FM - Contribuições em Revistas Científicas / Contribution to Journals
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- Acromegaly in humans and cats: pathophysiological, clinical and management resemblances and differencesPublication . Lopes-Pinto, Mariana; Marques, Patrícia Lunet; Lacerda-Nobre, Ema; Miceli, Diego; Leal, Rodolfo Oliveira; Marques, PedroObjective: Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species. Design: A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed. Results: Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine. Conclusion: Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found.
- And the quest continues…Publication . Mendes, Lígia
- Arthroscopic cam resection reduces femoroacetabular contact pressure: a cadaver studyPublication . Dantas, Pedro; Gonçalves, S. B.; Gonçalves, S. R.; Mascarenhas, V.; Martins, J.; Silva, M. Tavares da; Consciência, J. GuimarãesAims Arthroscopic cam resection in femoroacetabular impingement syndrome leads to clinical improvement, but biomechanical studies on the efect of surgical intervention are scarce. In this study, we compared the femoroacetabular contact pressure (CP) in an intact cam morphology and after arthroscopic cam resection. The hypothesis was that arthroscopic cam resection decreases the femoroacetabular CP. Methods A cadaveric study was performed on nine hips with a cam morphology (? angle > 60°). CP was assessed using a new hip-specifc device and an intracranial pressure (ICP) sensor. These evaluations were performed during hip arthroscopy, in the intact joint and after cam resection, with the joint in diferent positions. These measurements were normalized and reported as a percentage of the native intact joint. Results A statistically signifcant diference in the mean CP measured with the hip-specifc device was observed before and after cam osteoplasty at 0° (41.2% (SD 29.7%); p = 0.014), 30° (54.5% (SD 16.6%); p = 0.011), 60° (39.8% (SD 23.0%); p < 0.001), 80° of fexion (36.3% (SD 22.1%); p < 0.001), and 80° of fexion with 20° of internal rotation (26.0% (SD 22.4%); p < 0.001). The ICP sensor is very fragile and difcult to handle in hip arthroscopy. Consequently, we limited the evaluations using this sensor to fve hips. A statistically signifcant diference in the CP was found before and after cam osteoplasty at 80° of fexion (57.6% (SD 29.1%); p = 0.004). Conclusion This biomechanical study evaluated a new hip-specifc device to intraoperatively measure the CP in arthroscopic surgery. It showed a signifcant decrease in the CP after arthroscopic cam resection with the joint in diferent positions. At 80° of fexion with 20° of internal rotation, a typical position to detect hip impingement, the CP was reduced to 26% after arthroscopic cam resection. The intraoperative measurement of CP provides surgeons with feedback to evaluate the efectiveness of the osteoplasty.
- Association of statin use on survival outcomes of patients with early-stage HER2-positive breast cancer in the APHINITY trialPublication . Maurer, Christian; Agostinetto, Elisa; Ameye, Lieveke; Lambertini, Matteo; Martel, Samuel; Ponde, Noam; Brandão, Mariana; Poggio, Francesca; Ferreira, Arlindo; Schiff, Rachel; Angelis, Carmine De; Gelber, Richard D.; Dent, Susan; Thomssen, Christoph; Piccart, Martine; Azambuja, Evandro dePurpose There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/ trastuzumab). Methods All patients (intent-to-treat population, n=4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started statins within 1 year from randomization were considered statin users. Survival curves were estimated using the Kaplan–Meier method. We used a Cox proportional hazards model for multivariate analysis. Results Overall, 423 (8.8%) patients were classifed as statin users. They were older, more often postmenopausal, had a higher body mass index, more often diabetes, hypertension, coronary heart disease and hyperlipidemia, had smaller sized tumors, were treated more often with breast conserving surgery, and less often with anthracycline-containing regimens. Overall, 508 IDFS events (12.8% among statin users and 10.4% among non-statin users) and 272 deaths (8.5% and 5.4%, respectively) occurred. In multivariate analysis, statin use was not associated with IDFS (HR, 1.11; 95% CI, 0.80–1.52), DRFI (HR, 1.21; 95% CI, 0.81–1.81) nor OS (HR, 1.16; 95% CI, 0.78–1.73). Conclusion In APHINITY, statin use was not associated with improved survival outcomes. These results must be interpreted with caution due to the exploratory nature of the analysis and the associated limitations.
- Beyond the apnea-hypopnea index: symptomatic assessment as a treatment pathway for obstructive sleep apnea managementPublication . Almeida, Fernanda R.; Falardo, Susana
- Breaking free from prognostic paralysis in chronic advanced diseasesPublication . Neto, Isabel Galriça; Sarmento, Teresa; Bruera, Eduardo
- Bringing hope to improve treatment in pancreatic ductal adenocarcinoma - a new tool for molecular profiling of KRAS mutations in tumor and plasma samplesPublication . Bravo, Ana Catarina; Morão, Bárbara; Luz, André; Dourado, Rúben; Oliveira, Beatriz; Guedes, Ana; Moreira-Barbosa, Catarina; Fidalgo, Catarina; Mascarenhas-Lemos, Luís; Costa-Santos, Maria Pia; Maio, Rui; Paulino, Jorge; Baptista, Pedro Viana; Fernandes, Alexandra R.; Cravo, MaríliaBackground/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.028, p = 0.029; HR 2.081, 95% CI 1.014–4.272, p = 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013–3.049, p = 0.045; HR 2.229, 95% CI 1.082–4.594, p = 0.030, respectively). Conclusions: ARMS–HRMA is a rapid and cost-effective method for detecting KRAS mutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis.
- CA2/3-dependent stability of frontal mnemonic representations predict episodic deficits in human amnesiaPublication . Miller, Thomas D.; Hickling, Alice L.; Wu, Yan I.; Zhou, Joseph H.; Handel, Adam E.; Coutinho, Ester; Pollak, Thomas A.; Zandi, Michael S.; Maguire, Eleanor A.; Rosenthal, Clive R.The hippocampus reconstructs past experiences by integrating sensory, perceptual, and conceptual information across a cortico-hippocampal autobiographical memory network. Here, in 18 human participants with amnesia, we decode the effects of bilateral focal hippocampal damage on distinct autobiographical representations using representational dissimilarity matrices (RDMs). Hippocampal pathology results in impaired generalized episodic memory retrieval RDM model fit in the left angular gyrus and in reduced distinct episodic memory RDM model fit in the right inferior frontal gyrus (rIFG), while right angular gyrus (rANG) and right orbitofrontal cortex (rOFC) fall below multiple correction thresholds. Trial-by-trial voxelrepresentational stability is reduced in the rANG, rIFG, and rOFC. The RDM model fits and mnemonic stability are predicted by total CA2/3 volumes. Trial-by-trial retrieval stability within the rOFC and rIFG predicts episodic memory performance, providing a direct neural correlation between hippocampal dysfunction, altered mnemonic representations, and amnesia.
- Cardiovascular prevention: current gaps and future directionsPublication . Dores, Hélder; Santos, José Ferreira; Gil, Victor; Gonçalves, Pedro de AraújoCardiovascular Disease (CVD) remains the leading cause of morbidity and mortality worldwide. Despite significant advances in diagnosis and treatment, the global burden of CVD remains high, underscoring the crucial need for more effective and comprehensive prevention strategies. This narrative overview aims to critically evaluate the current pillars of cardiovascular prevention, identify the gaps in approaches and outline promising future directions. Challenges and barriers in lifestyle adherence and pharmacological management are addressed, while the increasing role of non-traditional and emerging risk factors is discussed. Future directions include maximizing the value of digital health to improve patient engagement and adherence, adopting precision medicine to refine risk stratification and implementing public health policies for population-level interventions. The optimization of cardiovascular prevention requires a multi-level approach that integrates clinical strategies with personalized solutions and environmental policies to ultimately reduce the global impact of CVD.
- Deciphering the mechanisms: pathophysiology of migraine-related cognitive dysfunctionPublication . Fernandes, Catarina; Gil-Gouveia, RaquelMigraine is increasingly understood as a disorder of brain network dysfunction, where attack-related cognitive symptoms (attention deficits, slowed processing speed and executive dysfunction) can be as disabling as pain and may persist into the interictal period. Such symptoms are associated with functional and structural changes across the migraine cycle, involving the prefrontal cortex, thalamus, hypothalamus, hippocampus and cerebellum. Interictal deficits in working memory, visuospatial processing, verbal fluency and executive function are also documented. Rodent models show impairments in learning and memory, while humans studies suggest that cortical hyperresponsiveness and deficient sensory habituation contribute to altered attentional processing, reflecting thalamocortical dysfunction and abnormal synaptic plasticity as underlying mechanisms. Cognitive performance is modulated by disease severity, chronification, hormonal fluctuations, psychiatric comorbidities, sleep disturbances and medication use. Anxiety, depression and sleep disorders negatively affect working memory, executive function and attention, while medication overuse further impairs visuospatial skills and orientation. Dementia risk appears heightened in migraine patients with frequent and severe attacks, as clinic-based studies consistently report cognitive deficits in this cohorts, unlike population-based studies. While longitudinal cohorts find no increased dementia risk, meta-analyses suggest a modest risk elevation. Differences are likely due to methodological differences in cognitive testing and diagnostic approaches. Cognitive dysfunction in migraine is multidimensional, involving intrinsic neuronal mechanism and external modulators, supporting the need for rational management strategies and treatment interventions.