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.

Dos percursos clínicos às competências específicas em enfermagem de saúde infantil e pediátrica e a emergência da promoção da higiene do sono na infância como área crítica / From clinical pathways to specific competencies in child and pediatric health nursing and the emergence of sleep hygiene promotion in childhood as a critical area

O presente relatório final documenta os percursos clínicos efetuados na formação conducente ao grau de mestre em Enfermagem de Saúde Infantil e Pediatria, que são decisivos ao desenvolvimento das competências específicas na área. Os percursos experienciados e refletidos, vertidos neste relatório final, produziram evidências significativas no desenvolvimento dessas competências. Ao longo destes percursos clínicos foi ainda possível verificar a emergência de focos, ainda pouco trabalhados, que necessitam de desenvolvimento pelos enfermeiros nesta área. Um deles é a promoção do sono saudável/higiene do sono na infância. Assim, a promoção de um sono saudável emerge como área focal no Relatório, tendo sido realizado um novo percurso clínico em contexto de ambulatório pediátrico hospitalar, por forma a desenvolver uma compreensão mais estruturada e pormenorizada sobre o assunto. Objetivos: Deste modo, pretendeu-se: discutir as experiências nos percursos clínicos conducentes à formação especializada em EESIP, conducente ao grau de mestre; conhecer a perceção dos pais, num contexto de ambulatório pediátrico, sobre a importância da higiene do sono na primeira infância; realizar proposta de melhoria das práticas, por forma a incorporar esta área, higiene do sono/ sono saudável, como central em todas as situações de crianças em ambulatório. Metodologia: Foi efetuada uma análise às experiências clínicas do percurso formativo, do curso de pós-licenciatura em enfermagem de saúde infantil e pediátrica e do curso de mestrado, colheita de dados através de entrevistas aos pais, durante o estágio final, observação participante e análise a documentos no serviço. Resultados: O relatório escrito demonstra evidências das competências desenvolvidas nos percursos clínicos, incluindo intervenções do enfermeiro numa área tão significativa quanto a promoção do sono saudável em crianças, sabendo-se que as crianças em idade pré-escolar revelam frequentemente deficitária higiene do sono, sendo fulcral o papel do EESIP na correção de hábitos menos saudáveis, maximizando a saúde da criança. Conclusões: Parece possível implementar na consulta em contexto de ambulatório hospitalar uma parte destinada a esta atividade de vida, desde um screening com instrumento adequado a uma intervenção direta em função da avaliação imediata, reforçando o papel parental por via do seu empoderamento.

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.

Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial.

Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure ≤110 mm Hg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations.

The cannabinoid receptor 1 is involved in renal fibrosis during chronic allograft dysfunction: Proof of concept.

Chronic allograft dysfunction (CAD), defined as the replacement of functional renal tissue by extracellular matrix proteins, remains the first cause of graft loss. The aim of our study was to explore the potential role of the cannabinoid receptor 1 (CB1) during CAD. We retrospectively quantified CB1 expression and correlated it with renal fibrosis in 26 kidney-transplanted patients who underwent serial routine kidney biopsies. Whereas CB1 expression was low in normal kidney grafts, it was highly expressed during CAD, especially in tubular cells. CB1 expression significantly increased early on after transplantation, from day 0 (D0) to month 3 post-transplant (M3) (22.5% ± 15.4% vs 33.4% ± 13.8%, P < .01), and it remained stable thereafter. CB1 expression correlated with renal fibrosis at M3 (P = .04). In an in vitro model of tacrolimus-mediated fibrogenesis by tubular cells, we found that tacrolimus treatment significantly induced mRNA and protein expression of CB1 concomitantly to col3a1 and col4a3 up regulation. Administration of rimonabant, a CB1 antagonist, blunted collagen synthesis by tubular cells (P < .05). Overall, our study strongly suggests an involvement of the cannabinoid system in the progression of fibrosis during CAD and indicates the therapeutic potential of CB1 antagonists in this pathology.

Iron-induced thrombocytopenia in severe iron-deficiency anemia.

Iron deficiency anemia (IDA) is commonly associated with reactive thrombocytosis, but thrombocytopenia is relatively uncommon and generally associated with more severe IDA. Even more rarely described has been thrombocytopenia following iron replacement therapy to treat IDA, and the underlying mechanism remains unclear. The authors present the case of a patient with severe IDA, who developed thrombocytopenia after the initiation of iron therapy. An analysis is made of all the previous reports of similar cases, to compare and start on the path of understanding this rare entity.