Early detection of interstitial lung disease in rheumatic diseases: A joint statement from the Portuguese Pulmonology Society, the Portuguese Rheumatology Society, and the Portuguese Radiology and Nuclear Medicine Society.

INTRODUCTION: Interstitial lung disease (ILD) contributes significantly to morbidity and mortality in connective tissue disease (CTD). Early detection and accurate diagnosis are essential for informing treatment decisions and prognosis in this setting. Clear guidance on CTD-ILD screening, however, is lacking. OBJECTIVE: To establish recommendations for CTD-ILD screening based on the current evidence. METHOD: Following an extensive literature research and evaluation of articles selected for their recency and relevance to the characterization, screening, and management of CTD-ILD, an expert panel formed by six pulmonologists from the Portuguese Society of Pulmonology, six rheumatologists from the Portuguese Society of Rheumatology, and six radiologists from the Portuguese Society of Radiology and Nuclear Medicine participated in a multidisciplinary discussion to produce a joint statement on screening recommendations for ILD in CTD. RESULTS: The expert panel achieved consensus on when and how to screen for ILD in patients with systemic sclerosis, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome, idiopathic inflammatory myopathies and systemic lupus erythematous. CONCLUSIONS: Despite the lack of data on screening for CTD-ILD, an expert panel of pulmonologists, rheumatologists and radiologists agreed on a series of screening recommendations to support decision-making and enable early diagnosis of ILD to ultimately improve outcomes and prognosis in patients with CTD.

Seasonal and diel modulation of DOM in a mangrove-dominated estuary.

Rivers and estuaries are the main links between continents and oceans. The Paraíba do Sul River is among the most important rivers of the southeastern Brazilian region, carrying an average of 0.08 Tg of dissolved organic matter (DOM) to the ocean but has been facing significant changes in river discharge. In this study, we aimed to provide insights into the sources and transformations of chromophoric dissolved organic matter (CDOM) and fluorescent dissolved organic matter (FDOM) sources across a salinity gradient under changing river discharge scenarios. Three spatial surveys were performed covering the entire salinity gradient of the main estuarine channel and surrounding mangrove waters under contrasting river discharge (178 to 1240 m3 s-1), and diel sampling was conducted in the mangrove tidal creek. The characterization of DOM through the parallel factor analysis (PARAFAC) model identified six components across the river-ocean gradient and mangrove creek: terrestrial origin (C1 - fulvic acid and C2 and C3 - humic-like), protein-like (C4), tryptophan-like (C5), and tyrosine-like (C6). Our results showed a shift in DOM composition and contribution along the salinity gradient, from terrestrial (C3) to autochthonous (C5 and C6) signatures. The October-17 dry campaign was characterized by a higher proportion of microbial protein-like component C4 and a lower contribution of humic-like components compared to February-17 and March-18 across the salinity gradient with an increase in the mixing zone. The DOM compositions of the February 17 dry and March 18 wet campaigns were similar. Additionally, the March-18 wet campaign, marked by the highest river discharge, showed higher inputs of terrestrial DOM (C1-C3 components) compared to February-17 in the estuary, which allowed DOM to be transported rather than transformed. The mangrove diel study showed that tidal fluctuations are also an important driver of carbon input to the mangrove creek with a possible impact on DOM composition in estuarine waters.

Etanercept-induced granulomatous hepatitis as a rare cause of abnormal liver tests.

The authors report the case of a 76 year-old man with rheumatoid arthritis treated with prednisolone and etanercept. The patient was seen for persistent changes in liver tests lasting for six months, with a mixed pattern. The patient denied intake of new drugs or dietary/herbal supplements. Imaging studies showed mild steatosis. Additional study for chronic liver diseases only revealed positivity for anti-nuclear antibodies. Liver biopsy revealed noncaseating granulomas in some portal tracts. Consequent etiologic study for granulomatous diseases showed negative or normal results. So it was decided to suspend etanercept, with a subsequent gradual improvement on analytical parameters that normalized three months later. To date, only one case of granulomatous liver disease associated with an anti-TNF agent was described in the literature. This case also raises the question whether the development of granulomatous processes associated with anti-TNF agents has been underdiagnosed due to the presence of other concomitant immunosuppressant therapies.

LRP5 gene polymorphisms and radiographic joint damage in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is characterized by increased bone resorption and impaired bone formation. Osteoblast function is regulated by the canonical LRP5/Wnt/ß-catenin pathway. Bone mineral density and RA joint destruction are partially inherited. In line with this, we found significant associations between LRP5 SNPs (p.A1330V, p.N740N, p.V667M) and RA radiographic damage severity. INTRODUCTION: Increased bone resorption and impaired bone formation characterize rheumatoid arthritis (RA). Canonical Wnt/ß-catenin pathway, signalled by lipoprotein receptor-related protein-5 (LRP5), regulates osteoblast function. Since bone mineral density (BMD) and RA joint destruction are partially inherited, we studied their association with LRP5 single nucleotide polymorphisms (SNPs). METHODS: Clinical data and peripheral blood for biomarkers assessment and LRP5 genotyping were collected from 208 RA patients. Hands and feet X-rays were scored [modified Sharp/van der Heijde Score (SHS), joint space narrowing (JSN), and erosion scores]. Lumbar spine, total left proximal femur, and left hand BMD were assessed by dual-energy X-ray absorptiometry (DXA). RESULTS: TT genotypes for p.A1330V and p.N740N LRP5 SNPs associated with total SHS, erosion score, and hands erosion score; the same for p.A1330V with feet JSN score and p.N740N with hands total score. AG genotype for p.V667M associated with sclerostin and hands JSN score. Femoral BMD associated with TC genotype for p.N740N. Multiple test correction precluded a few of these associations. Among V667M-N740N-A1330V haplotypes: GTT associated with higher feet JSN score (OR = 3.80; p = 0.016) and ATT with higher JSN score (OR = 4.60; p = 0.032), hands total score (OR = 5.65; p = 0.022), and total SHS (OR = 6.74; p = 0.024). CONCLUSION: Significant associations between LRP5 SNPs (p.A1330V, p.N740N, and p.V667M) and the severity of radiographic damage reinforce the evidence of bone destruction heritability in RA.

Portuguese recommendations for the prevention, diagnosis and management of primary osteoporosis - 2018 update.

BACKGROUND: Advances in osteoporosis (OP)case definition, treatment options, optimal therapy duration and pharmacoeconomic evidence in the national context motivated the Portuguese Society of Rheumatology (SPR) to update the Portuguese recommendations for the diagnosis and management of osteoporosis published in 2007. METHODS: SPR bone diseases' working group organized meetings involving 55 participants (rheumatologists, rheumatology fellows and one OP specialist nurse) to debate and develop the document. First, the working group selected 11 pertinent clinical questions for the diagnosis and management of osteoporosis in standard clinical practice. Then, each question was investigated through literature review and draft recommendations were built through consensus. When insufficient evidence was available, recommendations were based on experts' opinion and on good clinical practice. At two national meetings, the recommendations were discussed and updated. A draft of the recommendations full text was submitted to critical review among the working group and suggestions were incorporated. A final version was circulated among all Portuguese rheumatologists before publication and the level of agreement was anonymously assessed using an online survey. RESULTS: The 2018 SPR recommendations provide comprehensive guidance on osteoporosis prevention, diagnosis, fracture risk assessment, pharmacological treatment initiation, therapy options and duration of treatment, based on the best available evidence. They attained desirable agreement among Portuguese rheumatologists. As more evidence becomes available, periodic revisions will be performed. Target audience and patient population: The target audience for these guidelines includes all clinicians. The target patient population includes adult Portuguese people. Intended use: These recommendations provide general guidance for typical cases. They may not be appropriate in all situations - clinicians are encouraged to consider this information together with updated evidence and their best clinical judgment in individual cases.

Effect of Comedication With Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study.

OBJECTIVE: To evaluate whether use of comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA). METHODS: Patients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time-fixed) variables were included, and a second model incorporating time-varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score. RESULTS: In total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow-up time of 2.5 years (range 0.08-13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59-1.16) nor during follow-up in the model adjusted for time-varying covariates (HR 1.07, 95% CI 0.68-1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment. CONCLUSION: Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.

Off-label Use of Tocilizumab in Psoriatic Arthritis: Case Series and Review of the Literature.

OBJECTIVE: To evaluate the efficacy of tocilizumab (TCZ) on three patients with psoriatic arthritis (PsA) and review the literature for other cases of PsA treated with TCZ. CLINICAL CASES: The first patient started TCZ treatment after the failure of adalimumab (ADA), and etanercept (ETA) (Disease Activity Score, DAS28: 6.66) to treat PsA. After 12 months, her DAS28 decreased to 3.26, and at present (24 months), she has achieved disease remission. The second patient started TCZ treatment after the failure of ADA. After 12 months, the DAS28 decreased from 4.90 to 3.99. After 48 months of treatment, the patient had a DAS28 of 3.76. The third case was treated with TCZ after the failure of both infliximab and rituximab therapy. After 12 months, the DAS28 dropped from 8.65 to 5.49. At present, after 37 months of treatment, the patient has a DAS28 of 4.67. In the literature, there are six cases of PsA, which have been treated with TCZ: in two of the cases, the patient showed a great improvement. Two cases failed to achieve disease remission, despite a moderate response to the treatment, and the other two cases showed no improvement. CONCLUSION: It can be concluded that TCZ cannot be recommended as an alternative treatment for PsA with predominant peripheral involvement.

Chromosomal evolution in the pallescens group (Hemiptera, Triatominae).

Rhodnius colombiensis, in conjunction with R. pallescens and R. ecuadoriensis, forms the monophyletic pallescens group. Cytogenetic analyses of these closely related species would further our understanding of the taxonomy and evolution of this group. In this study, R. colombiensis was cytogenetically analyzed, and the results were compared with cytogenetic data from other species of the pallescens group, particularly their chromosomal evolution. We found that this triatomine has heteropycnotic blocks in five autosomal bivalents at both metaphase I and II. The derivation of R. colombiensis from R. pallescens led to significant loss of heteropycnotic and heterochromatic regions (approximately 50%). R. ecuadoriensis is the most differentiated of the group because it has lost all heterochromatin and heteropyknotic blocks in the autosomes. Based on the heteropyknotic and heterochromatic pattern of R. colombiensis and the chromosomal evolution analysis of the pallescens group, we suggest that the karyotype of R. colombiensis and R. ecuadoriensis lost its heteropycnotic and heterochromatic blocks during speciation. Furthermore, this loss could be related to adaptation to different environments.

Characterization of damage in Portuguese lupus patients: analysis of a national lupus registry.

BACKGROUND: Although the survival rate has considerably improved, many patients with systemic lupus erythematosus (SLE) develop irreversible organ damage. OBJECTIVES: The objectives of this paper are to characterize cumulative damage in SLE patients and identify variables associated with its presence and severity. METHODS: A cross-sectional analysis of SLE patients from the Portuguese Lupus register Reuma.pt/SLE in whom damage assessment using the SLICC/ACR-Disability Index (SDI) was available was performed. Predictor factors for damage, defined as SDI ≥ 1, were determined by logistic regression analyses. A sub-analysis of patients with severe damage (SDI ≥ 3) was also performed. RESULTS: In total, 976 patients were included. SDI was ≥1 in 365 patients, of whom 89 had severe damage. Musculoskeletal (24.4%), neuropsychiatric (24.1%) and ocular (17.2%) domains were the most commonly affected. Older age, longer disease duration, renal involvement, presence of antiphospholipid antibodies and current therapy with steroids were independently associated with SDI ≥ 1. The subpopulation with severe damage had, in addition, a greater interval between the first manifestation attributable to SLE and the clinical diagnosis as well as and more frequently early retirement due to SLE. CONCLUSIONS: This large lupus cohort confirmed that demographic and clinical characteristics as well as medication are independently associated with damage. Additionally, premature retirement occurs more often in patients with SDI ≥ 3. Diagnosis delay might contribute to damage accrual.

Efeitos da própolis na proliferação de fibroblastos em lesões cutâneas de ratos / Effect of propolis on fibroblast proliferation in skin lesions in rats

O presente estudo teve por objetivo verificar o efeito tópico da própolis na proliferação de fibroblastos e a disposição e volume de fibras colágenas presentes durante o processo de reparo tecidual. Foram utilizados ratos wistar, machos, divididos em dois grupos: Grupo Controle (CC) n=16 lesão tratada com creme não-iônico; Grupo Própolis (PP) n=16 lesão tratada com creme não-iônico + Própolis 10%. Nos 4º, 7°, 14° e 21° dias de tratamento foram sacrificados 4 animais de cada grupo em câmara de gás carbônico. O tecido lesionado foi coletado e fixado em formalina a 10% por 48 horas, incluído em álcool a 70%, fixado em parafina e depositado em lâminas para análise histológica. Os resultados demonstraram um aumento no número de fibroblastos e também maior e melhor disposição de fibras colágenas no grupo PP em relação ao grupo CC. Assim, as evidências obtidas no estudo mostraram que o efeito da própolis na aceleração do processo de reparo tecidual não é somente por sua ação antiinflamatória, conforme diversos estudos demonstram, mas também por sua ação direta sobre a proliferação de fibroblastos, acelerando a reversão de fibrócito para fibroblasto, e, consequentemente favorecendo a síntese e deposição de fibras colágenas, melhorando o reparo tecidual e reduzindo o tempo de cicatrização...

This study aimed to verify the effect of topical propolis on fibroblast proliferation and disposicao and volume of collagen fibers present in the tissue repair process. We used male Wistar rats were divided into two groups: control (CC) n = 16 lesions treated with non-ionic cream; Propolis Group (PP) n = 16 lesion treated with non-ionic cream + 10% propolis. At 4, 7, 14 and 21 days of treatment where sacrificed four animals from each group in a carbon dioxide chamber. The injured tissue was collected and fixed in 10% formalin for 48 hours, then in 70% alcohol, embedded in paraffin and placed on slides for histological analysis. The results showed an increase in the number of fibroblasts and also bigger and better arrangement of collagen fibers in PP group than in CC group. Thus, the evidence obtained in the study showed that the effect of propolis to speed up tissuerepair process is not only for its anti-inflammatory action, as several studies show, but also by its direct action on the proliferation of fibroblasts, accelerating the rate at which fibrocytes revert to fibroblasts, and collagen fiber arrangement, improving tissue repair and reducing the healing time...

Nasal type extranodal NK/T cell lymphoma diagnosed in a patient with rheumatoid arthritis under methotrexate.

Rheumatoid arthritis (RA) patients have increased risk of lymphoma which seems associated mainly with high inflammatory state and disease activity, but also with immunosuppressive agents or Epstein-Barr virus (EBV) infection. Many case reports describe lymphoproliferative lesions arising during methotrexate therapy, often EBV positive with possible regression after methotrexate withdrawal. The authors report the case of an 85-year-old patient with erosive and seronegative RA, in remission under methotrexate who developed a midfacial destructive lesion with epistaxis and local inflammatory signs. The magnetic resonance imaging showed a large nasal septum defect. Anti-neutrophil cytoplasmic antibodies titres and angiotensin converting enzyme were normal. Biopsies of the lesion identified a NK/ T nasal type lymphoma. EBV latent membrane protein research on the lesion was negative. Polymerase chain reaction analysis of the bone marrow aspirate showed EBV DNA positivity. Withdrawal of methotrexate was performed without tumour regression. The authors described the single case of a patient with RA in stable remission under methotrexate who presented a rare type of lymphoma, a nasal type NK/T. EBV active replication was found in the bone marrow.

Silent Burdens in Disease: Fatigue and Depression in SLE.

At a time when health is being recognized as more than just avoiding death, age and comorbidity are becoming increasingly important aspects of chronic disease. Systemic Lupus Erythematous (SLE) is probably one of the best paradigms of modern chronic disease, sitting at the crossroads of numerous somatic health problems, immune activation, depression, pain, and fatigue. One hundred forty-eight female participants were enrolled in the present study: 50 diagnosed with SLE, 45 with major depressive disorder (MDD), and 53 age-matched controls. Statistically significant lower scores in quality-of-life dimensions related to physical impairment were found in SLE. Patients with MDD presented significant levels of pain, reduced physical summary component (PSC), and general health scores different from healthy controls. Fatigue was reported in 90% of women with SLE and 77.8% of the MDD patients in contrast with 39.6% in the control group. Significant correlations were seen among fatigue severity, age, and educational level in SLE. From our own previous work and more recent work on the association of immune activation and depression, unexplained fatigue in SLE may signify an early sign of immune activation flare-up. The search for cytokine markers should perhaps be extended to fatigue in SLE.

Land-sea interface features of four estuaries on the South America Atlantic coast.

The Brazilian coastal zone extends from 4º N to 34º S latitude and because of its long extension, the interface zone from continent to ocean includes a high diversity of geomorphologic and oceanographic characteristics. The rivers from the Northeast and East regions are marked by a typical unimodal seasonal flux patterns but with different amplitudes. As the climate indicates, the rivers from the Northeast are subject to an accentuated seasonal variability with an elevated input and flood pulses during the rainy season and low to negligible fluxes during the dry season. Small-scale rivers usually present typical torrential behaviour. In the humid eastern region, the unimodal seasonal cycle is dampened with a more constant input supply. Recently, some studies have shown that the material supply from rivers along the Northeast and Eastern coasts is diluted by surface tropical waters of oceanic currents and that the estuarine plume dispersal is restricted to a narrow coastal belt. However, human impacts of course mask or even override both natural hydrological cycles and CO2 emissions from terrestrial biomes, or depending on the nature of the human impact, can even increase extreme events. Henceforth this contribution addresses the typological, hydrological and biome diversity of the four estuarine systems fed and affected by the respective Amazon, São Francisco, Paraíba do Sul and Plata watersheds.

Reporting of ethical committee approval and patient consent in the Portuguese Journal of Pulmonology and in the other Portuguese medical journals with impact factor.

INTRODUCTION: Reporting of ethical committee (EC) approval and patient consent in publications involving human subjects may be lower than recommended. In this paper this ethical issue was analysed in the Portuguese Journal of Pulmonology and in the other two Portuguese medical journals with impact factor indexed in the ISI Web of Knowledge. METHODS: Reporting of EC approval and patient consent was searched in all publications involving human subjects published in the Acta Médica Portuguesa, Acta Reumatológica Portuguesa and Portuguese Journal of Pulmonology, from the 1(st) July 2010 until the 30(th) June 2011. The search also looked for the involvement of vulnerable and potentially identifiable subjects. RESULTS: Most of the analysed publications, which included a considerable proportion of vulnerable (23%) and of potentially identifiable case reports (14%), were case reports (49%). Overall EC approval ranged from 0% to 28%, in case reports and prospective studies, respectively, whereas overall patient consent ranged from 0% to 26%. There were not statistically significant differences in results among the selected journals. CONCLUSIONS: Reporting of EC approval and patient consent in the three leading Portuguese medical journals has been lower than in their leading world counterparts. This should be taken into account and further audited in future, not only for the protection of the research subjects but also to maintain public trust in the process.

Biochemical and microbiological tools for the evaluation of environmental quality of a coastal lagoon system in Southern Brazil.

This study aimed to evaluate the environmental quality of surface water of the Maricá Lagoon System through physicochemical, biochemical and microbiological parameters, in order to assess its environmental quality. Marine influence over the system was evidenced by the salinity and temperature gradients, where the most distant point, in Maricá Lagoon, presented the largest protein, lipid and biopolymeric carbon concentrations. Biopolymers, with predominance of lipids, presented a pattern that differs from the literature for coastal sediments. The concentration of thermotolerant coliforms characterised Maricá Lagoon and Boqueirão Channel as unfit for bathing (60.0 and 66.3 cells x mL(-1), respectively). The bacterioplankton in the system proved to be predominantly heterotrophic, a consumer of organic matter, with fermentative, denitrifying and sulfate-reducing metabolism. No esterase enzyme activity was detected, despite the presence of active metabolism, measured by the electron transport system (average of 0.025 µg O2 x h(-1) x mL(-1)). The bacterial biomass (autotrophic, heterotrophic and coliforms), bacterial respiratory activity and biopolymer parameters evinced a spatial degradation pattern in the Maricá Lagoon System, where the points with less water renewal are the most impacted.

Ascorbic acid for the healing of skin wounds in rats.

BACKGROUND: Healing is a complex process that involves cellular and biochemical events. Several medicines have been used in order to shorten healing time and avoid aesthetic damage. OBJECTIVE: to verify the topical effect of ascorbic acid for the healing of rats' skin wounds through the number of macrophages, new vessels and fibroblast verifications in the experimental period; and analyse the thickness and the collagen fibre organization in the injured tissue. METHODS: Male Rattus norvegicus weighing 270 +/- 30 g were used. After thionembutal anesthesia, 15 mm transversal incisions were made in the animals' cervical backs. They were divided into two groups: Control Group (CG, n = 12) - skin wound cleaned with water and soap daily; Treated Group (TG, n = 12) - skin wound cleaned daily and treated with ascorbic acid cream (10%). Samples of skin were collected on the 3rd, 7th and 14th days. The sections were stained with hematoxylin-eosin and picrosirius red for morphologic analysis. The images were obtained and analysed by a Digital Analyser System. RESULTS: The ascorbic acid acted on every stage of the healing process. It reduced the number of macrophages, increased the proliferation of fibroblasts and new vessels, and stimulated the synthesis of thicker and more organized collagen fibres in the wounds when compared to CG. CONCLUSION: Ascorbic acid was shown to have anti-inflammatory and healing effects, guaranteeing a suiTable environment and conditions for faster skin repair.

The Brazilian National Health Informatics Strategy.

This paper describes the Brazilian National Strategy for the development of the national Health Informatics Infrastructure. An overall description of the use of IT in the Brazilian Health scenario is presented with emphasis on the federal initiatives by DATASUS, the informatics division of the Ministry of Health. The national health card project is discussed and the strategies to establish interoperability among systems are presented. The adopted standards and methodologies used are also discussed.

Effect of different vitamin E levels on lipid peroxidation in streptozotocin-diabetic rats.

Administration of streptozotocin is used to induce diabetes in experimental models, causing a selective destruction of pancreatic beta islet cells associated with generation of free radicals. Supplementation with antioxidant vitamins such as vitamin E is a protective factor against free radicals. The objective of this study was to determine the effect of administration of a diet supplemented with, or deficient in vitamin E to streptozotocin diabetic rats, controlled or not with insulin, on plasma glucose, hepatic vitamin E and hepatic thiobarbituric acid reactive substance (TBARS) levels before streptozotocin and 24 hours and one and two weeks after drug administration. Deficiency of vitamin E alone increased TBARS levels, and streptozotocin elevated TBARS two times in deficient groups, regardless of insulin control. In rats supplemented with vitamin E, a reduction of plasma glucose and liver vitamin E was observed two weeks after streptozotocin administration (p < 0.05). In conclusion, vitamin E supplementation probably protected against lipoperoxidation and contributed to the absence of elevation of plasma glucose levels, and vitamin E deficiency produced an increase in hepatic TBARS levels in streptozotocin diabetic rats.