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1.
J Surg Res ; 246: 614-622, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30528925

RESUMO

BACKGROUND: The World Health Organization's (WHO) surgical safety checklist is meant to be customized to facilitate local implementation, encourage full-team participation, and promote a culture of safety. Although it has been globally adopted, little is known about the extent of checklist modification and the type of changes made. METHODS: Nonsubspecialty surgical checklists were obtained through online search and targeted hospital requests. A detailed coding scheme was created to capture modifications to checklist content and formatting. Descriptive statistics were performed. RESULTS: Of 155 checklists analyzed, all were modified. Compared with the WHO checklist, those in our sample contained more lines of text (median: 63 [interquartile range: 50-73] versus 56) and items (36 [interquartile range: 30-43] versus 28). A median of 13 new items were added. Items most frequently added included implants/special equipment (added by 84%), deep vein thrombosis prophylaxis/anticoagulation (added by 75%), and positioning (added by 63%). Checklists removed a median of 5 WHO items. The most frequently removed item was the pulse oximeter check (removed in 75%), followed by 4 items (each removed in 39%-48%) that comprise part of the WHO Checklist's "Anticipated Critical Events" section, which is intended for exchanging critical information. The surgeon was not explicitly mentioned in the checklist in 12%; the anesthesiologist/certified registered nurse anesthetist in 14%, the circulator in 10%, and the surgical tech/scrub in 79%. CONCLUSIONS: Checklists are highly modified but often enlarged with items that may not prompt discussion or teamwork. Of concern is the frequent removal of items from the WHO's "Anticipated Critical Events" section.


Assuntos
Lista de Checagem/normas , Relações Interprofissionais , Salas Cirúrgicas/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Segurança do Paciente/normas , Erros Médicos/prevenção & controle , Salas Cirúrgicas/normas , Equipe de Assistência ao Paciente/normas , Organização Mundial da Saúde
3.
J Clin Oncol ; 36(19): 1963-1972, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29746225

RESUMO

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Sobreviventes de Câncer/estatística & dados numéricos , Glioma/diagnóstico , Adolescente , Adulto , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/terapia , Criança , Pré-Escolar , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/terapia , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Sistema de Registros , Adulto Jovem
5.
J Neurooncol ; 134(1): 231-240, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28560664

RESUMO

We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in the SIOPE DIPG Registry, and includes age <3 years, longer symptom duration and receipt of chemotherapy as favorable predictors, and presence of ring-enhancement on MRI as unfavorable predictor. Model performance was evaluated by analyzing the discrimination and calibration abilities. External validation was performed using an unselected cohort from the International DIPG Registry, including patients from United States, Canada, Australia and New Zealand. Basic comparison with the results of the original study was performed using descriptive statistics, and univariate- and multivariable regression analyses in the validation cohort. External validation was assessed following a variety of analyses described previously. Baseline patient characteristics and results from the regression analyses were largely comparable. Kaplan-Meier curves of the validation cohort reproduced separated groups of standard (n = 39), intermediate (n = 125), and high-risk (n = 78) patients. This discriminative ability was confirmed by similar values for the hazard ratios across these risk groups. The calibration curve in the validation cohort showed a symmetric underestimation of the predicted survival probabilities. In this external validation study, we demonstrate that the DIPG survival prediction model has acceptable cross-cohort calibration and is able to discriminate patients with short, average, and increased survival. We discuss how this clinico-radiological model may serve a useful role in current clinical practice.


Assuntos
Neoplasias do Tronco Encefálico/mortalidade , Glioma/mortalidade , Sistema de Registros , Adolescente , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/terapia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Glioma/diagnóstico por imagem , Glioma/terapia , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Prognóstico , Análise de Regressão
6.
J Neurooncol ; 132(2): 255-266, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28110411

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico por imagem , Glioma/diagnóstico por imagem , Serviços de Informação , Cooperação Internacional , Imagem por Ressonância Magnética , Sistema de Registros , Criança , Pré-Escolar , Europa (Continente) , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Ponte/diagnóstico por imagem , Adulto Jovem
7.
J Neurooncol ; 132(2): 323-331, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28093680

RESUMO

Diffuse intrinsic pontine glioma (DIPG), a rare, often fatal childhood brain tumor, remains a major therapeutic challenge. In 2012, investigators, funded by the DIPG Collaborative (a philanthropic partnership among 29 private foundations), launched the International DIPG Registry (IDIPGR) to advance understanding of DIPG. Comprised of comprehensive deidentified but linked clinical, imaging, histopathological, and genomic repositories, the IDIPGR uses standardized case report forms for uniform data collection; serial imaging and histopathology are centrally reviewed by IDIPGR neuro-radiologists and neuro-pathologists, respectively. Tissue and genomic data, and cell cultures derived from autopsies coordinated by the IDIPGR are available to investigators for studies approved by the Scientific Advisory Committee. From April 2012 to December 2016, 670 patients diagnosed with DIPG have been enrolled from 55 participating institutions in the US, Canada, Australia and New Zealand. The radiology repository contains 3558 studies from 448 patients. The pathology repository contains tissue on 81 patients with another 98 samples available for submission. Fresh DIPG tissue from seven autopsies has been sent to investigators to develop primary cell cultures. The bioinformatics repository contains next-generation sequencing data on 66 tumors. Nine projects using data/tissue from the IDIPGR by 13 principle investigators from around the world are now underway. The IDIPGR, a successful alliance among philanthropic agencies and investigators, has developed and maintained a highly collaborative, hypothesis-driven research infrastructure for interdisciplinary and translational projects in DIPG to improve diagnosis, response assessment, treatment and outcome for patients.


Assuntos
Neoplasias do Tronco Encefálico/epidemiologia , Neoplasias do Tronco Encefálico/patologia , Glioma/epidemiologia , Glioma/patologia , Cooperação Internacional , Ponte/patologia , Sistema de Registros , Adolescente , Adulto , Austrália , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/terapia , Canadá , Criança , Pré-Escolar , Feminino , Glioma/diagnóstico por imagem , Glioma/terapia , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Nova Zelândia , Ponte/diagnóstico por imagem , Estados Unidos , Adulto Jovem
8.
Biochemistry ; 51(24): 4773-5, 2012 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-22662746

RESUMO

The identification of structure-function relationships in allosteric enzymes is essential to describing a molecular mechanism for allosteric processes. The enzyme α-isopropylmalate synthase from Mycobacterium tuberculosis (MtIPMS) is subject to slow-onset, allosteric inhibition by l-leucine. Here we report that alternate amino acids act as rapid equilibrium noncompetitive inhibitors of MtIPMS failing to display biphasic inhibition kinetics. Amino acid substitutions on a flexible loop covering the regulatory binding pocket generate enzyme variants that have significant affinity for l-leucine but lack biphasic inhibition kinetics. Taken together, these results are consistent with the flexible loop mediating the slow-onset step of allosteric inhibition.


Assuntos
2-Isopropilmalato Sintase/antagonistas & inibidores , 2-Isopropilmalato Sintase/química , Mycobacterium tuberculosis/enzimologia , 2-Isopropilmalato Sintase/genética , 2-Isopropilmalato Sintase/metabolismo , Regulação Alostérica , Domínio Catalítico , Cinética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Mutação
9.
Circ Cardiovasc Genet ; 3(5): 426-35, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20733065

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are a newly discovered endogenous class of small, noncoding RNAs that play important posttranscriptional regulatory roles by targeting messenger RNAs for cleavage or translational repression. Human embryonic stem cells are known to express miRNAs that are often undetectable in adult organs, and a growing body of evidence has implicated miRNAs as important arbiters of heart development and disease. METHODS AND RESULTS: To better understand the transition between the human embryonic and cardiac "miRNA-omes," we report here the first miRNA profiling study of cardiomyocytes derived from human embryonic stem cells. Analyzing 711 unique miRNAs, we have identified several interesting miRNAs, including miR-1, -133, and -208, that have been previously reported to be involved in cardiac development and disease and that show surprising patterns of expression across our samples. We also identified novel miRNAs, such as miR-499, that are strongly associated with cardiac differentiation and that share many predicted targets with miR-208. Overexpression of miR-499 and -1 resulted in upregulation of important cardiac myosin heavy-chain genes in embryoid bodies; miR-499 overexpression also caused upregulation of the cardiac transcription factor MEF2C. CONCLUSIONS: Taken together, our data give significant insight into the regulatory networks that govern human embryonic stem cell differentiation and highlight the ability of miRNAs to perturb, and even control, the genes that are involved in cardiac specification of human embryonic stem cells.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/fisiologia , Regulação da Expressão Gênica , Coração , MicroRNAs/metabolismo , Animais , Linhagem Celular , Corpos Embrioides/citologia , Corpos Embrioides/fisiologia , Células-Tronco Embrionárias/citologia , Perfilação da Expressão Gênica , Coração/embriologia , Coração/crescimento & desenvolvimento , Humanos , Camundongos , MicroRNAs/genética , Análise em Microsséries , Dados de Sequência Molecular , Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Técnicas de Patch-Clamp , Transdução de Sinais
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