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- Human stem cells for cardiac disease modeling and preclinical and clinical applications—are we on the road to success?Publication . Correia, Cátia; Ferreira, Anita; Fernandes, Mónica T.; Silva, Bárbara M.; Esteves, Filipa; Leitao, Helena; Bragança, José; Calado, SofiaCardiovascular diseases (CVDs) are pointed out by the World Health Organization (WHO) as the leading cause of death, contributing to a significant and growing global health and economic burden. Despite advancements in clinical approaches, there is a critical need for innovative cardiovascular treatments to improve patient outcomes. Therapies based on adult stem cells (ASCs) and embryonic stem cells (ESCs) have emerged as promising strategies to regenerate damaged cardiac tissue and restore cardiac function. Moreover, the generation of human induced pluripotent stem cells (iPSCs) from somatic cells has opened new avenues for disease modeling, drug discovery, and regenerative medicine applications, with fewer ethical concerns than those associated with ESCs. Herein, we provide a state-of-the-art review on the application of human pluripotent stem cells in CVD research and clinics. We describe the types and sources of stem cells that have been tested in preclinical and clinical trials for the treatment of CVDs as well as the applications of pluripotent stem-cell-derived in vitro systems to mimic disease phenotypes. How human stem-cell-based in vitro systems can overcome the limitations of current toxicological studies is also discussed. Finally, the current state of clinical trials involving stem-cell-based approaches to treat CVDs are presented, and the strengths and weaknesses are critically discussed to assess whether researchers and clinicians are getting closer to success.
- Charting the path: navigating embryonic development to potentially safeguard against congenital heart defectsPublication . Bragança, José; Pinto, Rute L.; Silva, Barbara S.; Marques, Nuno; Leitao, Helena; Fernandes, Mónica T.Congenital heart diseases (CHDs) are structural or functional defects present at birth due to improper heart development. Current therapeutic approaches to treating severe CHDs are primarily palliative surgical interventions during the peri- or prenatal stages, when the heart has fully developed from faulty embryogenesis. However, earlier interventions during embryonic development have the potential for better outcomes, as demonstrated by fetal cardiac interventions performed in utero, which have shown improved neonatal and prenatal survival rates, as well as reduced lifelong morbidity. Extensive research on heart development has identified key steps, cellular players, and the intricate network of signaling pathways and transcription factors governing cardiogenesis. Additionally, some reports have indicated that certain adverse genetic and environmental conditions leading to heart malformations and embryonic death may be amendable through the activation of alternative mechanisms. This review first highlights key molecular and cellular processes involved in heart development. Subsequently, it explores the potential for future therapeutic strategies, targeting early embryonic stages, to prevent CHDs, through the delivery of biomolecules or exosomes to compensate for faulty cardiogenic mechanisms. Implementing such non-surgical interventions during early gestation may offer a prophylactic approach toward reducing the occurrence and severity of CHDs.
- Potentially inappropriate medication: a pilot study in institutionalized older adultsPublication . Andrade, Amanda de Oliveira; Nascimento, Tânia; Cabrita, Catarina; Leitao, Helena; Pinto, EzequielInstitutionalized older adults often face complex medication regimens, increasing their risk of adverse drug events due to polypharmacy, overprescribing, medication interactions, or the use of Potentially Inappropriate Medications (PIM). However, data on medication use and associated risks in this population remain scarce. This pilot study aimed to characterize the sociodemographic, clinical and pharmacotherapeutic profiles, and the use of PIM among institutionalized elders residing in Residential Structures for Elderly People (ERPI) in the Faro municipality, located in the Portuguese region of the Algarve. We conducted a cross-sectional study in a non-randomized sample of 96 participants (mean age: 86.6 ± 7.86 years) where trained researchers reviewed medication profiles and identified potentially inappropriate medications using the EU(7)-PIM list. Over 90% of participants exhibited polypharmacy (≥5 medications), with an average of 9.1 ± 4.15 medications per person. About 92% had potential drug interactions, including major and moderate interactions. More than 86% used at least one potentially inappropriate medication, most commonly central nervous system drugs. This pilot study demonstrates that institutionalized older adults may be at high risk of potential medication-related problems. Implementing comprehensive medication review programs and promoting adapted prescribing practices are crucial to optimize medication use and improve the well-being of this vulnerable population.
- Comparing the diagnostic performance of ultrasound elastography and magnetic resonance imaging to differentiate benign and malignant breast lesions: a systematic review and meta-analysisPublication . Gomes, Ana Filipa; Justino, David; Tomás, Carina; Jesus, Diogo; Macedo, Ana; Pinto, Ezequiel; Leitao, HelenaObjective: The purpose of this systematic review and meta-analysis was comparing diagnostic performance of ultrasound elastography (UE), strain UE and shear wave elastography (SWE), with magnetic resonance imaging (MRI) in differentiating benign and malignant breast lesions. Methods: Literature search of MEDLINE, Web of Science, SCOPUS and Google Scholar was performed in June 2023. Included studies used Breast Imaging Reporting and Data System (BI-RADS) and histopathology as reference standard. A bivariate random-effects model was used to calculate sensitivity, specificity, diagnostic odds ratio (DOR), positive and negative likelihood ratios and area under the curve (AUC). Meta-regression subgroup analysis was performed. Results: Nine studies and 536 lesions were included. Pooled sensitivity was not different between MRI vs UE [MRI: 94% (95% CI: 88.2%-96.9%) vs UE: 90% (95% CI: 84.7%-93.1%); P=0.153] but a difference was found for specificity [UE: 78% (95% CI: 66.3%-86.4%) vs MRI: 71.3% (95% CI: 52.1%-85%); P=0.0065]. Strain UE showed higher specificity and similar sensitivity to SWE [strain UE: 0.85 (95% CI: 0.71-0.93) vs SWE: 0.72 (95% 0.58-0.83); P=0.017 and strain UE: 0.87 (95% CI 0.79-0.93) vs SWE: 0.91 (95% CI 0.85-0.95); P=0.311, respectively]. AUC was similar between MRI vs UE [0.91 (95% CI 0.87-0.95) vs 0.92 (95% CI 0.88-0.95); P=0.452, respectively] as was DOR [MRI: 38.083 (95% CI: 12.401-116.957) vs UE: 30.395 (95% CI: 16.572-55.75); P > 0.05]. Meta-regression analysis found no significant differences in the diagnostic accuracy between MRI, strain UE and SWE. Conclusion: Our results show that UE when compared to MRI has adequate performance in differentiating benign and malignant breast lesions.