Browsing by Author "Marreiros, Ana"
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- Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significantPublication . Correia, Lizelle; Magno, Ramiro; Xavier, JM; Almeida, Bernardo; Duarte, Isabel; Esteves, Filipa; Ghezzo, Marinella; Eldridge, Matthew; Sun, Chong; Bosma, Astrid; Mittempergher, Lorenza; Marreiros, Ana; Bernards, Rene; Caldas, Carlos; Chin, Suet-Feung; Maia, Ana-TeresaPIK3CA mutations are the most common in breast cancer, particularly in the estrogen receptor-positive cohort, but the benefit of PI3K inhibitors has had limited success compared with approaches targeting other less common mutations. We found a frequent allelic expression imbalance between the missense mutant and wild-type PIK3CA alleles in breast tumors from the METABRIC (70.2%) and the TCGA (60.1%) projects. When considering the mechanisms controlling allelic expression, 27.7% and 11.8% of tumors showed imbalance due to regulatory variants in cis, in the two studies respectively. Furthermore, preferential expression of the mutant allele due to cis-regulatory variation is associated with poor prognosis in the METABRIC tumors (P = 0.031). Interestingly, ER-, PR-, and HER2+ tumors showed significant preferential expression of the mutated allele in both datasets. Our work provides compelling evidence to support the clinical utility of PIK3CA allelic expression in breast cancer in identifying patients of poorer prognosis, and those with low expression of the mutated allele, who will unlikely benefit from PI3K inhibitors. Furthermore, our work proposes a model of differential regulation of a critical cancer-promoting gene in breast cancer.
- Benefits of tranexamic acid in total knee arthroplasty: a classification and regression tree analysis in function of instrumentation, BMI, and genderPublication . Pereira, Eduardo; Carvalho, Maria Miguel; Oliveira, Tiago; Sacramento, Telmo; Cruz, Henrique; Viegas, Rui; Fontes, Ana Paula; Marreiros, Ana; Sousa, João PauloTranexamic acid (TXA) is an antifibrinolytic drug that reduces blood loss in patients that undergo Total knee arthroplasty (TKA). Few studies compare its effect on conventional instrumentation (CI) versus patient-specific instrumentation (PSI). The main objective of this study was to understand analytically how TXA usage in both instrumentations influenced blood loss in TKA differently and see if the differences seen could be explained by the patient’s body mass index (BMI) and gender. This nonrandomized retrospective study sample consisted of 688 TKA procedures performed on patients who had symptomatic arthrosis resistant to conservative treatment. Descriptive analysis was used to evaluate blood loss using hemoglobin (Hb) mean values and mean variation (%). The Classification and Regression Tree (CRT) method was applied to understand how the independent variables affected the dependent variable. Comparing patients submitted to the same instrumentation, where some received TXA and others did not, patients that received TXA had lower blood loss. Comparing patients who underwent TKA with different instrumentations and without the use of TXA, it was found that patients who underwent TKA with PSI had lower blood loss than those who underwent TKA with CI. However, when these same instruments were compared again, but associated with the use of TXA, the opposite was true with patients undergoing TKA with PSI showing greater blood loss than patients undergoing TKA with CI. TXA usage in TKA is significantly beneficial in minimizing blood loss and regardless of instrumentation. When using TXA, the lowest blood loss was obtained in patients with higher BMI and submitted to TKA with CI. This is most likely explained by the synergistic antifibrotic effect of TXA with adipokines, such as plasminogen activator inhibitor-1 (PAI-1), found in the femoral bone marrow which is perforated using CI. If, however, TXA wasn’t used, the lowest blood loss was obtained in patients submitted to TKA with PS
- Blood management in total knee arthroplasty: an exploratory study regarding the use of drain and tranexamic acid in two types of instrumentationPublication . Dias, Pedro Alexandre; Caldeira-Dantas, Sofia; Carvalho, Maria Miguel; Marreiros, Ana; de Almeida Fontes, Ana Paula; Sousa, João PauloBackground: This study investigates how presence or absence of drain or tranexamic acid (TXA) in 2 different types of instrumentation with invasion/sparing femoral canal affects hemoglobin drop after total knee arthroplasty (TKA). Methods: This was a retrospective observational study that included 736 individuals divided in five groups, regarding conventional instrumentation (CI) or patient specific instrumentation (PSI), presence or absence of drain and TXA. Mean percentage of hemoglobin drop after the first postoperative day was compared for each group. Results: Patients submitted to CI using drain and no TXA revealed the highest value (21,3%±9,1; p<0,001). Groups who received TXA and drain was not used, presented the lowest blood loss. Moreover, with the introduction of TXA PSI lost its advantage over CI. Conclusions: TKA using CI, without drain and with TXA administration showed better results, reducing mean percentage of hemoglobin drop after surgery.
- Characterization of the knee joint phenotype in the Portuguese populationPublication . Seica, Emanuel Cortesao de; Armada, Lucas; Marreiros, Ana; de Almeida Fontes, Ana Paula; Carvalho, Maria Miguel; Sousa, João PauloBackground: Neutral constitutional alignment and neutral joint line obliquity has been the standard alignment strategy for total knee arthroplasty. This one-for-all measure may negatively impact gait pattern and knee biomechanics. Novel alignment strategies surged, considering the variability in phenotypes found across the literature, as different populations may present different phenotype distributions. The Portuguese population has a distinct genetic origin, with no phenotype distribution data. Our objective was to characterise the population’s knee morphology, searching and analysing adjacent joint osteoarthrosis, and calculating the pre-disease coronal alignment. Methods: A retrospective cohort study was conducted. Full-length X-rays performed between 2016-2023 were analysed. Five alignment parameters were measured (LDFA, MPTA, JLCA, TJLA, HKA), and two parameters were calculated (aHKA, JLO). Knees were classified according to the CPAK classification. Results: For the arthritic cohort, CPAK-I (23%) II (20%) were most common, aHKA increases as KL increases (r=0.8352; p<0.001). For the healthy, Type-II (42%) and Type-I (15%) were most common. For paediatric, Type-II (43%) and Type-V (21%) were most common. CPAK Types-VII/VIII/IX were rare. Differences between genders for healthy and arthritic cohorts were statistically significant. The arthritic had higher prevalence of adjacent joint osteoarthritis. Conclusions: The Portuguese population presents a similar knee phenotype comparing with other populations, some differences have been found regarding the Asian continent. The most common phenotype was a neutral alignment if either healthy or paediatric, or a varus alignment if knee OA. Coronal alignment may not have a major impact in the prevalence of ankle and hip osteoarthritis; however, higher prevalence is observed in patients with knee OA.
- Comparing conventional and patient specific instrumentation in total knee arthroplasty: an early analysis of function and satisfactionPublication . Vaz Pinto, Goncalo; Dantas, Sofia Caldeira-Dantas; Bessa Magalhães, Tiago; Fontes, Ana Paula; Marreiros, Ana; Ribeiro De Sousa, João PauloBackground: Patient specific instrumentation (PSI) in TKA is a surgical technique created to improve the accuracy of implantation, surgical time, blood loss and workflow that has been a growing trend over the past decade. Our work aims to determine if there are improvements in patient satisfaction and functional results using PSI in comparison with conventional instrumentation (CI) in TKA. Methods: The authors evaluated 716 patients from the past 10 years that underwent TKA, either by PSI (n=456) or by CI (n=260). The authors recorded the WOMAC index, articular range of motion, and the six-minute walking test at preop and day 90 post-op. T-student and Mann-Whitney tests were used considering p<0.05. Results: The functional scores achieved 90 days after surgery were better for PSI compared to CI. The respective differences are found in the extension (p=0.022), gait distance (p=0.010) and in the pain and function WOMAC index (respectively p=0.018 and p=0.020). No statistical differences were found in satisfaction. Conclusions: 90 days after TKA, the functional scores achieved with PSI were better compared to CI. However, better results in this area did not translate to significantly higher satisfaction in the patients. There seems to be a tendency in favor of better functional results in patients that underwent TKA by PSI in comparison to those submitted to CI. These results seem to follow the tendencies demonstrated in available literature.
- Contralateral carotid stenosis is a predictor of long-term adverse events in carotid endarterectomyPublication . Moreira, Rita; Duarte-Gamas, Luís; Pereira-Macedo, Juliana; Pereira-Neves, António; Domingues-Monteiro, Diogo; Jácome, Filipa; Andrade, José P.; Marreiros, Ana; Rocha-Neves, JoãoContralateral carotid stenosis (cICS) has been described as a perioperative predictor of mortality after carotid endarterectomy (CEA). However, its predictive value on long-term cardiovascular events remains controversial. The study aims to assess the potential role of cICS as a long-term predictor of major adverse cardiovascular events (MACE) in patients who underwent CEA. From January 2012 to July 2020, patients undergoing CEA under regional anesthesia for carotid stenosis in a tertiary care and referral center were eligible from a prospective database, and a post hoc analysis was performed. The primary outcome consisted in the occurrence of long-term MACE. Secondary outcomes included all-cause mortality, stroke, myocardial infarction, acute heart failure, and major adverse limb events. A total of 192 patients were enrolled. With a median 50 months follow-up, chronic kidney disease (CKD) (mean survival time (MST) 51.7 vs. 103.3, P < 0.010) and peripheral artery disease (PAD) (MST 75.1 vs. 90.3, P = 0.001) were associated with decreased survival time. After propensity score matching (PSM), CKD (MST 49.1 vs. 106.0, P = 0.001) and PAD (MST 75.7 vs. 94.0, P = 0.001) maintained this association. On multivariate Cox regression analysis, contralateral stenosis was associated with higher MACE (hazard ratio (HR) = 2.035; 95% CI: 1.113-3.722, P = 0.021 and all-cause mortality (HR = 2.564; 95% CI: 1.276-5,152 P = 0.008). After PSM, only all-cause mortality (HR 2.323; 95% CI: 0.993-5.431, P = 0.052) maintained a significant association with cICS. On multivariable analysis, cICS (aHR 2.367; 95% CI: 1.174-4.771, P = 0.016), age (aHR 1.039, 95% CI: 1.008-1.070), CKD (aHR 2.803; 95% CI: 1.409-5.575, P = 0.003) and PAD (aHR 3.225, 95% CI: 1.695-6.137, P < 0.001) were independently associated with increased all-cause mortality. Contrary to MACE, cICS is a strong predictor of long-term all-cause mortality after CEA. However, MACE risk may compromise CEA benefits by other competitive events. Therefore, further studies are needed to establish the role of cICS on postoperative events and on patients' specific assessments in order to determine the best medical treatment and easy access to surgical intervention.
- Cryoprotectants synergy improve zebrafish sperm cryopreservation and offspring skeletogenesisPublication . Diogo, Patricia; Martins, Gil; Nogueira, Rita; Marreiros, Ana; Gavaia, Paulo; Cabrita, ElsaThe synergy obtained by the combination of cryoprotectants is a successful strategy that can be beneficial on the optimization of zebrafish sperm cryopreservation. Recently, a protocol was established for this species using an electric ultrafreezer (-150 degrees C) performing cooling rate (-66 degrees C/min) and storage within one step. The ultimate objective of sperm cryopreservation is to generate healthy offspring. Therefore, the objective of this study was to select the most adequate cryoprotectant combination, for the previously established protocol, that generate high quality offspring with normal skeletogenesis. Among the permeating cryoprotectant concentrations studied 12.5% and 15% of N,N-dimethylformamide (DMF) yielded high post-thaw sperm quality and hatching rates. For these two concentrations, the presence of bovine serum albumin (10 mg/mL), egg yolk (10%), glycine (30 mM) and bicine (50 mM) was evaluated for post-thaw sperm motility, viability, in vitro fertilization success and offspring skeletal development (30 days post fertilization). Higher concentration of permeating cryoprotectant (15%) decreased the incidence of deformed arches and severe skeletal malformations, which suggests higher capacity to protect the cell against cold stress and DNA damage. Extender containing 15% DMF with Ctrl, Bicine and egg yolk were the non-permeating cryoprotectants with higher post-thaw quality. The use of these compounds results in a reduction in vertebral fusions, compressions and severity of skeletal malformations in the offspring. Therefore, these extender compositions are beneficial for the quality of zebrafish offspring sired by cryopreserved sperm with 66 degrees C/min freezing rate. To the best of our knowledge, this is the first report on skeletal development of the offspring sired by cryopreserved sperm performed with different freezing media compositions in zebrafish.
- Data on the evaluation of FGF2 gene expression in Colorectal CancerPublication . Caiado, Helena; Conceição, Natércia; Tiago, Daniel; Marreiros, Ana; Vicente, Susana; Enriquez, Jose Luis; Vaz, Ana Margarida; Antunes, Artur; Guerreiro, Horacio; Caldeira, Paulo; Cancela, M. LeonorThe data presented in this article is related with the research paper entitled "Evaluation of MGP gene expression in colorectal cancer", available on Gene journal [1]. From all the transcription factors known to regulate MGP, FGF2 is the most described in colon adenocarcinoma and colon tumor cell lines, where it was shown to: i) contribute for the invasiveness potential; and ii) promote proliferation and survival of colorectal cancer cells. These in vitro studies pose the hypothesis that FGF2 associated signaling pathways could be promoting the regulation of others genes, such as MGP, that may lead to tumor progression which ultimately could result in poor prognosis in colon adenocarcinoma.
- Determinants of health-related quality of life in spondyloarthritis and rheumatoid arthritis - data from the COMOSPA and COMORA studiesPublication . Carvalho, Pedro David; Vieira-Sousa, Elsa; Hmamouchi, Ihsane; Marreiros, Ana; Machado, Pedro MObjectives: To assess the hierarchy of outcomes contributing to health-related quality of life (HRQoL) in spondyloarthritis (SpA) and rheumatoid arthritis (RA). Methods: Data from the international cross-sectional COMOSPA and COMORA studies were used. HRQoL was assessed using the EuroQOL 5-dimension 3-level (EQ-5D-3 L). First, multivariable linear regression models were used to identify associations between EQ-5D-3 L (dependent variable) and several demographic and clinical variables (independent variables). Second, a decision tree was built using Chi-square Automatic Interaction Detector, a method of unbiased hierarchical multivariable analysis (dependent variable: EQ-5D-3 L). Results: In total, 3984 patients with SpA and 3920 patients with RA were included. In SpA, HRQoL was associated with BASFI (adjusted B=-0.006; 95%CI=-0.007 to -0.005), ASDAS (-0.052; -0.071 to -0.033), work productivity loss score (-0.002; -0.003 to -0.002), NSAID treatment (-0.052; -0.083 to -0.020), bDMARD treatment (-0.051; -0.082 to -0.021), university education (-0.051; -0.075 to -0.027) and radiographic sacroiliitis (0.035; 0.004 to 0.030). In RA, HRQoL was associated with modified Health Assessment Questionnaire (MHAQ) (-0.220, -0.253 to -0.188), DAS28-CRP-3v (-0.027, -0.036 to -0.018), work productivity loss score (-0.003, -0.003 to -0.002), presence of erosions (-0.042, -0.065 to -0.020), alcohol consumption >= 3 units/day (0.012, 0.001 to 0.024)) and csDMARD treatment (0.034, 0.001 to 0.066). The decision tree revealed BASFI and MHAQ as first variables with the most discriminative power on EQ-5D-3 L, followed by work productivity loss and disease activity, in both SpA and RA cohorts. Conclusion: In SpA and RA, physical function is the main contributor to HRQoL measured by EQ-5D-3 L, followed by disease activity and work productivity loss.
- Determining factors related to impaired spinal and hip mobility in patients with axial spondyloarthritis: longitudinal results from the DESIR cohortPublication . PD, Carvalho; Ruyssen-Witrand, Adeline; Fonseca, Joao; Marreiros, Ana; Machado, Pedro MObjective To investigate the determinants of impaired spinal and hip mobility in patients with early axial spondyloarthritis (axSpA). Methods Five-year longitudinal data from the DEvenir des Spondyloarthrites Indifferenciees Recentes (DESIR) cohort were analysed. Associations were investigated using generalised estimating equations, using Bath Ankylosing Spondylitis Metrology Index (BASMI) linear or each of the five components of BASMI as dependent variables, and clinical and demographic variables as independent variables in univariable models. Multivariable analyses were performed, adjusting for potential confounders. Results Data from 644 patients and 5152 visits were analysed. Higher BASMI values were independently and positively associated with Ankylosing Spondylitis Disease Activity Score C reactive protein (ASDAS-CRP) (adjusted B (adjB)=0.21; 95% CI=0.15 to 0.28), MRI spinal inflammation score (adjB=0.11; 95% CI=0.04 to 0.19), enthesitis score (adjB=0.02; 95% CI=0.01 to 0.04) and age (adjB=0.02; 95% CI=0.01 to 0.03). All BASMI components were independently associated with ASDAS-CRP and MRI spinal inflammation, except for maximal intermalleolar distance (reflecting hip mobility), which was not associated with MRI spinal inflammation. Conclusion In early axSpA, spinal mobility impairment is independently determined by clinical disease activity, MRI spinal inflammation, enthesitis and age. The influence of spinal inflammation prevails in early axSpA, as opposed to spinal structural damage, which may become more relevant in later disease stages.