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- Description of the Hamburg Alexander Leukodystrophy Cohort—Insights into Practical Classification and the Care SituationPublication . Kokaly, Nadia; Guerreiro, Helena; Bredow, Janna; Dreha-Kulaczewski, Steffi; Ohlenbusch, Andreas; Köhler, Wolfgang; Reinhardt, Tabea; Schön, Gerhard; Volk, Alexander E.; Sigel, Helen; Bley, AnnetteBackground: Alexander disease (AxD) is a rare severe leukodystrophy that has no cure to date. A pathogenic gain-of-function variant in the GFAP gene affects the astrocytes and subsequently the function of the white matter in the CNS. Methods: We retrospectively analyzed the most frequent symptoms of nine AxD cases, classified them according to published classifications, and described the need of care and support. Results: The description of the courses of disease of nine cases with AxD reflects the broad spectrum of different phenotypes of AxD, with often occurring apnoea. Data about care and support for AxD patients indicate a high and heterogeneous need of support. Treatment with steroids reduced symptoms in two patients. Some patients showed lasting improvement during their course of disease. Conclusions: The course of AxD is very heterogeneous. Thus, we extracted relevant key features to describe the severity of the disease, namely feeding problems, epilepsy, age-appropriate motor function, failure to thrive, age-appropriate language and apnoea. We recommend early evaluation for clinical care and support. For some AxD patients, treatment with steroids may alleviate symptoms. Further development of efficient treatments is necessary
- Frailty and outcomes in elderly ICU patients: insights from a portuguese cohortPublication . Lourenço, Eva; Rodrigues, Isabel; Sampaio, Mário; da Costa, EmiliaBackground: Frailty is a key determinant of outcomes in critically ill elderly patients, but data from Portugal remain limited. To our knowledge, this is the first study to examine the prevalence and prognostic impact of frailty among elderly ICU patients in a Portuguese hospital setting. Objective: To determine the prevalence of frailty among elderly patients admitted to an intensive care unit (ICU) in southern Portugal and to examine its crude associations with illness severity, organ support, and mortality outcomes. Methods: We conducted a retrospective cohort study including 125 patients aged ≥ 65 years admitted to the polyvalent ICU of Hospital de Faro over the last six months of 2024. Data included demographics, comorbidities, Charlson Comorbidity Index (CCI), severity scores (SOFA, SAPS II, APACHE II), and frailty status assessed by the Clinical Frailty Scale (CFS). Outcomes were the need for organ support, ICU and hospital mortality, and length of stay. Results: Frailty (CFS ≥ 5) was identified in 30.4% of patients. Frail patients were older, had higher comorbidity burden (CCI), and presented with significantly higher severity scores at admission. They also required more invasive support, including vasopressors and invasive mechanical ventilation, while acute kidney injury (AKI) requiring renal replacement therapy (RRT) was similar between groups. ICU mortality was significantly higher among frail patients (50.0% vs. 31.0%), as was hospital mortality (76.3% vs. 33.3%). Length of ICU stay did not differ, although frail patients tended to have longer hospitalizations overall. Conclusions: Frailty was highly prevalent and strongly associated with increased severity, greater need for organ support, and higher mortality. Routine frailty assessment at ICU admission may enhance prognostic accuracy and support patient-centered decision-making.
- Genetic diversity of rotavirus A causing diarrhea in patients admitted to the Clinic University Hospital in Valencia, Spain (2022-2024)Publication . Conjo, Carolina da Glória Dinis; Ferreira, Bibiana I.; Gomez, Javier Buesa; Deus, Nilsa deA diarreia é uma das principais causas de mortalidade infantil em todo o mundo, e o rotavírus destaca-se como o principal agente etiológico associado. Neste contexto, muitos países introduziram a vacina contra o rotavírus no seu calendário de vacinação infantil, incluindo a Espanha. No entanto, a carga das doenças diarreicas continua elevada. Existe uma lacuna de informação em relação a infecção por rotavírus em pacientes que não tenham idade pediátrica e muitos fatores podem estar implicados na suscetibilidade a infeção por rotavírus entre eles os fatores genéticos do hospedeiro denominados Histo Blood Group Antigens (HBGA´s), que podem reconhecer agentes entéricos que modulam doenças entéricas infecciosas, conferindo risco ou suscetibilidade à população. Foi realizada uma análise transversal de dados de base hospitalar, de abril de 2022 a fevereiro de 2024, em 136 pacientes atendidos com diarreia no Hospital Clínico Universitário de Valência. A triagem inicial das amostras foi feita por Real-Time PCR no Hospital Clínico Universitário de Valencia, 136 amostras foram positivas para Rotavírus A (RVA) e testadas por RT-PCR para a identificação do genótipo no laboratório de Microbiologia da Universidade de Valência. A maior diversidade de estirpes de rotavírus foi encontrada em crianças menores de 2 anos e os genótipos mais comuns nesta faixa etária foram G4P[8] e G12P[8]. Cerca de 26,5% das amostras eram não tipificáveis, 16,9% correspondiam a G4P[8], 16,2% eram NTP[8] e 11,8% eram G12P[8]. A sazonalidade foi associada à distribuição das estirpes de rotavírus (p-valor<0,001), com maior pico de infecção em maio, julho e abril de 2023. O status secretor do gene FUT2 foi determinado em 7,7% (2/26) das amostras testadas. A presente análise mostrou uma alta proporção de infecção e diversidade genotípica em crianças com menos de 24 meses de idade. No futuro, será necessário investigar a diversidade genética e a dinâmica evolutiva das estirpes de rotavírus. Embora o estudo tenha encontrado dificuldades na determinação do status secretor para FUT2 a partir das amostras fecais, apresentou informações inovadoras sobre o potencial e as limitações desta abordagem.
- Letter to the editor: robustness of osteoporosis risk prediction models with enhanced statistical analysesPublication . Pires de Carvalho, Filipe Ricardo; Gavaia, PauloIn response to Oka et al.’s letter, we conducted additional statistical analyses to validate the robustness of our osteoporosis risk prediction model using NHANES 2007–2014 data (n = 7924). We evaluated 10 key predictors through Spearman’s rho, Kendall’s tau, Mutual Information (MI), and Total Correlation. Weight (BMX_BMXWT) and arm circumference (BMX_BMXARMC) showed strong negative correlations with osteoporosis risk (rho: 0.49, 0.47, p < 1e-270; MI: 0.17, 0.15), while age (DEMO_RIDAGEYR) exhibited a positive correlation (rho: 0.33, p < 1e-128; MI: 0.08). Total Correlation (32.68) confirmed significant multivariate interactions among predictors. These findings reinforce the model’s predictive strength, addressing Oka et al.’s recommendations and affirming the importance of anthropometric and demographic factors in osteoporosis risk assessment.
- Mitochondrial dysfunction in lysosomal storage disordersPublication . De la Mata, Mario; Cotán, David; Villanueva-Paz, Marina; De Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Suárez-Rivero, Juan; Tiscornia, Gustavo; Oropesa-Ávila, ManuelLysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS), where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (∆Ψm), diminished ATP production and increased generation of reactive oxygen species (ROS). Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD), the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase). Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs.
- Molecular tools to study SCA2: from new advanced disease models to CRISPR-mediated editing approachesPublication . Gonçalves, Rebekah Cavaco Koppenol; Nóbrega, Clévio; Matos, Carlos A.; Almeida, Luís Pereira deSpinocerebellar ataxia type 2 (SCA2) is a rare neurodegenerative disease caused by an abnormal expansion of the trinucleotide CAG in the coding region of ATXN2. This overexpanded CAG region is translated into an abnormally long tract of glutamines within the ATXN2 protein, which above 32 repetitions drives pathology. SCA2 comprehends a complex network of pathological mechanisms, progressively leading to neuronal dysfunction and cell death. As a result of the expanded ATXN2-mediated neurodegeneration, especially affecting the cerebellum and the brainstem, SCA2 patients suffer from several motor and non-motor signs and symptoms, with ataxia as the most frequent. Currently, there is no therapy capable of delaying or stopping disease progression, leading to the premature death of patients. Disease models have proven to be a valuable tool for the study of the pathological mechanisms underlying SCA2. In this work we develop a new transgenic mouse model for SCA2 with early motor and neuropathologic phenotype to study the role of the ATXN2 expanded protein in the pathogenesis of the disease. Additionally, we generated a SCA2 patient-derived iPSC line to serve as a platform to test new advanced therapeutic strategies. Taking advantage of the CRISPR toolbox to manipulate gene expression, we designed three CRISPRbased strategies targeting the ATXN2 gene: a CRISPR-Cas9 indel directing the nuclease activity of Cas9 to an early site of the ATXN2 gene; a CRISPRi using the dCas9-KRAB complex to hinder transcription; and a CRISPR-Cas9 excision directing Cas9 to two sites of the ATXN2 to excise the CAG region. We tested these strategies in the newly generated SCA2 patient-derived iPSC line, inducing its differentiation into mature neurons. The CRISPR strategies resulted in a decrease of the ATXN2 protein levels or the complete ablation of ATXN2 expression, preventing several pathological traits of SCA2. The tools developed in this project support the development of CRISPR-based disease-modifying strategies for SCA2, enlightening the action of ATXN2-mediated pathogenesis.
- P0397 Soluble transferrin receptor as a reliable inflammation-independent marker of iron deficiency in crohn’s disease and ulcerative colitisPublication . Portela, F.; Santos, M. P. Ministro dos; Sousa, Helena Tavares; Roseira, Joana; Fernandes, S. R.; Crespo, R.; Domingues, B.; Santiago, M.; Miranda, R.; Dias, S.; Dias, C. C.; Magro, F.Background: Iron deficiency is a common complication in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD).1 However, standard iron markers are influenced by inflammation, complicating the diagnosis of true iron deficiency.1,2 Soluble transferrin receptor (sTfR) has been proposed as a more reliable, inflammation-independent marker of iron demand.3 This study aimed to assess the utility of sTfR in identifying iron deficiency without anaemia (IDWA). Methods: The ID_IBD study was a multicentre, cross-sectional study. Iron status was classified using two approaches: the ECCO consensus definition, focusing on ferritin thresholds adjusted for inflammatory markers (C-reactive protein [CRP] and faecal calprotectin [FCAL]), and a stricter definition that adds transferrin saturation to the ECCO criteria. sTfR levels were compared across groups, and ROC curve analysis was used to identify optimal diagnostic cut-offs. Results: This analysis included 411 IBD patients (130 UC, 281CD) and 178 controls. sTfR showed no correlation with CRP or FCAL. In UC, patients with IDWA had significantly higher sTfR levels (median 1.20mg/L, IQR 1.02-1.42) compared to non-IDWA patients (median 1.05mg/L, IQR 0.92-1.22; p=0.013). Anaemic UC patients also showed elevated sTfR levels (median 1.27mg/L, IQR 1.14-1.59) compared to non-IDWA individuals (patients but was significantly higher in anaemic patients (p=0.003). Conclusion: sTfR appears to be an inflammation-independent marker of iron status in IBD. It showed potential for identifying IDWA in UC, while in CD it mainly reflected increased iron demand in anaemia. Further longitudinal studies are warranted to validate its role and assess its clinical utility in IBD.
- Risk factors for non-communicable diseases in refugees, asylum seekers, and subsidiary protection beneficiaries resettled or relocated in Portugal between 2015 and 2020Publication . Pinto de Oliveira, Ana; Conceição, Cláudia; Fronteira, InêsAbstract: Non-communicable diseases, previously thought of as a problem of high-income countries, now coexist in low- and middle-income countries, including the countries of origin for many refugees traveling to Europe. We aimed to describe the prevalence of risk factors for non-communicable diseases among refugees, asylum seekers, and subsidiary protection beneficiaries resettled or relocated in Portugal between 2015 and 2020 and compare these to the prevalence of risk factors in the 12 months before they left their country of origin. A cross-sectional study was conducted between 2019 and 2020 of all refugees, asylum seekers, and subsidiary protection beneficiaries attending a Lisbon, Portugal refugee center. Behavioral and biological risk factors were assessed using the WHO STEPwise modified questionnaire. A descriptive statistical analysis was conducted, which included 80 respondents, mainly men, with an average age of of 30.3 ± 9.8 years. The prevalence of several behavioral risk factors for non-communicable diseases among refugees, asylum seekers, and subsidiary protection beneficiaries was higher at the time of the study than in the 12 months before leaving the country of origin. Differences between men and women were noted in tobacco (49.1% vs. 25.9%) and alcohol use (43.4% vs. 18.5%) in the receiving country. Overweight and obesity also showed differences by gender (7.5% vs. 11.1% and 39.6% vs. 48.1%). The prevalence of suicidal ideation and suicidalplanning was high, and varied from 6.3% and 20% in the country of origin to 16.3% and 38.5% respectively in the receiving country, however the prevalence of suicide attempts was lower in the receiving country (66.7%) compared to the country of origin (100.0%). Information on health and social determinants is critical to identify priorities and increase access to access to gender-specific health and community level interventions, including mental health, to reduce risk factors associated with refugee relocation and resettlement.
- Sarcopenia in women with anorectal dysfunctions—a female sarcopelvic studyPublication . Vieira, Ana Margarida Duarte da Silva; Pais, Sandra; Martins, Viviana; Castelo, Barbara; Saraiva, Miguel MascarenhasAnorectal dysfunctions (ARDs) include fecal incontinence (FI) and functional defecation disorders (FDDs). The pelvic floor muscles play a central role in the physiology of continence and defecation. We aimed to investigate the prevalence of sarcopenia in a female group with anorectal dysfunctions and compare them with a healthy female age-matched group. As secondary objectives, the relationship between anorectal dysfunction outcomes and sarcopenia was analyzed. Methods: We conducted a single-center cross-sectional, interventional, controlled, and double-blind study involving female adults admitted to an ARD outpatient clinic assessed for FI and/or FDD. A control group was also included of age-matched women without ARD. Sarcopenia was evaluated in the entire cohort, according to the latest criteria. Statistical analysis was performed using SPSS software v.29, considering a confidence interval of 95%. Results: A total of 130 participants were included, equally divided by the two groups. The median age was 64 years. Both groups were also similar regarding body mass index (BMI), physical activity index values, and dietary patterns. Among the 130 investigated women, there were no cases of confirmed sarcopenia or severe sarcopenia, but 15 women (11.5%) had probable sarcopenia or dynapenia. The case group had significantly more probable sarcopenia than women in the control group (14 (21.5%) vs. 1 (1.5%), p < 0.001). The presence of relevant comorbidities, such as irritable bowel syndrome (IBS), urinary incontinence (UI), and meat dietary pattern (MDP), was a risk factor for probable sarcopenia. The binomial logistic regression analysis showed that probable sarcopenia (OR 3.9; CI 1.1–14.1, p = 0.039) was associated with a worse treatment response. Conclusions: Probable sarcopenia or dynapenia was significantly more prevalent in women with ARD and was a predictive factor of a worse treatment response, regardless of the ARD severity. Concomitant UI, MDP, IBS, and psychiatric conditions were significantly associated with dynapenia. The inclusion of the evaluation of sarcopenia in these patients should be considered.
- Sources of discomfort and treatment strategies for trauma patients in the pre-hospital setting: a scoping reviewPublication . Melo, Filipe; Santos, Margarida Reis; Sousa, Miguel Castelo-Branco; Mota, Cátia; Mota, MauroIntroduction: Trauma remains a leading cause of mortality and long-term disability worldwide, often causing significant discomfort during prehospital care. Addressing these discomforts effectively is crucial for improving patient outcomes. This scoping review aimed to identify and categorize the types of discomforts experienced by adult trauma victims in prehospital settings and map the pharmacologic and nonpharmacologic interventions used to mitigate them. Methods: This scoping review followed the Joanna Briggs Institute framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A comprehensive search was performed in databases including MEDLINE, CINAHL, Scopus, Embase, PsycINFO, Joanna Briggs Institute Evidence Synthesis, Cochrane Database, and relevant gray literature sources. Studiesinvolving adult trauma patients(>_18 years) in prehospital care that reported on discomfort and interventions were included without restrictions on publication date. Results: Seventeen studies met the inclusion criteria, covering various international contexts. Acute pain was the most frequently reported discomfort, followed by anxiety, fear, cold-induced discomfort, and discomfort caused by immobilization. Pharmacologic interventions predominantly included opioids, nonsteroidal anti-inflammatory drugs, paracetamol, ketamine, and methoxyflurane, whereas nonpharmacologic interventions comprised acupressure, transcutaneous electrical nerve stimulation, cryotherapy, warming measures, communication strategies, and emotional support. Nonpharmacologic interventions, especially acupressure and communication techniques, showed promising results in reducing pain and anxiety. Discussion: The findings underline the multidimensional nature of discomfort in prehospital trauma care and highlight effective interventions, including pharmacologic and complementary nonpharmacologic strategies. However, significant gaps remain regarding standardized assessment tools for non–pain-related discomforts and combined interventions. This review underscores the necessity for comprehensive management protocols and further research to optimize patient comfort and care outcomes in trauma settings.