A cirurgia reconstrutiva em patologia oncológica do nariz : paralisia do nervo facial anatomia cirurgia do nariz

RESUMO: Os carcinomas localizados no nariz são muito frequentes em todas as séries conhecidas. São de diagnóstico clínico fácil e a sua confirmação por biópsia é muito segura. As terapêuticas mais indicadas são a cirurgia e a radioterapia, genericamente eficazes. Verifica-se, no entanto, que os pacientes continuam a solicitar tratamento em estádios muito avançados, mesmo conhecendo o diagnóstico e tendo acesso aos serviços sem custos. Esta situação poderá explicar-se face ao curso relativamente lento de muitos destes tumores e à idade geralmente avançada dos doentes que, de acordo com alguns inquéritos, receiam mais a terapeûtica do que a doença. Para obtenção de informação útil para condução deste problema, foram ainda analisados outros parâmetros. A maioria dos pacientes continua a solicitar tratamento quando as lesões envolvem duas subunidades nasais. Esta circunstância permite planear o tratamento cirúrgico com relativa facilidade, isto é, com exérese e reconstrução cujo resultado estético final é bastante aceitável. Os tumores de grandes dimensões, envolvendo várias subunidades, sendo frequentes, raramente implicam rinectomia total. Pelo contrário, são mais frequentes os tumores que envolvem metade do nariz e as estruturas vizinhas tais como o maxilar, a órbita e o lábio superior, atingindo mesmo a base do crânio. O controlo da doença nestes estádios é muito difícil. Não raramente, quando se crê que a doença está controlada, a cirurgia reconstrutiva bem como outras formas de reabilitação conjugadas, deixam ainda muita insatisfação. A nossa actividade tem-se desenvolvido seguindo os critérios adoptados nos melhores centros, isto é, as técnicas clássicas, complementadas com refinamentos recentes. Porém reflectindo sobre os resultados obtidos no tratamento de tumores do nariz, surge-nos um conjunto de questões para as quais ainda não encontrámos respostas cabais. Actuando de acordo com os princípios que definem o estado da arte, não obtivemos ainda resultados que satisfaçam tanto os doentes quanto os cirurgiões. Incessantemente procuramos novos dados técnicos e científicos que nos permitam sair deste ciclo vicioso em que o doente retarda a procura de assistência, receoso de que a terapêutica o deixe desfigurado. Tendo sempre em vista a obtenção dos melhores resultados com o mínimo de tempos cirúrgicos, valorizamos alguns detalhes praticados nos retalhos com padrão vascular bem definido. Dado que as sequelas na zona dadora de tecidos são uma incontornável preocupação, procuramos refinar a sua aplicação no sentido de as atenuarmos. A fronte, excelente zona dadora para reconstrucção nasal major, era sede de sequelas actualmente inaceitáveis. Estudado o comportamento dos tecidos na fronte, depois de levantado o retalho e efectuado o seu encerramento com uso da técnica de expansão intra-operatória, determinámos a presença do Factor de Crescimento Vascular Endotelial no próprio retalho e na zona dadora, tendo em vista que a sua presença poderá explicar o comportamento dos tecidos que foram submetidos a esta técnica. Procurou-se estudar a qualidade da reconstrução em 45 pacientes submetidos a cirurgia de exérese e reconstrução nasal major, assim como a qualidade de vida, relacionada com a doença e a terapêutica. Embora se possa admitir a existência de dados sugestivos de estratégias mais adequadas, não foi possível relacionar a qualidade da reconstrução com qualidade de vida dos pacientes. Poderá eventualmente concluir-se que a observação permanente da reconstrução, com qualidade estética e funcional, será o melhor método de alterar a ideia clássica, ainda muito divulgada, mas já ultrapassada, de que a cirurgia reconstrutiva do nariz não é mais que transformar um defeito horroroso num defeito ridículo.---------------ABSTRACT: Malignant tumours found in the nose are very frequent in all known series. Clinical diagnosis is simple and confirmation of biopsy diagnosis is accessible and safe. The most advisable therapies are surgery and radiotherapy. Despite everything patients continue to wait until the tumour is in an advanced stage before asking for therapy, although they know the diagnosis and have free access to specialised services. This situation could probably be explained by the slow development rate of the tumours which is associated with the age of the patient. Upon inquiry, it was found that a significant number of patients are more afraid of therapy than of the disease itself. Other parameters have been analysed in order to obtain useful information about the management of this problem. The majority of patients seek adequate treatment when the lesions involve two nasal subunits. This allows the programming of surgical therapy with relative ease as they may be removed and reconstructed with interesting final aesthetical results. Large tumours involving several subunits are frequent, but they rarely call for total rhinectomy. On the contrary, tumours more frequently involve half of the nose and their neighbouring structures: for example, maxillary, orbital and upper lip, even reaching as far as the base of the skull. The control of the disease is very difficult in these stages.In cases in which it is believed that the disease is under control, reconstructive surgery in conjunction with other forms of rehabilitation still result in a lot of dissatisfaction. In our activity we try to follow the criteria adopted by the best centres following classic techniques, complemented with recent refinements. Reflecting on the treatment of tumours of the nose has led us to a series of questions to which we haven’t yet found the answers. In accordance with the defined principles of ‘the state of the art’ it still doesn’t satisfy either the patients or the surgeons. We are looking for new technical and scientific data which allows us to leave this vicious cycle, in that the deferred patient avoids looking for assistance, based on the fear that therapy could leave them disfigured. We attach importance to some practiced details on the well-defined vascular pattern of the flaps, with the principle aim of obtaining a good result, from the minimum number of operations. It is known that sequels in donor sites are a concern, so applied refinements are used in order to reduce the defect. The forehead has been considered an excellent donor site for major nasal reconstruction but the area of sequel is nowadays unacceptable. We tried to study the behaviour of the tissues of the forehead after taking the flap and closing the wound, using the intraoperative expansion technique. We determined the presence of Vascular Endothelial Growth Factor in the flaps and in the donor site, in which its presence could explain the behaviour of the tissues of the forehead that are submitted to this technique. The quality of the reconstruction was studied in 45 patients who were submitted to surgical exeresisand major nasal reconstruction, as was the relationship between the disease and the therapy regarding quality of life. It was not possible to directely relate the quality of the reconstruction to the quality of patients life, although some suggestive data of more adequate manegement may be interesting. One might eventually conclude that, permanent exposure of the reconstruction with aesthetic and funcional quality would be the best method in order to modify the classic idea which is still known although overridden today, that nasal reconstruction could transform a horrible defect into a ridiculous one.-------RÉSUMÉ: Les carcinomes situés sur le nez sont très fréquents dans toutes les séries connues. Ils sont de diagnostic facile et la confirmation de ce dernier par une biopsie, est accessible et très fiable. La chirurgie et la radiothérapie sont les thérapeutiques les mieux indiquées. Toutefois les patients continuent de solliciter un traitement, seulement dans des états très avancés bien qu’ils aient eu connaissance du diagnostic et ayant accès aux services. Cette situation pourra probablement s’expliquer par l’évolution relativement indolente de beaucoup de tumeurs, associée à l’âge des malades; bien que selon quelques enquêtes réalisées un nombre élevé de malades craint davantage la thérapeutique que la maladie. D’autres paramètres sont analysés en vue d’obtenir des informations utiles pour l’accompagnement de ce problème. La majorité de nos patients sollicite le traitement adéquat quand les lésions entourent deux sous-unités nasales, ce qui permet de planifier le traitement chirurgique avec une certaine facilité, c’est à dire l’exérèse et la reconstruction ayant un résultat final esthétique généralement très acceptable. Les tumeurs de grandes dimensions entourant différentes sous-unités sont fréquentes mais elles impliquent rarement une amputation nasal total. Au contraire, les tumeurs les plus fréquentes sont celles qui entourent la moitié du nez et les structures voisines comme le maxillaire, l’orbite et la lèvre supérieure, parfois, elles peuvent même atteindre la base du crâne. Le contrôle de la maladie dans ces états est très difficile et quand nous pensons que la maladie est contrôlée, la chirurgie reconstructrice associée à d’autres formes de réhabilitation provoquent encore une grande insatisfaction. Nous exerçons notre activité en essayant de suivre les critères adoptés dans les meilleurs centres. Nous appliquons les techniques classiques complétées de retouches pour obtenir un meilleur resultat. Le fait de traiter les tumeurs nasales nous fait réfléchir et poser un ensemble de questions auxquelles nous n’avons pas pu trouver de réponses. En actuant en accord avec les principes qui définissent l’état de l’art, nous n’avons pas obtenu de résultats qui satisfassent les malades et les chirurgiens. Nous recherchons de nouvelles données techniques et scientifiques qui nous permettent de sortir de ce cercle vicieux dans lequel le patient retarde la recherche d’aide craignant que la thérapeutique le défigure. Nous valorisons certains détails pratiqués sur les lambeaux de patron vasculaire bien défini et ayant comme principaux objectifs l’obtention d’un bon résultat en moins de temps de chirurgie. Nous savons que les séquelles de la zone donneuse de tissus sont préoccupantes, ainsi, que les retouches qui ont été appliqués dans l’objectif de les atténuer. Le front, excellente zone donneuse pour la reconstruction nasale majeure, était une source de séquelle actuellement inacceptable. Nous avons étudié le comportement des tissus du front après avoir relevé le lambeau et effectué la fermeture avec la technique de l’expansion intraoperative. Nous avons déterminé la présence du Facteur de Croissance Vasculaire Endothéliale dans le propre lambeau et dans la zone donneuse, celle-ci pourra expliquer le comportement des tissus du front qui ont été soumis à cette technique. On a essayé d´etudier la qualité de la reconstruction sur 45 patients soumis à la chirurgie d´exérèse et la reconstruction nasal majeure, ainsi comme la qualité de vie en relation avec la maladie et la thérapie. Quoique l´on puisse conclure par l´existence des données subjectives des stratégies plus justes, il est impossible de faire un rapport sur la qualité de la reconstruction avec la qualité de vie des patients. Eventuellement l´on purrait conclure que l´observation permanente de la reconstruction avec qualité esthétique et fonctionnelle, se serait la meilleure méthod de changer l´idée classique, mais depassée, de que la rhinopoièse n´est pas que transformer un affreux défaut par un défaut ridicule.

Vibroacoustic disease II: The biological and acoustical basis of low frequency noise induced pathology

Proceedings Institute of Acoustics (UK); vol. 25, nº2, p. 72-78.

Juvenile Parkinson disease caused by parkin mutations: large deletions and pathogenic mechanisms

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Algorithm for the Parkinson’s disease behavioural models characterization using a biosensor

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Anti-apolipoprotein A-I antibodies in the pathogenesis of Alzheimer disease : project plan

RESUMO: A doença de Alzheimer (AD) é a forma mais comum de demência em todo o mundo e sua prevalência deverá duplicar até 2050. Os mecanismos precisos responsáveis pela AD são desconhecidas mas as características histopatológicas estão bem caracterizadas. A hipótese mais importante para a perda neuronal e declínio cognitivo na AD é a cascata amilóide que indica que AD é o resultado da sobreprodução de beta amilóide (Aβ) e / ou remoção ineficaz; a acumulação do BA no cérebro seria o passo crítico na patogénese da AD. Actualmente, a identificação de proteínas que se ligam ao Aβ e modulam a sua agregação e neurotoxicidade pode proporcionar a base para novas abordagens terapêuticas. A apolipoproteína AI (ApoA-I), o principal componente das HDL humanas, interage com o domínio extracelular da proteína precursora de amilóide (APP), bem como com o Aβ. Estudos epidemiológicos têm mostrado uma diminuição acentuada da ApoA-I plasmática em doentes com AD, com uma correlação inversa entre o nível de ApoA-I e o risco de AD. Este trabalho pretende apresentar um projecto que tem como objectivo investigar se os anticorpos anti-apo AI podem impedir a formação de complexos Aβ / ApoA-I, bloqueando o efeito protector da ApoA-I. A hipótese baseia-se na possibilidade dos doentes com AD terem anticorpos anti-ApoA-I plasmáticos e de estes poderem interferir com a formação do complexo no LCR.------- ABSTRACT:Alzheimer’s disease (AD) is the most common form of dementia world-wide and its prevalence is expected to double by the year 2050. The precise mechanisms responsible for AD are unknown but the histopathologic features are well-characterised. The most compelling hypothesis for neuronal loss and cognitive decline in AD is the amyloid cascade hypothesis which states that AD is the result of amyloid beta (Aβ) overproduction and/or ineffective clearance and its accumulation in the brain would be the critical step in AD pathogenesis. Currently, identification of proteins that bind Aβ and modulate its aggregation and neurotoxicity could provide the basis for novel treatment approaches. Apolipoprotein A-I (ApoA-I), the main constituent of human HDL, ApoA-I interacts with the extracellular domain of amyloid precursor protein (APP), as well as with Aβ itself. Epidemiological studies have shown a marked decrease of plasma ApoA-I levels in AD patients, with an inverse correlation between the ApoA-I level and the risk of AD. This work intends to present a project that aims to investigate if anti-ApoA-I antibodies may prevent the formation of the Aβ /ApoA-I complex and by doing so blocking the protective effect of ApoA-I in AD. We base the hypothesis on the possibility that patients with AD might have anti-ApoA-I antibodies in plasma and that these can interfere with the complex formation in the cerebrospinal fluid (CSF).

PROTEIN FOLDING AND DISEASE THE MITOCHONDRIAL PROTEIN FRATAXIN

This dissertation focuses on the study of frataxin, a small mitochondrial protein whose deficiency is associated with the neurodegenerative disease Friedreich's ataxia (FRDA). Aiming at a better understanding of frataxin conformational and functional properties, two lines of research were followed: first, the effect of FRDA-related mutations in human frataxin (FXN) were studied and the role of oxidative stress related modification addressed; second, yeast frataxin (Yfh1) orthologue was used to explore the conformational and functional properties of the protein.(...)

Dissecting gastrointestinal dysfunction and inflammation in a “pre-motor” rodent model of Parkinson’s disease

Research on Parkinson’s disease (PD) has mainly focused on the degeneration of the dopaminergic neurons of nigro-striatal (NS) pathway; also, post-mortem studies have demonstrated that the noradrenergic and the serotonergic transmitter systems are also affected (Jellinger, 1999). Degeneration of these neuronal cell bodies is generally thought to start prior to the loss of dopaminergic neurons in the NS pathway and precedes the appearance of the motor symptoms that are the “hallmark” of PD. Gastrointestinal (GI) motility is often disturbed in PD, manifesting chiefly as impaired gastric emptying and constipation. These GI dysfunction symptoms may be the result of a loss in noradrenergic and serotonergic innervation. GI deficits were evaluated using an organ bath technique. Groups treated with different combinations of neurotoxins (6-OHDA alone, 6-OHDA + pCA or 6-OHDA + DSP-4) presented significant differences in gut contractility compared to control groups. Since a substantial body of literature suggests the presence of an inflammatory process in parkinsonian state (Whitton, 2007), changes in pro-inflammatory cytokines in the gut were assessed using a cytokine microarray. It has been found in this work that groups with a combined dopaminergic and noradrenergic lesion have a significant increase in both expressions of IL-13 and VEGF. IL-6 also shows a decrease in treatment groups; however this decrease did not reach statistical significance. The therapeutic value of Exendin-4 (EX-4) was evaluated. It has been previously demonstrated that EX-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is neuroprotective in rodent models of PD (Harkavyi et al., 2008). In this thesis it has been found that EX-4 was able to reverse a decrease in gut contractility obtained through intracerebral bilateral 6-OHDA injection. Although more studies are required, EX-4 could be used as a possible therapy for the GI symptoms prominent in the early stages of PD.

The role of pneumococcal carbon metabolism in colonisation and invasive disease

Streptococcus pneumoniae is a common asymptomatic commensal of the human nasopharynx. However, it is better known as a threatening pathogen that causes serious diseases such as pneumonia, meningitis and sepsis, as well as other less severe but more prevalent infections (e.g. otitis media). With the increase of antibiotic resistance and the limited efficacy of vaccines, pneumococcal infections remain a major problem. Therefore, the discovery of new therapeutic targets and preventive drugs are in high demand.(...)

Exporting a model of integrated disease management: A cross-case study analysis and application to Associação Protectora dos Diabéticos de Portugal

Although literature is lacking in the topic of internationalization of services, we manage to apply both the Uppsala model and the Eclectic Theory to the healthcare service. A cross-case study analysis with three international hospitals is done in order to define an internationalization pattern and conditions for a successful process. This is then applied to Associação Protectora dos Diabéticos de Portugal with the purpose of defining an internationalization strategy to the Association.

The influence of menopausal status on bone turnover and disease control in breast cancer patients with metastatic bone disease treated with chemotherapy plus zoledronic acid : an exploratory retrospective cohort study

RESUMO: Introdução: Uma meta-análise recente demonstrou que uso adjuvante de ácido zoledrónico (AZ) em mulheres pós-menopáusicas com cancro da mama precoce (CM) conduz a redução do risco de morte por CM em 17%. Investigámos o efeito do estado hormonal (pré [PrM] vs pós-menopausa tardia [PoM]) na remodelação óssea e controlo de doença em mulheres com CM e metástases ósseas (MO) tratadas com AZ e quimioterapia (QT). Métodos: Neste estudo de coorte retrospetivo, colhemos variáveis clinico-patológicas e quantificámos o telopéptido N-terminal (NTX) urinário e marcadores tumorais (MT) séricos em mulheres com CM e MO tratadas com QT e AZ. As doentes foram divididas em PrM (<45 anos) e PoM (>60 anos). Endpoints do estudo: variação do NTX, CA15.3 e CEA nos meses 3, 6 e 9, tempo até falência de QT de primeira-linha e sobrevivência. Quando apropriado foram usados os testes de Wilcoxon rank-sum, modelo de efeitos lineares mistos, teste log-rank e modelo de Cox. Resultados: Quarenta doentes foram elegíveis para análise (8 PrM e 32 PoM). Depois da introdução de AZ e QT, os níveis de NTX e MT caíram no coorte global. O perfil de resposta não diferiu entre grupos no mês 3 ou em tempos posteriores (valor-p para interação tempo-estado hormonal no mês 3=0.957). Ademais, o perfil de resposta dos MT também não diferiu entre grupos. O tempo mediano até falência de primeira-linha de QT em PrM e PoM foi de 15.2 e 17.4 meses, respetivamente. Não foi identificada diferença significativa entre grupos, quer em análise univariada quer após controlo para envolvimento visceral (p=0.399 e 0.469, respetivamente). Igualmente, não houve diferenças em termos de sobrevivência. Conclusões: Neste coorte, não foram identificadas diferenças no controlo de NTX ou MT em função do estado menopausico. Igualmente, não foi identificada diferença no tempo até falência de primeira-linha de CT ou sobrevivência.----------- ABSTRACT: Background: A recent meta-analysis showed that the adjuvant use of zoledronic acid (ZA) in postmenopausal women with early breast cancer (BC) leads to a reduction in the risk of breast cancer death by 17%. We investigated the effect of the hormonal status (pre [PrM] vs late post menopause [PoM]) on bone turnover and disease control among women with BC and boné metastases (BM) treated with ZA and chemotherapy (CT). Methods: In this retrospective cohort study, we collected clinicopathologic variables, urinary Nterminal telopeptide (NTX) and serum tumor marker levels from women with BC and BM treated with CT and ZA. Patients were divided in PrM (<45 years) and PoM (>60 years). Study endpoints were NTX, CA15.3 and CEA variation at 3, 6 and 9 months, and time to first-line CT failure and survival. We performed multilevel mixed-effects linear regression models to assess the variation of repeated measures and cox regression models for time to event outcomes. Results: Forty patients were eligible for analysis (8 PrM and 32 PoM). After introduction of ZA and CT, NTX and tumor markers declined in the overall cohort. Response profile was similar between menopausal groups at month 3 and at later time points (p-value for time-hormonal status interaction at month 3=0.957). Furthermore, tumor markers response profile was also equal between groups. Median time to first-line CT failure in PrM and PoM women was 15.2 and 17.4 months, respectively. No significant difference between groups was found, either using a univariate analysis or after controlling for visceral disease involvement (p=0.399 and 0.469, respectively). Likewise, no differences in survival were found. Conclusions: In this cohort, no differences were found in terms of NTX or tumor markers control according to menopausal status. Similarly, no difference in time to first-line CT failure or survival was found.

Assessment by doppler ultrasound of entheseal lesions in spondyloarthritis : a longitudial study to determine structural damage and disease activity lesions

RESUMO: Enthesitis is the hallmark of spondyloarthritis (SpA), and is observed in all subtypes. Wide information on SpA abnormalities, including synovitis, tendinitis and enthesitis, can be efficiently perceived by Doppler ultrasound. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect enthesis alterations; and vascularized enthesitis detected by Doppler ultrasound appears to be a valuable diagnostic tool to confirm SpA diagnosis. However, data published until now concerning entheseal elementary alterations that characterize SpA enthesitis (enthesis inflammatory activity) or enthesopathy (permanent structural changes) reflect rather the authors’ empiric opinion than a methodological validation process. In this sense it seems crucial to identify elementary entheseal lesions associated with activity or damage, in order to improve monitoring and treatment response in SpA patients. The development of better assessment tools is today a challenge and a need in SpA. The first study of this thesis focused on the analysis of the reliability of inter-lector and inter-ultrasonography equipment of Madrid sonography enthesitis index (MASEI). Fundamental data for the remaining unrolling project validity. In the second and third studies we concerned about two entheseal elemental lesions: erosions and bursa. In literature erosions represent a permanent structural damage, being useful for monitoring joint injury, disease activity and therapeutic response in many rheumatic diseases; and to date, this concept has been mostly applied in rheumatoid arthritis (RA). Unquestionably, erosion is a tissue-related damage and a structural change. However, the hypothesis that we decided to test was if erosions represent a permanent structural change that can only grow and worsen over time, as occurs in RA, or a transitory alteration. A longitudinal study of early SpA patients was undertaken, and the Achilles enthesis was used as a model. Our results strongly suggested that previously detected erosions could disappear during the course of the disease, being consistent with the dynamic behavior of erosion over time. Based on these striking results it seems reasonable to suggest that the new-bone formation process in SpA could be associated with the resolution of cortical entheseal erosion over time. These results could also be in agreement with the apparent failure of anti-tumor necrosis factor (TNF) therapies to control bone proliferation in SpA; and with the relation of TNF-α, Dickkopf-related protein 1 (Dkk-1) and the regulatory molecule of the Wnt signaling pathway in the bone proliferation in SpA. In the same model, we then proceeded to study the enthesis bursa. Interestingly, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) enthesopathy definition does not include bursa as an elementary entheseal lesion. Nonetheless, bursa was included in 46% of the enthesis studies in a recently systematic literature review, being in agreement with the concept of “synovio-entheseal complex” that includes the link between enthesitis and osteitis in SpA. It has been clarified in recent data that there is not only a close functional integration of the enthesis with the neighboring bone, but also a connection between enthesitis and synovitis. Therefore, we tried to assess the prevalence and relevance of the bursa-synovial lesion in SpA. Our findings showed a significant increase of Achilles bursa presence and thickness in SpA patients compared to controls (healthy/mechanical controls and RA controls). These results raise awareness to the need to improve the enthesopathy ultrasonographic definition. In the final work of this thesis, we have explored new perspectives, not previously reported, about construct validity of enthesis ultrasound as a possible activity outcome in SpA. We performed a longitudinal Achilles enthesis ultrasound study in patients with early SpA. Achilles ultrasound examinations were performed at baseline, six- and twelve-month time periods and compared with clinical outcome measures collected at basal visit. Our results showed that basal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are higher in patients with Doppler signal in enthesis, and even that higher basal ESR, CRP and Ankylosing Spondylitis Disease Activity Score (ASDAS) predicted a higher Doppler signal (an ultrasound alteration accepted as representative of inflammation) six months later. Patients with very high disease activity assessed by ASDAS (>3.5) at baseline had significantly higher Achilles total ultrasound score verified at the same time; and ASDAS <1.3 predicted no Doppler signal at six and twelve months. This seems to represent a connection between classical biomarkers and clinical outcomes associated with SpA activity and Doppler signal, not only at the same time, but also for the following months. Remarkably, patients with inactive disease (ASDAS < 1.3) at baseline had no Doppler signal at six and twelve months. These findings reinforce the potential use of ultrasound related techniques for disease progression assessment and prognosis purposes. Intriguingly, Ankylosing Spondylitis Disease Activity Index (BASDAI) didn’t show significant differences between different cut-offs concerning ultrasound lesions or Doppler signal, while verified with ASDAS. These results seem to indicate that ASDAS reflects better than BASDAI what happens in the enthesis. The work herein discussed clearly shows the potential utility of ultrasound in enthesis assessment in SpA patients, and can be important for the development of ultrasound activity and structural damage scores for diagnosis and monitoring purposes. Therefore, local promotion of this technique constitutes a medical intervention that is worth being tested in SpA patients for diagnosis, monitoring and prognosis purposes.

Conception and first results of a cross-sectional national study on the demography, disease characteristics and socioeconomics status of the Portuguese patients with multiple sclerosis : the PORT-MS study

RESUMO: Introdução e objetivos: Não existia um estudo multicêntrico que descrevesse as características dos doentes com EM, da doença em si, ou do seu tratamento, em Portugal.Métodos: Doentes McDonald 2010 positivos foram sequencialmente recrutados em 7 centros entre Maio e Novembro 2014. Aplicou-se um Caderno de Recolha de Dados incidindo na demografia, doença, educação e emprego (estudo PORT-MS). Resultados: 561 doentes incluídos. Primeiros sintomas aos 30,2±10,5 anos (RRMS 29,2±10, PPMS 39,4±11,7, p<0,001); diagnóstico 3,2±5,3 anos depois (RRMS 3,0±5,1, PPMS 4,9±2,5, p=0,002); tempo de doença após diagnóstico 9,4±7,2 anos (semelhante RRMS no diagnóstico e PPMS); idade atual 42,9±12,4 anos (grupo RRMS no diagnóstico 42,0±12,1, PPMS 52,5±11,3, p<0,001); EDSS atual 2,5 (RRMS 2.0, PPMS 6.0); proporção feminino:masculino é 2,5:1 (RRMS semelhante, PPMS 1,1:1, p<0,05); no diagnóstico RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% dos RRMS encontravam-se em SP na inclusão (nomeadamente os com mais idade no diagnóstico e/ou atualidade ou tempo de doença mais prolongado). PPMS mais frequente em doentes diagnosticados mais tardiamente (p<0,001), onde aumenta também ligeiramente a proporção de mulheres na PPMS. Nas últimas décadas: novos casos mostram estabilidade na proporção de géneros e tipos de doença; idade nos primeiros sintomas e no diagnóstico aumentou ligeiramente, tempo entre eles diminuiu ligeiramente. Proporção sob DMT (Maio 2014): global 84,5%; atualmente RRMS 90,4%; SPMS 70,8%; PPMS 36,8%; progressivas agregadas 48%. Tipo de DMT, amostra global: interferões 56,5%, GA 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Global: economicamente ativos 61,5%, desemprego 13,5%, 74,1% dos não activos estão reformados por doença. Gravidezes após diagnóstico em 15% mulheres. Casos com história familiar positiva 7,8%. Discussão e conclusões: Incluída cerca de 10% da população portuguesa. Resultados congruentes com dados internacionais. Elevada proporção sob DMT, mesmo EDSS alto e formas progressivas. Terapêuticas de segunda linha sub representadas. Doentes jovens e com doença ligeira com vida económica ativa; restantes essencialmente reformados por doença.---------------- ABSTRACT : Background/aims: In Portugal, there wasn’t a multicentric study on the general characteristics (demography, disease milestones, DMT, socioeconomic status) of Multiple Sclerosis patients. Methods: Patients fulfilling McDonald 2010 criteria were sequentially recruited from May to November 2014 in 7 centers and data was systematically collected. Results: 561 patients included. First symptoms occurred at 30,2±10,5 years-old (RRMS 29,2±10, PPMS 39,4±11,7, p<0,001); diagnosis 3,2±5,3 years later (RRMS 3,0±5,1, PPMS 4,9±2,5, p=0,002); 9,4±7,2 years elapsed since diagnosis (similar for those is RRMS at diagnosis and PPMS); current age 42,9±12,4 years-old (group RRMS at diagnosis 42,0±12,1, PPMS 52,5±11,3, p<0,001); current EDSS 2,5 (RRMS 2.0, PPMS 6.0); females to males 2,5:1 (RRMS similar, PPMS 1,1:1, p<0,05); at diagnosis RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% of RRMS reached SP at inclusion (those older at diagnosis, in actuality, or with longer follow-up). PPMS more frequente in patients diagnosed at older ages (p<0,001), also slight increase in females. Along the last decades: new cases have showed stable proportions of gender and disease types; age at first symptoms and diagnosis slightly increased, time between them slightly decreased. Proportion on DMT (May 2014): 84,5% of all; 90,4% of currently in RRMS; 70,8% of SPMS; 36,8% of PPMS; 48% of progressive forms together. Type of DMT, all patients: interferons 56,5%, Glatiramer Acetate 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Economically active 61,5% of all, unemployment 13,5%, 74,1% of non-active are retired due to disease. Females pregnant after diagnosis 15%. Positive family cases in 7,8%. Discussion/Conclusions: 10% of the national MS population collected. Data generally consistente with international reports. Proportion under DMT relatively high in all disease types, but second line therapies underrepresented. Young patients with mild disease have an active economic life. Those not active are essentially retired due to disease.