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- Metabolism-Targeted Therapy in NSCLC - A New Theranostics Inhalation Approach Using Lactate Functionalized and Selenium-Chrysin Loaded Nanoparticles (SeChry@PURE-LA).Publication . Mendes, Cindy; Martins, Filipa; Granja, Sara; Gonçalves, Joana; Barros, Hélio; Casimiro, Teresa; Aguiar-Ricardo, Ana; Silva, Fernanda; Abreu, Bruna; Cristovão, Miguel; André, Saudade; Pereira, Sofia A; Baltazar, Fátima; Cabral-Marques, Helena; Gaspar, Maria Manuela; Gonçalves, Luís G; Bonifácio, Vasco D B; Serpa, JacintaLung cancer is one of the most lethal cancers globally, primarily due to delayed diagnosis and lack of specific and effective therapy. Increased lactate production and consumption, along with cysteine metabolic reliance, are features identified in NSCLC in our recent studies. Cancer metabolic remodeling leads to excessive ROS production, triggering oxidative stress, promoting angiogenesis, causing cellular and tissue damage, and contributing to various pathophysiological changes. This study aimed to investigate the therapeutic potential of selenium-chrysin (SeChry), a cysteine metabolism inhibitor, and its delivery targeted at MCT1 by encapsulation in fourth-generation polyurea dendrimers functionalized with lactic acid (PURE-LA), the nanoformulation SeChry@PURE-LA, in NSCLC. We explored the impact of SeChry nanoformulation on cell death mechanisms, including ferroptosis, and its influence on angiogenesis in in vitro and in vivo models. SeChry@PURE-LA induces cell death through the induction of intracellular ROS and lipid peroxides, resulting in distinct expression patterns of ferroptosis-associated genes across cell lines. Experiments using chicken embryo chorioallantoic membrane (CAM) and mouse orthotopic xenograft models revealed a trend toward decreased tumor growth and angiogenesis with SeChry@PURE-LA administration. These findings suggest the potential of SeChry@PURE-LA as an innovative therapeutic approach for NSCLC, highlighting its impact on cell death mechanisms and anti-angiogenic effects.
- Impact of Anatomical Resection on Non-transplantable Recurrence Among Patients with Hepatocellular Carcinoma: An International Multicenter Inverse Probability of Treatment Weighting Analysis.Publication . Kawashima, Jun; Endo, Yutaka; Khalil, Mujtaba; Woldesenbet, Selamawit; Akabane, Miho; Ruzzenente, Andrea; Ratti, Francesca; Marques, Hugo; Oliveira, Sara; Balaia, Jorge; Cauchy, François; Lam, Vincent; Poultsides, George; Kitago, Minoru; Popescu, Irinel; Martel, Guillaume; Gleisner, Ana; Hugh, Thomas J; Aldrighetti, Luca; Endo, Itaru; Pawlik, Timothy MBackground: Among patients with hepatocellular carcinoma (HCC), the impact of anatomic resection (AR) versus non-anatomic resection (NAR) on non-transplantable recurrence (NTR) remains poorly defined. We sought to compare the risk of NTR among patients treated with AR versus NAR as the primary surgical strategy for HCC. Patients and methods: Patients with HCC within Milan criteria who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. The inverse probability of treatment weighting (IPTW) method was utilized to compare short- and long-term outcomes among patients undergoing AR versus NAR. Results: Among 1038 patients, 747 (72.0%) patients underwent AR, while 291 (28.0%) patients underwent NAR. After IPTW adjustment, patients who underwent AR had better 5-year recurrence-free survival than individuals treated with NAR (63.9 vs. 52.0%; hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.62-0.99); however, there was no difference in 5-year overall survival (80.2 vs. 75.6%; HR 0.76; 95% CI 0.55-1.05). Notably, individuals who underwent AR were less likely to have a NTR versus individuals treated with NAR (3-year NTR 9.8 vs. 14.4%; HR 0.62; 95% CI 0.40-0.96). In particular, AR was associated with a lower risk of NTR among patients with a medium tumor burden score (TBS) (HR 0.53; 95% CI 0.28-0.99), while the benefit among patients with a low TBS was less pronounced (HR 0.73; 95% CI 0.40-1.32). Conclusions: AR was associated with a lower risk of NTR and improved recurrence-free survival (RFS) among patients with HCC, especially individuals with higher TBS. An anatomically defined surgical approach should be strongly considered in patients with a higher HCC tumor burden.
- Decision-Making for Endovascular Thrombectomy in Patients With Large Vessel Occlusions and Mild Neurological Deficit: A Consensus Statement.Publication . Bosshart, Salome L; Kappelhof, Manon; Stebner, Alexander; Fujiwara, Satoru; Cimflova, Petra; Schüngel, Marie-Sophie; Milot, Genevieve; Mosimann, Pascal J; Schaafsma, Joanna D; Ribo, Marc; Paul, Alexandra R; Ulfert, Christian; Almekhlafi, Mohammed; Fragata, Isabel; Nardai, Sandor; Lopes, Demetrius K; Menon, Bijoy; Bhogal, Pervinder; Pensato, Umberto; Hawkes, Christine; Yoshimura, Shinichi; Inoa, Violiza; Ganesh, Aravind; Singh, Nishita; Volders, David; Moreu, Manuel; Uchida, Kazutaka; Nimjee, Shahid; Saver, Jeffrey L; Hill, Michael D; Ospel, Johanna MAcute ischemic stroke patients with mild deficits (National Institutes of Health Stroke Scale [NIHSS] of 0-5) but confirmed large vessel occlusions (LVO) present a clinical challenge for endovascular thrombectomy (EVT) decisions due to limited evidence and the absence of clear guidelines. A Delphi consensus was conducted at the 2024 5T (Teamwork, Training, Technology, Technique, Transport) Think Tank conference with 40 international stroke experts. Following a systematic literature review, three iterative Delphi rounds were employed to explore EVT decision-making in strokes due to LVO with low NIHSS. Data were collected through surveys and in-person discussions, focusing on disability evaluation, imaging markers, procedural risk, and outcome scales. Consensus was achieved on key factors influencing EVT decisions. Experts emphasized the importance of symptom-specific disability (e.g., aphasia, vision loss) over NIHSS scores alone. Early neurological deterioration (END) was perceived as main concern in this patient population. Imaging markers such as proximal occlusion, poor collaterals, and large penumbra were expected to be predictors of END. The anticipated technical difficulty and patient-specific factors, such as independence and quality of life, also guided decisions. The Potential of rtPA for Ischemic Strokes With Mild Symptoms (PRISMS) trial definition of disabling deficits and the 9-level modified Rankin Scale were favored as outcome measures for future studies. EVT decisions for acute ischemic strokes with mild deficit but proven LVO require nuanced, individualized approaches beyond NIHSS thresholds. Disability assessment, imaging-based risk evaluation, and patient-centered discussions are critical for optimizing outcomes, emphasizing the need for further research and standardized guidelines.
- Seizure Prediction in Cerebral Venous Thrombosis - a Retrospective Single-Centre Observational Study.Publication . Faustino, Patrícia; Melancia, DianaCerebral venous thrombosis (CVT) accounts for 0.5-1% of all strokes and 24-50% of these patients develop acute symptomatic seizures (AS). Clinical and radiological characteristics have been associated with an increased risk of AS in CVT. We aimed to identify clinical and imaging predictors associated with a higher risk of AS in CVT patients.We conducted a single-centre, retrospective cohort study and included all patients with CVT admitted to our stroke unit between January/2011-December/2022. Our primary outcome was AS occurence. Clinical and radiological characteristics were compared through a logistic binary regression, followed by a multivariable analysis.We included 156 patients, 80.8% female and a mean age of 41.5 ± 15.2 years. Fifty-two patients (33.3%) had a seizure during follow-up, the majority as AS (30.1%). We found an increased risk of AS in patients with focal signs at presentation (OR 5.35), superior longitudinal sinus (SLS) or cortical vein involvement (OR 5.03; OR 3.94), hemorrhagic lesions or oedema (OR 3.88; OR 4.17) and lesions located in the frontal or the parietal lobe (OR 4.61; OR 4.61). A multivariable analysis was also conducted and only SLS involvement (OR 6.06), cortical vein involvement (OR 2.76) and hemorrhagic lesion (OR 3.47) remained statistically significant.Seizures occurred in about a third of our CVT patients, the majority as AS. Haemorrhagic lesions, SLS and cortical vein involvement had a stronger association with AS that may raise our awareness for the risk of seizures in this population during the acute phase.
- Prediction of Response to Cardiac Resynchronization Therapy Using Electrocardiographic Criteria: a Systematic Review.Publication . Dias Costa, Paulo; Bessa, João Pedro; Canelas Pais, Mariana; Ferreira-Santos, Daniela; Montenegro Sá, Fernando; Monteiro-Soares, Matilde; Hipólito-Reis, António; Martins Oliveira, Mário; Pereira Rodrigues, PedroBackground: Cardiac resynchronization therapy (CRT) is an established therapeutic option for heart failure, but despite careful selection around 30% of the patients still do not respond to this therapy. The standard electrocardiogram (ECG) is a practical and inexpensive tool to assess potential responders to CRT but with conflicting evidence regarding the value of different ECG parameters. As such, we conducted a systematic review of real-world studies to assess the value of pre-implantation standard ECG parameters in predicting response to CRT. Methods: We searched on PubMed, Scopus, and Web of Knowledge online databases to identify analytic studies and synthesized results through evidence tables. Results: Sixty-two eligible articles were included in this review. Traditional predictors of response were QRS duration ≥150 ms and the presence of left bundle branch block morphology. Contemporary ECG parameters, such as the presence of QRS notching or fragmentation, the S wave assessment, the time to intrinsicoid deflection (ID) in lateral leads, and a lead one ratio ≥12 also showed great potential in assessing response to CRT. Conclusions: This review highlights the promising capability of the standard ECG in predicting response to CRT, particularly when using more contemporary predictors, while emphasizing the necessity for further research to validate the prognostic value of these predictors.
- Systemic Effects of Anabolic-Androgenic Steroid Abuse: A Case in Primary Care.Publication . de Carvalho Vilarinho, Margarida; Cernadas, Joana; Marques Ferreira, MiguelAnabolic-androgenic steroid (AAS) abuse is a growing public health concern due to its wide-ranging physical and psychological effects. This case report highlights the multisystemic consequences of prolonged AAS use in a 30-year-old male presenting initially with a minor respiratory infection during a consultation in his healthcare center. Despite his primary complaint, upon physical examination, muscle hypertrophy, bilateral gynecomastia, and suspected testicular atrophy were observed, prompting further investigation. Laboratory findings showed high levels of testosterone, suppressed gonadotropins, elevated estradiol, dyslipidemia, and liver enzyme elevation, consistent with chronic AAS abuse. Imaging confirmed gynecomastia, and the patient was diagnosed with hypertension, likely secondary to AAS use. Despite counseling on the potential short- and long-term health risks, the patient chose to continue AAS use. Ongoing follow-up in primary care, however, made it possible for the patient to return to care after one year, when he presented with depressive symptoms and body image dissatisfaction following steroid cessation, demonstrating the critical role of family physicians in early detection, patient education, and motivational support. This case shows the importance of a thorough approach in identifying AAS abuse and managing its systemic effects to mitigate potentially perilous health outcomes.
- Recomendações sobre Contraceção em Mulheres com Cancro Ginecológico: Do Diagnóstico ao Pós-Tratamento.Publication . Correia, Lúcia; Teves, Mariana; Pires, Mónica; Pacheco, Amália; Palma, FátimaA incidência de cancro ginecológico em mulheres durante a idade fértil está a aumentar, suscitando uma preocupação crescente com a preservação da fertilidade. Nesse contexto, torna-se essencial oferecer aconselhamento contracetivo adequado a estas doentes. Na escolha do método contracetivo, é fundamental considerar o tipo histológico do tumor e a sua expressão de recetores hormonais, bem como o momento em que o aconselhamento está a ser prestado no cuidado da doente oncológica, seja na fase de diagnóstico, de tratamento ou após o tratamento oncológico. A Sociedade Portuguesa da Contraceção e a Secção de Ginecologia Oncológica da Sociedade Portuguesa de Ginecologia apresentam recomendações sobre contraceção nas mulheres com diagnóstico de cancro ginecológico submetidas a tratamentos preservadores da fertilidade, desde o diagnóstico até ao término da idade fértil
- Persistent Proinflammatory Cytokine Profile in the Tear Fluid of Stable Keratoconus: Rethinking Clinical Quiescence.Publication . Gil, Pedro; Quadrado Gil, João; Cruz, Nuno; Costa, Celso; Rodrigues-Santos, Paulo; Sousa, Luana Madalena; Almeida, Jani Sofia; Fernandes, Rosa; Alves, Nuno; Rosa, Andreia; Murta, JoaquimPurpose: Keratoconus is traditionally classified as a noninflammatory corneal ectasia, despite growing evidence suggesting an underlying inflammatory component. This study evaluates whether patients with stable keratoconus exhibit persistent inflammatory activity in tear fluid compared to healthy controls. Methods: Cross-sectional case-control study. Keratoconus progression was evaluated using tomographic and clinical criteria. Tear fluid samples were collected under standardized conditions and concentrations of nine cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, and TNF-α) were quantified using a multiplex assay. Group comparisons, correlation analyses, and receiver operating characteristic (ROC) curves were performed to evaluate cytokine expression and network behavior. Results: A total of 23 stable keratoconus patients and 25 age-matched healthy controls were included. The stable keratoconus group exhibited significantly elevated levels of tear fluid inflammatory cytokines compared to controls (all P < 0.05, except IL-2). Spearman correlation heatmaps revealed a coordinated cytokine network in the keratoconus group, suggesting persistent immunological activation despite clinical quiescence. No significant correlations were observed between cytokine levels and keratoconus staging indices. ROC analysis indicated moderate discriminatory performance of IL-6 (area under the curve = 0.68). Conclusions: Even clinically stable keratoconus is associated with a distinct proinflammatory tear fluid cytokine profile, challenging the traditional paradigm of keratoconus as a noninflammatory disease. These findings highlight the potential utility of tear fluid-based inflammatory biomarkers in keratoconus and suggest inflammation may persist independently of clinical progression. Translational relevance: This study highlights the potential role of tear-based inflammatory biomarkers for monitoring disease activity, understanding keratoconus pathophysiology and guiding adjunctive anti-inflammatory therapies in keratoconus beyond structural stabilization.
- Ergo4Workers: A User-Centred App for Tracking Posture and Workload in Healthcare Professionals.Publication . Sabino, Inês; Fernandes, Maria do Carmo; Antunes, Ana; Monteny, António; Mendes, Bruno; Caldeira, Carlos; Guimarães, Isabel; Grazina, Nidia; Probst, Phillip; Cepeda, Cátia; Quaresma, Cláudia; Gamboa, Hugo; Nunes, Isabel L; Gabriel, Ana TeresaHealthcare professionals (namely, occupational therapists) face ergonomic risk factors that may lead to work-related musculoskeletal disorders (WRMSD). Ergonomic assessments are crucial to mitigate this occupational issue. Wearable devices are a potential solution for such assessments, providing continuous measurement of biomechanical and physiological parameters. Ergo4workers (E4W) is a mobile application designed to integrate data from independent wearable sensors-motion capture system, surface electromyography, force platform, and smartwatch-to provide an overview of the posture and workload of occupational therapists. It can help identify poor work practices and raise awareness about ergonomic risk factors. This paper describes the development of E4W by following a User-Centred Design (UCD) approach. The initial stage focused on specifying the context of use in collaboration with six occupational therapists. Then the app was implemented using WordPress. Three iterations of the UCD cycle were performed. The usability test of prototype 1 was carried out in a laboratory environment, while the others were tested in a real healthcare work environment. The Cognitive Walkthrough was applied in the usability tests of prototypes 1 and 2. The System Usability Scale evaluated prototype 3. Results evidenced positive feedback, reflecting an easy-to-use and intuitive smartphone app that does not interfere with daily work activities.