Transcatheter pulmonary valve implantation: systematic literature review

Surgical repair of some complex congenital heart diseases involves reconstruction of the right ventricular outflow tract using homografts, bioprostheses, bovine jugular grafts or other valved conduits between the right ventricle and the main pulmonary artery. Although these surgical procedures may be performed with low mortality rates, the life span of these implanted valves or conduits is usually short (< 10 years) due to either degeneration and/or calcification. Variable degrees of pulmonary stenosis, often associated with pulmonary insufficiency, are consequences of conduit degeneration. In 2000, Bonhoeffer et al. were the first to report the transcatheter pulmonary valve implantation (TPVI) of a bioprosthetic pulmonary valve later named Melody® valve (Medtronic, Minneapolis, USA). The technique was initially developed to limit the need for multiple surgical procedures, and, ultimately, to work as a surrogate of a new surgical valve replacement. Subsequent clinical studies in Europe and the United States confirmed the safety and efficacy of this technique in a larger number of patients. Since the National Sanitary Surveillance Agency (Agência Nacional de Vigilância Sanitária - Anvisa) granted approval for clinical use of the Melody® transcatheter pulmonary biological valve in February 2103, we deemed that a judicious assessment of this new technology was timely and necessary before the widespread use in our country. The objective of this study was to perform a systematic literature review on the use of TPVI in patients with dysfunctional homografts, valved conduits and bioprostheses implanted surgically in the right ventricular outflow tract.A correção cirúrgica de algumas cardiopatias congênitas complexas envolve a reconstrução da via de saída do ventrículo direito com a interposição de homoenxertos, biopróteses, enxertos de jugular bovina ou outros condutos valvulados entre o ventrículo direito e o tronco da artéria pulmonar. Apesar de essas cirurgias poderem ser realizadas com baixa mortalidade, a vida útil das válvulas ou dos condutos implantados é normalmente pequena (< 10 anos), seja por degeneração e/ou calcificação. Graus variáveis de estenose pulmonar na maioria das vezes associada a insuficiência pulmonar são consequências da degeneração dos condutos. Em 2000, Bonhoeffer et al. foram os primeiros a relatar o implante transcateter de bioprótese valvular pulmonar (ITVP) com um dispositivo que posteriormente foi denominado de válvula Melody® (Medtronic, Minneapolis, Estados Unidos). A técnica foi inicialmente desenvolvida para limitar a necessidade de múltiplos procedimentos cirúrgicos, substituindo, em última análise, uma nova troca cirúrgica valvular. Estudos subsequentes na Europa e Estados Unidos atestaram para a segurança e eficácia dessa técnica em um número maior de pacientes. Como a Agência Nacional de Vigilância Sanitária (Anvisa) concedeu a aprovação para o uso clínico da válvula biológica pulmonar transcateter Melody® em fevereiro de 2013, consideramos necessária e oportuna a avaliação judiciosa da utilização dessa nova tecnologia antes que ela fosse aplicada em larga escala em nosso país. O objetivo deste estudo foi realizar uma revisão sistemática da literatura sobre o ITVP em pacientes com disfunções de homoenxertos, condutos valvulados e biopróteses implantados cirurgicamente na via de saída do ventrículo direito.Evidências - Credibilidade CientíficaHospital da Unimed João PessoaFundação Universitária de Cardiologia Instituto de Cardiologia Setor de Cardiologia Intervencionista em Cardiopatias CongênitasComplexo Hospitalar Santa Casa de Porto Alegre Serviço de Cardiologia Pediátrica e Cardiologia IntervencionistaHospital Beneficência Portuguesa de São Paulo Setor de Intervenções em Cardiopatias CongênitasUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Setor de Cardiologia PediátricaInstituto Dante Pazzanese de Cardiologia Seção Médica de Intervenções em Valvopatias AdquiridasUniversidade Federal de Minas Gerais Hospital de Clinicas Departamento de Cardiopatias CongênitasHospital Laranjeiras Instituto Nacional de Cardiologia Serviço de Cardiologia da Criança e do AdolescenteHospital Federal dos Servidores do Estado Setor de Cardiologia Intervencionista dos Defeitos Estruturais e CongênitosInstituto de Medicina Integral Prof. Fernando Figueira Setor de Hemodinâmica em Cardiopatias CongênitasHospital Biocor Departamento de Cardiologia Pediátrica IntervencionistaInstituto Dante Pazzanese de Cardiologia Seção Médica de Intervenções em Cardiopatias CongênitasUNIFESP, EPM, Setor de Cardiologia PediátricaSciEL

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Hipertensão pulmonar em lactente associada a pulmão em ferradura: relato de caso

Relatamos caso de lactente jovem com desconforto respiratório precoce e hipertensão pulmonar, diagnosticado como variante de pulmão em ferradura, e revisamos literatura a cerca desta rara malformação pulmonar e suas repercussões cardíacas e hemodinâmicas

Evaluación de calidad en frutos de 41 genotipos de nanche (Byrsonima crassifolia L. HBK) de Nayarit, México

Nanche is a harvest fruit whose fruits are prized for their bittersweet. The objective was to evaluate the quality of fruits of 41 nanche genotypes (Byrsonima crassifolia L. HBK) from the warm climate of Nayarit, Mexico. The quality variables analyzed in the fruit were: color, fresh weight (PFF), length (LF), diameter (DF), total soluble solids (°Brix), titratable acidity (percentage of citric acid) and pH of fruit. Furthermore, the dry weight of the seed (PSS) was determined. Multivariate statistical analysis of main components for data processing was used. Three principal components (CP's) explained 80.61% of total variance (VT). CP1 contributed with 38.58 of VT, where morphological variables of importance were: weight, diameter, length and size of the fruit while in CP2 represented 24.78% of VT, where chemical characteristics were relevant: percentage of citric acid pulp (AC) and pH of fruit juice. In CP3 were important total soluble solids (°Brix), and °Brix/pH ratio of the pulp that contributed with 17.25% of total variance. The °Brix/AC ratio, plus weight, size and yellowing of skin of the fruit were quality parameters that could be used as genetic qualities to select nanche genotypesEl nanche es un frutal de recolección cuyos frutos son apreciados por su sabor agridulce. El objetivo fue evaluar la calidad en frutos de 41 genotipos de nanche (Byrsonima crassifolia L. HBK) procedentes de la zona de clima cálido de Nayarit, México. Las variables de la calidad analizadas en los frutos: color, peso fresco (PFF), longitud (LF), diámetro (DF), sólidos solubles totales (°Brix), acidez titulable (porcentaje de ácido cítrico), pH de frutos. Además, se determinó el peso seco de la semilla (PSS). Se usó análisis estadístico multivariado de componentes principales para el procesamiento de datos. Tres componentes principales (CP�s) explicaron 80.61% de la varianza total (VT). El CP1 contribuyó con 38.58 de la VT en donde resultaron de importancia las variables morfológicas: peso, diámetro, longitud y tamaño de fruto mientras que el CP2 representó 24.78% de la VT, donde resultaron relevantes las características químicas: porcentaje de ácido cítrico de la pulpa (AC) y pH del jugo del fruto. En el CP3 resultaron importantes los sólidos solubles totales (°Brix), y la relación °Brix/pH de la pulpa que contribuyeron con 17.25% de la varianza total. La relación °Brix/AC, más el peso, tamaño y color amarillo de la epidermis del fruto fueron los parámetros de calidad que podrían usarse como cualidades genéticas para seleccionar genotipos de nanch

Checkpoint kinase 1/2 inhibition potentiates anti-tumoral immune response and sensitizes gliomas to immune checkpoint blockade

Whereas the contribution of tumor microenvironment to the profound immune suppression of glioblastoma (GBM) is clear, tumor-cell intrinsic mechanisms that regulate resistance to CD8 T cell mediated killing are less understood. Kinases are potentially druggable targets that drive tumor progression and might influence immune response. Here, we perform an in vivo CRISPR screen to identify glioma intrinsic kinases that contribute to evasion of tumor cells from CD8 T cell recognition. The screen reveals checkpoint kinase 2 (Chek2) to be the most important kinase contributing to escape from CD8 T-cell recognition. Genetic depletion or pharmacological inhibition of Chek2 with blood-brain-barrier permeable drugs that are currently being evaluated in clinical trials, in combination with PD-1 or PD-L1 blockade, lead to survival benefit in multiple preclinical glioma models. Mechanistically, loss of Chek2 enhances antigen presentation, STING pathway activation and PD-L1 expression in mouse gliomas. Analysis of human GBMs demonstrates that Chek2 expression is inversely associated with antigen presentation and T-cell activation. Collectively, these results support Chek2 as a promising target for enhancement of response to immune checkpoint blockade therapy in GBM

ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma

International audienceIn two cohorts of patients with glioblastoma who received anti-PD-1, Sonabend and colleagues show that ERK1/2 phosphorylation, detected by immunohistochemistry, provides a biomarker for MAPK/ERK pathway activity and better survival on this therapy. Only a subset of recurrent glioblastoma (rGBM) responds to anti-PD-1 immunotherapy. Previously, we reported enrichment of BRAF/PTPN11 mutations in 30% of rGBM that responded to PD-1 blockade. Given that BRAF and PTPN11 promote MAPK/ERK signaling, we investigated whether activation of this pathway is associated with response to PD-1 inhibitors in rGBM, including patients that do not harbor BRAF/PTPN11 mutations. Here we show that immunohistochemistry for ERK1/2 phosphorylation (p-ERK), a marker of MAPK/ERK pathway activation, is predictive of overall survival following adjuvant PD-1 blockade in two independent rGBM patient cohorts. Single-cell RNA-sequencing and multiplex immunofluorescence analyses revealed that p-ERK was mainly localized in tumor cells and that high-p-ERK GBMs contained tumor-infiltrating myeloid cells and microglia with elevated expression of MHC class II and associated genes. These findings indicate that ERK1/2 activation in rGBM is predictive of response to PD-1 blockade and is associated with a distinct myeloid cell phenotype

ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma

Only a subset of recurrent glioblastoma (rGBM) responds to anti-PD-1 immunotherapy. Previously, we reported enrichment of BRAF/PTPN11 mutations in 30% of rGBM that responded to PD-1 blockade. Given that BRAF and PTPN11 promote MAPK/ERK signaling, we investigated whether activation of this pathway is associated with response to PD-1 inhibitors in rGBM, including patients that do not harbor BRAF/PTPN11 mutations. Here we show that immunohistochemistry for ERK1/2 phosphorylation (p-ERK), a marker of MAPK/ERK pathway activation, is predictive of overall survival following adjuvant PD-1 blockade in two independent rGBM patient cohorts. Single-cell RNA-sequencing and multiplex immunofluorescence analyses revealed that p-ERK was mainly localized in tumor cells and that high-p-ERK GBMs contained tumor-infiltrating myeloid cells and microglia with elevated expression of MHC class II and associated genes. These findings indicate that ERK1/2 activation in rGBM is predictive of response to PD-1 blockade and is associated with a distinct myeloid cell phenotype

Revista Temas Agrarios Volumen 26; Suplemento 1 de 2021

1st International and 2nd National Symposium of Agronomic Sciences: The rebirth of the scientific discussion space for the Colombian Agro.1 Simposio Intenacional y 2 Nacional de Ciencias Agronómicas: El renacer del espacio de discusión científica para el Agro colombiano

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)