Publications by authors named "Catarina Vieira"

43 Publications

Pelvic floor dysfunction after vaginal delivery: MOODS-a prospective study.

Int Urogynecol J 2021 Sep 25. Epub 2021 Sep 25.

Department of Obstetrics and Gynecology, Hospital de Braga, Sete Fontes - São Victor, 4710-243, Braga, Portugal.

Introduction And Hypothesis: Labor is a known risk factor for pelvic floor dysfunction (PFD); however, the impact of operative vaginal delivery (OVD), particularly spatulas, remains unclear. The aim of this study was to compare postpartum PFD symptoms in women undergoing spontaneous vaginal delivery (SVD) and those undergoing OVD.

Methods: An observational prospective study (MOODS: Maternal-neonatal Outcomes in Operative Vaginal Delivery) was enrolled at Hospital de Braga from February to October 2018. All singleton term OVD (Thierry spatulas and vacuum extractor) and a convenience SVD sample were recruited, in a 2:1 ratio. To assess PFD symptoms Pelvic Floor Distress Inventory-20 (PFDI-20) was applied at 3, 6, and 12 months postpartum. The questionnaire is divided into three subscales: Urinary (UDI), Colorectal-Anal (CRADI), and Pelvic Organ Prolapse Distress Inventory (POPDI).

Results: Of the 304 women recruited, 207 were included, 34.3% with SVD and 65.7% with OVD. Thierry spatulas were used in 53.7% of women undergoing OVD. Frequency of nulliparous (p < 0.001), episiotomy (p < 0.001), neuraxial anesthesia (p < 0.001), postpartum pain (p = 0.001) and occiput-posterior fetal position (p < 0.001) were significantly higher in OVD. Second phase of labor duration was longer in OVD (p = 0.001). At 3 months postpartum, women undergoing OVD and spatula-assisted delivery had higher UDI score, POPDI score, and global score, with no differences at 6 months and 1 year. After controlling for confounding variables, OVD and spatulas were still associated with greater POPDI scores at 3 months postpartum.

Conclusions: Operative vaginal delivery, particularly with spatulas, seems to be associated with a higher prevalence of early PFD symptoms, mainly regarding pelvic organ prolapse.
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http://dx.doi.org/10.1007/s00192-021-04982-wDOI Listing
September 2021

Serious Game Design and Clinical Improvement in Physical Rehabilitation: Systematic Review.

JMIR Serious Games 2021 Sep 23;9(3):e20066. Epub 2021 Sep 23.

Research Center for Science and Technology of the Arts, Universidade Católica Portuguesa, Porto, Portugal.

Background: Serious video games have now been used and assessed in clinical protocols, with several studies reporting patient improvement and engagement with this type of therapy. Even though some literature reviews have approached this topic from a game perspective and presented a broad overview of the types of video games that have been used in this context, there is still a need to better understand how different game characteristics and development strategies might impact and relate to clinical outcomes.

Objective: This review assessed the relationship between the characteristics of serious games (SGs) and their relationship with the clinical outcomes of studies that use this type of therapy in motor impairment rehabilitation of patients with stroke, multiple sclerosis, or cerebral palsy. The purpose was to take a closer look at video game design features described in the literature (game genre [GG], game nature [GN], and game development strategy [GDS]) and assess how they may contribute toward improving health outcomes. Additionally, this review attempted to bring together medical and game development perspectives to facilitate communication between clinicians and game developers, therefore easing the process of choosing the video games to be used for physical rehabilitation.

Methods: We analyzed the main features of SG design to obtain significant clinical outcomes when applied to physical rehabilitation of patients recovering from motor impairments resulting from stroke, multiple sclerosis, and cerebral palsy. We implemented a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) database-adjusted electronic search strategy for the PubMed, IEEE Xplore, and Cochrane databases.

Results: We screened 623 related papers from 2010-2021 and identified 12 that presented results compatible with our inclusion criteria. A total of 512 participants with stroke (8 studies, 417 participants), cerebral palsy (1 study, 8 participants), and multiple sclerosis (2 studies, 46 participants) were included; 1 study targeting the elderly (41 participants) was also included. All studies assessed motor, sensory, and functional functions, while some also measured general health outcomes. Interventions with games were used for upper-limb motor rehabilitation. Of the 12 studies, 8 presented significant improvements in at least one clinical measurement, of which 6 presented games from the casual GG, 1 combined the casual, simulation, and exergaming GGs, and 2 combined the sports and simulation GGs.

Conclusions: Of the possible combinations of game design features (GG, GN, and GDS) described, custom-made casual games that resort to the first-person perspective, do not feature a visible player character, are played in single-player mode, and use nonimmersive virtual reality attain the best results in terms of positive clinical outcomes. In addition, the use of custom-made games versus commercial off-the-shelf games tends to give better clinical results, although the latter are perceived as more motivating and engaging.
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http://dx.doi.org/10.2196/20066DOI Listing
September 2021

Laparoscopic pelvic and lumbo-aortic lymphadenectomy and hysterectomy by total left lateral approach.

Int J Gynecol Cancer 2021 Sep 17. Epub 2021 Sep 17.

Department of Obstetrics and Gynecology, CHU Estaing Pôle Femmes et Enfants, Clermont-Ferrand, Auvergne-Rhône-Alpes, France.

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http://dx.doi.org/10.1136/ijgc-2021-002823DOI Listing
September 2021

Prognostic impact of iron deficiency in acute coronary syndromes.

Rev Port Cardiol (Engl Ed) 2021 Aug 27;40(8):525-536. Epub 2021 Jul 27.

Serviço de Cardiologia, Hospital de Braga, Braga, Portugal. Electronic address:

Background: Iron deficiency (IDef) is a prevalent condition in patients with heart disease and in those with heart failure (HF). Evidence has shown that this deficit is associated with worse prognosis. Data in literature are scarce on the prognostic impact of IDef in acute coronary syndromes (ACS), which is the main objective of this study.

Methods: Observational, retrospective study which included 817 patients admitted for ACS. Two groups were defined according to the presence (n=298) or absence of IDef (n=519) on admission. The clinical event under study was the occurrence of death or severe HF in the long term. Independent predictors of prognosis were determined with logistic regression analysis.

Results: Thirty-six percent of patients had IDef. There was higher mortality (p=0.004), higher incidence of HF (p=0.011) during follow-up and a higher rate of hospital readmissions (p=0.048) in this group. IDef was an independent predictor of death or severe HF in follow-up, along with anemia, left ventricular dysfunction, renal dysfunction and the absence of revascularization. IDef also enabled us to further stratify the prognosis of patients without anemia based on the occurrence of death or severe HF and those with lower Killip classes (≤2) based on the occurrence of death.

Conclusion: IDef was an independent predictor of death or severe HF in patients admitted with ACS and enabled additional stratification for those without anemia on admission and in those with Killip classes ≤2.
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http://dx.doi.org/10.1016/j.repce.2020.09.005DOI Listing
August 2021

Fabrication and modification of homemade paper-based electrode systems.

Talanta 2021 Mar 7;224:121861. Epub 2020 Nov 7.

BioMark/ISEP, School of Engineering of the Polytechnic Institute of Porto, Portugal; BioMark/UC, Department of Chemical Engineering, Faculty of Sciences and Technology, Coimbra University, Portugal. Electronic address:

This work reports the simple and inexpensive fabrication of homemade paper-based carbon-printed electrodes (HP C-PEs), aiming to produce an alternative way to generate electrochemical biosensors to all and promoting their wide use. This is especially important in times of pandemics, considering the excellent features of electrochemical biosensing, which may ensure portability, low-cost and quick responses. HP C-PEs were fabricated using a standard cellulose filter paper that was first modified with wax, to make it hydrophobic. Then, the electrodes were manually printed on top of this cellulose/wax substrate. The electrodes were designed by having standard configurations for potentiometric and electrochemical readings, combining two or three electrodes. In general, both electrode systems showed excellent electrochemical and mechanical features, which were better in specific cases than commercial devices. The 3-electrode system displayed high current levels with low peak-to-peak potential separation, yielding highly stable signals after consecutive electrode bending that corresponded to high active areas. The possibility of modifying the devices with polymers produced in-situ was also explored and proven successful, providing also advantageous features when compared to other devices. The 2-electrode system was also proven highly stable and capable of subsequent use in potentiometric sensing development. Overall, the fabrication process of the 2- and 3-electode systems described herein may be employed in laboratories to produce successful electrochemical biosensors, with the final devices displaying excellent electrochemical and mechanical features. This procedure offers the advantages of being simple and inexpensive, when compared to other commercial devices, while using materials that are promptly available and that may undergo a worldwide use.
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http://dx.doi.org/10.1016/j.talanta.2020.121861DOI Listing
March 2021

Consensus document on chronic coronary syndrome assessment and risk stratification in Portugal: A position paper statement from the [Portuguese Society of Cardiology's] Working Groups on Nuclear Cardiology, Magnetic Resonance and Cardiac Computed Tomography, Echocardiography, and Exercise Physiology and Cardiac Rehabilitation.

Rev Port Cardiol (Engl Ed) 2020 Dec 18. Epub 2020 Dec 18.

Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.

Despite constant medical evolution, the reimbursement policy of Portuguese National Health Service (NHS) for the study and risk stratification of coronary heart disease has remained unchanged for several decades. Lack of adjustment to contemporary clinical practice has long been evident. However, the recent publication of the European Guidelines for diagnosis and treatment of chronic coronary syndromes further highlighted this gap and the urgent need for a change. Prompted by these Guidelines, the Working Group on Nuclear Cardiology, Cardiac Magnetic Resonance and Cardiac CT, the Working Group on Echocardiography and the Working Group on Stress Pathophysiology and Cardiac Rehabilitation of the Portuguese Society of Cardiology, began a process of joint reflection on the current limitations and how these recommendations could be applied in Portugal. To this end, the authors suggest that the new imaging methods (stress echocardiogram, cardiac computed tomography and cardiac magnetic resonance), should be added to exercise treadmill stress test and myocardial perfusion scintigraphy in the available exam portfolio within the Portuguese NHS. This change would allow full adoption of European guidelines and a better use of tests, according to clinical context, availability and local specificities. The adoption of clinical guidance standards, based on these assumptions, would translate into a qualitative improvement in the management of these patients and would promote an effective use of the available resources, with potential health and financial gains.
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http://dx.doi.org/10.1016/j.repc.2020.10.009DOI Listing
December 2020

It Takes a Big Chamber to Disguise a Giant.

Circ Cardiovasc Imaging 2020 12 3;13(12):e010695. Epub 2020 Dec 3.

Department of Cardiology of Hospital de Braga, Portugal.

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http://dx.doi.org/10.1161/CIRCIMAGING.120.010695DOI Listing
December 2020

Pericardial agenesis: a rare cause of chest pain.

Eur Heart J 2021 01;42(3):282

Cardiology Department, Hospital de Braga, Sete Fontes - São Victor, 4710-243 Braga,, Portugal.

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http://dx.doi.org/10.1093/eurheartj/ehaa666DOI Listing
January 2021

A heart with red flags.

Int J Cardiovasc Imaging 2020 Sep 11;36(9):1749-1750. Epub 2020 May 11.

Cardiology Department, Hospital de Braga, Braga, Portugal.

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http://dx.doi.org/10.1007/s10554-020-01879-5DOI Listing
September 2020

Intrathecal Baclofen Infusion Pumps in the Treatment of Spasticity: A Retrospective Cohort Study in a Portuguese Centre.

Acta Med Port 2019 Dec 2;32(12):754-759. Epub 2019 Dec 2.

Department of Anaesthesiology. Centro Hospitalar São João. Porto. Portugal.

Introduction: Spasticity is a complex problem in patients with neurological disorders and may distress their quality of life. Intrathecal baclofen infusion pumps reduce spasticity with low doses and minimal side effects but are not free from complications. We aimed to evaluate the efficacy and safety of intrathecal baclofen infusion pumps as well as patients' satisfaction.

Material And Methods: Retrospective cohort study including all intrathecal baclofen infusion pumps placed up to December 2015. Demographic characteristics, clinical diagnoses, date of placement or withdrawal/replacement of intrathecal baclofen infusion pumps, baclofen dosage and complications of intrathecal baclofen infusion pumps were collected. Assessments from the Ashworth and Penn's scales, Katz index and patients' global satisfaction were analysed.

Results: In 19 years we placed 251 intrathecal baclofen infusion pumps in 155 patients. The mean age was 41.1 ± 15.8 years. The most frequent conditions were: trauma (34%), cerebral palsy (14%), multiple sclerosis (12%) and stroke (12%). Eighty-five patients (55%) required a second pump, and eleven (7%) a third one. The lifetime of the first pump was 72 (36 - 89) and the total follow-up time was 96 (9 - 132) months. The causes of withdrawal/replacement were: battery failure (57%), catheter migration/kinking (24%), infection (14%) and pump displacement/exteriorization (7%). The complication rate was 0.21 events/month. There was a significant improvement in the Ashworth and Penn's scales after the placemen of intrathecal baclofen infusion pumps (p < 0.001 for all diagnoses) and the patients were satisfied with the treatment.

Discussion: The incidence of complications was within range of other international studies despite our long follow-up time. Events per month, loss to follow-up, re-intervention rate, incidence of infection and mortality were similar to other studies.

Conclusion: Intrathecal baclofen infusion pumps are safe and effective in the treatment of spasticity. Infusion pumps provide a high level of satisfaction regarding treatment and quality of life.
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http://dx.doi.org/10.20344/amp.10482DOI Listing
December 2019

Apert syndrome: prenatal diagnosis challenge.

BMJ Case Rep 2019 Dec 9;12(12). Epub 2019 Dec 9.

Gynecology and Obstetrics, Hospital de Braga, Braga, Portugal.

Apert syndrome is a rare genetic disorder that manifests as craniosynostosis, craniofacial and limb dysmorphic features. Mutations in fibroblast growth factor receptor 2 (FGFR2) gene account for almost all cases. Given the impact it can have throughout life, prenatal management becomes a challenge. A healthy 33-year-old woman, gravida 4, para 0, was referred to routine ultrasound at 22 weeks of gestation. Atypical cranial morphology with prominent forehead, ocular proptosis, hypertelorism and mitten hands were detected. Genetic investigation revealed an FGFR2 gene mutation (c.755C>G(p.Ser252Trp)), confirming the diagnosis. Magnetic resonance showed brachycephaly, turricephaly and cortical malformation. Following counselling, parents requested medical termination of pregnancy. Macroscopic features were consistent with ultrasound findings. This case emphasises the importance of early diagnosis to provide the best family counselling and prenatal management. A multidisciplinary team, consisting of an obstetrician with ultrasonography experience, a medical geneticist and a fetal pathologist, should conduct these cases.
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http://dx.doi.org/10.1136/bcr-2019-231982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904201PMC
December 2019

Nonbacterial thrombotic endocarditis.

Rev Port Cardiol (Engl Ed) 2019 Jul 13;38(7):511-514. Epub 2019 Sep 13.

Serviço de Cardiologia e Medicina Interna, Hospital de Braga, Braga, Portugal.

An 83-year-old woman with a 10-year history of rheumatoid arthritis was admitted for urinary tract infection with exacerbation of chronic kidney disease and decompensated heart failure of unknown etiology. Transesophageal echocardiography (TEE) showed a vegetation involving the posterior mitral valve leaflet, and a hypothesis of infective endocarditis was proposed. Empirical antibiotic therapy was initiated. TEE was repeated after antibiotic therapy, and showed persistence of the original vegetation and revealed the presence of another, smaller vegetation. Clinical investigation revealed no infectious process, and so a diagnosis of nonbacterial thrombotic endocarditis (NBTE) was established. Anticoagulant therapy was started immediately. The NBTE lesion had disappeared on the follow-up echocardiogram two months after anticoagulant therapy.
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http://dx.doi.org/10.1016/j.repc.2018.05.021DOI Listing
July 2019

Dressler's syndrome: are we underdiagnosing what we think to be rare?

BMJ Case Rep 2019 May 21;12(5). Epub 2019 May 21.

Cardiology Department, Hospital de Braga, Braga, Portugal.

A 46-year-old man was admitted to the emergency department with fever and pleuritic thoracic pain. Six weeks prior to admission, the patient had undergone cardiac surgery. The ECG showed diffuse ST segment elevation and PR segment depression. The blood tests revealed increased inflammatory markers and negative myocardial necrosis markers. Pericardial and left-sided pleural effusion were noted. Sterile blood cultures were negative. Hence, the hypothesis of Dressler's syndrome was established. The patient improved clinically and analytically with a short course of anti-inflammatory therapy and was discharged with colchicine and acetylsalicylic acid. A thoracic radiography performed 2 months after showed complete remission of pleural effusion.
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http://dx.doi.org/10.1136/bcr-2018-227772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559812PMC
May 2019

Pulmonary arteriovenous malformation in hereditary haemorrhagic telangiectasia.

BMJ Case Rep 2019 Feb 9;12(2). Epub 2019 Feb 9.

Centro Hospitalar Barreiro Montijo EPE, Barreiro, Portugal.

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http://dx.doi.org/10.1136/bcr-2018-228456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441247PMC
February 2019

An Unusual Cause of Aborted Sudden Cardiac Death in a Middle-Aged Female Marathoner.

Can J Cardiol 2018 09 2;34(9):1233.e9-1233.e11. Epub 2018 Aug 2.

Department of Cardiothoracic Surgery, Hospital S. João, Porto, Portugal.

Although most congenital coronary artery anomalies have no prognostic implications, associations with sudden cardiac death have been described, particularly in the young. We report an exercise-associated collapse in an otherwise asymptomatic middle-aged female marathoner. The aborted sudden cardiac death approach revealed an unexpected initial presentation of a malignant anomalous left main coronary artery origin, with ostial stenosis and interarterial course. The present case illustrates an unusually longstanding coexistence of a malignant anatomical variant with a persistent trigger.
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http://dx.doi.org/10.1016/j.cjca.2018.05.012DOI Listing
September 2018

Modified shock index: A bedside clinical index for risk assessment of ST-segment elevation myocardial infarction at presentation.

Rev Port Cardiol (Engl Ed) 2018 Jun 26;37(6):481-488. Epub 2018 May 26.

Cardiology Department, Braga Hospital, Braga, Portugal.

Introduction: Prompt identification of higher-risk patients presenting with ST-segment elevation myocardial infarction (STEMI) is crucial to pursue a more aggressive approach.

Objective: We aimed to assess whether the modified shock index (MSI), the ratio of heart rate to mean arterial pressure, could predict six-month mortality among patients admitted with STEMI.

Methods: A retrospective observational cohort study was performed in a single center including 1158 patients diagnosed with STEMI, without cardiogenic shock on admission, between July 2009 and December 2014. They were divided into two groups: group 1 - patients with MSI<0.93 (72%); group 2 - patients with MSI≥0.93 (28%). The primary endpoint was six-month all-cause mortality.

Results: MSI≥0.93 identified patients who were more likely to have signs of heart failure (p=0.002), anemia (p<0.001), renal insufficiency (p=0.014) and left ventricular systolic dysfunction (p=0.045). They more often required inotropic support (p<0.001), intra-aortic balloon pump (p<0.001) and mechanical ventilation (p<0.001). Regarding in-hospital adverse events, they had a higher prevalence of malignant arrhythmias (p=0.01) and mechanical complications (p=0.027). MSI≥0.93 was an independent predictor of overall six-month mortality (adjusted HR 2.00, 95% CI 1.20-3.34, p=0.008).

Conclusion: MSI was shown to be a valuable bedside tool which can rapidly identify high-risk STEMI patients at presentation.
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http://dx.doi.org/10.1016/j.repc.2017.07.018DOI Listing
June 2018

Iatrogenic aortic dissection - Follow the image!

Rev Port Cardiol (Engl Ed) 2018 Jan 19;37(1):91-92. Epub 2017 Dec 19.

Cardiology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Espinho, Portugal.

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http://dx.doi.org/10.1016/j.repc.2017.02.018DOI Listing
January 2018

Isolated right ventricular infarction following aortic valve replacement.

BMJ Case Rep 2017 Apr 3;2017. Epub 2017 Apr 3.

Cardiology Department, Hospital de Braga, Braga, Portugal.

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http://dx.doi.org/10.1136/bcr-2016-218811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388009PMC
April 2017

An unusual trigger causing Takotsubo Syndrome.

Int J Cardiol 2016 Nov 9;223:118-120. Epub 2016 Aug 9.

Cardiology Department, Hospital de Braga, Braga, Portugal.

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http://dx.doi.org/10.1016/j.ijcard.2016.08.162DOI Listing
November 2016

[Portuguese Consensus on the Diagnosis, Prevention and Treatment of Anaemia in Inflammatory Bowel Disease].

Acta Med Port 2016 Feb 29;29(2):144-56. Epub 2016 Feb 29.

Grupo de Estudo da Doença Inflamatória Intestinal. Lisboa. Serviço de Gastrenterologia. Hospital de Santa Maria. Centro Hospitalar Lisboa Norte. Lisboa.

Introduction: Anaemia can be considered the most common extra-intestinal manifestation in inflammatory bowel disease. Nevertheless, anaemia is often under-diagnosed and under-treated both in adults and children with inflammatory bowel disease. Herein, we report the consensus statements on the management of anaemia in inflammatory bowel disease developed by the Portuguese Working Group on Inflammatory Bowel Disease (known as Grupo de Estudo da Doença Inflamatória Intestinal - GEDII) to aid clinicians in daily management of inflammatory bowel disease patients.

Material And Methods: A comprehensive literature review was conducted in order to prepare consensus statements on the following topics: (1) prevalence and diagnosis of anaemia in inflammatory bowel disease, (2) iron supplementation for the prevention of anaemia in inflammatory bowel disease and (3) treatment of anaemia in inflammatory bowel disease. The final statements for each topic were discussed at a consensus meeting and rated according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.

Consensus: It was concluded that anaemia has a high incidence and prevalence in inflammatory bowel disease, particularly in those with active disease and hospitalised. Patients with anaemia had decreased quality of life and frequently complained of fatigue. Absolute indications for intravenous therapy should be considered: (1) moderate to severe anaemia (haemoglobin < 10.5 g/dL) or clearly symptomatic anaemia; (2) previous intolerance to oral iron supplements; (3) inappropriate response to oral iron; (4) active severe intestinal disease; (5) need for a quick therapeutic response (e.g. surgery in the short term); (6) concomitant therapy with erythropoiesis-stimulating agent; and (7) patient's preference.
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http://dx.doi.org/10.20344/amp.6058DOI Listing
February 2016

Isolated right ventricular infarction: a diagnostic challenge.

BMJ Case Rep 2016 May 3;2016. Epub 2016 May 3.

Department of Cardiology, Braga Hospital, Braga, Portugal.

A 73-year-old woman was admitted to the emergency room due to sudden-onset dyspnoea, altered mental status and haemodynamic instability. ECG showed a junctional rhythm, T-wave inversion in I, aVL and V2-V6 (present in a previous ECG), and no ST/T changes in the right precordial leads. Transthoracic echocardiography, however, revealed a severe depression of global systolic function of right ventricle with akinesia of free wall and a normal left ventricular function. Coronary angiography showed an occlusion of the proximal segment of the right coronary artery, which was treated with balloon angioplasty, and a chronic lesion of the anterior descending artery. The patient had a good recovery and was discharged on the 14th day. Myocardial perfusion scintigraphy (stress and rest) was performed a month later, showing a fixed perfusion defect in the apex and anterior wall (medium-apical), with no signs of ischaemia.
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http://dx.doi.org/10.1136/bcr-2016-215338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885266PMC
May 2016

MiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3.

Cell Rep 2015 Sep 28;12(10):1594-605. Epub 2015 Aug 28.

Stem Cells & Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid 28028, Spain; Stem Cells in Cancer & Ageing, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK. Electronic address:

Conquering obesity has become a major socioeconomic challenge. Here, we show that reduced expression of the miR-25-93-106b cluster, or miR-93 alone, increases fat mass and, subsequently, insulin resistance. Mechanistically, we discovered an intricate interplay between enhanced adipocyte precursor turnover and increased adipogenesis. First, miR-93 controls Tbx3, thereby limiting self-renewal in early adipocyte precursors. Second, miR-93 inhibits the metabolic target Sirt7, which we identified as a major driver of in vivo adipogenesis via induction of differentiation and maturation of early adipocyte precursors. Using mouse parabiosis, obesity in mir-25-93-106b(-/-) mice could be rescued by restoring levels of circulating miRNA and subsequent inhibition of Tbx3 and Sirt7. Downregulation of miR-93 also occurred in obese ob/ob mice, and this phenocopy of mir-25-93-106b(-/-) was partially reversible with injection of miR-93 mimics. Our data establish miR-93 as a negative regulator of adipogenesis and a potential therapeutic option for obesity and the metabolic syndrome.
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http://dx.doi.org/10.1016/j.celrep.2015.08.006DOI Listing
September 2015

Impact of atrial fibrillation type during acute coronary syndromes: Clinical features and prognosis.

Rev Port Cardiol 2015 Jun 29;34(6):403-10. Epub 2015 May 29.

Serviço de Cardiologia, Hospital de Braga, Braga, Portugal.

Introduction: Atrial fibrillation (AF) is widely recognized as an adverse prognostic factor during acute myocardial infarction, although the impact of AF type - new-onset (nAF) or pre-existing (pAF) - is still controversial.

Objectives: To identify the clinical differences and prognosis of nAF and pAF during acute coronary syndromes (ACS).

Methods: We performed a retrospective observational cohort study including 1373 consecutive patients (mean age 64 years, 77.3% male) admitted to a single center over a three-year period, with a six-month follow-up.

Results: AF rhythm was identified in 14.5% patients, of whom 71.4% presented nAF and 28.6% pAF. When AF types were compared, patients with nAF more frequently presented with ST-elevation ACS (p=0.003). Patients with pAF, in turn, were older (p=0.032), had greater left atrial diameter (p=0.001) and were less likely to have significant coronary lesions (p=0.034). Regarding therapeutic strategy, nAF patients were more often treated by rhythm control during hospital stay (p<0.001) and were less often anticoagulated at discharge (p=0.001). Compared with the population without AF, nAF was a predictor of death during hospital stay in univariate (p<0.001) and multivariate analysis (OR 2.67, p=0.047), but pAF was not. During follow-up, pAF was associated with higher mortality (p=0.014), while nAF patients presented only a trend towards worse prognosis.

Conclusions: AF during the acute phase of ACS appears to have a negative prognostic impact only in patients with nAF and not in those with pAF.
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http://dx.doi.org/10.1016/j.repc.2015.01.010DOI Listing
June 2015

Nicotine promotes initiation and progression of KRAS-induced pancreatic cancer via Gata6-dependent dedifferentiation of acinar cells in mice.

Gastroenterology 2014 Nov 12;147(5):1119-33.e4. Epub 2014 Aug 12.

Stem Cells and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Centre for Stem Cells in Cancer & Ageing, Barts Cancer Institute, Queen Mary University of London, UK. Electronic address:

Background & Aims: Although smoking is a leading risk factor for pancreatic ductal adenocarcinoma (PDAC), little is known about the mechanisms by which smoking promotes initiation or progression of PDAC.

Methods: We studied the effects of nicotine administration on pancreatic cancer development in Kras(+/LSLG12Vgeo);Elas-tTA/tetO-Cre (Ela-KRAS) mice, Kras(+/LSLG12D);Trp53+/LSLR172H;Pdx-1-Cre (KPC) mice (which express constitutively active forms of KRAS), and C57/B6 mice. Mice were given nicotine for up to 86 weeks to produce blood levels comparable with those of intermediate smokers. Pancreatic tissues were collected and analyzed by immunohistochemistry and reverse transcriptase polymerase chain reaction; cells were isolated and assayed for colony and sphere formation and gene expression. The effects of nicotine were also evaluated in primary pancreatic acinar cells isolated from wild-type, nAChR7a(-/-), Trp53(-/-), and Gata6(-/-);Trp53(-/-) mice. We also analyzed primary PDAC cells that overexpressed GATA6 from lentiviral expression vectors.

Results: Administration of nicotine accelerated transformation of pancreatic cells and tumor formation in Ela-KRAS and KPC mice. Nicotine induced dedifferentiation of acinar cells by activating AKT-ERK-MYC signaling; this led to inhibition of Gata6 promoter activity, loss of GATA6 protein, and subsequent loss of acinar differentiation and hyperactivation of oncogenic KRAS. Nicotine also promoted aggressiveness of established tumors as well as the epithelial-mesenchymal transition, increasing numbers of circulating cancer cells and their dissemination to the liver, compared with mice not exposed to nicotine. Nicotine induced pancreatic cells to acquire gene expression patterns and functional characteristics of cancer stem cells. These effects were markedly attenuated in K-Ras(+/LSL-G12D);Trp53(+/LSLR172H);Pdx-1-Cre mice given metformin. Metformin prevented nicotine-induced pancreatic carcinogenesis and tumor growth by up-regulating GATA6 and promoting differentiation toward an acinar cell program.

Conclusions: In mice, nicotine promotes pancreatic carcinogenesis and tumor development via down-regulation of Gata6 to induce acinar cell dedifferentiation.
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http://dx.doi.org/10.1053/j.gastro.2014.08.002DOI Listing
November 2014

Thromboembolic risk in atrial fibrillation: association between left atrium mechanics and risk scores. A study based on 3D wall-motion tracking technology.

Echocardiography 2015 Apr 5;32(4):644-53. Epub 2014 Aug 5.

Cardiology Department, Hospital Clínico San Carlos, Madrid, Spain.

Background/objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a significantly high risk of stroke and systemic embolism. The aim of our study was to assess the association between left atrium (LA) mechanics measured by 3D wall-motion tracking (3DWMT) technology and the most common thromboembolic risk scores (CHADS2, CHA2DS2-VASc).

Methods: A total of 101 consecutive patients with permanent AF referred were included. Conventional bidimensional (2D) LA parameters, and LA mechanics by means of 3DWMT were studied. Association between LA 2D and 3DWMT parameters and both risk scores was evaluated as well as its correlation with every component of the score individually.

Results: Mean age was 78 ± 10 years. Mean CHADS2 was 2.7 ± 1.3 and mean CHA2DS2-VASc was 4.4 ± 1.7. Values of 2D and 3DWTM LA parameters were: 2D area 26.4 ± 9.7 cm(2) , 2D volume index 49.4 ± 10.1 mL/m(2) , 3DWMT left atrial emptying fraction (LAEF) 15.9 ± 8.4%, longitudinal strain 9.1 ± 4.5% and area strain 14.9 ± 8.8%. Linear regression analysis showed statistically significant correlation between LA longitudinal strain and LAEF with CHADS2 and CHA2DS2-VASc scores. For each 10% variation in longitudinal strain, CHADS2 and CHA2DS2-VASc scores change in 0.7 and 0.8 points, respectively.

Conclusions: Left atrial longitudinal strain and emptying fraction assessed by 3D WMT technology have correlation with both CHADS2 and CHA2DS2-VASc scores. Each 10% of variation in longitudinal strain represents a 0.7 and 0.8 points change in those risk scores. LA mechanics evaluation might provide additional value to risk scores and could be considered to be a predictor of stroke in patients with AF.
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http://dx.doi.org/10.1111/echo.12711DOI Listing
April 2015

New-onset atrial fibrillation during acute coronary syndromes: predictors and prognosis.

Rev Port Cardiol 2014 May 13;33(5):281-7. Epub 2014 Jun 13.

Serviço de Cardiologia, Hospital de Braga, Braga, Portugal.

Introduction: New-onset atrial fibrillation (AF) frequently complicates myocardial infarction, with an incidence of 6-21%.

Objective: To assess the predictors and prognosis of new-onset AF during acute coronary syndromes (ACS).

Methods: We performed a retrospective observational cohort study including 902 consecutive patients (mean age 64 years, 77.5% male) admitted to a single center over a two-year period, with a six-month follow-up.

Results: AF rhythm was identified in 13.8% patients, of whom 73.3% presented new-onset AF and 26.8% pre-existing AF. New-onset AF was more frequent in older (p<0.001) and hypertensive patients (p=0.001) and in those with previous valvular heart disease (p<0.001) and coronary artery bypass grafting (p=0.049). During hospitalization, patients with new-onset AF more often had respiratory infection (p=0.002) and heart failure (p<0.001), and higher values of NT-proBNP (p=0.007) and peak creatinine (p=0.001). On echocardiography they had greater left atrial (LA) diameter (p<0.001) and more frequent significant mitral regurgitation (p<0.001) and left ventricular ejection fraction (LVEF) ≤40% (p<0.001) and were less likely to have significant coronary lesions (p=0.009) or to have undergone coronary revascularization (p<0.001). In multivariate analysis, age (OR 1.06, p=0.021), LVEF ≤40% (OR 4.91, p=0.002) and LA diameter (OR 1.14, p=0.008) remained independent predictors of new-onset AF. Together with age, diabetes and maximum Killip class, this arrhythmia was an independent predictor of overall mortality (OR 3.11, p=0.032).

Conclusions: Age, LVEF ≤40% and LA diameter are independent predictors of new-onset AF during ACS. This arrhythmia is associated with higher overall mortality (in-hospital and in follow-up).
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http://dx.doi.org/10.1016/j.repc.2013.10.017DOI Listing
May 2014

Chloroquine targets pancreatic cancer stem cells via inhibition of CXCR4 and hedgehog signaling.

Mol Cancer Ther 2014 Jul 30;13(7):1758-71. Epub 2014 Apr 30.

Authors' Affiliations: Stem Cells & Cancer Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO); Barts Cancer Institute, Queen Mary University of London, London, United Kingdom

Pancreatic ductal adenocarcinoma is one of the deadliest carcinomas and is characterized by highly tumorigenic and metastatic cancer stem cells (CSC). CSCs evade available therapies, which preferentially target highly proliferative and more differentiated progenies, leaving behind CSCs as a putative source for disease relapse. Thus, to identify potentially more effective treatment regimens, we screened established and new compounds for their ability to eliminate CSCs in primary pancreatic cancer (stem) cells in vitro and corresponding patient-derived pancreatic cancer tissue xenografts in vivo. Intriguingly, we found that in vitro treatment with the antimalarial agent chloroquine significantly decreased CSCs, translating into diminished in vivo tumorigenicity and invasiveness in a large panel of pancreatic cancers. In vivo treatment in combination with gemcitabine was capable of more effectively eliminating established tumors and improved overall survival. The inhibitory effect of chloroquine was not related to inhibition of autophagy, but was due to inhibition of CXCL12/CXCR4 signaling, resulting in reduced phosphorylation of ERK and STAT3. Furthermore, chloroquine showed potent inhibition of hedgehog signaling by decreasing the production of Smoothened, translating into a significant reduction in sonic hedgehog-induced chemotaxis and downregulation of downstream targets in CSCs and the surrounding stroma. Our study demonstrates that via to date unreported effects, chloroquine is an effective adjuvant therapy to chemotherapy, offering more efficient tumor elimination and improved cure rates. Chloroquine should be further explored in the clinical setting as its success may help to more rapidly improve the poor prognosis of patients with pancreatic cancer.
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http://dx.doi.org/10.1158/1535-7163.MCT-13-0948DOI Listing
July 2014

Multimarker approach with cystatin C, N-terminal pro-brain natriuretic peptide, C-reactive protein and red blood cell distribution width in risk stratification of patients with acute coronary syndromes.

Rev Port Cardiol 2014 Mar 24;33(3):127-36. Epub 2014 Mar 24.

Department of Cardiology of Hospital de Braga, Braga, Portugal.

Introduction And Aim: Biomarkers have emerged as interesting predictors of risk in patients with acute coronary syndromes (ACS). The aim of this study was to determine the utility of the combined measurement of cystatin C (CysC), C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and red blood cell distribution width (RDW) in the risk stratification of patients with ACS.

Methods: In this prospective study including 682 patients consecutively admitted to a coronary care unit for ACS, baseline measurements of CysC, CRP, NT-proBNP and RDW were performed. Patients were categorized on the basis of the number of elevated biomarkers at presentation. The primary outcome was 6-month mortality.

Results: The number of biomarkers elevated on admission (study score) was an independent predictor of 6-month mortality; patients with four biomarkers elevated on admission had a significantly higher risk of 6-month mortality compared with patients with none or one. In addition, in patients with high risk defined by the GRACE score, our multimarker score was able to further categorize their risk of 6-month mortality.

Conclusions: A multimarker approach using CysC, NT-proBNP, CRP and RDW was an independent predictor of 6-month mortality and added prognostic information to the GRACE risk score in patients with ACS and high risk defined by GRACE, with increasing mortality in patients with a higher number of elevated biomarkers on admission.
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http://dx.doi.org/10.1016/j.repc.2013.09.013DOI Listing
March 2014

Anomalous coronary origin: from suspicion to surgical revascularization.

Rev Port Cardiol 2014 Jan 14;33(1):53.e1-5. Epub 2014 Jan 14.

Centro de Cirurgia Cardiotorácica, Hospital de São João, Porto, Portugal.

Congenital anomalies of the coronary arteries are uncommon and can present a diagnostic challenge. The authors present the case of a patient with recurrent chest pain during exertion admitted for acute coronary syndrome. Coronary angiography revealed no coronary lesions but showed that the right coronary artery originated from the anterolateral aortic wall, above the sinuses of Valsalva, leading to suspicion of compression by the pulmonary artery, confirmed by CT angiography. The patient underwent surgical revascularization with a good result. The authors highlight the need to consider compression of an anomalous coronary artery by the pulmonary artery in the differential diagnosis of recurrent chest pain on exertion and acute myocardial infarction without significant coronary stenosis.
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http://dx.doi.org/10.1016/j.repc.2013.07.010DOI Listing
January 2014

Mesalamine-induced myocarditis following diagnosis of Crohn's disease: a case report.

Rev Port Cardiol 2013 Sep 30;32(9):717-20. Epub 2013 Aug 30.

Serviço de Cardiologia, Hospital de Braga, Braga, Portugal. Electronic address:

Mesalamine is a common treatment for Crohn's disease, and can be rarely associated with myocarditis through a mechanism of drug hypersensitivity. We present the case of a 19-year-old male who developed chest pain two weeks after beginning mesalamine therapy. The electrocardiogram showed slight ST-segment elevation with upward concavity in the inferolateral leads; blood tests demonstrated elevated troponin I and the echocardiogram revealed moderately depressed left ventricular systolic function with global hypocontractility. Cardiac magnetic resonance imaging confirmed the diagnosis of myocarditis, revealing multiple areas of subepicardial fibrosis. The onset of symptoms after mesalamine, and improvement of chest pain, cardiac biomarkers and left ventricular systolic function after discontinuing the drug, suggest that our patient suffered from a rare drug-hypersensitivity reaction to mesalamine.
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http://dx.doi.org/10.1016/j.repc.2012.12.018DOI Listing
September 2013
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