Biphasic cuirass ventilation in the escalation of non-invasive ventilation in COVID-19: Case report and review.

Ventilatory alternatives to prolong noninvasive ventilation in COVID-19 patients are attractive and poorly understood. New devices to deliver negative noninvasive ventilation as biphasic cuirass ventilation (BCV) have been introduced. BCV device assist in spontaneous breathing and support ventilation. We describe a case of the combination of BCV with high-flow nasal oxygenation (HFNO) in the treatment of a COVID-19 pneumonia patient that required prolonged NIV leading to face mask intolerance, ventilator dependency secondary to residual lung fibrosis and respiratory muscular weakness. BCV provides an efficient non-invasive approach in de-escalation of therapy and weaning of prolonged NIV.

GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis.

OBJECTIVES: To assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis. METHODS: Multicentre, investigator-initiated, randomised, double-blind, placebo-controlled, parallel-design phase 3b trial in 11 Portuguese rheumatology centres. Patients with PsA along with active dactylitis and naive to MTX and biologic disease-modifying antirheumatic drugs (bDMARDs) were randomly assigned to golimumab or placebo, both in combination with MTX. The primary endpoint was Dactylitis Severity Score (DSS) change from baseline to week 24. Key secondary endpoints included DSS and Leeds Dactylitis Index (LDI) response, and changes from baseline in the LDI and MRI dactylitis score. Analysis was by intention-to-treat for the primary endpoint. RESULTS: Twenty-one patients received golimumab plus MTX and 23 MTX monotherapy for 24 weeks. One patient from each arm discontinued. Patient inclusion was halted at 50% planned recruitment due to a favourable interim analysis. Median baseline DSS was 6 in both arms. By week 24, patients treated with golimumab plus MTX exhibited significantly greater improvements in DSS relative to MTX monotherapy (median change of 5 vs 2 points, respectively; p=0.026). In the golimumab plus MTX arm, significantly higher proportions of patients achieved at least 50% or 70% improvement in DSS and 20%, 50% or 70% improvement in LDI in comparison to MTX monotherapy. CONCLUSIONS: The combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis. TRIAL REGISTRATION NUMBER: NCT02065713.

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. Two groups of VAS were used, RA and psoriatic arthritis (Global VAS) and another specific for spondyloarthrites (Spa-VAS). Paper questionnaires were filled 15 min before touch-screen formats. Agreement between formats (validity) was assessed by intraclass correlation coefficient (ICC), while internal consistency of scales (reliability) was assessed by Cronbach's alpha. Overall, 134 patients were included with a mean age of 51 years, 74.6 % female and 57.5 % presenting RA. BASDAI, BASFI, HAQ and ASQoL showed high ICC between paper and touch-screen formats (0.977, 0.958, 0.974 and 0.940, respectively). ICC for Global VAS ranged from 0.906 to 0.921, while Spa-VAS ranged from 0.867 to 0.943. The mean ICC for all SF-36 domains was 0.889 (ICC for each domain ranged from 0.781 to 0.944). Touch-screen standard Portuguese formats of these PROs may be valid and reliable tools for PRO measurement in rheumatology.

Empyema necessitans: After recent thoracostomy in an immunocompromised patient.

This paper consists of a clinical image of an unexpected complication of a pleural space infection that dissects through the pleura into the soft tissues of the chest in an immunocompromised patient.

Pneumonitis Associated with Fluoropolymer Waterproofing Agents: Case Report.

Pneumonitis associated with fluoropolymer waterproofing agents, an entity with few reported cases, can result from occupational exposure. This condition has a rapid onset after exposure, usually resolves with supportive treatment but there could be chronic sequelae. The authors report the case of a 48-year-old male patient admitted to hospital with acute onset of dyspnea and chest pain after using an aerosolized fluoropolymer-containing waterproofing product. He presented tachypnea, leukocytosis, elevated C reactive protein, elevated serum lactate dehydrogenase and hypoxemic respiratory failure. Chest computed tomography revealed bilateral ground-glass opacities with peribronchovascular distribution. The patient was treated with oxygen and corticosteroid therapy, with clinical improvement. This chemical pneumonitis represents a diagnostic challenge since it implies a history of exposure to toxic agents and the pathophysiological mechanisms and safe exposure limits are still unknown.

A pneumonite associada a impermeabilizantes com fluoropolímeros é uma entidade com poucos casos relatados e que pode resultar duma exposição ocupacional. Esta condição tem um início rápido após a exposição, que geralmente se resolve com tratamento de suporte, podendo resultar em sequelas crónicas. Os autores relatam o caso de um homem de 48 anos admitido no hospital com quadro agudo de dispneia e dor torácica após uso de impermeabilizante que continha fluoropolímeros em aerossol. Apresentava taquipneia, leucocitose, proteína C reativa elevada, níveis séricos de lactato desidrogenase elevados e insuficiência respiratória hipoxémica. A tomografia computadorizada do tórax revelou opacidades em vidro despolido bilaterais com distribuição peribroncovascular. O doente foi tratado com oxigenoterapia e corticoterapia com melhoria clínica. Esta pneumonite química representa um diagnóstico desafiante já que implica uma história de exposição a tóxicos, sendo que a fisiopatologia e os limites de segurança de exposição ainda são desconhecidos.

Domiciliary High-Flow Nasal Therapy in Primary Ciliary Dyskinesia.

We report the case of an adolescent with severe primary ciliary dyskinesia (PCD) phenotype associated with a rare genotype. His clinical condition deteriorated, with daily cough and breathlessness, hypoxemia, and lung function decline. Despite being started on home noninvasive ventilation (NIV), the symptoms progressed to dyspnea at rest and thoracic pain. High-flow nasal cannula (HFNC) was started during the daytime as an adjuvant to NIV, and he was started on regular oral opioids for pain and dyspnea control. There was a clear improvement in comfort and dyspnea and breathing work relief. Additionally, better exercise tolerance was also noted. He is currently on the lung transplant waiting list. We aim to emphasize the benefits of HFNC as an add-on therapy for the management of chronic breathlessness since our patient experienced an improvement in breathing and exercise tolerance. However, there is a paucity of studies regarding domiciliary HFNC, particularly in pediatric age. Therefore, further studies are needed to achieve optimal and personalized care. Close monitoring and frequent reassessment in a specialized center are key to adequate management.

Efficacy of ultrasound-guided infiltration with levobupivacaine and triamcinolone for myofascial pain syndrome of the quadratus lumborum: a retrospective observational study.

INTRODUCTION AND OBJECTIVES: Myofascial Pain Syndrome (MPS) of the Quadratus Lumborum muscle (QL) is a frequent cause of chronic low back pain. With this study, we aimed to assess the efficacy of ultrasound-guided infiltration with 0.25% levobupivacaine and 40.ßmg triamcinolone for MPS of the QL. METHODS: Observational and retrospective study of participants submitted to ultrasound-guided infiltration of the QL muscle from January 1, 2015 to June 31, 2019. Pain intensity was assessed using the five-point pain Numeric Rating Scale (NRS): pre-intervention, at 72.ßhours, 1 month, 3 months and 6 months post-intervention. Additional data collected were demographic characteristics, opioid consumption, and adverse effects. RESULTS: We assessed 90 participants with mean age of 55.2 years. Sixty-eight percent of participants were female. Compared to the pre-intervention assessment, there was an improvement in pain at 72.ßhours (Mean Difference [MD.ß=.ß3.085]; 95% CI: 2.200...3.970, p.ß<.ß0.05), at the 1st month (MD.ß=.ß2.644; 95% CI: 1.667...3.621, p.ß<.ß 0.05), at the 3rdmonth (MD.ß=.ß2.017; 95% CI: 0.202...2.729, p.ß<.ß0.05) and at the 6th month (MD.ß=.ß1.339; 95% CI 0.378...2.300, p.ß<.ß0.05), post-intervention. No statistically significant differences in opioid consumption were observed. No adverse effects associated with the technique were reported. CONCLUSIONS: Ultrasound-guided infiltration of the QL muscle is a safe and effective procedure for the treatment of pain in the QL MPS within 6 months post-intervention.

Expanding the Phenotypic Spectrum of HIVEP2-Related Intellectual Disability: Description of Two Portuguese Patients and Review of the Literature.

Introduction: Pathogenic variants in HIVEP2 have been associated with a neurodevelopmental disorder mainly characterized by intellectual disability, severe language impairment, and motor developmental delay. Since its first description in 2016, only 15 patients have been described in the literature. Methods: Here, we report 2 additional unrelated Portuguese children presenting intellectual disability and motor delay in whom de novo nonsense pathogenic variants in HIVEP2 have been identified by next-generation sequencing analysis. Results: In patient 1, the variant c.2827C>T, p.(Arg943*) was detected, whereas patient 2 carried the variant c.6667C>T, p.(Arg2223*). Interestingly, patient 1 presented with a rapid growth of the occipitofrontal diameter in the first months of life due to external hydrocephalus, a feature that, as far as we know, has never been reported in patients with HIVEP2 pathogenic variants. Conclusion: This report expands the phenotypic spectrum of this rare syndrome and provides deeper insights by comparing the clinical features of our patients with previously reported affected individuals.

Variability in the management and imaging use in paediatric minor head trauma in European emergency departments. A Research in European Pediatric Emergency Medicine study.

OBJECTIVE: The objective of the study was to assess the variability in the management of paediatric MHT in European emergency departments (EDs). METHODS: This was a multicentre retrospective study of children ≤18 years old with minor head trauma (MHT) (Glasgow Coma Scale ≥14) who presented to 15 European EDs between 1 January 2013 and 31 December 31. Data on clinical characteristics, imaging tests, and disposition of included patients were collected at each hospital over a 3-year period. RESULTS: We included 11 212 patients. Skull radiography was performed in 3416 (30.5%) patients, range 0.4-92.3%. A computed tomography (CT) was obtained in 696 (6.2%) patients, range 1.6-42.8%. The rate of admission varied from 0 to 48.2%. CONCLUSION: We found great variability in terms of the type of imaging and rate of CT scan obtained. Our study suggests opportunity for improvement in the area of paediatric head injury and the need for targeted individualised ED interventions to improve management of MHT.

The extracellular linker of pro-neuregulin-alpha2c is required for efficient sorting and juxtacrine function.

The neuregulins (NRGs) play important roles in animal physiology, and their disregulation has been linked to diseases such as cancer or schizophrenia. The NRGs may be produced as transmembrane proteins (proNRGs), even though they lack an N-terminal signal sequence. This raises the question of how NRGs are sorted to the plasma membrane. It is also unclear whether in their transmembrane state, the NRGs are biologically active. During studies aimed at solving these questions, we found that deletion of the extracellular juxtamembrane region termed the linker, decreased cell surface exposure of the mutant proNRG(DeltaLinker), and caused its entrapment at the cis-Golgi. We also found that cell surface-exposed transmembrane NRG forms retain biological activity. Thus, a mutant whose cleavage is impaired but is correctly sorted to the plasma membrane activated ErbB receptors in trans and also stimulated proliferation. Because the linker is implicated in surface sorting and the regulation of the cleavage of transmembrane NRGs, our data indicate that this region exerts multiple important roles in the physiology of NRGs.

'I saw it as a second chance': A qualitative exploration of experiences of treatment failure and regimen change among people living with HIV on second- and third-line antiretroviral therapy in Kenya, Malawi and Mozambique.

Increasing numbers of people living with HIV (PLHIV) in sub-Saharan Africa are experiencing failure of first-line antiretroviral therapy and transitioning onto second-line regimens. However, there is a dearth of research on their treatment experiences. We conducted in-depth interviews with 43 PLHIV on second- or third-line antiretroviral therapy and 15 HIV health workers in Kenya, Malawi and Mozambique to explore patients' and health workers' perspectives on these transitions. Interviews were audio-recorded, transcribed and translated into English. Data were coded inductively and analysed thematically. In all settings, experiences of treatment failure and associated episodes of ill-health disrupted daily social and economic activities, and recalled earlier fears of dying from HIV. Transitioning onto more effective regimens often represented a second (or third) chance to (re-)engage with HIV care, with patients prioritising their health over other aspects of their lives. However, many patients struggled to maintain these transformations, particularly when faced with persistent social challenges to pill-taking, alongside the burden of more complex regimens and an inability to mobilise sufficient resources to accommodate change. Efforts to identify treatment failure and support regimen change must account for these patients' unique illness and treatment histories, and interventions should incorporate tailored counselling and social and economic support.

Erk5 nuclear location is independent on dual phosphorylation, and favours resistance to TRAIL-induced apoptosis.

Nucleocytoplasmic shuttling of multiple signalling proteins is critical in the control of processes such as cell proliferation, differentiation, or apoptosis. One group of proteins whose activity depends on this nucleocytoplasmic traffic includes the mitogen-activated protein kinases. Usually, these kinases reside in the cytoplasm and move to the nucleus upon dual phosphorylation. One of these kinases, Erk5, has been found to reside in the nucleus of breast cancer cells that overexpress the ErbB2 receptor. This raises questions with respect to the mechanisms implicated in Erk5 nuclear location in these cells, as well as the biological consequences of this nuclear residency. In breast cancer cells overexpressing ErbB2, Erk5 dual phosphorylation required ErbB2 tyrosine kinase activity; however, Erk5 nuclear residency did not require ErbB2 activity. Furthermore, translocation of Erk5 from the cytosol to the nucleus occurred in the absence of dual phosphorylation. Nuclear residency of Erk5 in these cells depended on the integrity of a nuclear localization signal present in the unique C-terminus of Erk5. The Erk5 form expressed by these breast cancer cells included the N- and C-terminal cytoplasmic targeting signals, yet Erk5 was nuclear, and remained at this location throughout the interphase without being tightly bound to DNA. Biological studies using a mutant Erk5 that accumulates in the nucleus indicate that nuclear Erk5 favours MEF2-dependent transcriptional activity, and inhibits TRAIL-induced cell death.

Efficacy of ultrasound-guided infiltration with levobupivacaine and triamcinolone for myofascial pain syndrome of the quadratus lumborum: a retrospective observational study

Abstract Introduction and objectives: Myofascial Pain Syndrome (MPS) of the Quadratus Lumborum muscle (QL) is a frequent cause of chronic low back pain. With this study, we aimed to assess the efficacy of ultrasound-guided infiltration with 0.25% levobupivacaine and 40 mg triamcinolone for MPS of the QL. Methods: Observational and retrospective study of participants submitted to ultrasound-guided infiltration of the QL muscle from January 1, 2015 to June 31, 2019. Pain intensity was assessed using the five-point pain Numeric Rating Scale (NRS): pre-intervention, at 72 hours, 1 month, 3 months and 6 months post-intervention. Additional data collected were demographic characteristics, opioid consumption, and adverse effects. Results: We assessed 90 participants with mean age of 55.2 years. Sixty-eight percent of participants were female. Compared to the pre-intervention assessment, there was an improvement in pain at 72 hours (Mean Difference [MD = 3.085]; 95% CI: 2.200-3.970, p < 0.05), at the 1st month (MD = 2.644; 95% CI: 1.667-3.621, p < 0.05), at the 3rdmonth (MD = 2.017; 95% CI: 0.202-2.729, p < 0.05) and at the 6th month (MD = 1.339; 95% CI 0.378-2.300, p < 0.05), post-intervention. No statistically significant differences in opioid consumption were observed. No adverse effects associated with the technique were reported. Conclusions: Ultrasound-guided infiltration of the QL muscle is a safe and effective procedure for the treatment of pain in the QL MPS within 6 months post-intervention.

The GO-DACT protocol: a multicentre, randomized, double-blind, parallel-group study to compare the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy.

The GO-DACT is an investigator-initiated, national, multicentric randomized placebo-controlled double-blinded trial, that assesses dactylitis as primary endpoint. Psoriatic arthritis patients naïve to methotrexate and biologic disease modifying anti-rheumatic drugs, with at least one active dactylitis, were assigned to golimumab in combination with methotrexate or placebo in combination with methotrexate, for 24 weeks. Both clinical (dactylitis severity score and the Leeds dactylitis index) and imaging (high resolution magnetic resonance imaging), among others, were assessed as outcomes. The main objective of GO-DACT is to provide evidence to improve the treatment algorithm and care of psoriatic arthritis patients with active dactylitis. In this manuscript we describe the GO-DACT protocol and general concepts of the methodology of this trial.

Anticentromere antibody positive Ackerman's Syndrome with Granulomatous Anterior Uveitis.

Ackerman's Syndrome or Intersticial Granulomatous Dermatitis with Arthritis has been an issue of increasing number of reports in the last decade which had focused its heterogeneous cutaneous and rheumatologic expression besides the initial manifestations reported by Ackerman and his group. Granulomatosis anterior uveitis has not been previously described. Some patients are reported to have positive autoantibodies but association with anticentromere antibodies has not been previously described as well, to our knowledge. We report a new case of Ackerman Syndrome with cutaneous, articular and ocular involvement with positive anticentromere antibodies successfully treated with systemic steroids, methotrexate, hydroxychloroquine and cyclosporine. The ocular involvement and the association of anticentromere antibodies lead us to hypothesize that constellation of symptoms and autoimmune mechanisms of this uncommon multisystemic syndrome are yet to be clarified.

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. The patient was started on urate lowering therapy, with poor compliance, and evolved with sustained hyperuricemia, recurrent episodes of arthritis, and growth of gouty tophi on the elbows, wrists, hands and knees. In 2011, the patient presented with radiculopathy. When pain recurred, a Computed Tomography was performed and it showed alterations compatible with spinal tophi formation and nerve root involvement. DISCUSSION/CONCLUSIONS: Our clinical case is another example of how gout can produce spinal inflammation and nerve damage and superimpose on previously damaged joints and how patients' compliance to therapeutics may have an important impact on prognosis.

[Impact of postoperative cognitive decline in quality of life: a prospective study]. / Impacto do declínio cognitivo pós­operatório na qualidade de vida: estudo prospectivo.

BACKGROUND: Regardless the progress in perioperative care postoperative cognitive decline (PCD) has been accepted unequivocally as a significant and frequent complication of surgery in older patients. The aim of this study was to evaluate the incidence of postoperative cognitive decline and its influence on quality of life three months after surgery. METHODS: Observational, prospective study in a Post-Anesthesia Care Unit (PACU) in patients aged above 45 years, after elective major surgery. Cognitive function was assessed with Montreal Cognitive Assessment (MOCA); Quality of life (QoL) was assessed using SF-36 Health Survey (SF-36). Assessments were performed preoperatively (T0) and 3 months after surgery (T3). RESULTS: Forty-one patients were studied. The incidence of PCD 3 months after surgery was 24%. At T3 MOCA scores were lower in patients with PCD (median 20 vs. 25, p=0.009). When comparing the median scores for each of SF-36 domains, there were no differences between patients with and without PCD. In patients with PCD, and comparing each of SF-36 domains obtained before and three months after surgery, had similar scores for every of the 8 SF-36 areas while patients without PCD had better scores for six domains. At T3 patients with PCD presented with higher levels of dependency in personal activities of daily living (ADL). CONCLUSION: Three months after surgery patients without PCD had significant improvement in MOCA scores. Patients with PCD obtained no increase in SF-36 scores but patients without PCD improved in almost all SF-36 domains. Patients with PCD presented higher rates of dependency in personal ADL after surgery.