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- Safeguarding patients, relatives, and nurses: A screening approach for detecting 5-FU residues on elastomeric infusion pumps using HPLC-DADPublication . Cardoso, Andreia; Jesus, Ângelo; Barreiros, Luísa; Carvalho, Daniel; Sá, Maria dos Anjos; Carvalho, Susana; Correia, Patrícia; Moreira, Fernando; Moreira, Fernando; Correia, Patrícia Carla dos Santos ; Barreiros, Luisa; Jesus, ÂngeloThe leakage of 5-fluorouracil (5-FU) from elastomeric infusion pumps used in cancer therapy poses a potential risk of unintentional exposure to multiple individuals, including patients’ relatives and healthcare professionals, and may also compromise the accurate administration of 5-FU dosages to patients. This study aimed to develop, validate, and apply an analytical method to detect and quantify 5-FU residues on the external surfaces of infusion pumps. A high-performance liquid chromatography with diode-array detection (HPLC-DAD) method was optimized for the quantification of 5-FU contamination across different components of the infusion pump, including the hard casing, infusion tubing, and catheter connection port. A mobile phase containing 5% acetic acid was used to obtain more efficient separation of 5-FU and the detection was performed at 260 nm. The method was evaluated for linearity, sensitivity, precision, accuracy, selectivity, robustness, and stability. The method demonstrated linearity within the range of 0.150 to 3.000 µg/cm2, with limits of detection and quantification of 0.05 µg/cm2 and 0.14 µg/cm2, respectively. Relative standard deviations ranged from 1.8% to 12.7%, and accuracy exceeded 85%. In real sample analysis, detectable residues were found around the catheter connection port. This screening-oriented method addresses an existing gap, as previous contamination reports were based solely on self-reported user observations. The detection of 5-FU residues highlights the critical need for safe handling practices and the consistent use of personal protective equipment (PPE) to protect healthcare workers, especially nursing staff involved in the removal of the infusion pumps, after treatment.
- Factors influencing the prescription of first-line treatment for type 2 diabetes mellitus: a systematic reviewPublication . Moreira, Helena Silva; Moreira, Fernando; Jesus, Ângelo; Soares, Matilde Monteiro; Santos, Paulo; Moreira, FernandoUnderstanding prescribing patterns for type 2 diabetes mellitus, a complex condition affecting over 10% of the global adult population, can optimise prescribing practices, guide policymakers in promoting evidence-based medicine, and help tailor first-line treatments to individual characteristics or specific subgroups, improving patient outcomes. This study aimed to identify factors influencing the prescription and non-prescription of metformin, the recommended first-line therapy in Western guidelines, and to evaluate whether these prescribing patterns align with evidence-based recommendations. It also explores factors associated with initial combination therapy, a more recent and controversial approach compared to stepwise therapy. We conducted a systematic search in PubMed, Scopus, and Web of Science on 25 August 2023, without language or time restrictions, to identify observational analytical studies assessing factors associated with the initiation of metformin or combination therapy in adults with type 2 diabetes mellitus who were naïve to antidiabetic medications. Studies involving pregnant or breastfeeding women were excluded. A narrative synthesis was conducted. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklists (PROSPERO registration number CRD42023438313). Thirty studies were included, evaluating 105 variables, most of which (62%) were assessed in one study. The 25 variables using combination therapy as the outcome were mostly (72%) evaluated also in one study. Initial metformin prescription was strongly and positively associated with younger age, lower glycated haemoglobin levels, higher body mass index, and absence of renal impairment. Initial combination therapy was associated with higher HbA1c levels and a lower burden of comorbidities. Findings also highlighted a discrepancy between clinical practice and evidence-based recommendations. However, concerns were raised regarding both the internal and external validity of the included studies. Our systematic review, which offers insights into real-world clinical practices, indicated that there is a misalignment between clinical practices and evidence-based recommendations, supporting the need for interventions in this field.
- Altered NRF2 signalling in systemic redox imbalance: Insights from non-communicable diseasesPublication . Santos, Marlene; Morgenstern, Christina; Santos, MarleneThe balanced activity of the cytoprotective transcription factor NRF2 is central for maintaining redox, metabolic-energetics, and proteome homeostasis, as well as for regulating inflammatory responses, among other functions. Activated NRF2 regulates the expression of hundreds of genes containing antioxidant response elements (AREs) or electrophile response elements (EpRE) in their regulatory regions, often promoting cytoprotection under stress conditions and contributing to defence against various pathologies and non-communicable diseases (NCDs). The products of increased NRF2 activity, detected systemically, may originate from either the white blood cells, the cells of the vasculature or tissue-derived products that could be secreted into biological fluids. Therefore, assessing basal and inducible NRF2 activity in blood or other biofluids is crucial for inferring NRF2 responses in local and often inaccessible tissues. In previous work, we identified a panel of six biomarkers - Glutamate-cysteine ligase catalytic subunit (GCLC), Glutamate-cysteine ligase modifier subunit (GCLM), Haem oxygenase 1 (HMOX1), NAD(P)H quinone dehydrogenase 1 (NQO1), Sulfiredoxin 1 (SRXN1), and Thioredoxin reductase 1 (TXNRD1) - as indicators of NRF2 activity. In the current study, we assess their utility in a clinical setting to measure NRF2 activation in a disease context. Here we discuss findings on how NRF2 activity in accessible human samples can reveal its involvement in various NCDs and its connection to clinical aspects such as diagnosis, disease progression and response to therapy.
- A preliminary assessment of a stool-based microRNA profile for early colorectal cancer screeningPublication . Santos, Daniela A. R.; Eiras, Mariana; Gonzalez-Santos, Miguel; Santos, Marlene; Pereira, Carina; Santos, Lúcio Lara; Dinis-Ribeiro, Mário; Lima, Luís; Santos, MarleneColorectal cancer screening methods are well established worldwide as a fundamental pilar in CRC management, namely through non-invasive faecal occult blood testing. However, the limited sensitivity of faecal occult blood test for detecting precancerous lesions highlights the need to search for alternative tools, such as microRNAs (miRs). The main aim of this study was to identify stoolbased miR profiles for early colorectal cancer detection. A panel with miR-21-5p, miR-199a-5p, and age showed a moderate performance for colorectal cancer detection (sensitivity: 88%). Additionally, miR-451a, miR-21-5p, miR-199a-5p, age, and gender showed high performance for discriminating high-grade dysplasia lesions (sensitivity: 91%). Moreover, when we obtained a positive result in either panel, we achieved a sensitivity of 96% for high-grade dysplasia lesions identification. Finally, when a negative result was obtained in these panels after a positive faecal occult blood test result, we accurately identified individuals without lesions. These findings demonstrate the potential of miR panels as non-invasive biomarkers for colorectal cancer and high-grade dysplasia lesions detection and could constitute a secondary screening method following a positive faecal occult blood test.
- Immunogenicity as a predictor of Influenza vaccine efficacy: A systematic reviewPublication . Martins, André Miguel; Juan, Luis Félix Valero; Santos, Marlene; Martins, João Paulo; Santos, Marlene; Oliveira Martins, João PauloInfluenza represents a significant burden on global public health, and vaccination is the most effective strategy to reduce it. The large investment in vaccination programs and the need for adjustments in vaccine serotypes are important reasons for evaluating the influenza vaccine’s efficacy every year. Establishing a relationship between immunogenicity data and efficacy is also crucial for predicting the efficacy of a vaccine during its development. Antibody response measurement is one of the most common methods for evaluating immunogenicity, particularly in vaccines and biologics. The aim of this systematic review was to define a model that relates the immunogenicity of a given vaccine to its efficacy, based on hemagglutination inhibition titer levels. To achieve this goal, information was gathered from articles linking immunogenicity with the efficacy of the influenza vaccine in the Medline and Scopus databases. Different mathematical models were developed and applied to assess the relationship between HAI titers and the effectiveness of the flu vaccine. This analysis was conducted for the various existing vaccines, for the different influenza virus strains, and for their efficacy in paediatric populations. The r2 obtained ranged from 0.2579 to 0.966, which points to the importance of this immunological factor in the efficacy of the influenza vaccine. Conclusions: The efficacy values for titer level 40 confirm the validity of the data provided by Hobson.
- Therapeutic drug monitoring education: The current statePublication . Petrova, Guenka; Blagova, Stiliyana; Tachkov, Konstantin; Santos, Marlene; Bluett, James; Rumano, Merita; Kkolou, Elena; Drakalska, Elena; Arev, Marija; Barsbay, Mehtap Cakmak; Mulleman, Denis; Santos, MarleneTo evaluate available information on therapeutic drug monitoring (TDM) education programmes and their implementation across different countries. The study was performed in two phases. First, a scoping review of scientific literature on available education programmes was performed. Afterwards, a questionnaire was distributed among a worldwide network of professionals engaged in the practice of TDM. Eight scientific articles discussing TDM educational programmes were found. They described in depth an educational programme on TDM, which was primarily offered as postgraduate education programme for hospital staff. We received a total 23 responses (30% response rate); of these, 68% were from academia. For 70% of respondents, TDM is part of the educational programme of healthcare professionals, and for 56% it is offered at both undergraduate and postgraduate level, aimed mainly at physicians (39%) and pharmacists (65%). TDM is mainly performed in infectious diseases (n = 15), neurology (n = 14) and psychiatry (n = 12), as well as for antibiotics (83%), monoclonal antibodies (53%), and oncology and psychotropics (48%). Funding for TDM is derived mostly from public health insurance (48%), hospital (44%), patients (39%). In some cases, patients might co-pay to hospital or to health insurance fund. Education on TDM is scattered across different subjects, disciplines and degrees. It is oriented essentially towards physicians and pharmacists, and its funding is mainly public. General guidelines are lacking. In light of this, it is necessary to consider developing a comprehensive educational programme on TDM, oriented towards relevant drugs and diseases, and encompassing appropriate analytical and pharmacological methods.
- Sequencing technologies in forensic microbiology: current trends and advancementsPublication . Oliveira, Manuela; Dias da Silva, Diana Cristina; Marszałek, Kamila; Kowalski, Michał; Frolova, Alina; Łabaj, Paweł P.; Branicki, Wojciech; Carvalho, Áurea Madureira; Silva, Diana Dias da; Oliveira, Ricardo Jorge DinisForensic microbiology is a subject of interest and research development across the forensic community. Studies of pathogen outbreaks, biocrime or bioterrorism attacks, and analyses of crime scenes fall within this field. Significant progress has been made in evolving DNA sequencing technologies in recent decades. These newly emerged transformative tools have become available to both biomedicine and forensics. Based on the published literature, this review provides an overview of the current trends and developments of NGS (next-generation sequencing) technologies applied to forensic microbiology. These new methods present numerous advantages over traditional sequencing technology and are useful in several practical applications within this forensic field. This article then examines the main challenges and limitations of this technology in forensics, providing a comprehensive review of NGS technology capabilities in expanding the precision and effectiveness of microbial forensic investigations—with the aim of inspiring scientists, forensic experts, lawyers, public health professionals, and policymakers alike to approach this newly powerful sequencing tool appropriately.
- Influence of puncture devices on the accuracy of cyclophosphamide dosing for chemotherapy administrationPublication . Carvalho, Susana; Cardoso, Andreia; Ferreira, Débora; Silva, Diana Dias da; Moreira, Fernando; Moreira, Fernando; Dias da Silva, Diana CristinaCyclophosphamide is one of the most commonly used cytotoxic drugs in chemotherapy protocols. Its preparation in the hospital setting involves handling concentrated solutions, which pose occupational exposure risks and potential variations in the final dose administered. The aim of this study was to evaluate the effect of aspiration devices on the concentration of cyclophosphamide in reconstituted solutions. An analytical method was validated using high-performance liquid chromatography coupled to a diode-array detector (HPLC-DAD) for quality control. Cyclophosphamide solutions were prepared and aspirated using either a conventional needle or spike device with or without a filtration system. The validated method demonstrated linearity (R2 = 0.9999), high precision (0.22–4.59%) and accuracy (88.9–99.4%), with a limit of quantification of 4.03 µg/mL. Significant differences (p < 0.001) were observed between samples aspirated with a needle and those aspirated with a spike fitted with a 5 µm filter, with the latter showing lower cyclophosphamide concentrations, suggesting partial retention of the drug. No significant differences were found between the needle and filterless spike preparations. These results suggest that the choice of aspiration device influences the final drug concentration, potentially affecting therapeutic efficacy. Standardisation of preparation techniques and an awareness of device limitations are essential to ensure accurate chemotherapy dosing and patient safety.
- An overview of the recent advances in antimicrobial resistancePublication . Oliveira, Manuela; Antunes, Wilson; Mota, Salete; Carvalho, Áurea Madureira; Oliveira, Ricardo Jorge Dinis; Silva,Diana Dias daAntimicrobial resistance (AMR), frequently considered a major global public health threat, requires a comprehensive understanding of its emergence, mechanisms, advances, and implications. AMR’s epidemiological landscape is characterized by its widespread prevalence and constantly evolving patterns, with multidrug-resistant organisms (MDROs) creating new challenges every day. The most common mechanisms underlying AMR (i.e., genetic mutations, horizontal gene transfer, and selective pressure) contribute to the emergence and dissemination of new resistant strains. Therefore, mitigation strategies (e.g., antibiotic stewardship programs—ASPs—and infection prevention and control strategies—IPCs) emphasize the importance of responsible antimicrobial use and surveillance. A One Health approach (i.e., the interconnectedness of human, animal, and environmental health) highlights the necessity for interdisciplinary collaboration and holistic strategies in combating AMR. Advancements in novel therapeutics (e.g., alternative antimicrobial agents and vaccines) offer promising avenues in addressing AMR challenges. Policy interventions at the international and national levels also promote ASPs aiming to regulate antimicrobial use. Despite all of the observed progress, AMR remains a pressing concern, demanding sustained efforts to address emerging threats and promote antimicrobial sustainability. Future research must prioritize innovative approaches and address the complex socioecological dynamics underlying AMR. This manuscript is a comprehensive resource for researchers, policymakers, and healthcare professionals seeking to navigate the complex AMR landscape and develop effective strategies for its mitigation.
- Beer with probiotics: Benefits and challenges of their incorporationPublication . Santos, Diana; Barreiros, Luisa; Jesus, Ângelo; Silva, Ana Luísa; Martins, João Paulo; Oliveira, Ana Isabel; Pinho, Cláudia; Jesus, Ângelo; Oliveira, Ana Isabel; Barreiros, LuisaBeer is considered one of the most consumed beverages worldwide and a potential vehicle for probiotics. However, there are several technical challenges to overcome during the production and storage of beers, as probiotics must remain viable until the moment of consumption. Therefore, this work aims to discuss how the incorporation of probiotics improves or adds value to beer and which variables influence the viability of the process. This is a narrative review of the literature with research in the PubMed, Web of Science, and b-on databases for articles related to the incorporation of probiotics in beer and the variables that influence the process. The results demonstrated that the incorporation of probiotics into beer faces technical challenges such as probiotic selection, pH, the presence of alcohol, and beer’s production and storage temperatures. However, strategies such as immobilizing probiotics in alginate, alginate–silica, and durian husk powder, fermentation with the yeast Saccharomyces cerevisiae var. boulardii, and co-fermentation with probiotics permit us to overcome these barriers. Thus, incorporating probiotics into beer brings added value, potentially increasing antioxidant activity and phenolic compound content and providing unique flavors and aromas. Nevertheless, strict control of the technical conditions involved is necessary to ensure probiotic viability and the health benefits they confer.