk using the Framingham equation was significantly higher among psoriasis patients (38.5%; 80/208) than among the controls with other dermatological diseases (23.4%; 50/214, P<.05). No significant differences were observed between the 2 groups with respect to cardiovascular risk using the SCORE risk charts (P=.591). The case group included a greater proportion of obese and morbidly obese patients, as well as patients with higher triglyceride and low density lipoprotein cholesterol levels (P<.05); while high density lipoprotein cholesterol levels were significantly more favorable in patients in the control group (P<.05). CONCLUSIONS: Cardiovascular risk was greater in patients with moderate to severe psoriasis than in patients with other dermatological conditions, suggesting that early detection and tailored management of risk factors is essential to reducing cardiovascular morbidity in these patients.


Assuntos
Doenças Cardiovasculares/etiologia , Lipídeos/sangue , Psoríase/complicações , Dermatopatias/epidemiologia , Adulto , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade Mórbida/epidemiologia , Psoríase/patologia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
10.
Eur J Sport Sci ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965684

RESUMO

The present study aims to test a model in which basic psychological needs (BPN) satisfaction in physical-sport activity contexts is associated with self-determined motivation, which, in turn, would predict the social inclusion of people with intellectual disabilities. A total of 286 people with intellectual disabilities (53.5% men) who reported engaging in physical-sport activities responded to a validated questionnaire about the satisfaction of their BPN, motivation (using the Self-determination index [SDI]), and social inclusion. A Pearson's bivariate correlation and structural equation modeling were conducted. The resulting model was reanalyzed in a multigroup analysis to test its invariance across self and proxy reports. Positive associations were found between the satisfaction of the BPN and the SDI. However, the SDI and social inclusion were positively associated only in proxy reports (ßself = 0.07 vs. ßproxy = 0.30). The tested model established positive relationships between the BPN and SDI in autonomy (ßself = 0.21 vs. ßproxy = 0.18), competence (ßself = 0.47 vs. ßproxy = 0.53), and relatedness (ßself = 0.21 vs. ßproxy = 0.23). Further research is needed to understand the factors leading to discrepancies between participants and proxies when relating the SDI to social inclusion in the context of physical-sport activity. However, the results obtained suggest that it would be optimal to develop contexts of practice for people with intellectual disabilities in which the satisfaction of their BPN is favored and that this has a positive impact on their motivation and social inclusion.

11.
Bone Marrow Transplant ; 59(3): 359-365, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38167647

RESUMO

Curative potential of allogeneic transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (NHL) could be enhanced by the integration of Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, due to an antitumor effect and a role over graft-versus-host disease (GVHD). In this phase II trial (NCT01613300), we investigated safety and effectiveness of OFA-based reduced intensity conditioning (RIC). High-risk B-cell NHL patients with chemorrefractory disease or post-autologous SCT relapse were eligible. OFA was added to a standard RIC regimen. Primary endpoint was grade 3-4 aGVHD rate, while secondary endpoints included CR and survival rates. Thirty-three patients were included (median age 51; diffuse large B-cell:68%, HLA-identical donor: 74%). No grade >2 OFA toxicity was observed. Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively. OFA-RIC regimen is safe and effective, though acute GVHD remains a significant complication. However, data suggest that OFA could mitigate its severity.


Assuntos
Anticorpos Monoclonais Humanizados , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células B , Linfoma não Hodgkin , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Doença , Estudos Prospectivos , Recidiva Local de Neoplasia , Linfoma de Células B/tratamento farmacológico , Linfoma não Hodgkin/terapia , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante/efeitos adversos
13.
Cancers (Basel) ; 15(5)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36900222

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous disease classified into three risk categories (favorable, intermediate and adverse) with significant differences in outcomes. Definitions of risk categories evolve overtime, incorporating advances in molecular knowledge of AML. In this study, we analyzed the impacts of evolving risk classifications in 130 consecutive AML patients in a single-center real-life experience. Complete cytogenetic and molecular data were collected using conventional qPCR and targeted Next Generation Sequencing (NGS). Five-year OS probabilities were consistent among all classification models (roughly 50-72%, 26-32% and 16-20% for favorable, intermediate and adverse risk groups, respectively). In the same way, the medians of survival months and prediction power were similar in all models. In each update, around 20% of patients were re-classified. The adverse category consistently increased over time (31% in MRC, 34% in ELN2010, 50% in ELN2017), reaching up to 56% in the recent ELN2022. Noteworthily, in multivariate models, only age and the presence of TP53 mutations remained statistically significant. With updates in risk-classification models, the percentage of patients assigned to the adverse group is increasing, and so will the indications for allogeneic stem cell transplantation.

14.
Dermatology ; 225(3): 220-30, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23235195

RESUMO

BACKGROUND: The efficacy of etanercept in the treatment of psoriasis has been demonstrated in several clinical trials, but information regarding results derived from prospective observational studies in clinical practice is scarce. OBJECTIVES: To evaluate the efficacy and safety of etanercept administration according to routine clinical use in moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: Postauthorization, prospective study, carried out at 59 dermatology units in Spain. Patients diagnosed with moderate-to-severe plaque psoriasis received etanercept during a 12-month period. RESULTS: Altogether, 444 patients were enrolled. Overall, 325 patients (73.2%) initiated etanercept treatment at a dose of 50 mg twice weekly; 96 patients (21.6%) received etanercept as a continuous regimen for the entire study period, and 348 patients (79.4%) an intermittent regimen. Among these, 185 patients (41.6% overall) received one course of treatment, stopped at various study points and did not restart etanercept treatment, whereas the remaining 163 patients (36.7% overall) stopped etanercept treatment, lost response, relapsed and were retreated. Most patients who interrupted etanercept treatment did so at month 6. Altogether, 79.7% of patients completed the study period. Etanercept treatment resulted in significant improvement in disease activity. A Psoriasis Area and Severity Index (PASI) 75 response was achieved by 76.1% of patients at month 6. Out of 252 adverse events reported, 31 were considered severe. Three possibly treatment-related malignancies were detected during the study. No opportunistic infections, tuberculosis or demyelinating events were reported. CONCLUSION: The PASI 75 response rate at month 6 in this observational, naturalistic study is similar to those observed in recent published trials with etanercept, and within the range of those reported for other marketed biologicals.


Assuntos
Imunoglobulina G/administração & dosagem , Imunossupressores/administração & dosagem , Psoríase/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/administração & dosagem , Índice de Gravidade de Doença , Adulto , Etanercepte , Feminino , Seguimentos , Humanos , Imunoglobulina G/efeitos adversos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Resultado do Tratamento
15.
Front Psychol ; 13: 852977, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35519625

RESUMO

Objective: Research has supported a link between insecure attachment and eating disorders (EDs); however, little is known about how this influence is exerted in young female EDs patients. This study tested, for the first time, a multiple mediational model, wherein the four Fairburn's transdiagnostic mechanisms mediated the relationship between attachment to the mother and ED symptoms. Methods: A total of 101 female young EDs patients aged 15-24 were administered the Inventory of Parent and Peer Attachment, Eating Disorder Inventory-3 and Eating Attitudes Test-26 to assess attachment, the four transdiagnostic maintaining mechanisms and ED symptoms, respectively. Results: Comparison analyses showed that there were no significant differences between the diagnostic groups in terms of attachment and the transdiagnostic variables. Multiple mediational analyses indicated that low self-esteem and clinical perfectionism were significant mediators between insecure attachment to the mother and ED symptoms, while controlling for depressive symptoms. Conclusion: These findings suggest that the distal risk influence of insecure attachment to the mother in the development of ED symptoms might be explained by low self-esteem and high clinical perfectionism, controlling for depressive symptoms. Further investigation into the efficacy of cognitive-behavioral treatments targeting insecure attachment representations for young EDs patients is recommended.

16.
Nanomedicine (Lond) ; 17(14): 999-1012, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-36004616

RESUMO

Background: Filamentous plant virus-derived nanoparticles are biodegradable and noninfectious to humans. Their structure is also amenable to chemical modifications. They constitute an appealing material for biomedical applications including imaging and drug delivery. We had previously used turnip mosaic virus-derived nanoparticles (TuMV-NPs) to increase antibody-sensing in vivo, to prevent biofilm formation and to build biological nanoscaffolds. Materials & methods: We analyzed TuMV-NP biodistribution and tumor homing using in vivo imaging. We studied in vitro the interaction with human cancer cell lines and the antiproliferative effect of epigallocatechin gallate-functionalized TuMV-NPs. Results & conclusion: TuMV-NPs are efficiently internalized by human cells and show good tumor homing. The antiproliferative effect of epigallocatechin gallate-TuMV-NPs suggests that they could offer a potential anticancer therapy.


Cancer is the second leading cause of death worldwide, just behind cardiovascular disease. It accounts for nearly 10 million deaths annually, and new strategies to improve early detection and drug delivery are urgently needed. Nanoparticles are small structures within the nanometer range (1 billionth of a meter) that can be used to deliver either an imaging probe (tracer) to allow the detection of a tumor or drugs to kill tumor cells. There are many types of nanoparticles; those based on plant viruses are especially appealing for biomedical purposes because they are biodegradable and noninfectious to humans. Also, their physicochemical properties, such as symmetry, uniformity and loading capacity, make them excellent nanocarriers. We report here for the first time the ability of nanoparticles derived from the turnip mosaic virus (TuMV), a well-known virus naturally infecting cruciferous plants (e.g., broccoli, turnip, radish, cabbage) but not humans, to deliver a fluorescent imaging probe that allows tumor detection in vivo. Moreover, TuMV nanoparticles were used to deliver a natural chemotherapeutic agent of plant origin to different types of tumor cells (lung, colorectal, breast, and head and neck), showing increased antiproliferative capacity compared to the nonvehiculized drug.


Assuntos
Nanopartículas , Potyvirus , Humanos , Polifenóis/farmacologia , Distribuição Tecidual
17.
Front Immunol ; 13: 986823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159839

RESUMO

Virus-like particles (VLPs) have been gaining attention as potential platforms for delivery of cargos in nanomedicine. Although animal viruses are largely selected due to their immunostimulatory capacities, VLPs from plant viruses constitute a promising alternative to be considered. VLPs derived from Turnip mosaic virus (TuMV) have proven to present a tridimensional structure suited to display molecules of interest on their surface, making them interesting tools to be studied in theragnostic strategies. Here, we study their potential in the treatment of food allergy by genetically coupling TuMV-derived VLPs to Pru p 3, one of the most dominant allergens in Mediterranean climates. VLPs-Pru p 3 were generated by cloning a synthetic gene encoding the TuMV coat protein and Pru p 3, separated by a linker, into a transient high-expression vector, followed by agroinfiltration in Nicotiana benthamiana plants. The generated fusion protein self-assembled in planta to form the VLPs, which were purified by exclusion chromatography. Their elongated morphology was confirmed by electron microscopy and their size (~400 nm), and monodispersity was confirmed by dynamic light scattering. Initial in vitro characterization confirmed that they were able to induce proliferation of human immune cells. This proliferative capability was enhanced when coupled with the natural lipid ligand of Pru p 3. The resultant formulation, called VLP-Complex, was also able to be transported by intestinal epithelial cells, without affecting the monolayer integrity. In light of all these results, VLP-Complex was furtherly tested in a mouse model of food allergy. Sublingual administration of VLP-Complex could effectively reduce some serological markers associated with allergic responses in mice, such as anti-Pru p 3 sIgE and sIgG2a. Noteworthy, no associated macroscopic, nephritic, or hepatic toxicity was detected, as assessed by weight, blood urea nitrogen (BUN) and galectin-3 analyses, respectively. Our results highlight the standardized production of allergen-coated TuMV-VLPs in N. benthamiana plants. The resulting formula exerts notable immunomodulatory properties without the need for potentially hazardous adjuvants. Accordingly, no detectable toxicity associated to their administration was detected. As a result, we propose them as good candidates to be furtherly studied in the treatment of immune-based pathologies.


Assuntos
Hipersensibilidade Alimentar , Vacinas , Alérgenos/genética , Animais , Hipersensibilidade Alimentar/terapia , Galectina 3 , Humanos , Imunoterapia , Ligantes , Lipídeos , Camundongos , Potyvirus
18.
Stem Cells Transl Med ; 11(4): 343-355, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35348788

RESUMO

Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7-66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years' survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Ensaios de Uso Compassivo/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Pessoa de Meia-Idade , Esteroides/uso terapêutico , Adulto Jovem
19.
Transplant Cell Ther ; 28(4): 204.e1-204.e10, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35108627

RESUMO

Post-transplantation cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT) and achieves low rates of GVHD in HLA-identical transplantation. To compare the outcomes of haploidentical versus HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY. We conducted a retrospective study of 229 patients undergoing first HSCT for AML using PTCY with additional immunosuppression, 99 from matched sibling or unrelated donor (MSD/MUD) performed in 3 hospitals and 130 from haploidentical donors (haplo group) performed in 20 hospitals within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cellular Therapy. Peripheral blood stem cells were used as graft in 89% of patients; myeloablative conditioning was used in 56%. There were significantly more patients with active disease (5% versus 20%, P = .001), high/very high disease risk index (DRI) (32% versus 67%, P = .000) and prior auto-HSCT (2% versus 11%, P = .010) in the haplo group. Median follow-up was 27 and 62.5 months for MSD/MUD and haplo, respectively. At 2 years, no significant differences were observed in overall survival (OS) (72% versus 62%, P = .07), event-free survival (EFS) (70% versus 54%, P = .055), cumulative incidence of relapse (19% versus 25%, P = .13), non-relapse mortality (14% versus 19%, P = .145), and the composite endpoint of GVHD and relapse-free survival (49% versus 42%, P = .249). Multivariate analysis identified only age and active disease as significant risk factors for OS and EFS; reduced-intensity conditioning, high/very high DRI, and haplo donor were nearly statistically significant for these outcomes. Grade II-IV acute GVHD was lower in MSD/MUD (14% versus 47%, P = .000). Cumulative incidences of grade III-IV acute GVHD (4% versus 9%, P = .14) and moderate-severe chronic GVHD (22% versus 19%, P = .28) were similar. Limitations of our study include limited sample size, differences between haplo and MSD/MUD groups and heterogeneous additional immunosuppression and PTCY timing in MSD/MUD. The use of an HLA-identical donor with PTCY in patients with AML showed lower incidence of clinically significant grade II-IV acute GVHD compared to haplo donors. Further studies with larger sample sizes should be performed to establish a possible benefit of HLA-identical donor on survival. © 2022 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.


Assuntos
Leucemia Mieloide Aguda , Condicionamento Pré-Transplante , Ciclofosfamida/uso terapêutico , Humanos , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos , Doadores não Relacionados
20.
Nurse Educ Pract ; 63: 103394, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35797831

RESUMO

AIM: To analyze the attitude of university nursing students at Spanish universities toward organ donation and transplantation and the factors affecting to their attitude. BACKGROUND: The opinion of future nurses toward organ transplant donation could have an important influence on the population. Knowing that opinion and what factors influence it is important to improve the attitude towards organ donation and transplantation. DESIGN: A multicenter, sociological, interdisciplinary and observational study including university nursing diploma students in a complete academic year. METHODS: Selected and randomized sample was taken of students from 52 of the 111 faculties and nursing schools and faculties in Spain with teaching activity PARTICIPANTS: A sample of 10,566 students was selected stratified by geographical area and year. MEASUREMENT INSTRUMENT: The instrument used was a validated questionnaire of attitude toward organ donation and transplantation, self-administered and completed anonymously. RESULTS: Completion rate: 85 % (n = 9001). Of the students surveyed, 78 % (n = 7040) would donate their organs after dying. Variables related to a favourable attitude: (1) Interest in listening to a talk about organ donation and transplantation [Odds ratio 1.66, 95 % confidence interval 2.05-1.35]; (2) Family discussion [Odds ratio 2.30, 95 % confidence interval 2.79-1.90] or discussion with friends about organ donation and transplantation [Odds ratio 1.56, 95 % confidence interval 1.86-1.31]; (3) Knowing that one's father [Odds ratio 1.54, 95 % confidence interval 1.94-1.22], mother's [Odds ratio 1.44, 95 % confidence interval 1.82-1.13] or partner [Odds ratio 1.28, 95 % confidence interval 1.60-1.03] has a favourable opinion; (4) Having a good self-assessment of information about organ donation and transplantation [Odds ratio 2.94, 95 % confidence interval 4.90-1.78]; (5) Not being worried about possible mutilation of the body after donation [Odds ratio 2.73, 95 % confidence interval 3.36-1.72]. CONCLUSIONS: Nursing students in Spain tend to have a favourable attitude toward organ donation and transplantation although more than 20 % of those surveyed are not in favour. TWEETABLE ABSTRACT: To maintain a high rate of organ donation for organ transplantation, it is necessary to improve the social awareness of future generations of nurses towards organ donation.


Assuntos
Transplante de Órgãos , Estudantes de Enfermagem , Obtenção de Tecidos e Órgãos , Atitude , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA