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- The Gupta perioperative risk for myocardial infarct or cardiac arrest (MICA) calculator as an intraoperative neurologic deficit predictor in carotid endarterectomyPublication . Pereira-Macedo, Juliana; Fernandes, Beatriz; Duarte-Gamas, Luís; Pereira-Neves, António; Mourão, Joana; Khairy, Ahmed; Andrade, José Paulo; Marreiros, Ana; Rocha-Neves, JoãoBackground: Patients undergoing carotid endarterectomy (CEA) may experiment intraoperative neurologic deficits (IND) during carotid cross-clamping. This work aimed to assess the impact of the Gupta Perioperative Myocardial Infarct or Cardiac Arrest (MICA) risk calculator in the IND. Methods: From January 2012 to April 2021, patients undergoing CEA with regional anaesthesia for carotid stenosis with IND and consecutively control operated patients without IND were selected. A regressive predictive model was created, and a receiver operating characteristic (ROC) curve was applied for comparison. A multivariable dependence analysis was conducted using a classification and regression tree (CRT) algorithm. Results: A total of 97 out of 194 included patients developed IND. Obesity showed aOR = 4.01 (95% CI: 1.66–9.67) and MICA score aOR = 1.21 (1.03–1.43). Higher contralateral stenosis showed aOR = 1.29 (1.08–1.53). The AUROC curve was 0.656. The CRT algorithm differentiated obese patients with a MICA score ≥ 8. Regarding non-obese patients, the model identified the presence of contralateral stenosis ≥ 55% with a MICA ≥ 10. Conclusion: MICA score might play an additional role in stratifying patients for IND in CEA. Obesity was determined as the best discrimination factor, followed by a score ≥ 8. A higher ipsilateral stenosis degree is suggested to have a part in avoiding procedure-related IND. Larger studies might validate the benefit of MICA score regarding the risk of IND.
- Out-of-hospital cardiac arrest in the Algarve region of Portugal: a retrospective registry trial with outcome dataPublication . Carvalho, Nuno Mourão; Martins, Cláudia; Cartaxo, Vera; Marreiros, Ana; Justo, Emília; Raposo, Carlos; Binnie, AlexandraBackground and importanceOut-of-hospital cardiac arrest is a leading cause of death in Europe. An understanding of region-specific factors is essential for informing strategies to improve survival. DesignThis retrospective observational study included all out-of-hospital cardiac arrest patients attended by the Emergency Medical Service of the Algarve in 2019. Outcome data were derived from hospital records. Main resultsIn 2019, there were 850 out-of-hospital cardiac arrests treated with cardiopulmonary resuscitation in the Algarve, representing a population incidence of 189/100 000. Return of spontaneous circulation occurred in 83 patients (9.8%), of whom 17 (2.0%) had survival to hospital discharge and 15 (1.8%) had survival with good neurologic outcome. Among patients in the Utstein comparator group, survival to hospital discharge was 21.4%. Predictors of return of spontaneous circulation were age, witnessed arrest, initial shockable rhythm, time of year, time to cardiopulmonary resuscitation, and time to advanced life support. Predictors of survival to hospital discharge were age, initial shockable rhythm, time to rhythm analysis, and time to advanced life support. Predictors of survival with good neurologic outcome were age, initial shockable rhythm, and time to return of spontaneous circulation. ConclusionsThe incidence of out-of-hospital cardiac arrest with cardiopulmonary resuscitation in the Algarve was higher than in other jurisdictions while return of spontaneous circulation, survival to hospital discharge, and survival with good neurologic outcome were comparatively low. An aging population, a geographically diverse region, and a low incidence of bystander cardiopulmonary resuscitation may have contributed to these outcomes. These results confirm the importance of early cardiopulmonary resuscitation, early rhythm assessment, and early advanced life support, all of which are potentially modifiable through public education, broadening of the defibrillator network and increased availability of advanced life support teams.
- Prediction of short-term prognosis in elderly patients with spontaneous intracerebral hemorrhagePublication . Batista, António; Osório, Rui; Varela, Ana; Guilherme, Patrícia; Marreiros, Ana; Pais, Sandra; Nzwalo, HipólitoAim The incidence of spontaneous intracerebral hemorrhage (SICH) increases with age. Data on SICH mortality in the very old are sparse. We aimed to describe the predictors of 30-day SICH mortality in the very elderly in southern Portugal. Methods A total of 256 community representative SICH patients aged >= 75 years (2009-2016) were included. Multiple logistic regression was used to identify predictors of 30-day mortality. Results Mean age was 82.1 years; 57.4% males. The 30-day case fatality was 38.7%. The frequency of patients taking anticoagulants (29.3% vs. 11.5%); comatose (46.9% vs. 2.5%); with hematoma volume >= 30 mL (64.6% vs. 13.4%); intraventricular dissection (78.8% vs. 27.4%) was higher in deceased patients (p < 0.05). Survivors were more often admitted to stroke unit (SU) (68.2 vs. 31.3%) and had lower mean admission glycaemia values (p < 0.05). The likelihood of death was increased in patients with higher admission hematoma volume (>= 30 mL) (OR: 8.817, CI 1.753-44.340, p = 0.008) and with prior to SICH history of >= 2 hospitalizations OR = 1.022, CI 1.009-1.069, p = 0.031). Having higher Glasgow coma scale score, OR: 0.522, CI 0.394-0.692, p < 0.001, per unit was associated with reduced risk of death. Age was not an independent risk factor of short-term death. Conclusions The short-term mortality is high in very elderly SICH. Prior to SICH history of hospitalization, an indirect and gross marker of coexistent functional reserve, not age per se, increases the risk of short-term death. Other predictors of short-term death are potentially manageable reinforcing the message against any defeatist attitude toward elderly patients with SICH. Key summary pointsAim Identification of predictors of short-term death after spontaneous intracerebral hemorrhage (SICH) in the elderly. Findings The short-term case fatality (38.7%) after SICH is high in the elderly. Hematoma volume, decreased level of consciousness and functional reserve, but not age per se, increase the risk of short-term death. Message Age per se should not justify any decision of withholding best treatment in elderly SICH patients. Offering the best acute treatment can potentially improve the clinical outcome.
- Predictors of pneumonia in patients with acute spontaneous intracerebral hemorrhage in Algarve, Southern PortugalPublication . Soares, Rita; Fernandes, Adriana; Taveira, Isabel; Marreiros, Ana; Nzwalo, HipólitoIntroduction: Following the hyperacute phase of spontaneous intracerebral hemorrhage (SICH), the severest form of stroke, pneumonia emerges as the leading cause of morbidity and mortality. Prevention of stroke associated pneumonia (SAP) is fundamental to improve the prognosis of SICH patients. Aim: Identify clinical, sociodemographic and process of care factors associated with occurrence of SAP after SICH in Algarve, southern Portugal. Methods: Observational, retrospective study of community representative consecutive case series of patients with SICH admitted to the sole public hospital in the region. Logistic regression was used to identify predictors of SAP after SICH. Results: A total of 525 patients were included. The mean age was 71 ( +/- 13) years and 64% were men. SAP occurred in 165 (31.5%). Lower Glasgow Coma Scale score (GCS score): <= 8 (OR= 2.087; 95% CI= [1.027;4.424]; p = 0.042) and GCS 9-12 (OR= 1.775; 95% CI= [1.030;3.059]; p = 0.039); prolonged emergency room stay (OR= 8.066; 95%CI=[3.082;21.113]; p < 0.001) and hyperactive delirium (OR=2.860; 95% CI= [1.661;4.925]; p < 0.001) increased the likelihood of SAP. Being younger, = 59 years (OR= 0.391; 95% CI= [0.168; 0.911]; p = 0.029) and 60-71 years (OR= 0.389; 95% CI= [0.185; 0.818]; p = 0.013); and having less severe SICH/intracerebral hemorrhage score (ICH score) <= 2 (OR=0.601; 95% CI= [0.370; 0.975]; p = 0.039), decreased the risk of SAP. Conclusion: After SICH, SAP occurs in approximately a third of patients. Non preventable (admission severity, ageing) and potentially preventable (prolonged emergency room stay, hyperactive delirium) determine the occurrence of SAP. Intensification of preventive intervention in high-risk patients, delirium prevention and improvement of the process of care can potentially reduce the occurrence of SAP after SICH.
- 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.
- 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.
- Long‐term association between disease activity and disability in early axial Spondyloarthritis: Results from a prospective observational study of inflammatory back painPublication . PD, Carvalho; Ruyssen‐Witrand, Adeline; Marreiros, Ana; Machado, Pedro M.Objective Our primary objective was to study the long-term association between disease activity and disability in axial spondyloarthritis (SpA). Our secondary objective was to define patient profiles according to their level of disability. Methods We analyzed data collected during the first 5 years of follow-up of a large early axial SpA cohort, the Devenir des Spondylarthropathies Indifferenciees Recentes (DESIR) cohort. Multivariable models were built to study the association between the Health Assessment Questionnaire for Ankylosing Spondylitis (HAQ-AS) and the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), adjusting for potential confounders. Hierarchical multivariable analysis was conducted using the chi-square automatic interaction detector (CHAID) method, to help determine how variables best cluster to explain HAQ-AS. Results Data from 644 patients and 5,152 visits were analyzed. HAQ-AS was longitudinally, independently, and positively associated with ASDAS-CRP (adjusted B [adjB] 0.205 [95% confidence interval (95% CI) 0.187, 0.222]), the enthesitis score (adjB 0.011 [95% CI 0.008, 0.015]), the Bath Ankylosing Spondylitis Metrology Index (adjB 0.087 [95% CI 0.069, 0.105]), and female sex (adjB 0.172 [95% CI 0.120, 0.225]). The CHAID decision tree revealed ASDAS-CRP as the first variable with discriminative power on HAQ-AS. The cutoffs that separated different patient disability profiles were obtained. Conclusion Disease activity contributes longitudinally to disability and is hierarchically superior to any other variable in explaining this health domain. Enthesitis and spinal mobility are also key drivers of disability in early axial SpA. ASDAS-CRP cutoffs that separated different patient disability profiles largely mimicked the cutoffs previously defined for ASDAS-CRP disease activity states.
- 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.
- Evaluation of MGP 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; Leonor Cancela, M.Purpose: Matrix Gla protein (MGP) is a vitamin K-dependent, gamma-carboxylated protein that was initially found to be a physiological inhibitor of ectopic calcifications affecting mainly cartilage and the vascular system. Mutations in the MGP gene were found to be responsible for a human pathology, the Keutel syndrome, characterized by abnormal calcifications in cartilage, lungs, brain and vascular system. MGP was recently implicated in tumorigenic processes such as angiogenesis and shown to be abnormally regulated in several tumors, including cervical, ovarian, urogenital and breast. This fact has triggered our interest in analyzing the expression of MGP and of its regulator, the transcription factor runt related transcription factor 2 (RUNX2), in colorectal cancer (CRC). Methods: MGP and RUNX2 expression were analyzed in cancer and non-tumor biopsies samples from 33 CRC patients and 9 healthy controls by RT-qPCR. Consequently, statistical analyses were performed to evaluate the clinical-pathological significance of MGP and RUNX2 in CRC. MGP protein was also detected by immunohistochemical analysis. Results: Showed an overall overexpression of MGP in the tumor mucosa of patients at mRNA level when compared to adjacent normal mucosa and healthy control tissues. In addition, analysis of the expression of RUNX2 mRNA demonstrated an overexpression in CRC tissue samples and a positive correlation with MGP expression (Pearson correlation coefficient 0.636; p <= 0.01) in tumor mucosa. However correlations between MGP gene expression and clinical-pathological characteristics, such as gender, age and pathology classification did not provide relevant information that may shed light towards the differences of MGP expression observed between normal and malignant tissue. Conclusions: We were able to associate the high levels of MGP mRNA expression with a worse prognosis and survival rate lower than five years. These results contributed to improve our understanding of the molecular mechanism underlying MGP deregulation in cancer.
- Short Inflammatory Bowel Disease Questionnaire: translation and validation to the Portuguese languagePublication . Roseira, Joana; Sousa, Helena Tavares; Marreiros, Ana; Contente, Luís F.; Magro, FernandoBackground The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a widely used instrument to assess Health-related Quality of Life (HRQoL) among inflammatory bowel disease (IBD) patients. Our aim was to translate and adapt the SIBDQ so that it could be adequately used in Portugal. Methods This is a prospective design cohort study undertaken at a tertiary hospital. This study took place simultaneously with the first part of the SexIDI study, a study aiming to assess the impact of IBD on patients’ sexual QoL. The original SIBDQ was translated by two independent translators and adapted by an IBD expert panel following the opinions of a convenient sample of 5 IBD patients. Afterwards, IBD patients from the outpatient clinic were consecutively invited to fill the Portuguese version of the questionnaire (SIBDQ-PT) at three different timepoints (0, 2, 4 weeks). Ninety-two patients completed the SIBDQ-PT at baseline, whereas 33 did so after 2 and 4 weeks (approximately). Statistical analysis was performed using SPSS version 25, and the following aspects were analysed: reliability (through internal consistency, test–retest and intraclass correlation), validity (through exploratory factor analysis [EFA], and Pearson correlation coefficient for linear correlations), score distribution, and responsiveness analysis (through t-student tests). Results Overall, SIBDQ-PT was shown to have a high internal consistency (Cronbach's α = 0.80) and a high test–retest reliability (0.80 [CI 0.74–0.86] and 0.69 [CI 0.50–0.82]). EFA detected four dimensions—bowel, social, emotional and systemic. As expected, an overall SIBDQ-PT score was positively correlated with sexual satisfaction (r = 0.27; p < 0.05) and negatively correlated with depression (r = − 0.63; p < 0.01). Moreover, SIBDQ-PT was found to have an adequate score distribution, and to be responsive, as there was a significant subscore change for patients who reported an “overall worsening in general well-being” (0.93 ± 0.13 decrease; p < 0.01). Conclusions The Portuguese version of the SIBDQ hereby presented is a reliable, valid and responsive instrument that can be used to measure HRQoL among Portuguese IBD patients.