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2.
Neurosurg Focus ; 42(5): E8, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28463615

RESUMO

OBJECTIVE The purpose of this study was to compare the accuracy of Neurolocate frameless registration system and frame-based registration for robotic stereoelectroencephalography (SEEG). METHODS The authors performed a 40-trajectory phantom laboratory study and a 127-trajectory retrospective analysis of a surgical series. The laboratory study was aimed at testing the noninferiority of the Neurolocate system. The analysis of the surgical series compared Neurolocate-based SEEG implantations with a frame-based historical control group. RESULTS The mean localization errors (LE) ± standard deviations (SD) for Neurolocate-based and frame-based trajectories were 0.67 ± 0.29 mm and 0.76 ± 0.34 mm, respectively, in the phantom study (p = 0.35). The median entry point LE was 0.59 mm (interquartile range [IQR] 0.25-0.88 mm) for Neurolocate-registration-based trajectories and 0.78 mm (IQR 0.49-1.08 mm) for frame-registration-based trajectories (p = 0.00002) in the clinical study. The median target point LE was 1.49 mm (IQR 1.06-2.4 mm) for Neurolocate-registration-based trajectories and 1.77 mm (IQR 1.25-2.5 mm) for frame-registration-based trajectories in the clinical study. All the surgical procedures were successful and uneventful. CONCLUSIONS The results of the phantom study demonstrate the noninferiority of Neurolocate frameless registration. The results of the retrospective surgical series analysis suggest that Neurolocate-based procedures can be more accurate than the frame-based ones. The safety profile of Neurolocate-based registration should be similar to that of frame-based registration. The Neurolocate system is comfortable, noninvasive, easy to use, and potentially faster than other registration devices.


Assuntos
Procedimentos Neurocirúrgicos , Técnicas Estereotáxicas/instrumentação , Cirurgia Assistida por Computador , Tato/fisiologia , Encefalopatias/cirurgia , Eletrodos Implantados , Eletroencefalografia/métodos , Humanos , Procedimentos Neurocirúrgicos/instrumentação , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Robótica , Cirurgia Assistida por Computador/instrumentação , Cirurgia Assistida por Computador/métodos
4.
Lancet ; 388(10043): 476-87, 2016 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-27289174

RESUMO

BACKGROUND: Metachromatic leukodystrophy (a deficiency of arylsulfatase A [ARSA]) is a fatal demyelinating lysosomal disease with no approved treatment. We aimed to assess the long-term outcomes in a cohort of patients with early-onset metachromatic leukodystrophy who underwent haemopoietic stem-cell gene therapy (HSC-GT). METHODS: This is an ad-hoc analysis of data from an ongoing, non-randomised, open-label, single-arm phase 1/2 trial, in which we enrolled patients with a molecular and biochemical diagnosis of metachromatic leukodystrophy (presymptomatic late-infantile or early-juvenile disease or early-symptomatic early-juvenile disease) at the Paediatric Clinical Research Unit, Ospedale San Raffaele, in Milan. Trial participants received HSC-GT, which consisted of the infusion of autologous HSCs transduced with a lentiviral vector encoding ARSA cDNA, after exposure-targeted busulfan conditioning. The primary endpoints of the trial are safety (toxicity, absence of engraftment failure or delayed haematological reconstitution, and safety of lentiviral vector-tranduced cell infusion) and efficacy (improvement in Gross Motor Function Measure [GMFM] score relative to untreated historical controls, and ARSA activity, 24 months post-treatment) of HSC-GT. For this ad-hoc analysis, we assessed safety and efficacy outcomes in all patients who had received treatment and been followed up for at least 18 months post-treatment on June 1, 2015. This trial is registered with ClinicalTrials.gov, number NCT01560182. FINDINGS: Between April, 2010, and February, 2013, we had enrolled nine children with a diagnosis of early-onset disease (six had late-infantile disease, two had early-juvenile disease, and one had early-onset disease that could not be definitively classified). At the time of analysis all children had survived, with a median follow-up of 36 months (range 18-54). The most commonly reported adverse events were cytopenia (reported in all patients) and mucositis of different grades of severity (in five of nine patients [grade 3 in four of five patients]). No serious adverse events related to the medicinal product were reported. Stable, sustained engraftment of gene-corrected HSCs was observed (a median of 60·4% [range 14·0-95·6] lentiviral vector-positive colony-forming cells across follow-up) and the engraftment level was stable during follow-up; engraftment determinants included the duration of absolute neutropenia and the vector copy number of the medicinal product. A progressive reconstitution of ARSA activity in circulating haemopoietic cells and in the cerebrospinal fluid was documented in all patients in association with a reduction of the storage material in peripheral nerve samples in six of seven patients. Eight patients, seven of whom received treatment when presymptomatic, had prevention of disease onset or halted disease progression as per clinical and instrumental assessment, compared with historical untreated control patients with early-onset disease. GMFM scores for six patients up to the last follow-up showed that gross motor performance was similar to that of normally developing children. The extent of benefit appeared to be influenced by the interval between HSC-GT and the expected time of disease onset. Treatment resulted in protection from CNS demyelination in eight patients and, in at least three patients, amelioration of peripheral nervous system abnormalities, with signs of remyelination at both sites. INTERPRETATION: Our ad-hoc findings provide preliminary evidence of safety and therapeutic benefit of HSC-GT in patients with early-onset metachromatic leukodystrophy who received treatment in the presymptomatic or very early-symptomatic stage. The results of this trial will be reported when all 20 patients have achieved 3 years of follow-up. FUNDING: Italian Telethon Foundation and GlaxoSmithKline.


Assuntos
Terapia Genética , Transplante de Células-Tronco Hematopoéticas , Leucodistrofia Metacromática/terapia , Adolescente , Idade de Início , Criança , Pré-Escolar , Feminino , Seguimentos , Terapia Genética/métodos , Humanos , Lactente , Itália , Lentivirus , Leucodistrofia Metacromática/genética , Leucodistrofia Metacromática/cirurgia , Masculino , Resultado do Tratamento
5.
ESMO Open ; 1(6): e000111, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28848658

RESUMO

OBJECTIVE: To identify imaging markers predicting clinical outcomes to regorafenib in metastatic colorectal carcinoma (mCRC). METHODS: The RadioCORRECT study is a post hoc analysis of a cohort of patients with mCRC treated within the phase III placebo-controlled CORRECT trial of regorafenib. Baseline and week 8 contrast-enhanced CT were used to assess response by RECIST 1.1, changes in the sum of target lesion diameters (ΔSTL), lung metastases cavitation and liver metastases density. Primary and secondary objectives were to develop ex novo univariable and multivariable models to predict overall survival (OS) and progression-free survival (PFS), respectively. RESULTS: 202 patients were enrolled, 134 (66.3%) treated with regorafenib and 68 (33.7%) with placebo. In the univariate analysis, PFS predictors were lung metastases cavitation at baseline (HR 0.50, 95% CI 0.27 to 0.92, p=0.03) and at week 8 (HR 0.58, 95% CI 0.36 to 0.93, p=0.02). Baseline cavitation (HR 0.23, 95% CI 0.08 to 0.66, p=0.007), RECIST 1.1 (HR 0.23, 95% CI 0.14 to 0.4, p <0.0001) and ΔSTL (HR 1.16, 95% CI 1.06 to 1.27, p=0.002) predicted OS. We found an increase of 9% of diameter as the best threshold for discriminating OS (HR 2.64, 95% CI 1.61 to 4.34, p <0.001). In the multivariate analysis, baseline and week 8 cavitation remained significant PFS predictors. Baseline cavitation, RECIST 1.1 and ΔSTL remained predictors of OS in exploratory multivariable models. Assessment of liver metastases density did not predict clinical outcome. CONCLUSIONS: RECIST 1.1 and ΔSTL predict favourable outcome to regorafenib. In contrast to liver metastases density that failed to be a predictor, lung metastases cavitation represents a novel radiological marker of favourable outcome that deserves consideration.

6.
Stem Cell Res ; 12(3): 659-72, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24675053

RESUMO

Human bone marrow stromal cells (BMSCs, also known as bone marrow-derived "mesenchymal stem cells") can establish the hematopoietic microenvironment within heterotopic ossicles generated by transplantation at non-skeletal sites. Here we show that non-mineralized cartilage pellets formed by hBMSCs ex vivo generate complete ossicles upon heterotopic transplantation in the absence of exogenous scaffolds. These ossicles display a remarkable degree of architectural fidelity, showing that an exogenous conductive scaffold is not an absolute requirement for bone formation by transplanted BMSCs. Marrow cavities within the ossicles include erythroid, myeloid and granulopoietic lineages, clonogenic hematopoietic progenitors and phenotypic HSCs, indicating that complete stem cell niches and hematopoiesis are established. hBMSCs (CD146(+) adventitial reticular cells) are established in the heterotopic chimeric bone marrow through a unique process of endochondral bone marrow formation, distinct from physiological endochondral bone formation. In this process, chondrocytes remain viable and proliferate within the pellet, are released from cartilage, and convert into bone marrow stromal cells. Once explanted in secondary culture, these cells retain phenotype and properties of skeletal stem cells ("MSCs"), including the ability to form secondary cartilage pellets and secondary ossicles upon serial transplantation. Ex vivo, hBMSCs initially induced to form cartilage pellets can be reestablished in adherent culture and can modulate gene expression between cartilage and stromal cell phenotypes. These data show that so-called "cartilage differentiation" of BMSCs in vitro is a reversible phenomenon, which is actually reverted, in vivo, to the effect of generating stromal cells supporting the homing of hematopoietic stem cells and progenitors.


Assuntos
Células da Medula Óssea/citologia , Diferenciação Celular , Condrócitos/citologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Mesenquimais/citologia , Nicho de Células-Tronco , Adolescente , Adulto , Animais , Cartilagem/citologia , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Transplante de Células-Tronco Mesenquimais , Camundongos , Camundongos SCID , Adulto Jovem
7.
Gene ; 537(2): 348-51, 2014 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-24334127

RESUMO

Metachromatic Leukodystrophy is a lysosomal storage disorder caused by Arylsulfatase A deficiency. Diagnosis is usually performed by measurement of enzymatic activity and/or characterization of the gene mutations. Here we describe a family case in which the determination of enzyme activity alone did not allow diagnosis of the pre-symptomatic sibling of the index case. Only combination of gene sequencing with thorough biochemical analysis allowed the correct diagnosis of the sibling, who was promptly directed to treatment.


Assuntos
Cerebrosídeo Sulfatase/genética , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/genética , Alelos , Cerebrosídeo Sulfatase/sangue , Feminino , Heterozigoto , Humanos , Lactente , Masculino
8.
Stem Cells Dev ; 21(9): 1466-77, 2012 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-22280094

RESUMO

Mucopolysaccharidosis type I (MPS IH; Hurler syndrome) is a rare genetic disorder that is caused by mutations in the α-L-iduronidase (IDUA) gene, resulting in the deficiency of IDUA enzyme activity and intra-cellular accumulation of glycosaminoglycans. A characteristic skeletal phenotype is one of the many clinical manifestations in Hurler disease. Since the mechanism(s) underlying these skeletal defects are not completely understood, and bone and cartilage are mesenchymal lineages, we focused on the characterization of mesenchymal cells isolated from the bone marrow (BM) of 5 Hurler patients. IDUA-mutated BM stromal cells (BMSC) derived from MPS IH patients exhibited decreased IDUA activity, consistent with the disease genotype. The expansion rate, phenotype, telomerase activity, and differentiation capacity toward adipocytes, osteoblasts, chondrocytes, and smooth muscle cells in vitro of the MPS I BMSC lines were similar to those of BMSC from age-matched normal control donors. MPS I BMSC also had a similar in vivo osteogenic capacity as normal BMSC. However, MPS I BMSC displayed an increased capacity to support osteoclastogenesis, which may correlate with the up-regulation of the RANKL/RANK/OPG molecular pathway in MPS I BMSC compared with normal BMSC.


Assuntos
Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Diferenciação Celular , Mucopolissacaridose I/metabolismo , Mucopolissacaridose I/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Adipócitos/metabolismo , Adipócitos/patologia , Criança , Feminino , Humanos , Iduronidase/genética , Iduronidase/metabolismo , Lactente , Masculino , Mucopolissacaridose I/genética , Osteoblastos/metabolismo , Osteoblastos/patologia , Ligante RANK/genética , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Células Estromais/metabolismo , Células Estromais/patologia
9.
RFO UPF ; 3(1): 35-40, jan.-jun. 1998. tab
Artigo em Português | LILACS, BBO - Odontologia | ID: lil-221019

RESUMO

Conhecendo o papel do açúcar na etiologia da cárie dentária, foi objetivo desta pesquisa constatar a provável influência das propagandas de televisäo nos hábitos de consumo de alimentos açucarados por crianças. O estudo foi realizado por seis academicos do nono semetre do curso de Odontologia da UFSM, que observaram a programaçäo veiculada da 8h às 12h, durante seis dias, de seis emissoras distintas de televisäo: Rede Globo, Cartoon Network, SBT, TV Educativa, TV Cultura e Manchete. Para a compilaçäo dos dados, foi utilizada uma ficha em que constava o horário e duraçäo de cada intervalo, o produto anunciado, bem como a sua influência sobre os hábitos dietéticos. Concluiu-se que os comerciais de produtos açucarados tem uma abordagem infantil com o objetivo de influenciar as crianças para que consumam. Isso reforça os hábitos dietéticos incorretos, socialmente aceitos como normais. Observou-se também que algumas emissoras näo apresentaram comerciais que infleunciassem os hábitos alimentares


Assuntos
Humanos , Masculino , Feminino , Criança , Cárie Dentária/etiologia , Sacarose na Dieta/efeitos adversos , Comportamento Alimentar , Modalidades Alimentares , Propaganda , Indústria do Açúcar , Televisão
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