FM - Contribuições em Revistas Científicas / Contribution to Journals
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- Development of digital self-management support for breast cancer survivors: ensuring evidence-based approaches and patient engagement from concept to implementationPublication . Franzoi, M. A.; Martin, E.; Ferreira, A. R.; Jacq, F.; Gillanders, E.; Meglio, A. Di; Vaz-Luis, I.Background: This study aimed to develop digital self-management programs incorporating evidence-based behavioral interventions to address the physical and psychosocial challenges faced by breast cancer survivors (BCS). Materials and methods: The development was guided by the Medical Research Council framework and involved five steps: (1) needs assessment and consultations with patients and providers (focus groups and surveys), (2) ranking of priority symptoms/conditions (evaluation of patient-reported outcomes within a large cohort), (3) identification of validated self-management programs (literature review), (4) prototype design, testing, and refinement (focus groups with patients for pilot testing), and (5) formal evaluation. This study focused on steps 1-4, including both quantitative and qualitative data collection. Results: In steps 1-2, six priority symptoms/conditions were identified: emotional distress, fatigue, insomnia, musculoskeletal pain, physical inactivity, and high body mass index. In steps 3-4, three digital behavioral programs were developed and tested: physical activity, mindfulness/meditation, and yoga. These programs incorporated educational content, video and podcast exercises, weekly live sessions, and moderated chat groups. During prototype testing, focus groups with 27 patients highlighted high satisfaction with the programs, noting their potential to increase access to care, empower patients, and improve symptom management. Engagement challenges were identified, including digital literacy aspects, the need for flexibility for autonomous practice, and the need for tools to boost motivation. Programs were refined and are being tested in hybrid efficacy implementation trials. Conclusions: Digital self-management programs intended to improve symptom management and quality of life for BCS were developed. By integrating evidence-based content and early patient feedback, these programs have the potential to enhance supportive care access and empower patients. Ongoing trials will assess their clinical efficacy and implementation, with an emphasis on equitable access and engagement across diverse populations.
- Unveiling the traits of HER2-low breast cancer: a comparative analysis of IHC1+ vs IHC2+/ISH-negative subgroups – insights from a 3-year cohort studyPublication . Correia, Jorge; Pulido, Catarina; Albuquerque, Joana; Prazeres, Gil; Margarido, Inês; Câmara, Mariana; Neto, Rita; Fernandes, Gonçalo; Godinho, João; Nave, Mónica; Mascarenhas, Francisco; Estudante, Isabel; Lopes, Paulina; Catarino, Ana; Passos-Coelho, José LuísBackground: Half of all breast cancer (BC) cases fall into the HER2-low category, defined as immunohistochemistry (IHC) 1+ or IHC 2+ in situ hybridization negative (ISH-). Two-thirds of these cases are IHC1+, while one-third is IHC2+/ISH-. New anti-HER2 antibody-drug conjugates (ADCs) have emerged as treatment options for metastatic or unresectable HER2-low BC patients. However, the heterogeneity between IHC1+ and IHC2+/ISH- subgroups and the clinical implications of varying HER2-low expression remain unclear. Objectives: This study aimed to compare demographic and clinicopathological differences between IHC1+ and IHC2+/ISH- subgroups and evaluate their response to neoadjuvant chemotherapy (NACT) in a cohort of patients with HER2-low BC. Methods: All consecutive patients diagnosed with HER2-low invasive BC between 2018 and 2020 at our institution were included in this retrospective cohort study. Clinicopathological characteristics were compared between IHC1+ and IHC2+/ISH- subgroups. Pathologic complete response (pCR) rates were assessed in patients undergoing NACT, and a multivariable logistic regression model was used to identify factors associated with pCR. Results: A total of 222 patients were included, evenly divided between IHC1+ (n=105, 47%) and IHC2+/ISH- (n=117, 53%) tumors, with no significant differences in baseline characteristics. Both subgroups predominantly comprised female patients (99% IHC1+ vs. 98% IHC2+/ISH-), postmenopausal (55% vs. 58%), with early-stage BC (94% vs. 98%) and estrogen receptor (ER)-positive tumors (90% vs. 90%). Around two-thirds had grade 2 tumors (63% vs. 64%), and the median Ki-67 index was 20% in both subgroups. Most BC were classified as luminal B-like (56% vs. 58%), followed by luminal A-like (35% vs. 34%), and TNBC (9% vs. 8%). Among the 43 patients with HER2-low BC who received NACT, 36% of IHC1+ patients achieved pCR, compared to only 5% in the IHC2+/ISH- subgroup (p = 0.021). Multivariable analysis revealed that IHC2+/ISH- status (vs. IHC1+) was significantly associated with lower odds of pCR (OR=0.07, 95% CI: 0.00–0.51, p = 0.025), while higher baseline Ki-67 and ER-negative status showed non-significant trends toward higher pCR rates after adjustment for other variables. Conclusion: Despite similar clinicopathological features, IHC2+/ISH- status was independently associated with lower pCR rates compared to IHC1+. These findings suggest that HER2-low subgroups may influence response to NACT and should be considered in multivariable prediction models, potentially informing stratified treatment approaches in the era of anti-HER2 ADCs.
- 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.
- A first case association of Lambert-Eaton Myasthenic Syndrome and first episode psychosis: a case reportPublication . Siopa, C.; Cordeiro, C.; Moura, B. M.Introduction: Lambert-Eaton Myasthenic Syndrome is an autoimmune neuromuscular junction disorder characterized by proximal weakness, autonomic dysfunction, and areflexia associated with antibodies against voltage-gated calcium channels. Psychotic symptoms can take place in many auto-immune neurological disorders, but their occurrence in myasthenic syndromes has rarely been observed. Objectives: We report a case of a 21-year-old female with primary autoimmune Lambert-Eaton Myasthenic Syndrome due to antivoltage-gated calcium channels antibodies subtype P/Q, who developed psychotic symptoms three years after motor symptom onset. Methods: The patient attended regular psychiatric follow-ups over three years. Results: With monthly administration, these psychotic symptoms improved after every cycle of intravenous immunoglobulin therapy. The patient displayed partial insight into the mental symptoms. Different causes of reversible psychosis were excluded, such as autoimmune encephalitis and paraneoplastic syndrome, though the patient tested positive for the anti-voltage-gated calcium channels antibodies subtype P/Q. Owing to muscle strength worsening and psychotic episodes, the patient was put on several treatments, including one admission to a Neurology unit. The patient then experienced psychotic exacerbation, leading to treatment with olanzapine at 20 mg/day. Psychotic symptoms persisted but were less severe, with greater intensity at night. After two years, the patient’s condition showed significant improvement, with olanzapine increased to 25 mg/day. Conclusions: This is, to our knowledge, the first described case of psychotic symptoms associated with Lambert-Eaton Myasthenic Syndrome. We speculate that voltage-gated calcium channel antibodies could have a role in developing mental symptoms. However, further hypotheses are discussed. Although the patient had received corticosteroid therapy before symptom onset, the timing and dosage make corticosteroid-induced psychosis unlikely. A primary psychotic disorder, such as schizophrenia, is considered improbable due to the atypical nature of the psychotic symptoms. This case underscores the need for further research on the neurobiological mechanisms linking VGCC antibodies to psychiatric symptoms.
- Multiple myeloma laboratory diagnostics made simple: practical insights and key recommendationsPublication . Portuguese Multiple Myeloma Grp; Sousa, Maria José Rego deMultiple myeloma is a clonal plasma cell malignancy with a highly variable range of clinical manifestations. Over recent decades, substantial progress has been made in laboratory diagnostics, which has deepened our understanding of disease biology, improved risk stratification, and informed treatment strategies. In an era of transformation and innovation, conventional laboratory methods remain essential, as cutting-edge technologies might not be immediately accessible to all laboratories. Nonetheless, even widely used laboratory methodologies present many challenges, such as variability in assay performance, interpretative criteria, and standardization. This review by the Portuguese Multiple Myeloma Group of the Portuguese Society of Hematology provides a comprehensive overview and practical appraisal of current conventional laboratory methods employed for multiple myeloma diagnosis.
- Diagnosis and laboratory follow-up of patients with multiple myeloma: guidelines from the Portuguese multiple myeloma groupPublication . Pires, Ana Marta; Barreto, João Pedro; Caetano, Joana; Soares, Maria José; Geraldes, Catarina; Fernandes, Bruno; Coucelo, Margarida; Chacim, Sérgio; Coelho, Henrique; Correia, Cecília; Cruz, Ana Paula; Cunha, Manuel; Cunha, Maria Rosário; Cunha, Nuno; Ferraz, Patrícia; Freitas, José Guilherme; Henrique, Rui; Lisboa, Susana; Lúcio, Paulo; Paiva, Artur; Pedrosa, Cláudia; Ramos, Inês; Sarmento, Ana Bela; Seabra, Patrícia; Sevilha, Joana; Sousa, Maria José Rego de; Sousa, Sara; Sousa, Teresa; Tavares, Márcio; Trigo, Fernanda; Bergantim, Rui; Roque, Adriana; João, CristinaMultiple myeloma is a neoplasm of plasma cells that in most cases is associated with the secretion of monoclonal immunoglobulins and can involve multiple organs. Its timely diagnosis is essential to limit or avoid irreversible damage and dysfunction of target organs. Appropriate initial stratification of patients allows for optimization in the selection and sequence of therapy, as well as proper follow-up during treatment and monitoring, impacting survival. These laboratory guidelines from the Portuguese Multiple Myeloma Group provide recommendations for the diagnosis and laboratory follow-up of patients with multiple myeloma. The follow-up and diagnosis of patients with other clinically significant monoclonal gammopathies were not included in this text. This article was based on international guidelines, scientific publications, and the experience of a panel of specialists in clinical and laboratory fields dedicated to the study and treatment of multiple myeloma.
- To silence or to stabilize: that is the questionPublication . Augusto, João Bicho
- Neuromyotonia and CASPR2 antibodies: electrophysiological clues to disease pathophysiologyPublication . Moura, João; Antenucci, Pietro; Coutinho, Ester; Bhatia, Kailash P.; Rocchi, Lorenzo; Latorre, AnnaContactin-associated protein-like 2 (CASPR2) is a transmembrane protein of the neurexin superfamily, essential for clustering voltage-gated potassium channels, particularly Kv1, at the juxtaparanodal regions of myelinated axons. This precise localisation is essential for maintaining normal axonal excitability and preventing aberrant signal propagation. Autoantibodies targeting CASPR2 have been associated with various neurological syndromes, notably peripheral nerve hyperexcitability (PNH), which presents clinically with neuromyotonia and myokymia. PNH is characterised by distinctive electrophysiological findings, including neuromyotonic discharges, myokymic discharges, and afterdischarges, which provide diagnostic value and insight into underlying pathophysiology. This review explores the mechanisms of anti-CASPR2-associated PNH, focusing on how antibody-mediated disruption of Kv1 channel clustering leads to altered axonal excitability. Current evidence suggests that both the distal and proximal segments of the axon are sites of pathological activity, where impairments in action potential termination and re-entry prevention result in spontaneous, repetitive discharges. While afterdischarges likely originate within the axon, the precise location—whether in the alpha-motoneuron soma or axon—is uncertain. The involvement of spinal inhibitory circuits has also been proposed, though it remains speculative. Understanding the neurophysiological features of anti-CASPR2-associated PNH is essential for improving diagnostic accuracy and guiding treatment strategies. Further research is needed to clarify the mechanisms of CASPR2-related hyperexcitability.
- 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.
- Intraindividual optic nerve sheath variation and intracranial pressure changes: a systematic review and meta-analysisPublication . Azevedo, Henrique; Neto, Lia Lucas; Berhanu, DavidBackground and Purpose: To review the existing evidence on multiple timepoint assessments of optic nerve sheath diameter (ONSD) as an indicator of intraindividual variation of intracranial pressure (ICP). Methods: A systematic search identified studies assessing intraindividual variation in ICP through multiple timepoint measurements of ONSD using ultrasonography. Meta-analysis of studies assessing intraindividual correlation coefficients between ONSD and ICP was performed using a random effects model, and we calculated the weighted correlation coefficient for the expected change in ICP associated with variations in ONSD. Results: A total of five studies, comprising 157 patients, were included in the review. ONSD was compared with invasive ICP measurement methods at multiple timepoints. Meta-analysis of intraindividual ONSD–ICP correlation demonstrated a correlation coefficient of 0.62 (CI: 0.50–0.71). Individual linear correlation analyses were performed in two of the studies, yielding correlation coefficients ranging from 0.79 to 1.00; however, widely variable individual slopes were found (1.51–41.43 mm/mmHg). ONSD variations ranged from 0.12 to 3.30 mm per 5 mmHg change in ICP, with a variation of 0.55 mm in adults with hypoxic brain injury and 0.77 mm in children with idiopathic intracranial hypertension. Conclusions: Our findings indicate that ONSD significantly correlates with ICP, and longitudinal intraindividual assessment shows a predominantly linear correlation between both variables. A personalized ONSD–ICP correlation equation may enable accurate ICP prediction, making ONSD a useful tool for follow-up in patients with previous invasive ICP measurements, when adjusted to each patient's characteristics and pathologies.