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Objective To assess the effect of the average adjusted global APS score (aGAPSS) over time on recurrence of clinical manifestations in APS patients through a retrospective longitudinal study. Material and methods The study included 200 patients with APS. The aGAPSS was calculated for each patient at baseline and on a yearly basis for either up to 6 years (minimum 3 years) or just before the clinical event in patients who experienced clinical recurrence. The mean score per patient was computed. In patients under vitamin K antagonists (VKA) the percentage of time spent within the therapeutic range (TTR) was calculated. Cox regression analysis was performed to determine the cut-off value of the aGAPSS with the strongest association with clinical recurrence. Results Higher average aGAPSS values were found in patients who experienced clinical recurrence in comparison to patients who did not [8.81 (95% CI 7.53, 10.08) vs 6.38 (95% CI 5.64, 7.12), P = 0.001], patients with thrombotic recurrence compared with patients with obstetric recurrence [9.48 (95% CI 8.14, 10.82) vs 4.25 (95% CI 0.85, 7.65), P = 0.006] and patients with arterial thrombosis compared with patients with venous thrombosis [10.66 (S.D. 5.48) vs 6.63 (S.D. 4.42), P = 0.01]. aGAPSS values >13 points were associated with the highest risk of recurrence in multivariate analysis [HR = 3.25 (95% CI 1.93, 5.45), P Conclusions Our data support the role of periodic (annual) monitoring of the aGAPSS score in predicting clinical recurrence in patients with APS.

Introduction: Some patients with positive antiphospholipid antibodies (aPL) have not been included in randomized clinical trials or observational registries and, therefore, information on their ris...

Hospitalizations are frequent in Systemic Lupus Erythematosus (SLE) and carry a significant economic burden. The focus of this review was to summarize the information available on the main causes of SLE hospitalizations over recent decades. A literature review was conducted, using PubMed and Scopus, for articles related to SLE hospital admissions from 1981 onward. Active disease/ flare and infection were the leading causes of admission across the study period. More recently, other comorbidities gained relevance, such as cardio and cerebrovascular disease, pregnancy-related morbidity, adverse drug reactions, thromboembolic events, malignancy and renal, pulmonary and gastrointestinal disease. African and Southeast Asian studies seemed to display particularly high percentages of patients admitted with active disease/flare, while European and North American studies appeared to report more admissions due to comorbidities and accumulated disease/treatment damage. Some data support a temporal change of certain admission causes, but the limited number, heterogeneity and variance among studies weakens a consistent analysis. In conclusion, despite the developments in SLE management, causes of hospitalization have not prominently changed across recent decades.

The classification criteria for antiphospholipid syndrome (APS) generate discussion, with a growing impression that certain patients not fulfilling these criteria might be inadequately excluded from the classification. Nonetheless, these "non-criteria" patients are heterogeneously defined across different publications. We reviewed the "non-criteria" APS subgroups depicted in the literature and attempted to organize these subsets in a nomenclature proposal that could be used for research purposes. We established four potential patient profiles, grouped under the broad term "non-criteria APS": (A) "Seronegative APS": patients fulfilling clinical criteria, plus "non-criteria" manifestations, with persistently negative antiphospholipid antibodies (aPL); (B) "Clinical non-criteria APS": patients with "non-criteria" manifestations, plus aPL positivity fulfilling the classification criteria; (C) "Incomplete laboratory APS": patients fulfilling clinical criteria, plus positive aPL, but not fulfilling the classification criteria (low titer aPL); and (D) "Laboratory non-criteria APS": patients fulfilling clinical criteria, with negative or low titer criteria aPL, plus positive "non-criteria" aPL. This categorization could allow for a more homogeneous research approach to APS, enabling more sustained and universal conclusions.

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Tuberculosis remains a worldwide public health problem. Cervical tuberculous lymphadenitis (TBL) or scrofula is the most common form of extrapulmonary tuberculosis, affecting the cervical lymph nodes. We report the case of a 93-year-old woman presenting with cervical adenopathies with 3 months duration. Fine needle aspiration (FNA) biopsy yielded a noncaseous granulomatous process, but was negative for Mycobacterium tuberculosis (MT). As the adenopathies had grown, an excisional biopsy was performed. An extensive study of infectious aetiologies was performed, including for MT, with a negative outcome. Owing to the persistence of cervical lymphadenitis with caseous granulomas, a diagnosis of TBL was strongly suspected and presumptive treatment was initiated. Afterwards, diagnostic confirmation was obtained by isolation of MT in the lymph node culture. The patient presented a favourable clinical outcome. This case highlights that a high index of suspicion is essential for the diagnosis of TBL, especially in the elderly, and emphasizes the importance of pursuing diagnostic confirmation, in which FNA and excisional biopsy plays a key role. LEARNING POINTS The diagnosis of tuberculous lymphadenitis should be considered in all patients presenting with cervical adenopathies, especially in endemic areas, irrespective of the patient’s age. A high index of suspicion is essential for the diagnosis due to the wide range of conditions that can mimic the disease. Fine needle aspiration biopsy is appropriate as an initial diagnostic approach, with excisional biopsy recommended when the former is not diagnostic.

Background: The relapse rate in antiphospholipid syndrome (APS) remains high, 20% at 5 years in thrombotic APS and 28% in obstetrical APS (1). Hydroxychloroquine (HCQ) appears as an additional therapy, with immunomodulatory and antithrombotic effects (2-5). Objectives: The main aim of this trial is to assess the efficacy of treatment with Hydroxychloroquine in preventing new events in primary antiphospholipid syndrome patients. Methods: We have performed a retrospective multicentre open-labelled study (2002-2018). Results: 812 patients with APS from 53 international centres from 16 countries were included. In all cases, the previous standard treatment was inefficient. The mean follow-up was 20.2 months (8- 144 mo), the mean age 39.5 years old. The type of clinical manifestations is described in figure 1. The obstetrical manifestations were various as described in figure 2. The number of thrombotic events were 190 arterial and 187 venous. Triple antiphospholipid antibody (tAPL) positivity was found in 20% of patients and lupus anticoagulant (LA) in 22%. No bleeding was registered in 99,6% of cases with treatment by HCQ. HCQ use was associated with favourable outcome in 96% of cases (figure 3). In multivariate analysis, age more than 65 years was associated with arterial events (odds-ratio 0.13 95%CI 0.03-0.32, p 0.005). Conclusion: HCQ could be effective in cases of refractory APS but prospective studies are necessary. References: [1] Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramon E, Buonaiuto V, Jacobsen S, Zeher MM, Tarr T, Tincani A, Taglietti M, Theodossiades G, Nomikou E, Galeazzi M, Bellisai F, Meroni PL, Derksen RH, de Groot PG, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC, Quere I, Hachulla E, Vasconcelos C, Fernandez-Nebro A, Haro M, Amoura Z, Miyara M, Tektonidou M, Espinosa G, Bertolaccini ML, Khamashta MA. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015;74:1011-8. [2] Belizna C. Hydroxychloroquine as an anti-thrombotic in antiphospholipid syndrome. Autoimmun Rev. 2015;14:358–62. [3] Nuri E, Taraborelli M, Andreoli L, Tonello M, Gerosa M, Calligaro A, Argolini LM, Kumar R, Pengo V, Meroni PL, Ruffatti A, Tincani A. Long-term use of hydroxychloroquine reduces antiphospholipid antibodies levels in patients with primary antiphospholipid syndrome. Immunol Res. 2017;65:17-24. [4] Schmidt-Tanguy A, Voswinkel J, Henrion D, Subra JF, Loufrani L, Rohmer V, et al. Antithrombotic effects of hydroxychloroquine in primary antiphospholipid syndrome patients. J Thromb Haemost JTH. 2013;11:1927–9. Disclosure of Interests: Cristina Belizna: None declared, Ljudmila Stojanovich: None declared, Patrick Saulnier: None declared, Francesca Pregnolato: None declared, Jaume Alijotas-Reig: None declared, Enrique Esteve-Valverde: None declared, Omar Latino: None declared, Sebastien Udry: None declared, Natasa Stanisavljevic: None declared, Alexander Makatsariya: None declared, Jamilya Khizroeva: None declared, Maarten Limper Consultant for: GSK, Roche and Thermofisher, Speakers bureau: GSK and Roche, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Laura Andreoli: None declared, Francesca Regola: None declared, Cecilia Chighizola Speakers bureau: Inova Diagnostics, Maria Orietta Borghi: None declared, Sule Apras Bilgen: None declared, Levent Kilic: None declared, Arsene Mekinian: None declared, Valentina Canti: None declared, Katrien Devreese: None declared, Gilberto Pires Rosa: None declared, Laura Damian: None declared, Fatma Said: None declared, Yehuda Shoenfeld: None declared, Ricard Cervera: None declared, Pier Luigi Meroni Consultant for: Inova, Thermofisher, Teofarma, Zahir Amoura: None declared

We report the case of a 50-year-old caucasian man presenting with lumbar pain, bilateral ataxia, central facial palsy, ophthalmoparesis and urinary retention. Cerebral MRI hinted a hyperintensity of the medulla oblongata and cervical medulla suggestive of myelitis. Cerebrospinal fluid displayed lymphocytic pleocytosis and elevated protein concentration. Without the possibility to rule out an infectious or inflammatory aetiology, antibiotics and corticosteroids were started. Nevertheless, neurological status deteriorated with loss of muscle strength and left eye amaurosis. A neuroaxis MRI exhibited encephalomyelitis with signal abnormalities involving the pons, medulla oblongata, left optic nerve and cervicodorsal medulla. Although negative for aquaporin-4-IgG antibodies, the patient fulfilled criteria for seronegative neuromyelitis optica spectrum disorder with the presence of multiple core clinical characteristics. Through early institution of corticosteroids, plasma exchange and rituximab, good functional recovery was achieved (Expanded Disability Status Scale score of 2). However, left eye amaurosis persisted despite salvage therapy with intravenous immunoglobulin.

The influence of fibrates on cardiovascular risk has been the focus of several clinical trials. This Cochrane Collaboration Systematic Review evaluated the efficacy of fibrates for secondary prevention of cardiovascular events and stroke, analyzing 13 randomized controlled trials, in a total of 16 112 participants with a history of cardiovascular disease. Fibrates showed a protective effect for the composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI) and vascular death, mainly due to reduction in the risk of non-fatal or fatal MI. Nonetheless, these results largely relied on studies including clofibrate, a drug withdrawn from the market in 2002. No statistically significant differences regarding adverse events were found between fibrates and placebo. Although insufficient to support the routine prescription of fibrates in this setting, this evidence should be taken into account when deciding on lipid-modifying therapy in dyslipidemic patients with a history of cardiovascular disease. Resumo: A influência dos fibratos no risco cardiovascular tem sido o foco de vários ensaios clínicos. Esta revisão sistemática da Cochrane Collaboration avaliou o efeito dos fibratos na prevenção secundária de eventos cardiovasculares e acidente vascular cerebral, incluindo 13 ensaios clínicos aleatorizados, num total de 16 112 participantes com antecedentes de doença cardiovascular. A terapêutica com fibratos demonstrou um efeito protetor no outcome composto acidente vascular isquémico não fatal, enfarte agudo do miocárdio não fatal e morte de causa vascular, especialmente devido à redução do risco de enfarte agudo do miocárdio fatal e não fatal. No entanto, estes resultados baseiam-se em grande parte em estudos que incluem o clofibrato, fármaco retirado do mercado em 2002. Não foram encontradas diferenças estatisticamente significativas relativamente a efeitos adversos entre fibratos e placebo. Embora insuficientes para sustentar uma prescrição rotineira de fibratos neste contexto, estes dados devem ser tidos em conta aquando da decisão terapêutica em doentes dislipidémicos com antecedentes de doença cardiovascular. Keywords: Fibrates, Cardiovascular events, Stroke, Secondary prevention, Systematic review, Palavras-chave: Fibratos, Eventos cardiovasculares, Acidente vascular cerebral, Prevenção secundária, Revisão sistemática

International audience; The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%–21% at 5 years in thrombotic APS and 20–28% in obstetrical APS [2, 3].Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4–16].Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency.Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial.This trial consists in two parts: a retrospective and a prospective study.The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.

Nontargeted late effects of radiation include an increased risk of cardiovascular disease, although this is still debatable in the context of low-dose radiation. Tinea capitis patients treated in childhood with X rays to induce scalp epilation received a low dose of radiation to their carotids. To better clarify this issue, we evaluated carotid atherosclerosis in a cohort of such patients treated in 1950-1963 in Portugal. A group of 454 individuals randomly chosen from previously observed Portuguese tinea capitis patients and a control group mainly composed of their spouses (n = 280) were enrolled. Cardiovascular risk factors such as waist circumference, body mass index, blood pressure and tobacco consumption, as well as biochemical measurements were obtained. Ultrasound imaging of carotid arteries for intima media thickness and stenosis evaluation were performed according to a standardized protocol. In comparison to the control group, the irradiated cohort members were significantly older, more frequently never smokers, hypertensive, and presented higher glycated hemoglobin and alkaline phosphatase levels. In addition, the irradiated cohort showed a higher frequency of carotid stenosis ≥30% than the nonirradiated group (13.9% vs. 10.7%), although this was not significant ( P = 0.20). Stenosis was ≥50% in 2.9% of the irradiated group and 0.4% of the nonirradiated group ( P = 0.02). Likewise, the frequency of intima media thickness ≥1 mm was significantly higher in the irradiated group (16.8% vs. 10.7%; P = 0.02). Multivariate analysis, including other cardiovascular risk factors, showed that exposure to low-dose radiation increased the risk of carotid stenosis by ≥50% [odds ratio (OR) = 8.85; P = 0.04] and intima media thickness by ≥1 mm (OR = 1.82; P = 0.02). These findings confirm that low-dose exposure is a risk factor of carotid atherosclerotic disease.

Azathioprine (AZA) is used in a wide array of autoimmune diseases, still corresponding to the mainstay maintenance therapy in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Although generally well-tolerated, several side effects are recognized. We report the case of a 50-year-old Caucasian man with kidney-limited ANCA myeloperoxidase (MPO) vasculitis who presented with general malaise, fever, worsening renal function, and elevated inflammatory markers 2 weeks after the initiation of therapy with oral AZA. Although a disease relapse was suspected, renal biopsy revealed an eosinophilic infiltrate, suggestive of acute interstitial nephritis. After suspension of AZA, a sustained improvement of renal function and normalization of inflammatory markers was observed. A diagnosis of allergic interstitial nephritis secondary to AZA was established, corresponding to the first biopsy-proven case described in an ANCA MPO vasculitis patient. Although rare, renal toxicity of AZA must be present in the clinician's mind, avoiding the straightforward assumption of disease relapse in the case of worsening renal function. info:eu-repo/semantics/publishedVersion

The satisfaction with the medical profession has been identified as an essential factor for the quality of care, the wellbeing of patients and the healthcare systems' stability. Recent studies have emphasized a growing discontent of physicians, mainly as a result of changes in labor relations.To assess the perception of Portuguese medical residents about: correspondence of residency with previous expectations; degree of satisfaction with the specialty, profession and place of training; reasons for dissatisfaction; opinion regarding clinical practice in Portugal and emigration intents.Cross-sectional study. Data collection was conducted through the "Satisfaction with Specialization Survey", created in an online platform, designed for this purpose, between May and August 2014.From a total population of 5788 medical residents, 804 (12.25 %) responses were obtained. From this sample, 77% of the responses were from residents in the first three years. Results showed that 90% of the residents are satisfied with their specialty, 85% with the medical profession and 86% with their place of training. Nevertheless, results showed a decrease in satisfaction over the final years of residency. The overall assessment of the clinical practice scenario in Portugal was negative and 65% of residents have plans to emigrate after completing their residency.Portuguese residents revealed high satisfaction levels regarding their profession. However, their views on Portuguese clinical practice and the results concerning the intent to emigrate highlight the need to take steps to reverse this scenario.Introdução: A satisfação com a profissão médica tem sido apontada como um fator essencial para a qualidade assistencial, o bemestar dos doentes e a estabilidade dos sistemas de saúde. Estudos recentes têm vindo a enfatizar um crescente descontentamento dos médicos, principalmente como consequência das alterações das relações laborais.Objetivos: Avaliar a perceção dos médicos de formação específica em Portugal, sobre as expectativas e grau de satisfação com a profissão, especialidade e local de formação; razões da insatisfação e intenção de emigrar.Material e Métodos: Estudo transversal. A colheita de dados foi efetuada entre Maio e Agosto de 2014 através de um Inquérito online sobre a âÄúSatisfação com a EspecialidadeâÄù.Resultados: De uma população total de 5788 médicos, foram obtidas 804 respostas (12,25% do total de médicos internos). Desta amostra, 77% das respostas correspondem a internos dos três primeiros anos de formação. Verificou-se que 90% dos médicos se encontram satisfeitos com a especialidade, tendo-se encontrado também níveis elevados de satisfação com a profissão (85%) e local de formação (86%). Por outro lado, constatou-se que estes diminuíam com a progressão ao longo dos anos de internato. A avaliação global sobre o panorama da prática médica foi negativa e 65% dos médicos responderam que consideram emigrar após conclusão do internato.Conclusão: Os médicos internos em Portugal apresentam níveis positivos de satisfação com a sua profissão. No entanto, a sua opinião sobre o panorama da Medicina e os resultados relativos à intenção de emigrar alertam para a necessidade de tomada de medidas para inverter este cenário.

Head and neck cancers, and cardiovascular disease have been described as late effects of low dose radiation (LDR) exposure, namely in tinea capitis cohorts. In addition to radiation dose, gender and younger age at exposure, the genetic background might be involved in the susceptibility to LDR late effects. The -174 G>C (rs1800795) SNP in IL6 has been associated with cancer and cardiovascular disease, nevertheless this association is still controversial. We assessed the association of the IL6-174 G>C SNP with LDR effects such as thyroid carcinoma, basal cell carcinoma and carotid atherosclerosis in the Portuguese tinea capitis cohort. The IL6-174 G>C SNP was genotyped in 1269 individuals formerly irradiated for tinea capitis. This sampling group included thyroid cancer (n = 36), basal cell carcinoma (n = 113) and cases without thyroid or basal cell carcinoma (1120). A subgroup was assessed for atherosclerosis by ultrasonography (n = 379) and included matched controls (n = 222). Genotypes were discriminated by real-time PCR using a TaqMan SNP genotyping assay. In the irradiated group, we observed that the CC genotype was significantly associated with carotid plaque risk, both in the genotypic (OR = 3.57, CI = 1.60–7.95, p-value = 0.002) and in the recessive (OR = 3.02, CI = 1.42–6.42, p-value = 0.004) models. Irradiation alone was not a risk factor for carotid atherosclerosis. We did not find a significant association of the IL6-174 C allele with thyroid carcinoma or basal cell carcinoma risk. The IL6-174 CC genotype confers a three-fold risk for carotid atherosclerotic disease suggesting it may represent a genetic susceptibility factor in the LDR context.