10-year experience of early arthritis clinic at a tertiary rheumatology center: achievements and challenges.

OBJECTIVES: To characterize patients evaluated in our Early Arthritis Clinic (EAC) in the first ten years; to assess diagnostic delay and its underlying causes; and to evaluate the level of agreement between the referring physician and the rheumatologist regarding the presence of referral criteria. METHODS: Cross-sectional study including patients attending EAC between 2012 and 2021. Demographic data, provenience, final diagnosis, referral criteria and time related to diagnosis delay were retrieved from clinical files and the Portuguese Registry of Rheumatic Patients (reuma.pt). Characteristics of the patients and the time variables were analysed with descriptive statistical analysis. The agreement between the referring physician and rheumatologist regarding the referral criteria was evaluated using Cohen's Kappa. RESULTS: A total of 440 patients (68.9% females, mean age of 54±16.7 years) were referred, mostly from primary care (71.6%). Inflammatory Rheumatic Disease was diagnosed in 65.7% of the patients, with 58.9% classified as early arthritis. The median time from onset of symptoms to referral for EAC was 76 days (IQR 33.5-144.0); the median time from referral to the first EAC was 34 (IQR 19.0-46.0) days, and the median time from onset of symptoms to first EAC was 114.5 (IQR 66.8-190.3) days (16.3 weeks). Only about 10% were observed by a Rheumatologist before six weeks after symptom onset. The level of agreement between the referring physician and the rheumatologist was slight to fair to clinical criteria and moderate to substantial to laboratory criteria. CONCLUSIONS: A significant delay still is observed in patients with early arthritis suspicion, being the time from onset of symptoms to referral is the most relevant. A low agreement between referral and Rheumatologists suggests that non-rheumatologists education/training is needed. Identifying the barriers that prevent the adequate referral of patients is necessary to define strategies to improve it.

Increased Galactosidase Beta 1 Expression as a Senescent Key Factor in ß-Cells Function Modulation at the Early Steps of Type 2 Diabetes.

BACKGROUND: In type 2 diabetes, insulin resistance is observed, and ß-cells are incapable of responding to glycemia demands, leading to hyperglycemia. Although the nature of ß-cells dysfunction in this disease is not fully understood, a link between the induction of pancreatic ß-cell premature senescence and its metabolic implications has been proposed. This study aimed to understand the relationship between diabetes and pancreatic senescence, particularly at the beginning of the disease. METHODS: C57Bl/6 J mice were fed two different diets, a normal diet and a high-fat diet, for 16 weeks. Pancreatic histomorphology analysis, insulin quantification, inflammation parameters, and senescence biomarkers for the experimental animals were assessed at weeks 12 and 16. RESULTS: The results proved that diabetes onset occurred at week 16 in the High Fat Diet group, supported by glycaemia, weight and blood lipid levels. Increased ß-cells size and number accompanied by increased insulin expression were observed. Also, an inflammatory status of the diabetic group was noted by increased levels of systemic IL-1ß and increased pancreatic fibrosis. Finally, the expression of galactosidase-beta 1 (GLB1) was significantly increased in pancreatic ß-cells. CONCLUSION: The study findings indicate that senescence, as revealed by an increase in GLB1 expression, is a key factor in the initial stage of diabetes.

Creation and Validation of the European Portuguese Version of the Systemic Lupus Erythematous Quality of Life Questionnaire.

(1) Background: Patients with systemic lupus erythematous (SLE) experience profound effects on health-related quality of life (HRQoL) that cannot be explained by objective indicators of mortality and morbidity. This study aimed to adapt the SLE Quality of Life (SLEQoL) questionnaire to the European Portuguese population and to assess its reliability and validity for patients with SLE. (2) Methods: Two independent translators translated the original version of the SLEQoL questionnaire into Portuguese. A back-translated version was produced. The Portuguese version of the questionnaire was reviewed and tested for validity and reliability. Cronbach's alpha and the internal validity index were calculated to verify the internal reliability and validity of the content. Rheumatologists filled out the SLE Disease Activity Score (SLE-DAS) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index SLICC/ACR-DI questionnaires. (3) Results: This study involved 180 patients, of which 93.8% were females. The results indicated very high internal consistency reliability (α = 0.949), low correlations between the SLEQoL and the SLE-DAS, a correlation between all SLEQoL dimensions and all SF-36 dimensions (except for "response to treatment" and "self-image"), and good correlation scores with both the EQ-5D-5L index and VAS. (4) Conclusion: The Portuguese version of the SLEQoL questionnaire is valid and reliable for the measurement of HRQoL in SLE patients.

Nutritional senolytics and senomorphics: Implications to immune cells metabolism and aging - from theory to practice.

Aging is a natural physiological process, but one that poses major challenges in an increasingly aging society prone to greater health risks such as diabetes, cardiovascular disease, cancer, frailty, increased susceptibility to infection, and reduced response to vaccine regimens. The loss of capacity for cell regeneration and the surrounding tissue microenvironment itself is conditioned by genetic, metabolic, and even environmental factors, such as nutrition. The senescence of the immune system (immunosenescence) represents a challenge, especially when associated with the presence of age-related chronic inflammation (inflammaging) and affecting the metabolic programming of immune cells (immunometabolism). These aspects are linked to poorer health outcomes and therefore present an opportunity for host-directed interventions aimed at both eliminating senescent cells and curbing the underlying inflammation. Senotherapeutics are a class of drugs and natural products that delay, prevent, or reverse the senescence process - senolytics; or inhibit senescence-associated secretory phenotype - senomorphics. Natural senotherapeutics from food sources - nutritional senotherapeutics - may constitute an interesting way to achieve better age-associated outcomes through personalized nutrition. In this sense, the authors present herein a framework of nutritional senotherapeutics as an intervention targeting immunosenescence and immunometabolism, identifying research gaps in this area, and gathering information on concluded and ongoing clinical trials on this subject. Also, we present future directions and ideation for future clinical possibilities in this field.

Ageing, cellular senescence and the impact of diet: an overview.

Ageing is a risk factor for chronic diseases including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndrome. Among others, senescence mechanisms have become a target of huge research on the topic of the ageing process. Cellular senescence is a state of an irreversible growth arrest that occurs in response to various forms of cellular stress and is characterized by a pro-inflammatory secretory phenotype. Multiple studies showed that cellular senescence occurs in both physiological and pathophysiological conditions. Senescent cells accumulate with ageing and can contribute to age-related decline in tissue function. Obesity is a metabolic condition that can accelerate the ageing process by promoting a premature induction of the senescent state of the cells. In contrast, caloric restriction without malnutrition is currently the most effective non-genetic intervention to delay ageing, and its potential in decreasing the cellular senescent burden is suggested. Here, it will be highlighted the cellular and molecular mechanisms involved in cellular senescence and discussed some of the research that is being done about how environmental conditions such as diet can affect the accumulation of senescent cells.

Tornar-se pai: Importância dos serviços de saúde na promoção da paternidade cuidadora / Becoming a father: The importance of health services in promoting caregiver paternity

Enquadramento: Tornar-se pai, hoje, é um processo de transformação com novos significados, sentimentos e responsabilidades. Reconhecem-se benefícios do exercício de uma paternidade cuidadora para as crianças, mulheres, homens e comunidade, contribuindo, para a igualdade de género, os/as enfermeiros/as especialistas em enfermagem de saúde materna e obstétrica têm uma ação essencial para a sua promoção. Objetivos: Conhecer as conceções e sentimentos dos homens/pais sobre paternidade; analisar as experiências dos pais nos serviços de saúde face à promoção da paternidade cuidadora; identificar os fatores condicionantes do exercício da paternidade cuidadora. Metodologia: Estudo de natureza qualitativa do tipo interpretativo. Participaram 10 homens, pais pela primeira vez, cujos filhos nasceram nas maternidades de Coimbra e com idades entre 6 meses e 1 ano. Acesso aos participantes através de ?bola de neve?. Dados colhidos através de entrevistas semiestruturadas. O estudo teve parecer favorável da Comissão de Ética da UICISA:E. Efetuada análise do conteúdo temático, segundo Minayo, Deslandes e Gomes (2009). Resultados: Emergiram duas áreas temáticas: paternidade (conceções, sentimentos e mudança/transformação); promoção da paternidade cuidadora (experiências nos serviços de saúde e fatores condicionantes). Verificamos uma conceção de paternidade que inclui o cuidar, estar presente e ser responsável, associados a sentimentos de choque, alegria e medo. Das experiências nos serviços de saúde, salienta-se o envolvimento para participar do pré ao pós-natal, na aquisição de competências para cuidar do/da filho/a e na promoção do vínculo na tríade. Em algumas situações sentiram-se excluídos, mas consideraram os serviços de saúde importantes para a promoção da paternidade cuidadora. Os fatores que condicionaram foram: atitudes dos profissionais de saúde, legislação, participação na preparação para o parto e parentalidade, estrutura física pouco adequada, horários rígidos, inexistência de serviços dirigidos aos homens/pais. Conclusão: Os serviços de saúde devem potencializar políticas de incentivo à promoção da paternidade cuidadora, ajustando os espaços físicos, as normas institucionais e o apoio sistemático à participação do pai do pré ao pós-parto. Sugerimos a consecução de estudos para aprofundar a análise de conceções, motivações, práticas e estratégias a desenvolver para adequar respostas dos serviços de saúde aos homens e promover a coparentalidade.

Genotypic diversity of environmental Cryptococcus neoformans isolates from Northern Portugal.

The Cryptococcus neoformans/C. gattii species complex members are the main agents of systemic cryptococcosis. This disease is believed to be acquired from the environment via fungal cell inhalation. Often, isolates recovered from environmental and clinical sources have proven to be genotypically similar. We assessed the occurrence of C. neoformans and C. gattii in environmental substrates collected in a Portuguese region. Twenty-eight isolates were identified as C. neoformans - five from decaying Eucalyptus leaves and 23 from domestic pigeon droppings. The isolates were genotyped using a URA5-RFLP approach. The C. neoformans VNIV (53.6%, n = 15) and VNI (32.1%, n = 9) genotypes were abundantly present among environmental isolates. The hybrid VNIII (14.3%, n = 4) genotype was underrepresented and the VNII was not found. Cryptococcus gattii was also not found although some isolates yielded a positive canavanine-glycine-bromothymol blue test.

[Bilateral hyperintensity of the pulvinar and dorsomedial nucleus of the thalamus in sporadic Creutzfeldt-Jakob disease]. / Hiperintensidade bilateral do pulvinar e núcleo dorso-medial do tálamo na forma esporádica da doença de Creutzfeldt-Jakob.

INTRODUCTION: Creutzfedt-Jakob Disease (CJD) is a rapidly progressive neurodegenerative disease caused by prions. Early diagnosis and the determination of its form are epidemiologically important, with strong impact on public health. Bilateral pulvinar hyperintensity, either alone (pulvinar sign) or in association with the dorsomedial nucleus of the thalamus (double hockey stick sign) on T2, FLAIR and diffusion weighted imaging (DWI), is a criterion for the probable diagnosis of the variant CJD (vCJD). Bilateral hyperintensity of the caudate, putamina and cortex is the usual pattern found in the sporadic CJD (sCJD). OBJECTIVE: Analysis of the imaging aspects on a sCJD patient showing T2 hyperintensity of the pulvinar and dorsomedial thalamic nucleus, in order to assess the magnetic resonance imaging (MRI) accuracy in the discrimination between vCJD and sCJD, when this lesion pattern is present. METHODS: We performed a MRI on a 62-year-old female with definitive diagnosis of sCJD made by anatomopathologic study of the brain tissue. Qualitative analysis of MRI, including DWI, T2 and FLAIR sequences, as well as lesional patterns found. RESULTS: Brain MRI showed hyperintensity of the caudate, putamina, pulvinar and dorsomedial nucleus of the thalamus, in DWI, T2 and FLAIR sequences; hypersignal of the caudate and putamina was greater than the signal intensity of the thalami. Hyperintensity of the hippocampus and frontal, temporal and parietal cortex were more obvious in FLAIR and DWI. COMMENT: Hyperintensity of the pulvinar and dorsomedial nucleus of the thalamus on sCJD may complicate the differential diagnosis with vCJD. True pulvinar sign and double hockey stick sign, consistent with vCJD, must only be considered if the hyperintensity is greater than signal intensity of the caudate and putamina.

Phaeohyphomycosis caused by Alternaria infectoria presenting as multiple vegetating lesions in a renal transplant patient

Las especies del género Alternaria son mohos ubicuos que se caracterizan por presentar colonias de color gris; parecen ser cada vez más frecuentes como agente causal de las feohifomicosis subcutáneas, en especial entre pacientes inmunocomprometidos. Un paciente de 53 años de edad, que se había sometido a un trasplante renal, consultó por presentar tumores verrugosos en el tercio distal de las extremidades. La histopatología y cultivo positivos, además de la secuenciación de la región de transcripción interna ITS del rDNA, permitieron la identificación del aislamiento fúngico como Alternaria infectoria. Se instauró tratamiento con itraconazol oral durante 10 meses y, a los 15 meses de seguimiento, se demostró la ausencia de signos de infección. Las manifestaciones clínicas de la alternariosis cutánea son muy variables y tan sólo se han descrito unos pocos casos en los que se presenta en forma de tumoraciones verrugosas. Aunque el tratamiento de elección sigue siendo motivo de controversia, el paciente presentado en este estudio fue tratado satisfactoriamente con itraconazol(AU)

The genus Alternaria is one of the most common black moulds and appears to be increasing as a causative agent of subcutaneous phaeohyphomycosis, particularly among immunosuppressed patients. A 53-year-old patient who had received a kidney transplant presented with multiple verrucous lesions on the distal extremities. Positive histopathology and cultures, in addition to rDNA ITS region sequencing, identified the fungal isolate as Alternaria infectoria. Oral itraconazole was administered for 10 months. A follow-up at 15 months demonstrated no signs of infection. Clinical manifestations of cutaneous alternariosis vary significantly and only a few cases have been described in the literature. Although optimal treatment options remain controversial, this case of phaeohyphomycosis was successfully treated with itraconazole monotherapy(AU)

Phaeohyphomycosis caused by Alternaria infectoria presenting as multiple vegetating lesions in a renal transplant patient.

The genus Alternaria is one of the most common black moulds and appears to be increasing as a causative agent of subcutaneous phaeohyphomycosis, particularly among immunosuppressed patients. A 53-year-old patient who had received a kidney transplant presented with multiple verrucous lesions on the distal extremities. Positive histopathology and cultures, in addition to rDNA ITS region sequencing, identified the fungal isolate as Alternaria infectoria. Oral itraconazole was administered for 10 months. A follow-up at 15 months demonstrated no signs of infection. Clinical manifestations of cutaneous alternariosis vary significantly and only a few cases have been described in the literature. Although optimal treatment options remain controversial, this case of phaeohyphomycosis was successfully treated with itraconazole monotherapy.

Atypical presentation of entomophthoromycosis caused by Conidiobolus coronatus.

A male patient from Guinea-Bissau was admitted to Egas Moniz Hospital, Lisbon, complaining of fever and exhibiting a productive cough with mucopurulent discharge and weight loss. He had been using empirical medication with dexamethasone to treat his generalized facial swelling. At admission, he was cachectic and presented with soft facial edema, oropharyngeal thrush, and two fistulas of the palate. Acid-fast bacilli were detected in the sputum and were later identified as Mycobacterium tuberculosis. Cultures of the palatine exudate and biopsy resulted in the growth of Candida albicans. The patient was administered antituberculosis drugs and fluconazole, but his clinical situation deteriorated progressively. Extensive investigation of his clinical condition did not result in a conclusive diagnosis until he began to experience respiratory distress and subcutaneous nodules appeared on his face. Biopsies of the hypopharynx and nodules revealed the presence of Conidiobolus coronatus. After initiating combined antifungal and antibiotic therapy, the patient's clinical condition improved significantly. We report an unusual presentation of entomophthoromycosis and describe the clinical difficulties that delayed this diagnosis.