Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Pediatr Blood Cancer ; 71(7): e30990, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38605511

RESUMO

BACKGROUND: Central venous catheter (CVC)-related complications remain a significant cause of morbidity in pediatric hematology-oncology. We prospectively surveyed the incidence of CVC-related complications in children with hematologic-oncologic diseases. PROCEDURE: Five-hundred-eighty-one CVCs were inserted in 421 patients from January 2010 to June 2022 (153,731 CVC days observation; follow-up data up to December 31, 2022). RESULTS: Overall, 671 complications were recorded (4.365/1000 CVC days): 49.7% malfunctions (1.88/1000 CVC days, 4.8% of CVC early removals), 23.9% bacteremia (0.90/1000, 15.1%), 19.6% mechanical complications (0.74/1000, 70.2%), 20.1% localized infections (0.76/1000, 17.1%), 0.5% thrombosis (0.02/1000, 33.3%). At multivariate analysis, risk factors for malfunction were Broviac-Hickman type of CVC (hazard ratio [HR] 2.5) or Port-a-cath (HR 3.4) or Proline (HR 4.3), p < .0001; for bacteremia double-lumen CVC (HR 3.2, p < .0001); for mechanical complications age at CVC insertion under median (HR 4.5, p < .0001) and Broviac-Hickman (HR 1.6) or Proline (HR 2.7), p = .01; finally for localized infections Broviac-Hickman (HR 2.9) or Proline (HR 4.4), p = .0001. The 2-year cumulative incidence of premature removal was 23.5%, and risk factors were age at CVC insertion under median (HR 2.4, p < .0001), Broviac-Hickman (HR 2.3) or Proline (HR 4.2), p < .0001. CONCLUSIONS: Premature removal occurs in approximately 20%-25% of long-term CVCs. A surveillance program has a fundamental role in identifying the risk factors for CVC complications and the areas of intervention to improve CVC management.


Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateteres Venosos Centrais , Neoplasias Hematológicas , Humanos , Feminino , Criança , Masculino , Estudos Prospectivos , Pré-Escolar , Cateteres Venosos Centrais/efeitos adversos , Adolescente , Lactente , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Cateterismo Venoso Central/efeitos adversos , Neoplasias Hematológicas/terapia , Seguimentos , Fatores de Risco , Bacteriemia/etiologia , Bacteriemia/epidemiologia , Incidência , Prognóstico
2.
Nat Commun ; 15(1): 3478, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658578

RESUMO

The expansion of the CRISPR-Cas toolbox is highly needed to accelerate the development of therapies for genetic diseases. Here, through the interrogation of a massively expanded repository of metagenome-assembled genomes, mostly from human microbiomes, we uncover a large variety (n = 17,173) of type II CRISPR-Cas loci. Among these we identify CoCas9, a strongly active and high-fidelity nuclease with reduced molecular size (1004 amino acids) isolated from an uncultivated Collinsella species. CoCas9 is efficiently co-delivered with its sgRNA through adeno associated viral (AAV) vectors, obtaining efficient in vivo editing in the mouse retina. With this study we uncover a collection of previously uncharacterized Cas9 nucleases, including CoCas9, which enriches the genome editing toolbox.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Microbiota , Edição de Genes/métodos , Humanos , Animais , Camundongos , Microbiota/genética , Dependovirus/genética , Proteína 9 Associada à CRISPR/metabolismo , Proteína 9 Associada à CRISPR/genética , RNA Guia de Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas/metabolismo , Retina/metabolismo , Clostridiales/genética , Clostridiales/enzimologia , Células HEK293 , Vetores Genéticos/metabolismo , Vetores Genéticos/genética
3.
Mol Ther ; 31(7): 2257-2265, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-36905119

RESUMO

Electroporation of the Cas9 ribonucleoprotein (RNP) complex offers the advantage of preventing off-target cleavages and potential immune responses produced by long-term expression of the nuclease. Nevertheless, the majority of engineered high-fidelity Streptococcus pyogenes Cas9 (SpCas9) variants are less active than the wild-type enzyme and are not compatible with RNP delivery. Building on our previous studies on evoCas9, we developed a high-fidelity SpCas9 variant suitable for RNP delivery. The editing efficacy and precision of the recombinant high-fidelity Cas9 (rCas9HF), characterized by the K526D substitution, was compared with the R691A mutant (HiFi Cas9), which is currently the only available high-fidelity Cas9 that can be used as an RNP. The comparative analysis was extended to gene substitution experiments where the two high fidelities were used in combination with a DNA donor template, generating different ratios of non-homologous end joining (NHEJ) versus homology-directed repair (HDR) for precise editing. The analyses revealed a heterogeneous efficacy and precision indicating different targeting capabilities between the two variants throughout the genome. The development of rCas9HF, characterized by an editing profile diverse from the currently used HiFi Cas9 in RNP electroporation, increases the genome editing solutions for the highest precision and efficient applications.


Assuntos
Sistemas CRISPR-Cas , Streptococcus pyogenes , Streptococcus pyogenes/genética , Edição de Genes , Proteína 9 Associada à CRISPR/genética , Eletroporação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA