Underuse of reperfusion therapy with systemic thrombolysis in high-risk acute pulmonary embolism in a Portuguese center.

INTRODUCTION: Reperfusion therapy is generally recommended in acute high-risk pulmonary embolism (HR-PE), but several population-based studies report that it is underused. Data on epidemiology, management and outcomes of HR-PE in Portugal are scarce. OBJECTIVE: To determine the reperfusion rate in HR-PE patients, the reasons for non-reperfusion, and how it influences outcomes. METHODS: In this retrospective cohort study of consecutive HR-PE patients admitted to a thromboembolic disease referral center between 2008 and 2018, independent predictors for non-reperfusion were assessed by multivariate logistic regression. PE-related mortality and long-term MACE (cardiovascular mortality, PE recurrence and chronic thromboembolic disease) were calculated according to the Kaplan-Meier method. Differences stratified by reperfusion were assessed using the log-rank test. RESULTS: Of 1955 acute PE patients, 3.8% presented with hemodynamic instability. The overall reperfusion rate was 50%: 35 patients underwent systemic thrombolysis, one received first-line percutaneous embolectomy and one rescue endovascular treatment. Independent predictors of non-reperfusion were: age, with >75 years representing 12 times the risk of non-treatment (OR 11.9, 95% CI 2.7-52.3, p=0.001); absolute contraindication for thrombolysis (31.1%), with recent major surgery and central nervous system disease as the most common reasons (OR 16.7, 95% CI 3.2-87.0, p<0.001); and being hospitalized (OR 7.7, 95% CI 1.4-42.9, p=0.020). At a mean follow-up of 2.5±3.3 years, the survival rate was 33.8%. Although not reaching statistical significance for hospital mortality, mortality in the reperfusion group was significantly lower at 30 days, 12 months and during follow-up (relative risk reduction of death of 64% at 12 months, p=0.013). Similar results were found for MACE. CONCLUSIONS: In this population, the recommended reperfusion therapy was performed in only 50% of patients, with advanced age and absolute contraindications to fibrinolysis being the main predictors of non-reperfusion. In this study, thrombolysis underuse was associated with a significant increase in short- and long-term mortality and events.

Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner.

Mammalian circadian clocks respond to feeding and light cues, adjusting internal rhythms with day/night cycles. Astrocytes serve as circadian timekeepers, driving daily physiological rhythms; however, it's unknown how they ensure precise cycle-to-cycle rhythmicity. This is critical for understanding why mistimed or erratic feeding, as in shift work, disrupts circadian physiology- a condition linked to type 2 diabetes and obesity. Here, we show that astrocytic insulin signaling sets the free-running period of locomotor activity in female mice and food entrainment in male mice. Additionally, ablating the insulin receptor in hypothalamic astrocytes alters cyclic energy homeostasis differently in male and female mice. Remarkably, the mutants exhibit altered dopamine metabolism, and the pharmacological modulation of dopaminergic signaling partially restores distinct circadian traits in both male and female mutant mice. Our findings highlight the role of astrocytic insulin-dopaminergic signaling in conveying time-of-feeding or lighting cues to the astrocyte clock, thus governing circadian behavior in a sex-specific manner.

Nuclease Activity of the Junín Virus Nucleoprotein C-Terminal Domain.

The mammarenavirus Junín (JUNV) is the causative agent of Argentine hemorrhagic fever, a severe disease of public health concern. The most abundant viral protein is the nucleoprotein (NP), a multifunctional, two-domain protein with the primary role as structural component of the viral nucleocapsids, used as template for viral polymerase RNA synthesis activities. Here, we report that the C-terminal domain (CTD) of the attenuated Candid#1 strain of the JUNV NP can be purified as a stable soluble form with a secondary structure in line with known NP structures from other mammarenaviruses. We show that the JUNV NP CTD interacts with the viral matrix protein Z in vitro, and that the full-length NP and Z interact with each other in cellulo, suggesting that the NP CTD is responsible for this interaction. This domain comprises an arrangement of four acidic residues and a histidine residue conserved in the active site of exoribonucleases belonging to the DEDDh family. We show that the JUNV NP CTD displays metal-ion-dependent nuclease activity against DNA and single- and double-stranded RNA, and that this activity is impaired by the mutation of a catalytic residue within the DEDDh motif. These results further support this activity, not previously observed in the JUNV NP, which could impact the mechanism of the cellular immune response modulation of this important pathogen.

Hypothalamic astrocytic-BMAL1 regulates energy homeostasis in a sex-dependent manner.

Here, we demonstrate that hypothalamic astrocytic BMAL1 computes cyclic metabolic information to optimize energetic resources in a sexually dimorphic manner. Knockdown of BMAL1 in female astrocytes leads to negative energy balance and alters basal metabolic cycles without affecting circadian locomotor activity. Thus, astrocytic BMAL1 contributes to the control of energy balance through the modulation of the metabolic rate, hepatic and white adipose tissue lipogenesis, and the activity of brown adipose tissue. Importantly, most of these alterations are specific to hypothalamic astrocytic BMAL1. Moreover, female mice with BMAL1 knockdown in astrocytes exhibited a "male-like" metabolic obese phenotype when fed a high-fat diet. Overall, our results suggest a sexually dimorphic effect of astrocytic BMAL1 on the regulation of energy homeostasis, which may be of interest in the physiopathology of obesity and related comorbidities.

Interventions for Caregivers of Heart Disease Patients in Rehabilitation: Scoping Review.

Map the interventions/components directed to the caregivers of heart disease patients in cardiac rehabilitation programs that promote their role and health. METHODS: The Joanna Briggs Institute method was used to guide this scoping review. Two independent reviewers assessed articles for relevance and extracted and synthesized data. Inclusion criteria comprised articles published in English, Spanish, and Portuguese since 1950. The following databases were searched: CINAHL Complete (Via EBSCO), Medline (via PubMed), Scopus, PEDro, and Repositórios Científicos de Acesso Aberto de Portugal (RCAAP). RESULTS: From 351 articles retrieved, 10 were included in the review. The interventions identified directed to the caregiver were: educational interventions and lifestyle changes; physical exercise; psychological interventions/stress management; and a category "Other" with training interventions in basic life support, elaboration of guidelines/recommendations, and training for the role of caregiver. CONCLUSIONS: It was found that most of the related cardiac rehabilitation interventions are aimed at the dyad heart failure patient and their caregivers/family. Including specific interventions targeting caregivers improves the caregiver's health and empowers them. Patient care planning should include interventions specifically aimed at them that result in health gains for caregivers and patients, striving to improve the quality of care. This study was not registered.

Cardiac Rehabilitation in a Transplanted Person with Emery-Dreifuss Muscular Dystrophy. / Reabilitação Cardíaca na Pessoa Transplantada com Distrofia Muscular de Emery-Dreifuss.

Emery-Dreifuss muscular dystrophy is a rare hereditary neuromuscular disease. Its manifestations begin primarily in childhood. The most frequent manifestations are progressive muscle weakness, atrophy that usually begins in the scapula-vertebral region, extending later to the pelvic girdle, and spinal stiffness. Patients can also manifest cardiac involvement as palpitations, syncope, exercise intolerance, congestive heart failure, and variable heart rhythm disturbances. 1 - 3 The presence and severity of these manifestations can vary according to the individual and the disease's subtypes. 2 Cardiac involvement is the most worrisome feature of this disease, and there are some reports of the need for heart transplantation in this dystrophy. 4.

A distrofia muscular de Emery-Dreifuss é uma doença neuromuscular hereditária rara. Suas manifestações começam principalmente na infância. As manifestações mais frequentes são fraqueza muscular progressiva, atrofia que geralmente se inicia na região escápulo-vertebral, estendendo-se posteriormente para a cintura pélvica e rigidez da coluna vertebral. Os pacientes também podem manifestar envolvimento cardíaco como palpitações, síncope, intolerância ao exercício, insuficiência cardíaca congestiva e distúrbios variáveis do ritmo cardíaco. 1 - 3 A presença e a gravidade dessas manifestações podem variar de acordo com o indivíduo e os subtipos da doença. 2 O envolvimento cardíaco é a característica mais preocupante desta doença, havendo alguns relatos da necessidade de transplante cardíaco nesta distrofia. 4.

Implementation Status of the Proposal for a Regulation of the European Health Data Space in Portugal: Are We Ready for It?

The European Health Data Space (EHDS) proposal aims to establish a set of rules and governance frameworks to promote the use of electronic health data for both primary and secondary purposes. This study aims at analysing the implementation status of the EHDS proposal in Portugal, particularly the points concerning the primary use of health data. The proposal was scanned for the points that gave member states a direct responsibility to implement actions, and a literature review and interviews were conducted to assess the implementation status of these policies in Portugal This study found that Portugal is well advanced in the implementation of policies concerning the rights of natural persons in relation to the primary use of their personal health data, but also identified challenges, which include the lack of a common interoperability framework for the exchange of electronic health data.

El proceso de transición y capacitación de la persona trasplantada al corazón y familia: ensayo teórico / The process of transition and training of the person transplanted to the heart and family: theoretical essay

La persona trasplantada de corazón y la familia experimentan diferentes tipos de transición, y un acompañante facilitador de su formación para una transición saludable es fundamental.La Enfermería de Rehabilitación (ER), debido a sus habilidades, puede ayudar a las personas a recuperar la estabilidad y el bienestar, sin embargo, existe poca difusión de su fundamento en lasteorías de enfermería. Objetivo: Analizar el aporte de la Teoría de las Transiciones en la práctica dela enfermería rehabilitadora orientada al empoderamiento de la persona trasplantada al corazón ya la familia. Metodología: Estudio crítico-reflexivo guiado por la Teoría de las Transiciones de AfafMeleis y por la legislación reguladora para la práctica del enfermero rehabilitador. Resultado: Sepercibe que la teoría de las Transiciones sustenta la intervención de Enfermería de Rehabilitaciónen las áreas de conocimiento y aprendizaje de habilidades de la persona trasplantada cardíaca y sufamilia, conduciendo a su empoderamiento, toma de decisiones y acción, haciendo que la personase sienta empoderada para superar los retos diarios derivados de su proceso de transición. Conclusión: Es fundamental demostrar la conceptualización en la práctica de enfermería, siendo la transición un foco significativo para la Enfermería de Rehabilitación.(AU)

Sphenopalatine ganglion block - a new treatment for burning mouth syndrome?: a case report

Abstract Burning mouth syndrome is a poorly understood entity for which current treatment modalities fail to provide effective relieve. Branches of the maxillary and mandibular nerves are responsible for the innervation of the affected area. These are also the nerves involved in trigeminal neuralgia, an entity where sphenopalatine block has proved to be effective. We present a case of a patient with burning mouth syndrome in whom a bilateral sphenopalatine ganglion block was successfully performed for pain treatment. It is an easy and safe technique that can be a valuable treatment option for these patients, although more studies are needed.

Blueprint for developing an effective pulmonary embolism response network.

INTRODUCTION: Acute pulmonary embolism (PE) is a major cause of morbidity and mortality in Portugal. It is the third most common cause of cardiovascular death after stroke and myocardial infarction. However, the management of acute PE remains poorly standardized, and there is a lack of access to mechanical reperfusion when indicated. METHODS AND RESULTS: This working group analyzed the current clinical guidelines for the use of percutaneous catheter-directed treatment in this setting and proposed a standardized approach for severe forms of acute PE. This document also proposes a methodology for the coordination of regional resources in order to create an effective PE response network, based on the hub-and-spoke organization design. CONCLUSION: This model can be applied at the regional level, but it is desirable to extend it to the national level.

Sphenopalatine ganglion block ... a new treatment for burning mouth syndrome?: a case report.

Burning mouth syndrome is a poorly understood entity for which current treatment modalities fail to provide effective relieve. Branches of the maxillary and mandibular nerves are responsible for the innervation of the affected area. These are also the nerves involved in trigeminal neuralgia, an entity where sphenopalatine block has proved to be effective. We present a case of a patient with burning mouth syndrome in whom a bilateral sphenopalatine ganglion block was successfully performed for pain treatment. It is an easy and safe technique that can be a valuable treatment option for these patients, although more studies are needed.

Reabilitação Cardíaca na Pessoa Transplantada com Distrofia Muscular de Emery-Dreifuss / Cardiac Rehabilitation in a Transplanted Person with Emery-Dreifuss Muscular Dystrophy

Resumo A distrofia muscular de Emery-Dreifuss é uma doença neuromuscular hereditária rara. Suas manifestações começam principalmente na infância. As manifestações mais frequentes são fraqueza muscular progressiva, atrofia que geralmente se inicia na região escápulo-vertebral, estendendo-se posteriormente para a cintura pélvica e rigidez da coluna vertebral. Os pacientes também podem manifestar envolvimento cardíaco como palpitações, síncope, intolerância ao exercício, insuficiência cardíaca congestiva e distúrbios variáveis do ritmo cardíaco. 1 - 3 A presença e a gravidade dessas manifestações podem variar de acordo com o indivíduo e os subtipos da doença. 2 O envolvimento cardíaco é a característica mais preocupante desta doença, havendo alguns relatos da necessidade de transplante cardíaco nesta distrofia. 4

Abstract Emery-Dreifuss muscular dystrophy is a rare hereditary neuromuscular disease. Its manifestations begin primarily in childhood. The most frequent manifestations are progressive muscle weakness, atrophy that usually begins in the scapula-vertebral region, extending later to the pelvic girdle, and spinal stiffness. Patients can also manifest cardiac involvement as palpitations, syncope, exercise intolerance, congestive heart failure, and variable heart rhythm disturbances.1 - 3 The presence and severity of these manifestations can vary according to the individual and the disease's subtypes. 2 Cardiac involvement is the most worrisome feature of this disease, and there are some reports of the need for heart transplantation in this dystrophy. 4

Severe and Apparently Irreversible Pulmonary Arterial Hypertension in a Patient with Ostium Secundum Atrial Septal Defect - A Successful Case of Treat and Close Strategy.

Irreversible pulmonary arterial hypertension is considered a contraindication for surgical or percutaneous closure of atrial septal defects (ASD) due to risk of right heart failure. We present a case of 37 years-old woman who was referred to our center due to progressive worsening fatigue and high probability of pulmonary hypertension on a transthoracic echocardiogram. The diagnostic work-up revealed the presence of an ostium secundum atrial septal defect and severe pre-capillary pulmonary hypertension on right heart cathetherization (RHC). The patient was considered inoperable and started medical therapy with sildenafil and bosentan. After one year of treatment, she repeated RHC that showed a significant reduction in pulmonary vascular resistance making her eligible for closure. Surgical closure of ASD with a fenestra was performed with success. Our case emphasizes the importance of individual assessment even if cases where initial evaluation is unfavorable to closure in accordance with the guidelines.

Morte e morrer: compreensão, aceitação e entraves da equipe de enfermagem / Death and dying: understanding, acceptance and barriers of the nursing team / Muerte y morir: comprensión, aceptación y barreras del equipo de enfermería

Objetivo: Descrever com o auxílio da literatura as diversas percepções relacionadas ao processo de morte e morrer na enfermagem. Metodologia: Pesquisa bibliográfica do tipo revisão integrativa da literatura, utilizaram-se estudos disponíveis em sua totalidade, publicados nos últimos dez anos, de 2010 até 2020, nos idiomas Português, Espanhol e Inglês, ao final doze (12) artigos atenderam a questão norteadora e foram adicionados ao estudo. Resultados: A maioria dos estudos sugerem que haja um preparo dos profissionais diante do processo morte e morrer do paciente e que isso deveria fazer parte da grade curricular dos cursos de graduação, pois o levantamento nos mostrou que a maioria dos profissionais ainda não estão aptos psicologicamente para esse processo, o que influenciará na vida profissional e pessoal do mesmo. Ainda quando a morte acontece na terceira idade é fato natural e aceitável, na idade adulta é frustrante por impossibilitar a fase idosa e quando é de uma criança a dificuldade de aceitar os sentimentos e frustrações apresentam-se com maior intensidade. Conclusão: A enfermagem desempenha papel fundamental no processo de morte/morrer e necessita de maior suporte e apoio para que este processo seja compreendido e trabalhado da melhor forma possível, para que se possa facilitar o enfrentamento e a aceitação, como ciclo vital.

Continuous Aspiration Mechanical Thrombectomy for the management of intermediate- and high-risk pulmonary embolism: Data from the first cohort in Portugal.

INTRODUCTION: This study describes the experience of a reference center using continuous aspiration mechanical thrombectomy for acute high- and intermediate-high-risk pulmonary embolism (PE). METHODS: Twenty-nine consecutive patients with acute central PE (48.3% high-risk PE; 82.8% in class >III from the original Pulmonary Embolism Severity Index score; median Charlson Comorbidity Index of 4) were treated with the Indigo® Mechanical Thrombectomy System between March 2018 and March 2020. Technical success was defined as successful placement of the device and initiation of aspiration thrombectomy. Clinical success was defined as any improvement in hemodynamic and/or oxygenation parameters, pulmonary hypertension or right heart strain at 48 hours, and survival to hospital discharge. Safety was defined as freedom from severe adverse events potentially related to the procedure. Three-month follow-up results were collected. RESULTS: Technical success was 96.6%. Miller index and systolic pulmonary arterial pressure were significantly reduced after the procedure (-5.5±3.0, and -10.2±11.5 mmHg, respectively, both p<0.001). There was a significant improvement in mean paO2/FiO2 ratio (+77.1±103.2; p=0.001), shock index (-0.4±0.4; p<0.001), need for aminergic support at 48 h after the procedure (-75.0%, p=0.006) and improvement in right ventricular function in 66.6% (p=0.008). Clinical success was 75.9%. Severe adverse event rate was 10.3%: two deaths during the procedure and one pulmonary macroembolization during device progression. In-hospital and three-month survival rates were 82.8% and 72.4%, respectively. CONCLUSIONS: Aspiration thrombectomy for acute high- and intermediate-high-risk PE is feasible with a high technical and clinical success rate. Nevertheless, all-cause mortality is still high, probably related to the baseline high-risk features of the studied population and associated comorbidities.

Capsaicin 8% for Peripheral Neuropathic Pain Treatment: A Retrospective Cohort Study.

BACKGROUND: Chronic neuropathic pain is a disabling condition that affects quality of life. Despite recommendations and guidelines, treatment remains suboptimal as it often does not result in significant symptom relief. Capsaicin 8% patch has been used for the treatment of several peripheral neuropathic pain etiologies with encouraging results. OBJECTIVES: To assess the results of capsaicin 8% patch on neuropathic pain by evaluating pain intensity and the painful treatment area. STUDY DESIGN: Observational retrospective cohort study. SETTING: All patients submitted to capsaicin treatment at the Chronic Pain Unit of the Hospital Centre of Tondela Viseu, from 2011 through 2019. METHODS: Records of capsaicin treatments were reviewed, and the data collected. The primary outcome was pain intensity and painful treatment area reduction between the first and last treatment. Also, the number of treatments performed, neuropathic pain duration, anatomic location, pain etiology, and concomitant oral pain medication at baseline and upon treatment conclusion was also listed. RESULTS: Postsurgical neuropathic pain was the most common etiology (49%), followed by postherpetic (28%). The median (interquartile range [IQR]) baseline pain intensity assessed by the Numeric Rating Scale (NRS-11) was 6 (5-8) and the median (IQR) final NRS-11 was 3 (1-5), with a median (IQR) relative difference of -0.5 (-0.85-0.17) with statistically significant differences (P < 0.001) between baseline and last pain intensity, regarding all groups. Also, there was a reduction in the painful treatment area between baseline and the last evaluation, with a median (IQR) relative difference of -0.4 (-0.625-0.167). LIMITATIONS: A relatively small sample and occasional different timing for pain intensity and pain treatment area assessment due to logistical difficulties. CONCLUSIONS: Capsaicin 8% patch is a valuable option for the treatment of peripheral neuropathic pain, providing a significant reduction in pain intensity and painful area. It is well tolerated and has a high treatment compliance.Ethics Committee Reference Number: 16/16//04/2021.

The Virus-Host Interplay in Junín Mammarenavirus Infection.

Junín virus (JUNV) belongs to the Arenaviridae family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in Argentina. At this moment, there are no effective antiviral therapeutics to battle pathogenic arenaviruses. Cumulative reports from recent years have widely provided information on cellular factors playing key roles during JUNV infection. In this review, we summarize research on host molecular determinants that intervene in the different stages of the viral life cycle: viral entry, replication, assembly and budding. Alongside, we describe JUNV tight interplay with the innate immune system. We also review the development of different reverse genetics systems and their use as tools to study JUNV biology and its close teamwork with the host. Elucidating relevant interactions of the virus with the host cell machinery is highly necessary to better understand the mechanistic basis beyond virus multiplication, disease pathogenesis and viral subversion of the immune response. Altogether, this knowledge becomes essential for identifying potential targets for the rational design of novel antiviral treatments to combat JUNV as well as other pathogenic arenaviruses.