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- Rediscovering digitalis in heart failure with reduced ejection fractionPublication . Valentim Gonçalves, António; Carvalheiro, Ricardo; Fiarresga, António; Pereira-da-Silva, Tiago; Cardim, Nuno; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Sociedade Portuguesa de Cardiologia | ElsevierDigitalis glycosides are among the oldest therapies for heart failure (HF) with reduced ejection fraction, yet their contemporary role remains debated. Clinical data now indicate that the predominant clinical benefits of digitalis appear to derive from autonomic and neurohormonal modulation (enhanced vagal activity, attenuation of sympathetic drive, and suppression of renin–angiotensin–aldosterone activation) rather than from classical positive inotropy. At low serum concentrations, these effects translate into improved rate control, reduced congestion, and fewer decompensations with a lower risk of toxicity, whereas higher “inotropic” levels are associated with proarrhythmia and excess mortality. This review summarises the mechanistic and pharmacokinetic differences between digoxin and digitoxin, appraises evidence from PROVED, RADIANCE and DIG, and integrates emerging outcome data from DIGIT-HF, which showed that low-dose digitoxin added to contemporary guideline-directed therapy reduces the composite of death or HF hospitalisation. Finally, this review also provides valuable insights from a 2025 survey of Portuguese HF specialists into real-world clinical practice regarding digitalis use. With 55 experts responding, the survey highlights a predominant, selective application of digitalis glycosides, primarily after optimization of foundational HF therapies, consistent with guideline recommendations. Perceived benefits focus on rate control and symptom relief, while concerns about toxicity, the need for monitoring, and gaps in modern trial evidence continue to restrict broader adoption. Together, current data support a repositioning of digitalis as a low-dose, concentration-guided, neurohormonal modulator and rate-control agent for carefully selected patients with HF with reduced ejection fraction, an approach that ongoing and future trials should further refine.
- Implementing the AI Act in the Portuguese Health SectorPublication . Frutuoso, João; Pereira, Juan; Pereira, Manuel; Donato, Helena; Vaz Carneiro, António; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Biblioteca Nacional de Portugal, Centro de Estudos Históricos, CELOMThe rapid expansion of artificial intelligence (AI) in the health sector has intensified the need for a robust regulatory framework capable of safeguarding patient safety, professional accountability, and public trust. We aimed to analyse the European Union Artificial Intelligence Act [AI Act, Regulation (EU) 2024/1689] and its implications for the healthcare sector in Portugal, presenting the institutional position of the Artificial Intelligence Committee of the Portuguese Medical Association (CPIA-OM). We conducted a narrative review based on official European legislation [AI Act, General Data Protection Regulation (GDPR), Medical Device Regulation (MDR) and In Vitro Diagnostic Medical Devices Regulation (IVDR)], institutional documents [including the 2025 White Paper on AI in Healthcare in Portugal, published by the Shared Services of the Ministry of Health (SPMS)], and peer-reviewed literature on artificial intelligence in medicine, ethics, and regulatory science. The AI Act introduces a risk-based classification of AI systems, ranging from prohibited “unacceptable risk” applications to minimal risk uses. Most medical AI applications, including diagnostic support, clinical monitoring, and therapeutic decision-making, are classified as “high risk” and are subject to stringent requirements regarding conformity assessment, technical documentation, human oversight, and data governance. The regulation interacts with existing frameworks such as the GDPR and MDR/IVDR, creating complex compliance obligations. Specific challenges include algorithmic bias, liability attribution, and the preservation of the physician-patient relationship. In Portugal, recent institutional initiatives within the National Health Service — including pilot projects in triage, frailty assessment, antibiotic stewardship, and medical imaging — illustrate opportunities for responsible AI integration, while academic reports highlight persistent concerns around transparency, trust, and professional substitution. The AI Act represents a landmark in European health regulation, balancing innovation with fundamental rights protection. For Portugal, its implementation requires coordinated action between the government, regulators, healthcare providers, and professional bodies. The CPIA-OM emphasises the need for continuous medical education in AI, the establishment of clinical oversight protocols, and the creation of observatories to monitor implementation and ensure ethical, safe, and patient-centred adoption.
- Social Prescribing in PortugalPublication . Sidiropoulou, Zacharoula; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Karger
- Exploring the impact of the GJA4 rs618675 variant on cardiovascular preventionPublication . Isabel Mendonça, Maria; Palma dos Reis, Roberto; Sá, Débora; Sousa, Francisco; Henriques, Eva; Borges, Sofia; Freitas, Sónia; Rodrigues, Mariana; Guerra, Graça; Drumond, António; Célia Sousa, Ana; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Sociedade Portuguesa de Cardiologia | ElsevierIntroduction and objectives: The gap junction alpha-4 (GJA4) gene, which encodes connexin37, regulates endothelial function and influences inflammation, platelet adhesion, and thrombus formation in vascular endothelial cells, which may favour atherosclerosis and cardiovascular (CV) events. The main objective was to assess whether the GJA4 rs618675 T>C variant is a risk factor for the onset of CV events in an asymptomatic Portuguese population. Methods: One thousand four hundred twenty-one individuals without CV disease (52.2±8.3 years, 73.6% male) were followed up during a mean of 7.3±6.0 years, and CV events were recorded. GJA4 rs618675 T>C was genotyped by real-time PCR (TaqMan), and four genetic models were created. We analyzed traditional, biochemical and clinical risk factors. We performed bivariate analysis and adjusted logistic regression with respective OR. Kaplan–Meier estimated event-free survival and Cox regression, adjusted for confounding, evaluated the association between four genetic models and CV events (HR). Results: Wild TT genotype, TC, and CC were 50.6%, 39.2%, and 10.1% in the CV events group and 66.2%, 30.4% and 3.4% in the non-events group (p=0.001). After logistic regression, the codominant model (CCvsTT and CTvsTT) showed an OR of 3.9 (p=0.002). Kaplan–Meier showed 87.6% event-free time for TT and 64.8% for CC (p=0.005). Adjusted Cox regression identified the codominant model as the best predictor (HR=2.8; p=0.008), together with male gender (HR=2.1; p=0.020), age (HR=1.1; p=0.001), hypertension (HR=1.9; p=0.014), smoking (HR=1.9; p=0.010), and leukocytosis (HR=1.2; p=0.003). Conclusion: We have demonstrated that the CC variant of GJA4 is significantly associated with CV events. Further investigations into this biomarker may improve CV risk prediction, leading to better primary prevention.
- Moral Distress, Work Engagement, and Meaningful Work in HealthcarePublication . Santos, Catarina; Da Ponte, Guida; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Biblioteca Nacional de Portugal, Centro de Estudos Históricos, CELOMThe psychological well-being of healthcare professionals is increasingly recognized as a critical determinant of patient safety, quality of care, and healthcare system sustainability. Among the constructs most relevant to this domain are moral distress, work engagement, and meaningful work. This narrative review aimed to synthesize conceptual and empirical evidence on these three constructs and to examine their interrelations and implications for healthcare practice. A selective narrative review of the literature was conducted, integrating theoretical frameworks, systematic and integrative reviews, and empirical studies, resulting in a final synthesis of 41 articles. Moral distress arises when clinicians are prevented from acting in accordance with their ethical convictions, often due to institutional or systemic constraints, and has been consistently associated with burnout, turnover, and compromised quality of care. In contrast, work engagement - characterized by vigor, dedication, and absorption - and meaningful work - reflecting the perception that professional activities have meaning and purpose - function as protective factors that enhance resilience and sustain intrinsic motivation. Evidence highlights the central role of organizational climate, leadership, resource availability, and ethical culture in shaping experiences of distress, engagement, and meaningfulness, a dynamic further intensified during the COVID-19 pandemic. The synthesis emphasizes that organizational and systemic interventions, including ethics consultation, supportive leadership, workflow redesign, and resilience-building programs, are essential to mitigate moral distress and promote engagement and meaningful work. The integration of these constructs aligns with the Quadruple Aim, reinforcing the premise that caring for healthcare professionals is indispensable to caring for patients.
- Serão preço e custo coincidentes na cirurgia cardíaca do idoso?Publication . Coelho, Pedro Nuno Martins Pires; Rodrigues, Vanessa; Miranda, Luís; Fragata, José Inácio Guerra; Barros, Pedro Pita; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); NOVA School of Business and Economics (NOVA SBE); Sociedade Portuguesa de Cardiologia | ElsevierIntroduction Payment for cardiac surgery in Portugal is based on a contract agreement between hospitals and the health ministry. Our aim was to compare the prices paid according to this contract agreement with calculated costs in a population of patients aged ≥65 years undergoing cardiac surgery in one hospital department. Methods Data on 250 patients operated between September 2011 and September 2012 were prospectively collected. The procedures studied were coronary artery bypass graft surgery (CABG) (n=67), valve surgery (n=156) and combined CABG and valve surgery (n=27). Costs were calculated by two methods: micro‐costing when feasible and mean length of stay otherwise. Price information was provided by the hospital administration and calculated using the hospital's mean case‐mix. Results Thirty‐day mortality was 3.2%. Mean EuroSCORE I was 5.97 (standard deviation [SD] 4.5%), significantly lower for CABG (p<0.01). Mean intensive care unit stay was 3.27 days (SD 4.7) and mean hospital stay was 9.92 days (SD 6.30), both significantly shorter for CABG. Calculated costs for CABG were €6539.17 (SD 3990.26), for valve surgery €8289.72 (SD 3319.93) and for combined CABG and valve surgery €11 498.24 (SD 10 470.57). The payment for each patient was €4732.38 in 2011 and €4678.66 in 2012 based on the case‐mix index of the hospital group, which was 2.06 in 2011 and 2.21 in 2012; however, the case‐mix in our sample was 6.48 in 2011 and 6.26 in 2012. Conclusion The price paid for each patient was lower than the calculated costs. Prices would be higher than costs if the case‐mix of the sample had been used. Costs were significantly lower for CABG.
- Lynch SyndromePublication . Rodrigues, Pedro; Matos, Paulo; Gonçalves, João; Jordan, Peter; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); MDPI AGIn 2022, colorectal cancer (CRC) was the third most common type of cancer worldwide and the second most common in Europe. CRC ranked as the second leading cause of cancer-related deaths both worldwide and in Europe, with 904,019 and 247,966 deaths, respectively. The majority of CRC cases are sporadic (60–75%); however, 10–35% of CRC are estimated to result from the interaction of heritable and environmental factors. Among these, 5–6% are caused by inherited variants in genes that predispose to the development of CRC. Among the known inherited causes, Lynch Syndrome (LS), formerly known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is the most frequent and accounts for approximately 3% of all CRC. Here we review and update on multiple aspects of LS in the context of CRC, including its genetic and molecular basis, current guidelines for molecular screening and variant classification. Furthermore, we review functional assays that have been used to determine the biological impact of genetic variants of uncertain significance (VUS) and discuss future perspectives in the field.
- Universal Screening for Sexually Transmitted Infections in PregnancyPublication . Bandeira, Swasilanne; Vasconcelos, Joana; Teixeira, Mariana; Costa, Beatriz; Rocha, Paula; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Biblioteca Nacional de Portugal, Centro de Estudos Históricos, CELOM
- Effects of digoxin in modern heart failure treatmentPublication . Valentim Gonçalves, António; Cardim, Nuno; Fiarresga, António; Pereira-da-Silva, Tiago; Ilhão-Moreira, Rita; Galrinho, Ana; Rio, Pedro; Carvalheiro, Ricardo; Ferreira, Fernando; Lopes, Julien; Marques Antunes, Miguel; Selas, Mafalda; Viana, Bruno; Domingues, Lúcia; Cruz Ferreira, Rui; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Sociedade Portuguesa de Cardiologia | ElsevierAims: Even though it is the oldest heart failure (HF) medication still in use, digoxin has not been evaluated alongside the updated algorithm for treating HF with reduced ejection fraction patients. This could help explain the low use of digoxin in recent HF studies. The main objective is to assess the effectiveness of digoxin in functional capacity and cardiac function when combined with modern HF therapy. Methods: An interventional, open-label, randomised, crossover trial among adults with chronic Heart Failure and reduced ejection fraction (≤45%) was designed to allocate 50 patients for 24 weeks in each arm (48 weeks of study). The arms are daily intake of digoxin 0.125 mg plus standard of care versus standard of care alone. Both patients with sinus rhythm and atrial fibrillation were enrolled. At the end of each 24-week arm, patients will undergo the co-primary outcome measurement of the peak oxygen consumption, evaluated through cardiopulmonary exercise test, and the global work index, measured by transthoracic echocardiography. Key secondary outcome includes a safety composite of death, need for urgent heart transplantation or mechanical assist device, total hospitalizations and sustained ventricular arrhythmias. The study completed recruitment in April 2025 and will complete follow up in March 2026. Conclusions: The use of digoxin could be significantly affected by evidence that it still has a considerable effect on functional capacity and cardiac function in HF patients. EU CT Number: 2024-513448-26-00.
- Metabolic reprogramming and molecular crosstalk at the cancer-endothelial interface in ovarian carcinomaPublication . Sousa, Bruna; Chiavassa, Adele; Delgado, Leonor; Gomes, Rafael; Mendes, Cindy; Serpa, Jacinta; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); BioMed Central (BMC)