FCB2-Artigos (em revistas ou actas indexadas)
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- Clinical and epidemiological characteristics of patients with functional stroke mimics: a case–control study from Southern PortugalPublication . Figueira Domingos, Miguel; Silva, Vítor Hugo; Schuh, Sara; Correia, Helena; Palma, Pedro; Pedro, João Pedroso; Nova, Bruno Vila; Marreiros, Ana; Félix, Ana Catarina; Nzwalo, HipólitoBackground: Patients with functional neurological disorder presenting as stroke mimics or functional stroke mimics (FSMs) pose significant diagnostic challenges. In the acute phase, especially when patients are present within the therapeutic window for acute reperfusion treatments, a misdiagnosis of FSM can lead to unnecessary and costly interventions. Despite its clinical importance, the literature on the risk factors for FSM is limited. This study aims to compare the clinical and epidemiological characteristics of patients with FSM to those with confirmed acute ischemic stroke (AIS). Methods: This case-control study involved temporal matching between consecutive series of patients with FSM and controls with AIS from a single tertiary university hospital in southern Portugal. Results: A total of 188 patients were included: 64 cases (FSM) and 188 controls (AIS). The rate of stroke code activation and use of ambulance between was comparable between the two groups. The group of patients with FSM was younger (53.2 years vs. 69.5 years, p < 0.001) and had a higher proportion of females (52.4% vs. 47.6%, p = 0.001). There was no difference in terms of clinical severity at presentation. The proportion of specific signs, such as transcortical aphasia (3.1% vs. 20.9%, p = 0.014), gait abnormalities (15.6% vs. 33.9%, p = 0.004), and cranial nerve abnormalities (31.2% vs. 43.5%, p = 0.042), was lower in the FSM group compared to the AIS group. The proportion of patients on antithrombotic therapy (90.9% vs. 9.1%, p = 0.007) and antihypertensive drugs (78.5%, vs. 21.5%, p < 0.001) prior to the event was significantly higher in the AIS group. Likewise, the prevalence of cerebrovascular risk factors such as diabetes mellitus (14.3% vs. 85.7%, p = 0.005), arterial hypertension (23.8% vs. 76.2%, p = 0.001), and smoking (43.7% vs. 56.3%, p = 0.005) was lower in the FSM group compared to the AIS group. No statistically significant differences were observed in cholesterol levels or the prevalence of dyslipidemia between the two groups. Psychiatric comorbidities, including generalized anxiety disorder (71.4% vs. 28.6%, p = 0.05) and major depressive disorder (61.9% vs. 28.1%, p = 0.01), were more prevalent in the FSM group. Conclusions: Patients with FSM display different clinical and epidemiological profiles, with a higher likelihood of being younger, female, having prior psychiatric conditions, and lacking traditional cerebrovascular risk factors.
- Role of ancillary techniques in the differential diagnosis of salivary gland carcinomasPublication . Paiva Correia, Antonio; Hellquist, Henrik; Apolónio, Joana; Castelo-Branco, PedroPaiva-Correia A, Hellquist H, Apolónio J, Castelo-Branco P. Role of ancillary techniques in the differential diagnosis of salivary gland carcinomas. The diagnosis of salivary gland carcinomas (SGC) rests mainly on histology, but immunohistochemical and molecular investigations are often necessary for differential diagnosis. This review is primarily aimed as a tool for pathologists in non-specialised head and neck hospitals who encounter a limited number of SGC annually. The use of testing an initial antibody panel, which may comprise both positive and negative expression for a suspected entity, and examples of different panels are outlined. We also focused on acinic cell carcinoma (AcCC), which is positive for DOG1 and negative for mammaglobin, whilst secretory carcinoma (SC) is positive for mammaglobin and negative for DOG1. In addition, the exclusive expression of androgen and HER2 in salivary duct carcinoma (SDC) and its use for differential diagnosis are also addressed. This review also highlights the particularities of mucoepidermoid carcinoma (MEC) and its negativity for S100 and SOX10, which distinguishes it from some of its mimics. In laboratories with limited access to antibodies for SGC, we recommend inclusion of mammaglobin. The use of molecular techniques for the diagnosis of MEC (MAML2), SC (ETV6), adenoid cystic carcinoma (MYB), and AcCC (NR4A3) is discussed. We highlight the role of commonly available antibodies for the histological classification of SGC.
- Comparing international guidelines for the remission of hypertension after bariatric surgeryPublication . Dias, Carina Vieira; Silva, Ana Lúcia; Dias, Joana; Cardoso, Paulo; Castanheira, Rute; Fernandes, Andreia; Nunes, Filipa; Sanai, Tina; Sanchez, Mercedes; Maia-Teixeira, João; De Sousa-Coelho, Ana LuísaBackground/Objectives: Obesity remains a global health concern and is associated with increased risk of type 2 diabetes, hypertension, and cardiovascular disease overall. Dissimilar hypertension guidelines are available for clinicians, namely those prepared by the American Heart Association (AHA) and the European Society of Cardiology (ESC), which may lead to distinctive appreciation of health outcomes of patients with obesity after bariatric and metabolic surgery, such as hypertension remission. The main goal of this study was to compare the effects of applying stricter (AHA) versus looser (ESC) blood pressure criteria on hypertension diagnosis pre-bariatric surgery and remission assessment one year post-op. Methods: A retrospective analysis of clinical data from patients who underwent surgical treatment for obesity at a single university hospital was performed. To evaluate the hypertension improvement or remission, two different types of blood pressure (BP) categorization were considered (based on AHA and ESC guidelines), in which each patient would fit according to their BP values pre- (m0) and 12 months postoperative (m12). Results: From a sample of 153 patients submitted for surgical treatment of obesity, more patients were considered with hypertension based on the AHA guideline (130 vs. 102; p < 0.001), while a higher rate of hypertension remission at 12 months after bariatric surgery was observed when following the ESC guideline (58.82 vs. 53.08%). Baseline patients' clinical characteristics based on each hypertension outcome were mostly independent of the guideline used (p > 0.05), where only age and systolic blood pressure were relatively higher in "ESC groups". Conclusions: We conclude that only minor differences exist between the two guidelines used. If evaluated based on ESC guidelines, it is expected that less patients are considered with hypertension, and the remission rate may be, at least numerically, higher.
- Amyloid-negative, neurodegeneration-negative amnestic mild cognitive impairmentPublication . Cardoso, Sandra; Guerreiro, Manuela; Montalvo, Alexandre; Silva, Dina; Alves, Luísa; Mendonça, Alexandre deBackground:The concept of amnestic mild cognitive impairment (aMCI) was developed to identify patients at an initial stage of Alzheimer's disease (AD). However, some patients with aMCI do not present biomarkers of amyloid pathology or neuronal injury.Objective:To know the natural history of amyloid-negative and neurodegeneration-negative patients with aMCI, namely to ascertain: 1) whether these patients remain cognitively stable or they present a slow decline in neuropsychological tests; 2) whether the memory complaints subside with the apparently benign clinical course of the disorder or if they persist along the time.Methods:Patients who fulfilled criteria for aMCI with no biomarkers of amyloid pathology or neuronal injury were selected from a large cohort of non-demented patients with cognitive complaints, and were followed with clinical and neuropsychological assessments.Results:Twenty-one amyloid-negative and neurodegeneration-negative aMCI patients were followed for 7.1 +/- 3.7 years. At the baseline they had more pronounced deficits in verbal learning (California Verbal Learning Test) and were also impaired in Word Recall and Logical Memory. However, they did not decline in any cognitive test during follow-up. The patients maintained a high level of subjective memory complaints from baseline (9.7 +/- 4.1) to the follow-up visit (9.2 +/- 4.1, a non-significant difference), in spite of a statistically significant decrease in the depressive symptoms, with Geriatric Depression Scale (15 items) score 4.9 +/- 2.8 at baseline and 3.2 +/- 1.8 at the follow-up visit. Conclusions: Amyloid-negative, neurodegeneration-negative aMCI is a chronic clinical condition characterized by the long-term persistence of cognitive deficits and distressing memory complaints. Adequate strategies to treat this condition are needed.
- Pre-hospital Identification of a Giant Bladder Calculus through Screening Sonography: A Case ReportPublication . Miravent, Sérgio; Gomes, Carla Marisa; Simãozinho, Paula; Vaz, Bruna; Lobo, Manuel Duarte; Almeida, RuiIntroduction: Screening ultrasound proves to be remarkably beneficial in pre-hospital settings, particularly in geographically remote areas with technological constraints and no medical specialties. Urological pathology has a high frequency of occurrence in the emergency department and is part of the wide range of occurrences that can benefit from this ultrasound screening as a clinical guide for patients. Case Presentation: In this case, a patient experiencing lower abdominal pain and symptoms of renal colic sought assistance at a basic emergency service facility. Utilizing a renal screening ultrasound executed by a sonographer, the clinical team identified images indicative of a significant bladder calculus. Subsequently, the patient was referred to a referral hospital for a comprehensive evaluation by medical specialties. Conclusion: The images obtained in both health units exhibited congruence, indicating that the screening ultrasound, while not intended to replace the specialized orthodox ultrasound executed by a radiologist, served as a crucial tool for diagnostic presumption, providing consistency in clinical decision-making for referring patients. This capability allowed emergency physicians to promptly transfer a patient requiring urgent further investigation to a referral hospital with compelling and substantiated data. This shift in the approach to patient triage in a remote setting could enhance patient safety.
- Brain-targeted drug delivery - nanovesicles directed to specific brain cells by brain-targeting ligandsPublication . Moreira, Ricardo; Nóbrega, Clévio; Almeida, Luís Pereira de; Mendonça, LilianaNeurodegenerative diseases are characterized by extensive loss of function or death of brain cells, hampering the life quality of patients. Brain-targeted drug delivery is challenging, with a low success rate this far. Therefore, the application of targeting ligands in drug vehicles, such as lipid-based and polymeric nanoparticles, holds the promise to overcome the blood-brain barrier (BBB) and direct therapies to the brain, in addition to protect their cargo from degradation and metabolization. In this review, we discuss the barriers to brain delivery and the different types of brain-targeting ligands currently in use in brain-targeted nanoparticles, such as peptides, proteins, aptamers, small molecules, and antibodies. Moreover, we present a detailed review of the different targeting ligands used to direct nanoparticles to specific brain cells, like neurons (C4-3 aptamer, neurotensin, Tet-1, RVG, and IKRG peptides), astrocytes (Aquaporin-4, D4, and Bradykinin B2 antibodies), oligodendrocytes (NG-2 antibody and the biotinylated DNA aptamer conjugated to a streptavidin core Myaptavin-3064), microglia (CD11b antibody), neural stem cells (QTRFLLH, VPTQSSG, and NFL-TBS.40–63 peptides), and to endothelial cells of the BBB (transferrin and insulin proteins, and choline). Reports demonstrated enhanced brain-targeted delivery with improved transport to the specific cell type targeted with the conjugation of these ligands to nanoparticles. Hence, this strategy allows the implementation of high-precision medicine, with reduced side effects or unwanted therapy clearance from the body. Nevertheless, the accumulation of some of these nanoparticles in peripheral organs has been reported indicating that there are still factors to be improved to achieve higher levels of brain targeting. This review is a collection of studies exploring targeting ligands for the delivery of nanoparticles to the brain and we highlight the advantages and limitations of this type of approach in precision therapies.
- Transcriptional regulation of the Human MGP promoter: Identification of downstream repressorsPublication . Caiado, Helena; Cancela, M. Leonor; Conceição, NatérciaMatrix Gla protein (MGP) is a vitamin K-dependent γ-carboxylated protein that was initially identified as a physiological inhibitor of ectopic calcification, primarily affecting cartilage and the vascular system. Mutations in the MGP gene were found to be responsible for the Keutel syndrome, a condition characterized by abnormal calcifications in the cartilage, lungs, brain, and vascular system. MGP has been shown to be dysregulated in several tumors, including cervical, ovarian, urogenital, and breast cancers. Using bioinformatic approaches, transcription factor binding sites (TFBSs) containing CpG dinucleotides were identified in the MGP promoter, including those for YY1, GATA1, and C/EBPα. We carried out functional tests using transient transfections with a luciferase reporter assay, primarily for the transcription factors YY1, GATA1, C/EBPα, and RUNX2. By co-transfection analysis, we found that YY1, GATA1, and C/EBPα repressed the MGP promoter. Furthermore, the co-transfection with RUNX2 activated the MGP promoter. In addition, MGP expression is negatively or positively correlated with the studied TFs’ expression levels in several cancer types. This study provides novel insights into MGP regulation by demonstrating that YY1, GATA1, and C/EBPα are negative regulators of the MGP promoter, and DNA methylation may influence their activity. The dysregulation of these mechanisms in cancer should be further elucidated.
- OrthoMortPred: predicting one-year mortality following orthopedic hospitalizationPublication . Pires de Carvalho, Filipe Ricardo; Gavaia, Paulo; Brito Camacho, AntónioObjective: Predicting mortality risk following orthopedic surgery is crucial for informed decision-making and patient care. This study aims to develop and validate a machine learning model for predicting one-year mortality risk after orthopedic hospitalization and to create a personalized risk prediction tool for clinical use. Methods: We analyzed data from 3,132 patients who underwent orthopedic procedures at the Central Lisbon University Hospital Center from 2021 to 2023. Using the LightGBM algorithm, we developed a predictive model incorporating various clinical and administrative variables. We employed SHAP (SHapley Additive exPlanations) values for model interpretation and created a personalized risk prediction tool for individual patient assessment. Results: Our model achieved an accuracy of 93% and an area under the ROC curve of 0.93 for predicting one-year mortality. Notably, ’EMERGENCY ADMISSION DATE TIME’ emerged as the most influential predictor, followed by age and pre-operative days. The model demonstrated robust performance across different patient subgroups and outperformed traditional statistical methods. The personalized risk prediction tool provides clinicians with real-time, patient-specific risk assessments and insights into contributing factors. Conclusion: Our study presents a highly accurate model for predicting one-year mortality following orthopedic hospitalization. The significance of ’EMERGENCY ADMISSION DATE TIME’ as the primary predictor highlights the importance of admission timing in patient outcomes. The accompanying personalized risk prediction tool offers a practical means of implementing this model in clinical settings, potentially improving risk stratification and patient care in orthopedic practice.
- Factors influencing community intensive care unit research participation: a qualitative descriptive studyPublication . Gehrke, Paige; Rego, Kian; Orlando, Elaina; Jack, Susan; Law, Madelyn; Cook, Deborah; Marticorena, Rosa M.; Binnie, Alexandra; Tsang, Jennifer L. Y.Purpose Community hospitals account for 90% of hospitals in Canada, but clinical research is mainly conducted in academic hospitals. Increasing community hospital research participation can improve generalizability of study results, while also accelerating study recruitment and increasing staff engagement. We aimed to identify and describe the factors that influence community intensive care unit (ICU) research participation and the development, implementation, and sustainability of a community ICU research program.MethodsWe conducted a qualitative descriptive study using semistructured interviews. Between April 2022 and May 2023, we interviewed a purposeful sample of individuals interested or involved in community hospital research in Canadian community ICUs. We analyzed qualitative data using both conventional content analysis and rapid qualitative analysis. Findings were deductively mapped out using the Ecological Model of Health Behavior. Quantitative survey data were analyzed using descriptive statistics.ResultsParticipants included 23 health care workers, ten research staff, and five hospital administrators (n = 38) from 20 community hospitals across six provinces in Canada. The main factors associated with community ICU research participation were 1) infrastructure, 2) personnel characteristics, 3) key relationships and connections, and 4) the COVID-19 pandemic.ConclusionIn this qualitative descriptive study, participants identified the physical resources, skills, and relationships required to start and sustain a clinical research program in a Canadian community ICU. Our findings suggest that all levels of the Canadian health care system need to invest in strengthening community hospital research capacity to increase research participation.
- Massive parallel sequencing of head and neck conventional squamous cell carcinomas: A comprehensive reviewPublication . Nadal, Alfons; Cardesa, Antonio; Agaimy, Abbas; Almangush, Alhadi; Franchi, Alessandro; Hellquist, Henrik; Leivo, Ilmo; Zidar, Nina; Ferlito, AlfioHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is a cause of signifcant mortality and morbidity. The epidemiology of this cancer varies worldwide due to either genetic diferences in populations or diferences in carcinogen exposure. The application of massive parallel sequencing-based techniques in HNSCC should provide a helpful understanding of the genetic alterations that eventually lead to HNSCC development and progression, and ideally, could be used for personalized therapy. In this review, the reader will fnd an overview of the mutational profle of conventional HNSCC according to published results on massive parallel sequencing data that confrm the pivotal role of TP53 and the frequent involvement of CDKN2A and PIK3CA. The reader will also fnd a more detailed description of the genes, such as NOTCH1 and FBXW7, that were not identifed in HNSCCs before the development of these techniques, the diferences that can be site-specifc, such as the diferent mutational signatures that indicate specifc carcinogens for various subsites of the head and neck, and fnally, the actionability of these fndings that should allow more personalized therapy for patients.