Predictors of right atrial dilatation and long-term function after right ventricular outflow tract surgical repair: Quantification of restrictive physiology matters

Right diastolic dysfunction; Right atrium function; Restrictive physiologyDisfunción diastólica derecha; Función de la aurícula derecha; Fisiología restrictivaDisfunció diastòlica dreta; Funció de l'aurícula dreta; Fisiologia restrictivaRight ventricular (RV) diastolic dysfunction in patients with a surgically-repaired RV outflow tract (RVOT) obstruction merits further studies. Right atrial (RA) dilation and function may be related to (RV) diastolic dysfunction in this setting. The end-diastolic forward flow (EDFF) in the pulmonary artery (PA) has been suggested as a non-invasive marker of poor RV compliance, however, there is controversy regarding its true significance; EDFF quantification may help elucidate this controversy. Objective to study predictors of RA enlargement and dysfunction in patients with a surgically-repaired RVOT obstruction and its relationship with quantitative EDFF. Methods In 81 consecutive patients (mean age: 37.5 (±7) years), transthoracic echocardiography (Echo) and cardiac magnetic resonance (CMR) were performed. Echo parameters: RA size (indexed RA area (iRAA)), RA function (RA global strain (RAGS)) and maximum EDFF velocity-time integral (VTI-EDFF) obtained during a whole respiratory cycle. CMR-indexed RA area (imRAA) was also obtained. Patients were divided into three groups according to iRAA, imRAA and RAGS; bivariate analysis was performed. A multivariate model was then applied using variables that were found to be statistically significant in the bivariate analysis. Results Upon multivariate analysis, higher VTI-EDFF values and the presence of significant tricuspid regurgitation proved to be independent factors associated with increased iRAA and imRAA and lower RAGS, whereas RV volumes, function and pulmonary regurgitant fraction were not. Conclusion VTI-EDFF linearly correlated with the degree of RA dilation and deformation; EDFF quantification as against qualitative assessment may be considered a non-invasive tool for diastolic RV dysfunction

Genetic Characterization of Cancer of Unknown Primary Using Liquid Biopsy Approaches

Cancers of unknown primary (CUPs) comprise a heterogeneous group of rare metastatic tumors whose primary site cannot be identified after extensive clinical–pathological investigations. CUP patients are generally treated with empirical chemotherapy and have dismal prognosis. As recently reported, CUP genome presents potentially druggable alterations for which targeted therapies could be proposed. The paucity of tumor tissue, as well as the difficult DNA testing and the lack of dedicated panels for target gene sequencing are further relevant limitations. Here, we propose that circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) could be used to identify actionable mutations in CUP patients. Blood was longitudinally collected from two CUP patients. CTCs were isolated with CELLSEARCH® and DEPArrayTM NxT and Parsortix systems, immunophenotypically characterized and used for single-cell genomic characterization with Ampli1TM kits. Circulating cell-free DNA (ccfDNA), purified from plasma at different time points, was tested for tumor mutations with a CUP-dedicated, 92-gene custom panel using SureSelect Target Enrichment technology. In parallel, FFPE tumor tissue was analyzed with three different assays: FoundationOne CDx assay, DEPArray LibPrep and OncoSeek Panel, and the SureSelect custom panel. These approaches identified the same mutations, when the gene was covered by the panel, with the exception of an insertion in APC gene. which was detected by OncoSeek and SureSelect panels but not FoundationOne. FGFR2 and CCNE1 gene amplifications were detected in single CTCs, tumor tissue, and ccfDNAs in one patient. A somatic variant in ARID1A gene (p.R1276∗) was detected in the tumor tissue and ccfDNAs. The alterations were validated by Droplet Digital PCR in all ccfDNA samples collected during tumor evolution. CTCs from a second patient presented a pattern of recurrent amplifications in ASPM and SEPT9 genes and loss of FANCC. The 92-gene custom panel identified 16 non-synonymous somatic alterations in ccfDNA, including a deletion (I1485Rfs∗19) and a somatic mutation (p. A1487V) in ARID1A gene and a point mutation in FGFR2 gene (p.G384R). Our results support the feasibility of non-invasive liquid biopsy testing in CUP cases, either using ctDNA or CTCs, to identify CUP genetic alterations with broad NGS panels covering the most frequently mutated genes

Spontaneous reperfusion enhances succinate concentration in peripheral blood from stemi patients but its levels does not correlate with myocardial infarct size or area at risk

Cardiovascular biology; Diagnostic markers; Prognostic markersBiología cardiovascular; Marcadores de diagnóstico; Marcadores pronósticosBiologia cardiovascular; Marcadors diagnòstics; Marcadors pronòsticsSuccinate is enhanced during initial reperfusion in blood from the coronary sinus in ST-segment elevation myocardial infarction (STEMI) patients and in pigs submitted to transient coronary occlusion. Succinate levels might have a prognostic value, as they may correlate with edema volume or myocardial infarct size. However, blood from the coronary sinus is not routinely obtained in the CathLab. As succinate might be also increased in peripheral blood, we aimed to investigate whether peripheral plasma concentrations of succinate and other metabolites obtained during coronary revascularization correlate with edema volume or infarct size in STEMI patients. Plasma samples were obtained from peripheral blood within the first 10 min of revascularization in 102 STEMI patients included in the COMBAT-MI trial (initial TIMI 1) and from 9 additional patients with restituted coronary blood flow (TIMI 2). Metabolite concentrations were analyzed by 1H-NMR. Succinate concentration averaged 0.069 ± 0.0073 mmol/L in patients with TIMI flow ≤ 1 and was significantly increased in those with TIMI 2 at admission (0.141 ± 0.058 mmol/L, p < 0.05). However, regression analysis did not detect any significant correlation between most metabolite concentrations and infarct size, extent of edema or other cardiac magnetic resonance (CMR) variables. In conclusion, spontaneous reperfusion in TIMI 2 patients associates with enhanced succinate levels in peripheral blood, suggesting that succinate release increases overtime following reperfusion. However, early plasma levels of succinate and other metabolites obtained from peripheral blood does not correlate with the degree of irreversible injury or area at risk in STEMI patients, and cannot be considered as predictors of CMR variables. Trial registration: Registered at www.clinicaltrials.gov (NCT02404376) on 31/03/2015. EudraCT number: 2015-001000-58.This work was supported by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (Grants PI17/01397 and CIBERCV) and the Spanish Society of Cardiology (Proyectos de la FEC para Investigación Básica en Cardiología 2018, Sociedad Española de Cardiología), and was cofinanced by the European Regional Development Fund (ERDF-FEDER, a way to build Europe). Antonio Rodríguez-Sinovas has a consolidated Miguel Servet contract

Incidência do câncer de pênis no Brasil

Penile Cancer (PC) is a genital tumor, it has a high incidence in underdeveloped countries, about 26,000 new cases each year. In Brazil, PC represents 2% of the types of cancer that affect males, with a higher incidence in the north and northeast, which can reach up to 10%. The appearance of PC is multifactorial and may be related to inadequate hygiene, phimosis in adults, smoking, many sexual partners and HPV. In general, PC is painless, but it can present pain, bleeding and bad smell. The characteristic symptoms are vegetating lesions and ulcers or intraurethral lesions and patients are often unaware of their presence. This article presents an integrative literature review based on relevant information to demonstrate the incidence of PC in Brazil and its main characteristics, such as: risk factors, symptoms, prevention and treatment. In view of the data presented by the articles, it is observed that the north and northeast regions are really the places in the country with the highest incidence. It is also analyzed that PC more often affects men aged close to 60, but young people can also be affected by the disease. The presence of phimosis makes it difficult to clean the organ that generates secretions that are irritating to the skin, so CP is quite present in men with this condition.El Cáncer de Pene (CP) es un tumor genital, tiene una alta incidencia en los países subdesarrollados, unos 26.000 casos nuevos cada año. En Brasil, el CP representa el 2% de los tipos de cáncer que afectan al sexo masculino, con mayor incidencia en el norte y noreste, que puede alcanzar hasta el 10%. La aparición de CP es multifactorial y puede estar relacionada con higiene inadecuada, fimosis en adultos, tabaquismo, muchas parejas sexuales y VPH. En general, la CP es indolora, pero puede presentar dolor, sangrado y mal olor. Los síntomas característicos son lesiones vegetantes y úlceras o lesiones intrauretrales y los pacientes muchas veces no son conscientes de su presencia. Este artículo presenta una revisión integrativa de la literatura basada en información relevante para demostrar la incidencia de CP en Brasil y sus principales características, tales como: factores de riesgo, síntomas, prevención y tratamiento. A la vista de los datos presentados por los artículos, se observa que las regiones norte y noreste son realmente los lugares del país con mayor incidencia. También se analiza que la CP afecta con mayor frecuencia a hombres con edades cercanas a los 60 años, pero los jóvenes también pueden verse afectados por la enfermedad. La presencia de fimosis dificulta la limpieza del órgano que genera las secreciones que son irritantes para la piel, por eso que lo CP está bastante presente en los hombres con esta condición.O Câncer de Pênis (CP) é um tumor genital, tem alta incidência em países subdesenvolvidos, cerca de 26.000 casos novos a cada ano.  No Brasil, o CP representa 2% dos tipos de canceres que afeta o sexo masculino, com maior incidência na região norte e nordeste, que pode chegar até 10%. O surgimento do CP é multifatorial e pode estar relacionado à higiene inadequada, fimose em adultos, tabagismo, muitos parceiros sexuais e HPV. Em geral o CP é indolor, mas pode apresentar dor, sangramento e mal cheiro. Os sintomas característicos são lesões vegetantes e úlceras ou lesões intrauretrais e muitas vezes os pacientes desconhecem sua presença. O presente artigo traz uma revisão integrativa de literatura baseada em informações relevantes para demonstrar a incidência do CP no Brasil e suas principais características, como: fatores de risco, sintomas, prevenção e tratamento. Diante dos dados apresentados pelos artigos é observado que as regiões norte e nordeste realmente são os locais do país com maior incidência. Também é analisado que o CP atinge com mais frequência homens com idade próxima a 60, porém jovens também podem ser acometidos pela doença. A presença da fimose dificulta a limpeza do órgão que gera secreções irritantes à pele, por isso o CP está bastante presente em homens com essa condição

Regional differences in the quality of maternal and neonatal care during the COVID-19 pandemic in Portugal: results from the IMAgiNE EURO study

Objective: To compare women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth across Nomenclature of Territorial Units for Statistics 2 (NUTS-II) regions in Portugal during the COVID-19 pandemic. Methods: Women participating in the cross-sectional IMAgiNE EURO study who gave birth in Portugal from March 1, 2020, to October 28, 2021, completed a structured questionnaire with 40 key WHO standards-based quality measures. Four domains of QMNC were assessed: (1) provision of care; (2) experience of care; (3) availability of human and physical resources; and (4) reorganizational changes due to the COVID-19 pandemic. Frequencies for each quality measure within each QMNC domain were computed overall and by region. Results: Out of 1845 participants, one-third (33.7%) had a cesarean. Examples of high-quality care included: low frequencies of lack of early breastfeeding and rooming-in (8.0% and 7.7%, respectively) and informal payment (0.7%); adequate staff professionalism (94.6%); adequate room comfort and equipment (95.2%). However, substandard practices with large heterogeneity across regions were also reported. Among women who experienced labor, the percentage of instrumental vaginal births ranged from 22.3% in the Algarve to 33.5% in Center; among these, fundal pressure ranged from 34.8% in Lisbon to 66.7% in Center. Episiotomy was performed in 39.3% of noninstrumental vaginal births with variations between 31.8% in the North to 59.8% in Center. One in four women reported inadequate breastfeeding support (26.1%, ranging from 19.4% in Algarve to 31.5% in Lisbon). One in five reported no exclusive breastfeeding at discharge (22.1%; 19.5% in Lisbon to 28.2% in Algarve). Conclusion: Urgent actions are needed to harmonize QMNC and reduce inequities across regions in Portugal.info:eu-repo/semantics/publishedVersio

Quality of health care around the time of childbirth during the COVID-19 pandemic: Results from the IMAgiNE EURO study in Norway and trends over time

Objective: To describe maternal perception of the quality of maternal and newborn care (QMNC) in facilities in Norway during the first year of COVID-19 pandemic. Methods: Women who gave birth in a Norwegian facility from March 1, 2020, to October 28, 2021, filled out a structured online questionnaire based on 40 WHO standards-based quality measures. Quantile regression analysis was performed to assess changes in QMNC index over time. Results: Among 3326 women included, 3085 experienced labor. Of those, 1799 (58.3%) reported that their partner could not be present as much as needed, 918 (29.8%) noted inadequate staff numbers, 183 (43.6%) lacked a consent request for instrumental vaginal birth (IVB), 1067 (34.6%) reported inadequate communication from staff, 78 (18.6%) reported fundal pressure during IVB, 670 (21.7%) reported that they were not treated with dignity, and 249 (8.1%) reported experiencing abuse. The QMNC index increased gradually over time (3.68 points per month, 95% CI, 2.83– 4.53 for the median), with the domains of COVID-19 reorganizational changes and experience of care displaying the greatest increases, while provision of care was stable over time. Conclusion: Although several measures showed high QMNC in Norway during the first year of the COVID-19 pandemic, and a gradual improvement over time, several findings suggest that gaps in QMNC exist. These gaps should be addressed and monitored

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements