Activation of the integrated stress response by inhibitors of its kinases.

Phosphorylation of the translation initiation factor eIF2α to initiate the integrated stress response (ISR) is a vital signalling event. Protein kinases activating the ISR, including PERK and GCN2, have attracted considerable attention for drug development. Here we find that the widely used ATP-competitive inhibitors of PERK, GSK2656157, GSK2606414 and AMG44, inhibit PERK in the nanomolar range, but surprisingly activate the ISR via GCN2 at micromolar concentrations.

Risk Factors for Infection, Predictors of Severe Disease, and Antibody Response to COVID-19 in Patients With Inflammatory Rheumatic Diseases in Portugal-A Multicenter, Nationwide Study.

Objective: To identify risk factors for SARS-CoV-2 infection and for severe/critical COVID-19, and to assess the humoral response after COVID-19 in these patients.

Methods: Nationwide study of adult patients with inflammatory RMDs prospectively followed in the Rheumatic Diseases Portuguese Register-Reuma.pt-during the first 6 months of the pandemic.

Sex differences in axial spondyloarthritis: data from a Portuguese spondyloarthritis cohort.

Background: Axial spondyloarthritis (axSpA), particularly ankylosing spondylitis was historically considered a male's disease and has been under-recognized in women. Emerging evidence reveals sex differences in pathophysiology, disease presentation and therapeutic efficacy.

Objective: To identify differences between sexes in a Portuguese cohort of patients with axSpA regarding clinical manifestations, disease activity, functional capacity, patient related outcomes and presence of sacroiliitis on x-ray or magnetic resonance imaging.

Real-world Longterm Effectiveness of Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis Patients from the Rheumatic Diseases Portuguese Register.

Objective: To assess longterm effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA) registered in the Rheumatic Diseases Portuguese Register, exposed to at least 1 TNFi, prospectively followed between 2001 and 2017.

Methods: Kaplan-Meier analysis was performed for first-, second-, and third-line TNFi. Responses included European League Against Rheumatism (EULAR) criteria, Disease Activity Index for Psoriatic Arthritis (DAPSA), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) at 3 and 6 months.

Radiculopathy in a patient with chronic tophaceus gout: vertebral imaging.

Introduction: Spinal involvement is infrequent in chronic gout. However, some cases of back pain with radiculopathy secondary to this etiology have been reported.

Case Report: 56-year old male patient, with history of arterial hypertension, hypertriglyceridemia, obesity, glucose intolerance and alcohol abuse, diagnosed with gout in his fifth decade of life.

Validation of Portuguese-translated computer touch-screen questionnaires in patients with rheumatoid arthritis and spondyloarthritis, compared with paper formats.

The aim of this paper was to assess the validity and reliability of the touch-screen standard Portuguese version of the following patient-reported outcomes (PROs), compared with paper format, in patients with rheumatoid arthritis (RA) and spondyloarthritis: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life scale (ASQoL), Short-Form 36 (SF-36), Health Assessment Questionnaire (HAQ) and visual analogue scales (VAS) measuring pain and burden of disease. Adult patients with RA and spondyloarthritis attending the Portuguese Institute of Rheumatology were recruited from March 2013 to January 2014. Patients filled the paper and touch-screen formats of the standard Portuguese versions of the PROs.

Comparative Effectiveness of Tocilizumab and TNF Inhibitors in Rheumatoid Arthritis Patients: Data from the Rheumatic Diseases Portuguese Register, Reuma.pt.

Objectives: To compare the effectiveness of TNF inhibitors (TNFi) and tocilizumab in rheumatoid arthritis (RA) treatment, according to different response criteria.

Methods: We included RA patients registered in the Rheumatic Diseases Portuguese Register treated with TNFi or tocilizumab for at least 6 months, between January 2008 and July 2013. We assessed remission/low disease activity (LDA) at 6 months according to DAS28, CDAI, and SDAI, as well as Boolean ACR/EULAR remission and EULAR response rate, adjusting for measured confounders.

[Portuguese recommendations for pain management by pharmocotherapy in inflammatory arthritis].

Objectives: To develop Portuguese evidence-based recommendations for pain management by pharmocotherapy in inflammatory arthritis.

Methods: The Portuguese project was integrated in the multinational 3E Initiative (Evidence, Expertise, Exchange) 2010 where a total of 453 rheumatologists from 17 countries have participated. The clinical questions concerning pain were formulated and the Portuguese group added 2 more questions.

2011 Portuguese recommendations for the use of biological therapies in patients with psoriatic arthritis.

Objective: To develop recommendations for the treatment of psoriatic arthritis (PsA) with biological therapies, endorsed by the Portuguese Society of Rheumatology.

Methods: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. A draft of the recommendations was first circulated to all Portuguese rheumatologists and their suggestions were incorporated in the draft.

[Current management of gout].

Gout, one of the most prevalent rheumatic diseases in the world, results from deposition of uric acid crystals in several locations, particularly in joints, subcutaneous tissues and kidney. The classical treatments, although effective, are often poorly tolerated or contraindicated. Recently, new drugs have emerged for the treatment of hyperuricemia and gout, including febuxostat and uricase, which proved to be quite promising.

Teaching enthesis ultrasound: experience of an ultrasound training workshop.

To evaluate a standardised enthesis ultrasound training method, a workshop was conducted to train rheumatologists on enthesis ultrasound. After a theoretical session about ultrasound elementary enthesis lesions (changes in tendon architecture/thickness, bone proliferation/erosion, bursitis or Doppler signal), a reading exercise of 28 entheses' ultrasonographic images (plantar fasciae, Achilles, origin and insertion of patellar tendon) was completed. Participants scored through an electronic multiple-choice device with six possible lesions in each enthesis.

[Analgesic prescription habits in a population of patients with chronic rheumatic disease].

Objectives: The aim of this study was to record the analgesic prescription commonly performed by Portuguese Rheumatologists in patients with chronic Rheumatologic disease, using the guidelines provided by the World Health Organization for treatment of chronic pain as comparative.

Material And Methods: We randomly selected the clinical records of 203 patients with complete clinical record. We excluded patients with less than a year of follow-up, last consultations over a year ago, age under 16 years, patients with no rheumatologic diagnose, being the final sample of 94 patients.

Association of ankle-arm index with inflammation and mineral bone disorder in hemodialysis patients.

Background: Reduced ankle-arm index (AAI), inflammation and mineral bone disorder (MBD) are all associated with increased risk of death and cardiovascular complications in patients on hemodialysis (HD), but the association between them deserves clarification.

Objective: To evaluate the association between abnormal AAI with MBD and inflammation in patients on HD.

Methods: This was a cross-sectional analysis of 478 patients on hemodialysis for at least one year.

[Colonic acute pseudo-obstruction: uncommon manifestation of vertebral fracture].

We report the clinical case of a 73-years-old woman with sarcoidosis since 29 years-old, on long-term corticosteroid therapy, who presented with symptoms of abdominal pain after an episode of acute and severe low back pain associated with significant functional impairment, in the context of D11 fracture. Although infrequent, recent spine fractures should be considered in osteoporotic or osteoporotic risk patients presenting with pain and abdominal distension.

[Applicability of syalometry and other instruments to evaluate xerostomia and xerophtalmia in a Sjögren's Syndrome outpatient clinic].

Objectives: To evaluate the applicability and utility of unstimulated syalometry and instruments of evaluation of sicca complaints in a Sjögren's syndrome outpatient clinic.

Material And Methods: We performed unstimulated syalometry to 45 consecutive Primary Sjögren's Syndrome patients (PSS) and 21 healthy asymptomatic individuals age and sex-matched. PSS patients were further evaluated with Schirmer's test.

Expression and subcellular localization of a novel nuclear acetylcholinesterase protein.

Acetylcholine is found in the nervous system and also in other cell types (endothelium, lymphocytes, and epithelial and blood cells), which are globally termed the non-neuronal cholinergic system. In this study we investigated the expression and subcellular localization of acetylcholinesterase (AChE) in endothelial cells. Our results show the expression of the 70-kDa AChE in both cytoplasmic and nuclear compartments.

VEGF and VEGFR-2 (KDR) internalization is required for endothelial recovery during wound healing.

Vascular endothelial growth factor (VEGF) receptor activation regulates endothelial cell (EC) survival, migration and proliferation. Recently, it was suggested the cross-talk between the VEGF receptors-1 (FLT-1) and -2 (KDR) modulated several of these functions, but the detailed molecular basis for such interactions remained unexplained. Here we demonstrate for the first time that VEGF stimulation of EC monolayers induced a rapid FLT-1-mediated internalization of KDR to the nucleus, via microtubules and the endocytic pathway, internalization which required the activation of PI 3-kinase/AKT.

[Tuberculosis in rheumatic patients treated with tumour necrosis factor alpha antagonists: the Portuguese experience].

In Portugal, 13 cases of tuberculosis (TB) were reported, in the period between 1999 and 2005, in 960 patients exposed to anti-TNFalpha treatment (1.35%), 8 females and 5 males. Mean age was 46.