10-year success story in CTEPH treatment: breaking the myth of rareness.

Unlike acute pulmonary embolism (PE), the resolution of thrombi is ineffective in chronic thromboembolic pulmonary hypertension (CTEPH), leading to reorganisation and fibrotic changes within the pulmonary arteries. The authors report the case of a man in his 60s with polycythemia vera, under warfarin, following an acute PE. He was admitted a year later with right heart failure and haemodynamic instability. Acute over chronic PE caused this severe presentation, confirmed by right heart catheterisation and pulmonary scintigraphy. The challenging diagnosis and management involved transfer to a centre specialised in pulmonary vascular disease. Normalisation of functional and haemodynamic parameters, sustained in 10-year follow-up, was achieved with anticoagulation and triple therapy with prostanoids as a bridge to pulmonary thromboendarterectomy. Targeted medical therapy, not standard at that time, was crucial to recovering conditions for transfer. An individualised approach, integrating multidisciplinary pulmonary hypertension expertise, provides the basis for the best care for CTEPH.

Epileptogenesis and drug-resistant in focal cortical dysplasias: Update on clinical, cellular, and molecular markers.

Focal cortical dysplasia (FCD) is a cortical malformation in brain development and is considered as one of the major causes of drug-resistant epilepsiesin children and adults. The pathogenesis of FCD is yet to be fully understood. Imaging markers such as MRI are currently the surgeons major obstacle due to the difficulty in delimiting the precise dysplasic area and a mosaic brain where there is epileptogenic tissue invisible to MRI. Also increased gene expression and activity may be responsible for the alterations in cell proliferation, migration, growth, and survival. Altered expressions were found, particularly in the PI3K/AKT/mTOR pathway. Surgery is still considered the most effective treatment option, due to drug-resistance, and up to 60 % of patients experience complete seizure control, varying according to the type and location of FCD. Both genetic and epigenetic factors may be involved in the pathogenesis of FCD, and there is no conclusive evidence whether these alterations are inherited or have an environmental origin.

Oromandibular Dystonia as a Side Effect of Methotrexate.

Oromandibular dystonia is a focal dystonia characterized by involuntary movements of the jaw, oropharynx, lips, and tongue. The diagnosis of oromandibular dystonia is clinical and can be complex. For effective treatment, it is essential to understand its underlying etiology. A 70-year-old man was referred to our center with a diagnosis of Meige's syndrome, which had been present for five and a half years, for receiving botulinum toxin-A (BoNT-A) injections. Upon physical examination, he exhibited oromandibular dystonia, with a score of 177 points on the Oromandibular Dystonia Rating Scale (OMDRS). He had a history of taking methotrexate for six years, as he was diagnosed with psoriatic arthritis during that time. The possibility of methotrexate-induced dystonia was considered. A switch from methotrexate to sulfasalazine was initiated. Subsequently, the patient showed progressive improvement in his symptoms, as reflected by an OMDRS score of 103 points. After eight weeks, the medical team decided to supplement the treatment with BoNT-A injections, resulting in an OMDRS score of 75. While there is currently no definitive evidence linking the use of methotrexate to the development of dystonia, it is advisable to consider oromandibular dystonia as a potential side effect of methotrexate until more robust evidence becomes available.

WNT pathway in focal cortical dysplasia compared to perilesional nonlesional tissue in refractory epilepsies.

BACKGROUND: Focal cortical dysplasia (FCD) is a malformation of cortical development that causes medical refractory seizures, and one of the main treatments may be surgical resection of the affected area of the brain. People affected by FCD may present with seizures of variable severity since childhood. Despite many medical treatments available, only surgery can offer cure. The pathophysiology of the disease is not yet understood; however, it is known that several gene alterations may play a role. The WNT/ß-catenin pathway is closely related to the control and balance of cell proliferation and differentiation in the central nervous system. The aim of this study was to explore genes related to the WNT/ß-catenin pathway in lesional and perilesional brain tissue in patients with FCD type II. METHODS: Dysplastic and perilesional tissue from the primary dysplastic lesion of patients with FCD type IIa were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array (super array) containing 84 genes related to the WNT pathway. RESULTS: Our results suggest the existence of molecular alteration in some genes of the WNT pathway in tissue with dysplastic lesions and of perilesional tissue. We call this tissue of normal-appearing adjacent cortex (NAAC). Of all genes analyzed, a large number of genes show similar behavior between injured, perilesional and control tissues. However, some genes have similar characteristics between the perilesional and lesional tissue and are different from the control brain tissue, presenting the perilesional tissue as a molecularly altered material. CONCLUSION: Our results suggest that the perilesional area after surgical resection of tissue with cortical dysplasia presents molecular changes that may play a role in the recurrence of seizures in these patients. The perilesional tissue should receive expanded attention beyond the somatic mutations described and associated with FCD, such as mTOR, for example, to new signaling pathways that may play a crucial role in seizure recurrence.

Cycling versus swapping strategies in psoriatic arthritis: results from the rheumatic diseases Portuguese register.

OBJECTIVE: To compare the 2-year retention rate between a second tumor necrosis factor alpha inhibitor (TNFi) and secukinumab (SEK) or ustekinumab (UST), in Psoriatic Arthritis (PsA) patients with previous inadequate response to their first TNFi. METHODS: Prospective longitudinal cohort study with a follow-up period of 2 years using the Nationwide Portuguese Reuma.pt database. Patients with a clinical diagnosis of PsA who also fulfill the CASPAR classification criteria, with previous treatment failure to a first-line TNFi and having started a second biotechnological drug (TNFi, SEK or UST) were included. The Cycling group was defined as switching from a first TNFi to a second TNFi, and the Swapping group as switching from a first TNFi to SEK or UST. Sociodemographic data, disease characteristics, disease activity scores and physical function at baseline and after 6, 12 and 24 months were recorded. Cox-proportional hazards regression was used to compare retention rates between Cycling and Swapping groups. To obtain a predictor model of 2-year discontinuation, a multivariable Cox regression model was performed. RESULTS: In total, 439 patients were included, 58% were female, with a mean age (standard deviation) of 49 (12) years. Globally, 75.6% initiated a second TNFi (Cycling group), and 24.4% started SEK/UST (Swapping group). The retention rates after 6, 12 and 24 months were 72%/66%/59% in the Cycling group; and 77%/66%/59% in the Swapping group. There were no significant differences in retention rates between both strategies (HR: 1.06, 95% CI 0.72-1.16). After 2 years of follow-up, 34.4% of patients discontinued their second biologic, mainly due to inefficacy (72.8%), with no differences found between groups. Baseline treatment with glucocorticoids was the only predictor of discontinuation after 2 years of follow-up (HR:1.668, 95% CI 1.154-2.409). CONCLUSIONS: After failure of a first TNF inhibitor, Cycling and Swapping strategies result in similar retention rates suggesting that both are acceptable in the management of patients with psoriatic arthritis.

Orthostatic hypotension as an unusual presentation of spinal calcium pyrophosphate deposition disease: case report and review of literature.

Calcium pyrophosphate crystal deposition disease (CPPD), also known as pseudogout, with spinal involvement, is associated with clinical manifestations of acute nerve compression or chronic spinal stenosis. Precipitation of crystals of calcium pyrophosphate dihydrate in connective tissues can lead to acute inflammatory arthritis, degenerative chronic arthropathies, and radiographic evidence of cartilage calcification. We present a case of an 87-year-old woman, with unstudied chronic polyarthralgia and symptomatic orthostatic hypotension. It were documented acute calcium pyrophosphate deposition wrist arthritis, and cervical CT and MRI was suggestive of spinal involvement of CPPD. Workup excluded other causes of OH. Surgical approach could be indicated to minimize the symptoms, but it was contra-indicated due to the patient's performance status, so histological diagnosis was not possible. Muscle atrophy played an important part in the rapid progression of this insidious chronic disease. Conservative and symptomatic treatment achieve scarce short-term clinical improvement. Spinal involvement of CPPD was thought to be rare but recent studies show a higher prevalence than expected. We call for attention to the extent of structural changes that may occur when not early diagnosed nor treated. High clinical suspicion is required and this is, to our knowledge, the first report of orthostatic hypotension as a presentation of CPPD.

A Rare Case of Mediastinal Mass: Thymoma and Thymic Tumor.

Thymomas and thymic carcinomas are rare mediastinal neoplasms arising from thymic epithelial cells, and the presence of synchronous or metachronous primary thymic neoplasms in a single patient is an extremely rare event. Thymoma patients appear to have an inherent predisposition toward developing additional neoplasms. This additionally presents a diagnostic challenge, revealing the importance of multidisciplinary expertise to the management of these patients. This is a case report of a patient with a thymoma and thymic carcinoma, submitted to surgical resection and postoperative radiotherapy.

Case Report and Literature Review of Cardiac Amyloidosis: A Not-So-Rare Cause of Heart Failure.

Restrictive cardiomyopathy secondary to cardiac amyloidosis is an underdiagnosed cause of heart failure and it is associated with significant morbidity and mortality. The most common types of amyloidosis are light chain amyloidosis, transthyretin amyloidosis and secondary amyloidosis. We report the case of a 84-year-old man that presented with new onset signs and symptoms of heart failure. Multimodality imaging with echocardiogram and bone tracer cardiac scintigraphy along with biomarkers, monoclonal proteins analysis and genetic test allowed to diagnosed a wild-type transthyretin amyloidosis. We discuss the clinical and diagnostic features and review the current literature about cardiac amyloidosis. This paper aims to increase clinicians' awareness of cardiac amyloidosis to promptly recognize, diagnose and treat it.

Well-being at work, productivity, and coping with stress during the COVID-19 pandemic.

This study aims to analyze the mechanisms through which the coronavirus disease (COVID-19) pandemic impacts on well-being at work and on productivity. The secondary objective is to identify stress management strategies for the work environment during the pandemic. This is an integrative review. Phase 1 consisted of searches of open access electronic databases (MEDLINE, SciELO, Bireme, and LILACS) for papers published in 2020 addressing mental health, work, and pandemics. Phase 2 consisted of selecting literature recommended by specialists in occupational psychiatry and positive psychology. These materials were read and critically analyzed. Forty references were included in the literature review. The articles reviewed were classified into the following categories: articles concerning work relationships in Brazil; articles describing the impact of pandemics on mental health and work; articles focusing on the work of health professionals during pandemics; articles about well-being at work; and papers proposing strategies to improve well-being and productivity and to promote mental health. The COVID-19 pandemic can have a significant impact on workers' mental health and productivity. Most professionals face a need to adapt to changes, which can decrease their feeling of well-being. Consequently, strategies to promote well-being and mental health in the work environment should be a priority. Work routines were modified after the COVID-19 pandemic set in and assessing these changes is essential to maintain workers' mental health. By so doing, it is possible to promote general well-being and post-traumatic recovery and reduce stress levels.

Well-being at work, productivity, and coping with stress during the COVID-19 pandemic

Abstract This study aims to analyze the mechanisms through which the coronavirus disease (COVID-19) pandemic impacts on well-being at work and on productivity. The secondary objective is to identify stress management strategies for the work environment during the pandemic. This is an integrative review. Phase 1 consisted of searches of open access electronic databases (MEDLINE, SciELO, Bireme, and LILACS) for papers published in 2020 addressing mental health, work, and pandemics. Phase 2 consisted of selecting literature recommended by specialists in occupational psychiatry and positive psychology. These materials were read and critically analyzed. Forty references were included in the literature review. The articles reviewed were classified into the following categories: articles concerning work relationships in Brazil; articles describing the impact of pandemics on mental health and work; articles focusing on the work of health professionals during pandemics; articles about well-being at work; and papers proposing strategies to improve well-being and productivity and to promote mental health. The COVID-19 pandemic can have a significant impact on workers' mental health and productivity. Most professionals face a need to adapt to changes, which can decrease their feeling of well-being. Consequently, strategies to promote well-being and mental health in the work environment should be a priority. Work routines were modified after the COVID-19 pandemic set in and assessing these changes is essential to maintain workers' mental health. By so doing, it is possible to promote general well-being and post-traumatic recovery and reduce stress levels.

Value-based decision-making for orphan drugs with multiple criteria decision analysis: burosumab for the treatment of X-linked hypophosphatemia.

OBJECTIVE: Burosumab is an orphan medicinal product (OMP) approved in Europe for the treatment of X-linked hypophosphatemia (XLH). The aim of this study was to assess the value of burosumab versus conventional therapy for the treatment of paediatric XLH, through a multi-criteria decision analysis (MCDA) framework for health technology assessment (HTA) of OMPs in Portugal. METHODS: The MCDA framework considered 14 criteria related to disease burden, therapeutic value and economic burden. A multidisciplinary panel of national stakeholders participated in a two-phase exercise. In the first phase, relative weights and part-worth utilities for the criteria and their levels were elicited and a reimbursement likelihood function was calibrated through adaptive conjoint analysis. In the second phase, burosumab and conventional therapy were assessed against the criteria, providing a global value score (0-100) and reimbursement likelihood (0-100%) for both. RESULTS: Of the 14 criteria, disease burden, therapeutic value and economic burden criteria represented 27.29%, 57.17% and 15.53% of the total weight in the decision, respectively. All disease burden and some therapeutic value criteria, typically not included in traditional HTA, represented 47.88% of the total weight. Burosumab was unanimously considered superior to conventional therapy, with an average (range) global value score of 84.96 (82.48-86.54) against 48.06 (43.37-57.68), and reimbursement likelihood of 97.50% (96.78%-98.32%) against 43.66% (31.48%-68.73%), respectively. CONCLUSIONS: MCDA represents a powerful tool in HTA decision-making for OMPs. The results of this MCDA acknowledge burosumab as a disease-modifying drug, deemed superior to conventional therapy for the treatment of paediatric XLH.

Impact of the Sampling Site in the Result of Wet Mount Microscopy.

OBJECTIVES: Wet mount microscopy (WMM) is an ancillary test in the diagnosis of vulvovaginitis. However, there are little data about the impact of the sampling site. Our main objective was to determine the agreement between samples collected from different vaginal sites. MATERIALS AND METHODS: Five vaginal samples (one from each of the fornices and one from the lower third) were collected from 50 consecutive women and evaluated using phase-contrast WMM, including the following: lactobacillary grade, presence of other bacteria, clue cells, inflammation, and atrophy. Global percentage of agreement, κ index [poor (<0), slight (0.01-0.20), fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.80), and almost perfect (0.81-1)], sensitivity and negative predictive value were calculated. RESULTS: Global percentage of agreement was high for all individual parameters (>75%), but low for the final diagnosis (57%). Agreement rate was substantial or almost perfect for the evaluation of normal versus abnormal flora, substantial for the presence of absence of bacteria other than lactobacilli and for the presence of clue cells, and moderate to almost perfect for the presence of dysbiosis and cytolysis. Agreement rates were worse for inflammation, atrophy, and the presence of Candida. The lower third of the vagina had the highest sensitivity for Candida (0.6, 95% CI = 0.41-0.86) and bacterial vaginosis (0.92, 95% CI = 0.73-1.00), whereas the anterior fornix performed better for cytolytic vaginosis (0.75, 95% CI = 0.43-0.93). CONCLUSIONS: There is some variation in the results according to the sampling site, which may be overcome by collecting 2 samples (anterior fornix and lower third of the vagina).