Browsing by Author "Ferreira, L"
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- Endothelial Progenitor Cells influence acute and subacute stroke hemodynamicsPublication . Sargento-Freitas, J; Aday, S; Nunes, C; Cordeiro, M; Gouveia, A; Silva, F; Machado, C; Rodrigues, B; Santo, GC; Ferreira, C; Castelo-Branco, M; Ferreira, L; Cunha, LBACKGROUND: Endothelial Progenitor Cells (EPCs) are a circulating stem cell population with in vivo capacity of promoting angiogenesis after ischemic events. Despite the promising preclinical data, their potential integration with reperfusion therapies and hemodynamic evolution of stroke patients is still unknown. Our aim was to determine the association of EPCs with acute, subacute and chronic hemodynamic features. METHODS: In this prospective study, we included consecutive patients with ages between 18 and 80years and non-lacunar ischemic stroke within the territory of a middle cerebral artery. All patients were subject to hemodynamic evaluation by ultrasound at baseline, seven days and three months. We quantified cerebral blood flow (CBF) and assessed early recanalization and collateral flow. Hemorrhagic transformation was graded in Magnetic Resonance imaging performed at seven days. EPCs were isolated from peripheral venous blood collected in the first 24h and seven days, counted and submitted to functional in vitro tests. RESULTS: We included 45 patients with a median age of 70±10years. The angiogenic and migratory capacities of EPCs were associated with increased collateral flow in the acute stage and day seven CBF, without statistically significant associations with recanalization nor haemorrhagic transformation. The number of EPCs was not associated with any hemodynamic variable. CONCLUSIONS: The functional properties of EPCs are associated with acute and subacute stroke hemodynamics, with no effect on haemorrhagic transformation.
- Estudo clínico, multicêntrico, aberto, comparativo, sobre eficácia e a segurança da sertalina vs clomipramina, no tratamento de doentes com depressão moderada a gravePublication . Vaz-Serra, A; Firmino, H; Albuquerque, A; Ferreira, L; Sousa, P; Vieira, CR; Figueira, ML
- Impactação de prótese dentária no esófago torácico: tratamento cirúrgico. A propósito de um caso clínicoPublication . Alexandrino, A; Fernandes, M; Ferreira, L; Tralhão, JG; Castro e Sousa, F
- Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapyPublication . Ferreira, L; Alexandrino, H; Soares Leite, J; Castro e Sousa, FColorectal cancer is a common malignant neoplasm and its treatment usually involves surgery associated, in some cases, depending on the staging, with chemoradiotherapy. Necrotising fasciitis of the perineum is a highly lethal infection of the perineum, perirectal tissues and genitals, requiring emergency surgical debridement, broad-spectrum antibiotics and control of sepsis. We present the case of a 59-year-old man with necrotising fasciitis of the perineum as the first clinical manifestation of locally advanced adenocarcinoma of the rectum, in which successful management consisted of early and aggressive surgical debridement, followed by multimodal therapy with curative intent. 2 years and 6 months after surgery the patient is well, with no evidence of local or systemic relapse.
- Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditionsPublication . Kostic, I; Fidalgo-Carvalho, I; Aday, S; Vazão, H; Carvalheiro, T; Grãos, M; Duarte, A; Cardoso, C; Gonçalves, L; Carvalho, L; Paiva, A; Ferreira, LSeveral clinical trials are exploring therapeutic effect of human CD34(+) cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34(+) cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to non-treated cells and prostaglandin E2-treated cells, respectively. The pro-survival effect of LPA is concentration- and time-dependent and it is mediated by the activation of peroxisome proliferator-activator receptor γ (PPARγ) and downstream, by the activation of pro-survival ERK and Akt signaling pathways and the inhibition of mitochondrial apoptotic pathway. In hypoxia and serum-deprived culture conditions, LPA induces CD34(+) cell proliferation without maintaining the their undifferentiating state, and enhances IL-8, IL-6 and G-CSF secretion during the first 12 h compared to non-treated cells. LPA-treated CD34(+) cells delivered in fibrin gels have enhanced survival and improved cardiac fractional shortening at 2 weeks on rat infarcted hearts as compared to hearts treated with placebo. We have developed a new platform to enhance the survival of CD34(+) cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction.
- Oxaliplatin toxicity presenting as a liver nodule - case reportPublication . Alexandrino, H; Oliveira, D; Cipriano, MA; Ferreira, L; Tralhão, JG; Castro e Sousa, FBACKGROUND: Oxaliplatin based chemotherapy is often used as adjuvant therapy in colon and rectal cancer. A reported side effect is Sinusoidal Obstruction Syndrome which is characterized by a spectrum of pathologic changes, from sinusoidal dilation, peri-sinusoidal haemorrhage, peliosis and nodular regenerative hyperplasia. Very rarely it can cause the development of liver nodules mimicking liver metastases. Herein, we report a case of Sinusoidal Obstruction Syndrome causing a liver nodule suspicious of liver metastasis on imaging. This is the third reported case of this complication of oxaliplatin toxicity, in which resection was performed and pathological diagnosis confirmed. CASE PRESENTATION: We report the case of a 59 year old man with stage III colon cancer who underwent sigmoidectomy followed by adjuvant chemotherapy with oxaliplatin. One year after surgery a liver nodule was detected and the patient underwent right hepatectomy. Pathology showed no liver nodule and diagnosed sinusoidal obstruction syndrome. CONCLUSION: We describe the third reported case of a liver lesion mimicking a liver metastasis after oxaliplatin-based chemotherapy for colon cancer. We suggest that in patients heavily treated with oxaliplatin with de novo liver nodules, this differential diagnosis should be considered. In particular, in this population of patients an intense imagiologic evaluation and even a preoperative biopsy should be pursued to confirm the diagnosis of malignancy and avoid overtreatment.
- Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and RecoveryPublication . Bernardo-Castro, S; Sousa, JA; Brás, A; Cecília, C; Rodrigues, B; Almendra, L; Machado, C; Santo, G; Silva, F; Ferreira, L; Santana, I; Sargento-Freitas, JThe blood-brain barrier (BBB) is a dynamic interface responsible for maintaining the central nervous system homeostasis. Its unique characteristics allow protecting the brain from unwanted compounds, but its impairment is involved in a vast number of pathological conditions. Disruption of the BBB and increase in its permeability are key in the development of several neurological diseases and have been extensively studied in stroke. Ischemic stroke is the most prevalent type of stroke and is characterized by a myriad of pathological events triggered by an arterial occlusion that can eventually lead to fatal outcomes such as hemorrhagic transformation (HT). BBB permeability seems to follow a multiphasic pattern throughout the different stroke stages that have been associated with distinct biological substrates. In the hyperacute stage, sudden hypoxia damages the BBB, leading to cytotoxic edema and increased permeability; in the acute stage, the neuroinflammatory response aggravates the BBB injury, leading to higher permeability and a consequent risk of HT that can be motivated by reperfusion therapy; in the subacute stage (1-3 weeks), repair mechanisms take place, especially neoangiogenesis. Immature vessels show leaky BBB, but this permeability has been associated with improved clinical recovery. In the chronic stage (>6 weeks), an increase of BBB restoration factors leads the barrier to start decreasing its permeability. Nonetheless, permeability will persist to some degree several weeks after injury. Understanding the mechanisms behind BBB dysregulation and HT pathophysiology could potentially help guide acute stroke care decisions and the development of new therapeutic targets; however, effective translation into clinical practice is still lacking. In this review, we will address the different pathological and physiological repair mechanisms involved in BBB permeability through the different stages of ischemic stroke and their role in the development of HT and stroke recovery.
- Permeability of the blood-brain barrier through the phases of ischaemic stroke and relation with clinical outcome: protocol for a systematic reviewPublication . Bernardo-Castro, S; Donato, H; Ferreira, L; Sargento-Freitas, JIntroduction: Ischaemic stroke is the most prevalent type of stroke and is characterised by a myriad of pathological events triggered by a vascular arterial occlusion. Disruption of the blood-brain barrier (BBB) is a key pathological event that may lead to fatal outcomes. However, it seems to follow a multiphasic pattern that has been associated with distinct biological substrates and possibly contrasting outcomes. Addressing the BBB permeability (BBBP) along the different phases of stroke through imaging techniques could lead to a better understanding of the disease, improved patient selection for specific treatments and development of new therapeutic modalities and delivery methods. This systematic review will aim to comprehensively summarise the existing evidence regarding the evolution of the BBBP values during the different phases of an acute ischaemic stroke and correlate this event with the clinical outcome of the patient. Methods and analysis: We will conduct a computerised search on Medline, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science. In addition, grey literature and ClinicalTrials.gov will be scanned. We will include randomised controlled trials, cohort, cross-sectional and case-controlled studies on humans that quantitatively assess the BBBP in stroke. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias of the selected studies. If possible, data will be combined in a quantitative meta-analysis following the guidelines provided by Cochrane Handbook for Systematic Reviews of Interventions. We will assess cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. Ethics and dissemination: Ethical approval is not needed. All data used for this work are publicly available. The result obtained from this work will be published in a peer-reviewed journal and disseminated in relevant conferences.
- The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing PoliciesPublication . Sá-Sousa, A; Fonseca, JA; Pereira, AM; Ferreira, A; Arrobas, A; Mendes, A; Drummond, M; Videira, W; Costa, T; Farinha, P; Soares, J; Rocha, P; Todo-Bom, A; Sokolova, A; Costa, A; Fernandes, B; Chaves Loureiro, C; Longo, C; Pardal, C; Costa, C; Cruz, C; Loureiro, CC; Lopes, C; Mesquita, D; Faria, E; Magalhães, E; Menezes, F; Todo-Bom, F; Carvalho, F; Regateiro, FS; Falcão, H; Fernandes, I; Gaspar-Marques, J; Viana, J; Ferreira, J; Silva, JM; Simão, L; Almeida, L; Fernandes, L; Ferreira, L; van Zeller, M; Quaresma, M; Castanho, M; André, N; Cortesão, N; Leiria-Pinto, P; Pinto, P; Rosa, P; Carreiro-Martins, P; Gerardo, R; Silva, R; Lucas, S; Almeida, T; Calvo, TThe Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.
- Therapeutic Nanoparticles for the Different Phases of Ischemic StrokePublication . Bernardo-Castro, S; Albino, I; Barrera-Sandoval, ÁM; Tomatis, F; Sousa, JA; Martins, E; Simões, S; Lino, MM; Ferreira, L; Sargento-Freitas, JStroke represents the second leading cause of mortality and morbidity worldwide. Ischemic strokes are the most prevalent type of stroke, and they are characterized by a series of pathological events prompted by an arterial occlusion that leads to a heterogeneous pathophysiological response through different hemodynamic phases, namely the hyperacute, acute, subacute, and chronic phases. Stroke treatment is highly reliant on recanalization therapies, which are limited to only a subset of patients due to their narrow therapeutic window; hence, there is a huge need for new stroke treatments. Nonetheless, the vast majority of promising treatments are not effective in the clinical setting due to their inability to cross the blood-brain barrier and reach the brain. In this context, nanotechnology-based approaches such as nanoparticle drug delivery emerge as the most promising option. In this review, we will discuss the current status of nanotechnology in the setting of stroke, focusing on the diverse available nanoparticle approaches targeted to the different pathological and physiological repair mechanisms involved in each of the stroke phases.