As complicações cardiovasculares da COVID-19 são aspectos importantes da patogênese e do prognóstico da doença. Evidências do papel prognóstico da troponina e da lesão miocárdica em pacientes hospitalizados com COVID-19 na América Latina são ainda escassos. Avaliar a lesão miocárdica como preditor independente de mortalidade hospitalar e suporte ventilatório mecânico em pacientes hospitalizados, do registro brasileiro de COVID-19. Este estudo coorte é um subestudo do registro brasileiro de COVID-19, conduzido em 31 hospitais brasileiros de 17 cidades, de março a setembro de 2020. Os desfechos primários incluíram mortalidade hospitalar e suporte ventilatório mecânico invasivo. Os modelos para os desfechos primários foram estimados por regressão de Poisson com variância robusta, com significância estatística de p<0,05. Dos 2925 pacientes , 27,3% apresentaram lesão miocárdica. A proporção de pacientes com comorbidades foi maior nos pacientes com lesão miocárdica [mediana 2 (1-2) vs. 1 (0-20)]. Os pacientes com lesão miocárdica apresentaram maiores valores medianos de peptídeo natriurético cerebral, lactato desidrogenase, creatina fosfoquinase, N-terminal do pró-peptídeo natriurético tipo B e proteína C reativa em comparação a pacientes sem lesão miocárdica. Como fatores independentes, proteína C reativa e contagem de plaquetas foram relacionados com o risco de morte, e neutrófilos e contagem de plaquetas foram relacionados ao risco de suporte ventilatório mecânico invasivo. Os pacientes com níveis elevados de troponina apresentaram um maior risco de morte  e suporte ventilatório mecânico , em comparação àqueles com níveis de troponina normais. Lesão cardíaca foi um preditor independente de mortalidade hospitalar e necessidade de suporte ventilatório mecânico em pacientes hospitalizados com COVID-19. A lesão miocárdica é comum em pacientes internados com COVID-19 e tem sido relatada em 7,2% a 36% de todos os pacientes. Embora essa condição tem sido associada a um pior prognóstico, evidências de seu papel prognóstico em pacientes internados com COVID-19 na América Latina ainda são escassas.Complicações cardiovasculares da doença causada pelo novo coronavírus (COVID-19) Ainda, existem vários polimorfismos, heterogeneidade, e miscigenação na população, o que pode influenciar nas taxas de lesão miocárdica e níveis de biomarcadores em pacientes com COVID-19. Em uma análise prévia realizada pelo nosso grupo de pesquisa, nós desenvolvemos e validamos um escore com alta capacidade discriminatória para predizer mortalidade em pacientes brasileiros usando dados facilmente disponíveis na admissão dos pacientes, o escore ABC2-SPH.No Brasil, muitas pessoas ainda são afetadas pela doença cardíaca chagásica e valvulopatia reumática.O presente estudo teve como objetivo avaliar a lesão miocárdica como um preditor independente de mortalidade hospitalar e suporte ventilatório mecânico invasivo em pacientes internados com COVID-19, a partir de dados do registro nacional. O estudo foi aprovado pela Comissão Nacional de Ética em Pesquisa (CAAE: 30350820.5.1001.0008). Houve dispensa do consentimento livre e esclarecido individual devido à gravidade da situação imposta pela pandemia e à natureza retrospectiva do estudo.Este estudo multicêntrico retrospectivo do tipo coorte é um subestudo do registro brasileiro de COVID-19, conduzido em 31 hospitais de 17 cidades de cinco estados , descrito em detalhes em um artigo anterior. admitidos nos hospitais participantes entre março e setembro de 2020 e que possuíam pelo menos um valor de troponina. Foram excluídos pacientes com diagnóstico de insuficiência cardíaca crônica no prontuário médico, pacientes com taxa de filtração glomerular (TFG) menor que 30 mL/min/1,73m2  e suporte ventilatório mecânico invasivo . Um maior número de comorbidades, maior taxa respiratória, e maiores níveis de PCR foram associados com um maior risco de mortalidade hospitalar e suporte ventilatório mecânico invasivo. Ainda, idade e uma razão SF mais baixa mostraram associação independente com mortalidade hospitalar, enquanto o número de neutrófilos associou-se com um risco aumentado de suporte ventilatório mecânico. Os pacientes com lesão miocárdica mostraram uma maior frequência de complicações cardiovasculares, sangramentos, eventos tromboembólicos, choque séptico, coagulação intravascular disseminada, infecção nosocomial, admissão à UTI, tempo de internação hospitalar e na UTI, e necessidade de terapia renal substitutiva. Não houve evidência de diferenças de sexos na prevalência das variáveis analisadas nos pacientes com lesão miocárdica, o que contrasta com dados publicados anteriormente na literatura. Na revisão sistemática realizada por Toraih et al., incluindo 17794 pacientes com lesão cardíaca avaliada por medida de troponina, os autores encontraram proporção significativamente maior de homens com doença crítica, definida como síndrome do desconforto respiratório agudo, ventilação mecânica invasiva, e admissão na UTI. Na presente análise, mulheres mais velhas com lesão miocárdica mostraram um risco significativamente maior de morte e maior necessidade (não estatisticamente significativa) de ventilação mecânica invasiva.Os achados do presente estudo estão de acordo com os resultados de estudos de outros países, descrevendo características muito similares de pacientes com COVID-19 que desenvolveram lesão miocárdica, incluindo idade avançada e uma alta prevalência de condições médicas subjacentes. e interação do SARS-CoV-2 com receptores da enzima conversora de angiotensina 2. Embora os mecanismos específicos da lesão miocárdica sejam incertos, os mecanismos propostos incluem resposta inflamatória e distúrbios do sistema imune durante a progressão da doença.De fato, os níveis de troponina e de outros biomarcadores são geralmente anormais em pacientes internados com COVID-19. Há diferentes mecanismos para o desenvolvimento de lesão cardíaca em pacientes com COVID-19, tais como esforço cardíaco aumentado na insuficiência respiratória aguda, Esse achado pode ser limitado pelo pequeno tamanho amostral e alto número de valores faltantes.Resultados dos testes usados para avaliar função e lesão cardíaca mostraram valores significativamente maior nos pacientes com COVID-19 que morreram que nos pacientes que receberam alta com vida. Nossos resultados corroboram esses achados, uma vez que BNP, creatina fosfoquinase, LDH, NT-proBNP, e PCR, um biomarcador da resposta inflamatória, eram mais altos nos pacientes com lesão miocárdica. Um estudo recente que incluiu 187 pacientes com COVID-19 hospitalizados no Rio de Janeiro também mostrou que a troponina foi um preditor independente de eventos adversos. Já o BNP não foi um preditor independente de mortalidade ou necessidade de suporte ventilatório mecânico. de estudos chineses do tipo coorte, mostrou que 45,2% dos pacientes com lesão miocárdica induzida por COVID-19 morreram. No presente estudo, a taxa de mortalidade foi 4,25 vezes maior nos pacientes com lesão miocárdica em comparação aos controles, além de um tempo mediano mais longo de internação hospitalar, e maior ocorrência de admissão na UTI e dos outros desfechos secundários mencionados anteriormente. Assim, os pacientes com COVID-19 e lesão cardíaca eram mais susceptíveis a complicações da doença e apresentaram piores diagnósticos. Esses achados são consistentes com os resultados descritos em estudos conduzidos em outros países.Uma revisão sistemática e meta-análise de Alzahrani e Al-Rabia, Em uma análise prévia, nosso grupo de pesquisa desenvolveu e validou um escore de predição de risco para mortalidade hospitalar em pacientes com COVID-19 (disponível em https://abc2sph.com/pt/), que inclui idade mais avançada, nitrogênio ureico no sangue, número de comorbidades, PCR, razão SF periférica, contagem de plaquetas, e frequência cardíaca como preditores. No entanto, a troponina não foi incluída em nossas análises. No presente estudo, a lesão cardíaca foi um fator de risco independente para mortalidade e suporte de ventilação mecânica invasiva, além das variáveis testadas anteriormente, que foi o principal achado das análises presentes. Esses resultados exercem um importante papel no cuidado do paciente, uma vez que podem auxiliar os profissionais da saúde a identificarem pacientes que possam ter um pior prognóstico, direcionando intervenções para o manejo das condições clínicas e melhorias no cuidado da saúde. Uma próxima etapa seria avaliar a inclusão da troponina ao escore de risco ABC2-SPH, um importante tópico para estudos futuros sobre ABC2-SPH. Esperamos que esta coorte também possa ser útil para estudos futuros no desenvolvimento de um escore preditivo para lesão miocárdica.Atualmente, vários estudos propuseram variáveis clínicas, achados laboratoriais e de radiografia do tórax para a predição do risco de progressão da COVID-19 grave e mortalidade. É importante mencionar que o período da pandemia quando os dados foram coletados envolveu uma população que não havia sido vacinada, e parte dos pacientes do grupo de estudo podem não ter desenvolvido lesão miocárdica, e sim infarto agudo do miocárdio. Devido ao risco potencial de transmissão da COVID-19, existe a possibilidade de que nenhuma técnica diferencial diagnóstica seja realizada em alguns casos. Ainda, uma vez que o presente estudo foi um estudo observacional, outras variáveis potencialmente não mensuráveis e de confusão ou não reconhecidas podem não ter sido coletadas ou analisadas.Este estudo possui limitações. Primeiramente, não podemos assegurar representatividade nacional dos hospitais. Uma vez que este estudo se trata de uma análise multicêntrica da COVID-19, os testes de troponina poderiam apresentar inconsistências, uma vez que múltiplos kits laboratoriais comerciais foram usados de modo interinstitucional e intrainstitucional, e diferentes valores de referência foram padronizados em cada estudo, levando ao viés de medida. Outra limitação foram as análises agrupadas que não permitiram o reconhecimento da contribuição de cada centro aos desfechos de morte e suporte ventilatório mecânico, bem como fatores institucionais relacionados à mortalidade.Quanto aos pontos fortes do estudo, um critério metodológico rigoroso foi usado neste estudo, o qual se baseou em uma amostra robusta de paciente, com diagnóstico confirmado de COVID-19. A amostra foi obtida com a colaboração de pesquisadores de 31 hospitais públicos, privados ou mistos, de diferentes tamanhos e níveis de complexidade, de diferentes regiões para garantir a diversidade da população estudada. Contudo, esses hospitais não são representativos de todo o sistema de saúde do país.A lesão cardíaca, medida pelos níveis de troponina elevados, foi um preditor independente de mortalidade e suporte ventilatório mecânico em pacientes internados com COVID-19, assim como as variáveis de um escore de predição de risco recentemente validado. Estratégias futuras envolvimento um monitoramento frequente dos níveis de troponina como biomarcadores de risco em pacientes com COVID-19 durante a hospitalização devem ser testadas para investigar seu papel na redução de risco de complicações e morte, e na melhoria do cuidado do paciente.Para informação adicional, por favor,clique aqui represent an important aspect of the disease’s pathogenesis and prognosis. Myocardial injury is common in hospitalized patients with COVID-19 and has been reported in 7.2% to 36% of all patients.This disease has proven to be associated with a poorer prognosis;however, evidence concerning its prognostic role in hospitalized COVID-19 patients in Latin America is still scarce.Cardiovascular complications of the coronavirus disease 19 (COVID-19)Furthermore, numerous polymorphisms, heterogeneity, and miscegenation exist among the population, which may influence rates of myocardial injury and levels of biomarkers in COVID-19 patients.In a previous analysis performed by our research group, we developed and validated a score with high discriminatory ability to predict mortality among Brazilian patients using data that are easily available on hospital admission, the ABC2-SPH score.In Brazil, many people are still affected by Chagas heart disease and rheumatic valvulopathy.The present study aimed to evaluate myocardial injury as an independent predictor of in-hospital mortality and invasive mechanical ventilation support in COVID-19 hospitalized patients, from the Brazilian COVID-19 Registry.The study was approved by the Brazilian National Ethics Committee in Research (CAAE: 30350820.5.1001.0008). Individual informed consent was waived due to the severity of the situation imposed by the pandemic and to the retrospective nature of the study.This multicenter retrospective cohort study is a substudy of the Brazilian COVID-19 Registry, conducted in 31 Brazilian hospitals in 17 cities from five states , detailed in a previous report.who were admitted to the participating hospitals between March and September 2020 and who had at least one troponin value. Patients with an underlying diagnosis of chronic heart failure (HF) in the medical records, with glomerular filtration rate (GFR) of lower than 30 mL/min/1.73m, those who were discharged in less than 24 hours, and those diagnosed with COVID during hospitalization were excluded from the study. Sample size calculation was not performed, all eligible patients were included.This study included consecutive adult patients (aged ≥18 years) with laboratory-confirmed COVID-19,at the Telehealth Center of the Federal University of Minas Gerais General Hospital. Comprehensive checks were undertaken to ensure a high-quality data collection. A code was developed in R software to identify non-conforming and inconsistency values, as previously described, based on expert-guided rules, and each study center was contacted to check and correct data, if needed.Demographic and clinical characteristics, exams , treatments, and outcome data were collected by trained healthcare professionals and interns in each health center, using the Research Electronic Data Capture (REDCap) tool (version 7.3.1),thpercentile, according to the Fourth Universal Definition of Myocardial Infarction.Troponin was measured at the discretion of the treating physician. Troponin values at hospital admission, as well as minimum and maximum values after 24 hours of hospitalization were collected. Any abnormal value among these measures was considered for analysis in the present study. The reference group was composed of patients with troponin values within the normal range.Myocardial injury was defined as an elevation of cardiac troponin (cTnI or cTnT) above the upper reference limit (URL) of the 99thpercentile for each test for men and women, as reported in the Supplemental Material (Table S1).Troponin assay varied among different centers. Due to the shortage of crucial chemicals at the beginning of the pandemic, some centers used more than one assay during the study period. Therefore, the analysis considered the URL of the 99The primary outcomes were in-hospital mortality and invasive mechanical ventilation support. Secondary outcomes included cardiovascular complications , bleeding, thromboembolic events, septic shock, disseminated intravascular coagulation, nosocomial infection, admission to the intensive care unit (ICU), ICU length of stay, hospital length of stay, and need for renal replacement therapy.Statistical analyses were performed in three main steps: (i) descriptive, (ii) bivariate , and (iii) multivariate analyses.Descriptive analyses were run to describe all variables, stratified into control and study groups . Categorical variables were described as absolute and relative frequencies. The Shapiro-Wilk normality test was performed to determine whether the continuous variables were normally distributed. As all variables were found to have a non-normal distribution, they were described as medians and interquartile ranges (IQR). The number of comorbidities was defined based on eight comorbidities that had been proved to have a prognostic impact on COVID-19 .a priori based on previous scientific evidence of variables associated with a worse prognosis of COVID-19.Laboratory tests were performed at the discretion of the attending physician. Imaging test results were not included, since they are not always performed on hospital admission, and their interpretation involves the examiner’s judgment.In the bivariate analysis, demographic and clinical variables, and outcomes were assessed using the Fisher’s exact test or the chi-square test to compare proportions, as appropriate. The Kruskal-Wallis test was used to compare medians of continuous variables, while the Dunn´s test was used as a post-hoc test. For the multivariate analyses, two predictive models were estimated to evaluate the role of elevated troponin on the primary outcomes: in-hospital mortality and invasive mechanical ventilation support. All variables included in the models were obtained at hospital admission. A set of potential predictive variables for the primary outcomes was selectedModels for the primary outcomes were estimated by Poisson regression with robust variance. In the model to predict invasive mechanical ventilation support, patients who were on invasive mechanical ventilation at admission were not included (n=72). Poisson regression was chosen due to the ability to estimate the relative risk (RR), which is the parameter of primary interest, since an elevated event rate was expected.mutually inserted in the regression models one to five. As the main goal of the analysis was to identify the association of myocardial injury with the study outcomes, this variable was tested in all five models. The first one included only myocardial injury. The second added age and sex, the third added the number of comorbidities, and the fourth added clinical characteristics on hospital admission. The fifth multivariate model contained only the variables with a 5% significance level after adjusting for the other variables added to the previous multivariate models. The variables were included from the largest to the least significance, to test which associations between the explicative variables and the outcomes would remain significant throughout the process.The shaping of the prediction models divided the variables into five blocks by a stepwise-forward approach,The statistical significance of the variables that were part of the models was evaluated by analyzing the RR and their respective 95% confidence intervals (95% CI), as well as by the p-value of the tests, aimed at reducing the probability of type I error. A comparison of the models’ goodness-of-fit tests was performed using the Akaike Information Criterion.For the regression models, the RR and their respective 95% CI were estimated. All analyses were performed in the STATA software  and R software (version 4.0.2), using the tidyverse, lubridate, stringi, rlang, jsonlite, Rcurl, writexl, openxlsx, readxl, and sandwich packages. A p-value <0.05 was considered statistically significant.2)/fraction of inspired oxygen (FiO2) ratio (SF ratio) at hospital admission. Regarding laboratory parameters, patients with myocardial injury had higher median levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), and N-terminal pro-brain natriuretic peptide (NT-proBNP)/brain natriuretic peptide (BNP), when compared to the controls. Electrocardiogram and echocardiogram results are reported in the supplemental material (Table S2).Of 7,760 patients, 2,925 were included in the present analyses . DemogrPatients with myocardial injury had higher in-hospital mortality and a higher frequency of all secondary outcomes . MultivIn this multicenter cohort study, with a large sample of 31 Brazilian hospitals, patients with myocardial injury were 10 years older (median) than the control, and had a higher prevalence of underlying comorbidities, worse clinical parameters at hospital admission, and higher levels of CRP, LDH, and NT-proBNP/BNP when compared to those without myocardial injury. Myocardial injury was an independent predictor of in-hospital mortality (RR: 2.03 [1.60-2.58]) and invasive mechanical ventilation support (RR: 1.87 [1.57-2.23]). Higher number of comorbidities, higher respiratory rate, and higher levels of CRP were associated with a higher risk of in-hospital mortality and invasive mechanical ventilation support. Additionally, age and lower SF ratio were also independently associated with in-hospital mortality, while the number of neutrophils was associated with an increased risk of invasive mechanical ventilation support. Patients with myocardial injury showed a higher frequency of cardiovascular complications, bleeding, thromboembolic events, septic shock, disseminated intravascular coagulation, nosocomial infection, admission to the ICU, ICU and hospital length of stay, and need for renal replacement therapy.There was no evidence of sex differences in the prevalence of the variables analyzed among patients with myocardial injury, which contrasts with data previously published in the literature. In the systematic review performed by Toraih et al.,including 17,794 patients with cardiac injury assessed by troponin measurement, the authors found a significantly higher proportion of men with critical illnesses, defined as acute respiratory distress syndrome, invasive mechanical ventilation, and ICU admission. In the present analysis, older women with myocardial injury showed a higher risk for death and the need for invasive mechanical ventilation, but with no statistical significance in the latter.The present study’s findings are in line with results of studies from other countries, which reported remarkably similar characteristics of COVID-19 patients who developed myocardial injury, including advanced age and a high prevalence of underlying medical conditions.and SARS-CoV-2 interaction with angiotensin-converting enzyme 2 receptors.Although the specific mechanisms of myocardial injury are uncertain, the mechanisms proposed include inflammatory response and immune system disorders during disease progression.In fact, troponin and other biomarkers are commonly abnormal in patients hospitalized with COVID‐19. There are different mechanisms for the development of cardiac damage in COVID-19 patients, such as increased cardiac effort in acute respiratory failure,This finding may be limited by the small sample size and high number of missing values.Results of the tests used to assess cardiac function and injury have shown significantly higher values in COVID-19 patients who died than those who were discharged alive. Our results are in line with these findings, as BNP, creatine phosphokinase, LDH, NT-proBNP, and CRP, which is a biomarker of inflammatory response, were higher in patients with myocardial injury. A recent study which included 187 COVID-19 patients hospitalized in Rio de Janeiro has also reported troponin as an independent predictor for adverse events. Meanwhile, BNP was not an independent predictor for mortality or the need for invasive mechanical ventilation support.showed that 45.2% of the patients with COVID-19-induced myocardial injury have died.In the present study, there was a 4.25-fold higher mortality rate in patients with myocardial injury when compared to the controls, as well as a higher median hospital length of stay, ICU admissions, and all other aforementioned secondary outcomes. Hence, COVID-19 patients with cardiac injury were more susceptible to disease complications and had poorer prognoses. These findings are consistent with results reported by studies performed in other countries.A systematic review and meta-analysis of Chinese cohort studies by Alzahrani and Al-RabiaIn a previous analysis, our research group developed and validated a risk prediction score for in-hospital mortality in COVID-19 patients (available through the link https://abc2sph.com/pt/), which includes older age, blood urea nitrogen, number of comorbidities, CRP, peripheral SF ratio, platelet count, and heart rate as predictors. However, troponin was not included in those analyses.In the present study, cardiac injury was an independent risk factor for mortality and invasive mechanical ventilation support, in addition to the variables previously tested, which was the most important finding of the current analyses. These results play an important role in patient care, as they can help healthcare professionals identify patients who may have a worse prognosis, guiding interventions for the management of clinical conditions and improvements in health care. A logical next step would be to assess the inclusion of troponin to the ABC2-SPH risk score, an important topic for future studies concerning ABC2-SPH. It is our hope that this cohort can also be useful in further studies to create a predictive score for myocardial injury.Currently, several studies have proposed clinical variables, laboratory and chest X-ray findings for the prediction of the risk of severe COVID-19 progression and mortality.It is important to mention that the pandemic period when the data were collected involved a population that had not been vaccinated yet,and part of the patients in the study group might not have developed myocardial injury, but rather acute myocardial infarction. Due to the potential risk of transmissibility of COVID-19, there is a possibility that no differential diagnostic technique is performed in some cases.Furthermore, since the present study was an observational study, other variables that may be confounding and unmeasurable or unrecognized may not have been collected or analyzed.This study has limitations. First, we cannot assure national representativeness of participating hospitals. Since this is a multicentric analysis of COVID-19, troponin tests could have inconsistencies, given that multiple commercial laboratory kits were used in an inter- and intra-institutional manner, and different reference values were standardized in each study, leading to measurement bias. Another limitation was that the grouped analyses did not allow the recognition of the contribution of each center to the outcomes of death and invasive mechanical ventilation support, as well as institutional factors related to mortality.Regarding the study’s strengths, a strict methodological criterion was used to perform this study, which was based on a robust patient sample, with a confirmed COVID-19 diagnosis. The sample was obtained by the collaboration of researchers from 31 public, private, and mixed hospitals of different sizes and complexity levels, from different Brazilian regions, in order to guarantee a diversity of the studied population. However, they are not representative of the entire healthcare system of the country.Cardiac injury, measured by elevated troponin levels, was an independent predictor of mortality and invasive mechanical ventilation support among hospitalized COVID-19 patients, as were the variables of a recently validated risk prediction score. Future strategies involving the frequent monitoring of troponin levels as risk biomarkers in patients with COVID-19 during their hospitalization should be tested to investigate their role in reducing the risk of complications and death, as well as in improving patient care.For additional information, please, click here


Aedes aegypti mosquitoes are the main vector of human arbovirosis in tropical and subtropical areas. Their adaptation to urban and rural environments generates infestations inside households. Therefore, entomological surveillance associated with spatio-temporal analysis is an innovative approach for vector control and dengue management. Here, our main aim was to inspect immature pupal stages in households belonging to municipalities at high risk of dengue in Cauca, Colombia, by implementing entomological indices and relating how they influence adult mosquitos’ density. We provide novel data for the geographical distribution of 3,806 immature pupal stages of Ae. aegypti. We also report entomological indices and spatial characterization. Our results suggest that, for Ae. aegypti species, pupal productivity generates high densities of adult mosquitos in neighbouring households, evidencing seasonal behaviour. Our dataset is essential as it provides an innovative strategy for mitigating vector-borne diseases using vector spatial patterns. It also delineates the association between these vector spatial patterns, entomological indicators, and breeding sites in high-risk neighbourhoods. Aedes aegypti son el principal vector de las arbovirosis humanas en zonas tropicales y subtropicales. Su adaptación a entornos urbanos y rurales genera infestaciones en el intradomicilio de las viviendas. De aquí que, la vigilancia entomológica en asociación con el análisis espacial y el análisis espacio-temporal sean un enfoque innovador para el control de vectores y la gestión del dengue. El objetivo principal de la investigación fue realizar una comparación de la vigilancia entomológica, mediante el uso de índices cuantitativos de pupas y de adultos en tres municipios de alto riesgo de dengue en el departamento del Cauca, con el fin de examinar cómo influye la productividad de pupas, entre otros índices entomológicos, en la densidad de mosquitos adultos y sus patrones espaciales y temporales. Como resultado aportamos datos novedosos sobre la distribución geográfica de 3.806 estadios inmaduros de Ae. aegypti, sus índices entomológicos y su caracterización espacial. Los resultados sugieren que, para las especies de Ae. aegypti, la productividad de pupas genera altas densidades de adultos en las viviendas vecinas, evidenciando un comportamiento estacional. Nuestro conjunto de datos es esencial, ya que proporciona una estrategia innovadora para entender las enfermedades transmitidas por vectores utilizando patrones espaciales de vectores. También delinea la asociación entre estos patrones espaciales de vectores, indicadores entomológicos y criaderos ubicados en barrios de alto riesgo.Los mosquitos  Aedes aegypti mosquito is the main vector of human arbovirosis, encompassing diseases such as yellow fever, dengue, chikungunya, and Zika, which are prevalent in tropical and subtropical areas . Its adaptation to local anthropic conditions, urban environments, together with the optimal temperature, precipitation, and relative humidity, among other environmental and socioeconomic factors, has given this mosquito the ability to establish reproductive populations spanning both urban and rural domains –4. In Colombia, Ae. aegypti is the main vector of the dengue virus and is reported at altitudes between sea level and 2,302 m. Therefore, the significant presence and abundance of this vector threaten public health within the country , 6.The Ae. aegypti, 8. The surveillance of these types of containers helps reduce the proliferation of pupae and, therefore, mosquito densities. Hence, mosquito sampling is an indispensable tool for designing approaches of entomological surveillance of the vector specific to each situation .Direct proximity to humans has allowed the hematophagous female to feed on human or domestic animal blood, causing infestations in different types of containers in and around households. In this context, the presence of artificial and natural containers, such as tanks, drums, bottles, tires, aquatic plants (bromeliads and water retained in plant axils), stagnant water, and pet drinking troughs, serve as potential breeding grounds for the immature stages of , 10, the inspection of potential breeding sites is determined with entomological indicators that make it possible to identify the index of pupae per person, pupal productivity, and the presence of immature stages in dwellings , 10. However, this is not done in all regions. The importance of using this type of entomological index lies in providing a representative approximation of the local adult populations of mosquitoes while requiring a relatively small sample size for household inspection , 11. Furthermore, the index of pupae per person makes it possible to calculate a minimum level of Ae. aegypti pupae infestation that significantly enhances the risk of dengue virus (DENV) transmission. Specifically, if the index of pupae per person ranges from 0.5 to 1.5 at 28 °C with 0% to 67% seroprevalence , making it possible to identify areas at higher risk.Following the methodologies established for Colombia Ae. aegypti mosquitoes has mainly relied on qualitative larval indices, bearing little relation to the number of female mosquitoes. Moreover, Ae. aegypti populations have been reported to be spatially heterogeneous in some areas . Thus, using spatio-temporal analyses to predict Ae. aegypti hot spots, i.e., groups of dwellings with higher pupal productivity, high vector density, and potential DENV transmission, is an innovative strategy that could help the prevention, vector control, and integrated management of dengue in high-risk municipalities. This is because this method allows detecting patterns of geographical distribution of the vector , 13. Consequently, it is fundamental to embrace this kind of infestation indices because immature stages, specifically the pupae, represent a precursor stage to adult mosquitos with very low mortality. This increases the correlation between Ae. aegypti density and dengue virus , 14.Surveillance of Thus, in this study, entomological surveillance was compared using quantitative indices of pupae and adults in three municipalities at high dengue risk: Patía (El Bordo), Miranda, and Piamonte in the Cauca department. Specifically, our study aimed at examining the influence of pupal productivity, among other entomological indices, on the density of adult mosquitoes, and their spatial and temporal patterns. Spatial regression and bivariate spatial autocorrelation analyses were carried out, allowing to model and explore spatial relationships, while capturing the relationship between variables even when they did not overlap within the same space.Ae. aegypti were collected from dwellings in the municipalities of Patía (El Bordo), Miranda, and Piamonte, within the department of Cauca, in the southwest of Colombia. These municipalities are part of an ongoing research project titled “Spatial stratification of dengue based on the identification of risk factors: a pilot trial in the department of Cauca” headed by the Entomology Group of the National Institute of Health, the Secretary of Health of Cauca, and the University of Applied and Environmental Sciences (UDCA). Among other objectives, this project seeks to evaluate the robustness of the link between entomological variables, which explains the spatial pattern observed in the distribution of dengue fever.A total of 160 biological records  of the immature stage (pupae) of The data were collected between 2021 and 2022 by a multidisciplinary team of environmental health technicians, geographic and environmental engineers, and professionals with extensive experience in medical entomology. In this dataset, we distinguish three sampling periods for each municipality. For Patía: March and October 2021, and March and April 2022; for Miranda: April and November 2021, and May 2022; and for Piamonte, July 2021, and February and July 2022. A fourth sampling period was performed in August and October 2022 in the municipalities of Patía and Miranda, respectively, to increase the sample size to carry out the serotyping of the specimens.The immature stages (pupae) were collected from the inspection of containers smaller or larger than 20 l, including tanks, drums, and tires, among others, from inside the houses of three municipalities. The municipalities were selected as study areas based on their endemic-epidemic behaviours for DENV transmission, as they are characterized by focal endemics, heterogeneous transmission scenarios, and temporal and cyclical patterns of at-risk populations.. A total of 3,480 adult individuals of the family Culicidae are included in this dataset. Of these, about 69% of the specimens were previously reported in 2021 , while 1,078 are the new records collected in 2022.The resulting pupae dataset is in Darwin Core file format, with 73 terms available. We included all mandatory fields, which were submitted to the Integrated Publishing Toolkit (IPT) for review by SiB-Colombia. Metadata fields are also available from the IPT website These biological registers are fundamental for the scientific community as they provide the geographical coordinates and entomological indices necessary for the public health surveillance performed by health entities. In particular, these measures are essential for preventing and controlling the etiological agent from houses and neighbourhoods with high infestation rates.Ae. aegypti pupae belonged to dwellings located in the municipalities of Patía (El Bordo), Miranda, and Piamonte, within the department of Cauca, Colombia  in the municipality  with a confidence level of 99% calculated by the Epi Info™ software, using the estimated population size and the clusters obtained in the Kernel analysis.The specimens of the immature stages of the a Figure . These mn = 580 households), in Miranda 12 neighbourhoods (n = 854 households), and in Piamonte four neighbourhoods (n = 485 households). In total, 1,919 dwellings were visited in 26 neighbourhoods during March, April, July, and October 2021, and February, March, May, July, August, and October 2022. In the municipality of Patía, 11 neighbourhoods were visited  and the existing water level were evaluated to calculate the calibration factor  and obtain the estimated number of pupae or the pupal productivity.A survey of the dwellings was carried out during the day between 8:00 a.m. and 5:00 p.m. Then, the parameters stipulated in the guide Management for the entomological surveillance and control of dengue transmission were followed Entomological inspections for adult mosquitoes were conducted during specific months in 2021  and 2022 . These inspections were performed between 8:00 a.m. and 5:00 p.m., averaging 10 min per house. In each dwelling, a search for adult mosquitoes was conducted in the living room, dining room, bathrooms, kitchens, laundry yard, and other areas; the mosquitoes were captured using a Prokopack aspirator. Using these procedures, during the examination, special attention was directed toward exploring shaded areas and locations near water containers. (1995) and Harrison et al.  (2016) to differentiate them from the immature stages and adults belonging to other species. Continuing with the field protocol, 3,806 pupae of Ae. aegypti were identified, of which 395 were preserved in 0.2 ml vials with RNAlater© for subsequent processing with molecular biology techniques at the Entomology group and the Genomics of Emerging Microorganisms group of the National Institute of Health  .After the collection of the immature stages (pupae) and adults, the species were identified and taxonomically classified by entomological experts supported by the taxonomic keys developed by Forattini ® Survey 123 application , which provided the geographic location of each specimen collected. A code was associated to each vial with the socio-demographic information of the survey. The total number of pupae recorded in each survey was used to determine the entomological indices of pupal productivity, female productivity, pupal index per person, Breteau’s pupal index , 10, and Aedes sp. pupae sex ratio F:M , as well as scatterplot matrices to evaluate the relationships between entomological variables: number of adult Ae. aegypti mosquitoes , total number of pupae, pupal productivity, female productivity, and number of pupae per person vs. the frequency of tanks for water storage, miscellaneous containers smaller than 20 l, and drums.The entomological information, together with the geographical block information of the municipalities, was used to perform scatterplot analyses (p ≤ 0.05) was performed to detect the distribution of variables related to spatial clustering. The Moran Index ranges from −1 to 1, where −1 indicates dispersed clustering patterns, 0 indicates randomness, and 1 suggests perfect association. Next, a Local Moran Index analysis distributed the significant (p = 0.05) clusters of dwelling blocks into four types of local spatial association. (I) high(x)-high(y) indicates areas with high values of the variable (x) surrounded by values above the mean of the variable under analysis (y); (II) low(x)-high(y) indicates areas with low values of the variable (x) surrounded by neighbouring areas with values above the mean of the variable (y); (III) low(x)-low(y) indicates areas with low values of the variable (x) surrounded by areas with values below the mean of the variable (y); and (IV) high(x)-low(y) indicates areas with high values of the variable (x) surrounded by areas below the mean of the variable (y) .A global bivariate Moran Index analysis .The above analyses were performed for two sampling periods in each municipality. For the municipality of Patía (El Bordo), samples were collected in March and October 2021, for Miranda samples were collected in April and November 2021, and for Piamonte samples were collected in July 2021 and February 2022, since the rainfall pattern was seasonal between these months. Finally, the analyses were performed using the GeoDa v1.20 program A total of 3,480 adult specimens were identified across 1,200 households, comprising 1,459 females and 2,021 males. In 2021, 2,402 records were documented, while 1,078 new records were added in 2022. In terms of municipal distribution, Miranda reported 500 individuals (14.36%), Patía 1,305 (37.5%), and Piamonte had the highest count with 1,675 (48.13%) adult individuals. Notably, 71 individuals were found within a Patía household, and an additional 125 individuals were identified within a different household in Piamonte.Ae. aegypti were identified, distributed among 160 records . For the municipality of Patía (El Bordo), 1,493 individuals were found in 67 positive dwellings, for Miranda 1,173 individuals were in 58 dwellings, and for Piamonte 1,140 individuals were found in 35 dwellings. The neighbourhoods with the highest number of specimens were Villa Los Prados (n = 519) and La Paz (n = 359) in Piamonte, followed by the San Antonio neighbourhood (n = 391) in Miranda, and the Libertador (n = 441) and Olaya Herrera (n = 438) neighbourhoods in Patía. It should be noted that 70 of the inspected dwellings were found with more than 15 pupae inside the house. The largest number of detected specimens belonged to a house in the municipality of Piamonte, with 280 pupae  of R = 0.7292; R2 = 0.53) and Miranda  and lower in Piamonte , highlighting the relevance of the adult index for entomological surveillance. In addition, a spatial autocorrelation was observed between the presence of pupa-positive houses and a higher density of adults in neighbouring blocks.For the wet season of the sampling, our spatial regression analysis found a positive correlation for the municipalities. Specifically, the determination coefficient between the captures of pupae and adults was higher than 50% in the municipalities of Patía  observed heterogeneous high-high and low-low spatial clusterings for each season, mainly in the Olaya Herrera neighborhood (March and October 2021). Variables such as the frequency of positive vases when rainfall reached only 1 mm (October 2021) explained the female pupal productivity by only 15%. However, in the period of higher precipitation , the tank container explained 37% of the female pupal productivity and, subsequently, the density of adult mosquitoes. This comparison is interesting, considering that the climate of the Patía municipality is bimodal, with peaks in April and November R2 model fit of 56% and a positive spatial autocorrelation in the season of lower rainfall, although with a high percentage of relative humidity, among the variables of female pupal productivity, explaining the number of adult mosquitoes. Positive autocorrelation was also found for the variables frequency-of-positive-low-TWS and pupae-productivity. However, for the period of higher precipitation and lower relative humidity, a negative spatial autocorrelation was found for the variables evaluated, i.e., with clustering patterns close to randomness  by 18%, with a positive bivariate spatial autocorrelation (Moran Index (MI) = 0.058). Miscellaneous containers smaller than 20 l, drums, and TWS presented non-significant positive autocorrelation of entomological indicators and number of adults. This latter finding is in contrast with the correlation between the percentage of positive buckets and pupae productivity (R2 = 37.7%) in the dry season of sampling.For Piamonte, during the wet season, the female-pupal-productivity variable explained the model fit  the blocks of neighbourhoods where this trend occurs, evidencing seasonal behaviour. While the spatial correlation linked the capture of pupae and adults in the same geographical space, the bivariate autocorrelation (MI) related these same variables, without necessarily coinciding in the same dwelling. Likewise, between municipalities, a greater positive spatial autocorrelation between pupae and adults was observed in Patía, especially when precipitation decreased before the onset of the rainy season. Our results are similar to other spatiotemporal studies of mosquito density , 27, showing heterogeneous patterns of occurrence for each territory, with seasonal behaviours registering higher infestation rates in seasons of higher rainfall.These findings suggest that for the species Our database and vector distribution map provide important resources for understanding the spatial patterns of the vector and its relationship with entomological indicators and breeding sites, which could increase dengue virus transmission in the municipalities.To improve the accessibility and usability of these data, they have been included in the GBIF. These data will be useful for making representative approximations of mosquito densities, mapping areas with high increases in pupal productivity, and linking other environmental, entomological, or socio-demographic determinants, providing essential information to generate innovative strategies for prevention, vector control, and management of dengue. We suggest others make their data available as well. Aedes aegypti es el principal vector de las arbovirosis humanas, tales como: fiebre amarilla, dengue, chikungunya y Zika, las cuales son prevalente en áreas tropicales y subtropicales . Su adaptación a condiciones antrópicas locales, ambientes urbanos, condiciones óptimas de temperatura, precipitación, humedad relativa entre otros factores ambientales y socioeconómicos le han conferido la capacidad de establecer sus poblaciones reproductivas entre las poblaciones urbanas y rurales –4.. Para el caso de Colombia, Ae. aegypti es el principal vector del virus dengue reportándose en altitudes entre el nivel del mar hasta los 2302 m. Por lo tanto, la presencia en un amplio rango altitudinal y la abundancia de este vector son una amenaza a la salud pública del país. , 6..El mosquito Ae. aegypti de hábitos hematófagos se alimente de sangre humana o de animales domésticos; causando infestaciones en diferentes tipos de contenedores en los domicilios y sus alrededores. En ese sentido, la presencia de contenedores artificiales y naturales como tanques, barriles, botellas, neumáticos, plantas acuáticas (bromelias y agua retenida en la parte axilar de las plantas), agua estancada, bebederos de mascotas, entre otros, se convierten en criaderos potenciales de estados inmaduros del mosquito Ae. aegypti , 8.. La vigilancia de este tipo de contenedores contribuye a reducir la proliferación de pupas y por ende densidades del mosquito, su muestreo se convierte en una herramienta indispensable para diseñar enfoques de vigilancia entomológica del vector, pertinentes a cada situación .El estrecho contacto con los seres humanos ha permitido que la hembra de , 10., la inspección se determina con indicadores entomológicos que permiten dar a conocer el índice de pupas por persona, productividad de pupas y la presencia de estadios inmaduros en las viviendas , 10.. Sin embargo, esto no se lleva a cabo en todas las entidades territoriales. La importancia de emplear este tipo de indicadores entomológicos es que proporcionan una aproximación representativa de las poblaciones locales adultas del mosquito requiriendo un tamaño muestral de inspección de casas relativamente pequeño , 11.. Por otra parte, el índice de pupas por persona posibilita calcular un umbral mínimo de infestación por pupas de Ae. aegypti para el riesgo de transmisión del virus dengue (DENV). Específicamente si este índice oscila entre 0,5 a 1,5 para temperaturas de 28 °C y seroprevalencias entre 0% a 67% , permite esclarecer zonas con mayor riesgo.De acuerdo con la metodología para la búsqueda activa de potenciales criaderos establecida para Colombia Ae. aegypti se ha basado principalmente en la obtención de los índices de larvas cualitativos, los cuales guardan poca relación con el número de hembras del mosquito. Por otra parte, se ha reportado que las poblaciones de Ae. aegypti son espacialmente heterogéneas en algunas zonas . Así pues, el uso del análisis espacio-temporal para predecir la aparición de puntos calientes de mosquitos Ae. aegypti, es decir, grupos de casas con elevados incrementos en la productividad de pupas, alta densidad del vector y potencial transmisión del DENV, es una de las estrategias innovadoras que pueden utilizarse para la prevención, control del vector y la gestión integrada del dengue en municipios de alto riesgo. Esto se debe a que este método permite detectar patrones de distribución geográfica del vector , 13.. Por tal motivo, es de suma importancia considerar este tipo de índices de infestación debido que los estadios inmaduros, específicamente las pupas representan el estadio anterior próximo al adulto con muy baja mortalidad. De esta manera aumenta la correlación entre la densidad de Ae. aegypti y el virus del dengue , 14..La vigilancia del mosquito Es así que, en este estudio, se comparó la vigilancia entomológica, mediante el uso de índices cuantitativos de pupas y de adultos en tres municipios de alto riesgo de dengue: Patía (El Bordo), Miranda y Piamonte en el departamento del Cauca. Principalmente con el fin de examinar cómo influye la productividad de pupas, entre otros índices entomológicos, en la densidad de mosquitos adultos y sus patrones espaciales y temporales. Para ello, se llevaron a cabo análisis de regresión espacial y de autocorrelación espacial bivariada, que permitieron modelar y explorar las relaciones espaciales, además de captar la relación entre los valores de dos variables, aun cuando estas no coincidían en el mismo espacio.Ae. aegypti provenientes de las viviendas de los municipios de Patía (El Bordo), Miranda y Piamonte; ubicados en el departamento del Cauca, al suroccidente de Colombia. Estos municipios forman parte de un proyecto de investigación en curso titulado “Estratificación espacial del dengue basado en la identificación de factores del riesgo: un ensayo piloto en el departamento del Cauca”, liderado por el Grupo de Entomología del Instituto Nacional de Salud, la Secretaría de Salud del Cauca y la Universidad de Ciencias Aplicadas y Ambientales (UDCA). El cual busca entre otros, evaluar la fuerza de asociación de las variables entomológicas en la explicación del patrón espacial observado en la distribución del dengue.Se documentan 160 registros biológicos (3.806 individuos) en estadio inmaduro (pupa) de la especie Los datos fueron recopilados entre los años 2021 y 2022 por un equipo multidisciplinar de técnicos de sanidad ambiental, ingenieros geógrafos y ambientales, y profesionales con amplia experiencia en entomología médica. En este conjunto de datos se diferenciaron tres periodos de muestreo para cada municipio, para Patía: marzo y octubre del 2021 y marzo y abril del 2022; para Miranda: abril y noviembre del 2021 y mayo del 2022; y para Piamonte julio del año 2021 y febrero y julio del 2022. Un cuarto período de muestreo se llevó a cabo en agosto y octubre del 2022 en los municipios de Patía y Miranda respectivamente, con el fin de incrementar el tamaño de muestra para llevar a cabo serotipificación de los ejemplares.Los estadios inmaduros (pupas) fueron recolectados de recipientes menores y mayores de 20 litros incluyendo, tanques, barriles, neumáticos, entre otros, provenientes del intradomicilio de las viviendas de los tres municipios. Los municipios fueron seleccionados como área de estudio por su comportamiento endemo-epidémico para la transmisión del virus dengue (DENV), caracterizado por presentar endemias focales, escenarios de transmisión heterogéneos, patrones temporales y cíclicos en poblaciones de riesgo.. También hacen parte de este conjunto de datos 3.480 individuos adultos de la familia Culicidae , de los cuales alrededor del 69% de los especímenes fueron colectados en el año 2021, mientras que 1.078 individuos fueron nuevos registros recolectados en el año 2022.El conjunto de datos de estadios inmaduros está en formato Darwin Core, con 73 términos disponibles. Todos los campos obligatorios están presentes y han sido sometidos a revisión en el IPT (Integrated Publishing Toolkit) del SiB-Colombia. Los campos de metadatos también están disponibles a través de las páginas disponibles en línea Estos registros biológicos son fundamentales para la comunidad científica ya que proporcionan las coordenadas geográficas, así como índices entomológicos necesarios para la vigilancia en salud pública que se lleva a cabo por parte de las entidades de salud. En particular, estas medidas son esenciales para construir estrategias que permitan prevenir y controlar el dengue en viviendas y barrios con altos índices de infestación del vector.Ae. aegypti fueron recolectados en viviendas ubicadas en los municipios de Patía (El Bordo), Miranda y Piamonte en el departamento del Cauca, Colombia   con un nivel de confianza del 99% mediante el software Epi Info™, utilizando el tamaño de población estimado y los conglomerados obtenidos en el análisis Kernel.Los especímenes de los estados inmaduros de a Figure . Estos mn = 580 viviendas), en Miranda 12 barrios (n = 854 viviendas) y en Piamonte cuatro barrios (n = 485 viviendas). En total, se visitaron 1.919 viviendas en 26 barrios durante los meses de marzo, abril, julio y octubre del año 2021, y febrero, marzo, mayo, julio, agosto y octubre de 2022. En el municipio de Patía se visitaron 11 barrios  y 2022 . Estas inspecciones se realizaron entre las 8:00 y las 17:00 horas, con una duración media de 10 minutos por vivienda. En cada hogar se buscaron mosquitos adultos en la sala, comedor, baños, cocinas, patio de lavado y otras áreas y se capturaron utilizando un aspirador Prokopack. Estos procedimientos se llevaron a cabo haciendo énfasis en la búsqueda en áreas sombreadas o lugares cercanos a recipientes con agua durante el recorrido.Ae. aegypti por expertos entomólogos con el apoyo de las claves taxonómicas desarrolladas por Forattini  (1995) y Harrison et al.,  (2016) para diferenciarlas de estadios inmaduros pertenecientes a otras especies. Continuando con el protocolo de campo, se identificaron 3.806 pupas de Ae. aegypti, de ellas, 395 fueron conservadas en viales de 0,2 mL con RNAlater© para su procesamiento con técnicas de biología molecular en el grupo de Entomología y el grupo de Genómica de Microorganismos Emergentes del Instituto Nacional de Salud  .Posterior a la captura de los estadios inmaduros y adultos, se identificó y se clasificó taxonómicamente la especie ® Survey 123 , la cual permitió obtener la ubicación geográfica de cada espécimen recolectado. Se asoció un código a cada vial con la información sociodemográfica de la encuesta y a partir del número total de pupas registradas en cada encuesta, se determinaron los índices entomológicos de productividad de pupas, productividad de hembras, índice de pupas por persona, índice pupal de Breteau , 10. y proporción de individuos F:M de pupas Aedes sp. , así como matrices de diagramas de dispersión para evaluar las relaciones entre las variables entomológicas: número de mosquitos adultos de Ae. aegypti , número total de pupas, productividad de pupas, productividad de hembras, número de pupas por persona con respecto a la frecuencia de contenedores de tipo tanques bajos, contenedores diversos menores a 20 L y barriles.La información entomológica en conjunto con la información de las manzanas geográficas de los municipios se empleó para realizar análisis de diagramas de dispersión  para detectar la distribución de las variables relacionadas con agrupaciones espaciales. El Índice de Moran se encuentra en un rango de −1 a 1, en donde −1 indica patrones de agrupación dispersos, 0 indica aleatoriedad y 1 asociación perfecta. Posteriormente, se ejecutó el análisis para el Índice de Moran Local que distribuyó los agrupamientos significativos  de las manzanas de las viviendas con cuatro tipos de asociación espacial local (I) alto (x)-alto (y) indica zonas con valores elevados de la variable rodeados de valores superiores a la media de la variable a analizar, (II) bajo (x)-alto(y) indica zonas con valores bajos de la variable rodeada de zonas vecinas con valores por encima de la media de la variable, (III) bajo (x)-bajo (y) indica zonas con bajos valores de la variable rodeados de zonas con valores por debajo de la media de la variable y (IV) alto(x)-bajo (y) zonas con valores elevados de la variable rodeados de zonas por debajo de la media de la variable a analizar .A su vez, se realizó un análisis espacial mediante el Índice de Moran bivariante global .Los anteriores análisis fueron realizados en dos épocas de muestreo en cada municipio, es decir, para el municipio de Patía (El Bordo) las muestras recolectadas en los meses marzo y octubre del año 2021, para Miranda las muestras correspondientes de abril y noviembre del año 2021; y para Piamonte las muestras de julio del año 2021 y febrero del año 2022 debido que entre esos meses se evidenció temporalidad en el patrón de precipitación de lluvias. Finalmente, los análisis se efectuaron en el programa GeoDa v1.20 Se identificaron 3.480 especímenes adultos en 1.200 viviendas, de los cuales 1.459 correspondían a hembras y 2.021 a machos. En el año 2021 se documentaron 2.402 registros, mientras que en el año 2022 se añadieron 1.078 nuevos registros. Con respecto a la distribución por municipios, Miranda reportó 500 individuos , Patía registró 1.305 individuos , y Piamonte presentó los registros más altos con 1.675  individuos adultos. Cabe destacar que se encontraron 71 individuos en una sola vivienda perteneciente al municipio de Patía y otros 125 individuos en una vivienda diferente del municipio de Piamonte.Ae. aegypti, distribuidos en 160 registros . Para el municipio de Patía (El Bordo) se hallaron 1.493 individuos en 67 viviendas positivas, para Miranda 1.173 individuos en 58 viviendas y para Piamonte se encontraron 1.140 individuos en 35 viviendas. Los barrios con mayor cantidad de especímenes fueron Villa Los Prados (n = 519) y La Paz (n = 359) en Piamonte, seguido del barrio San Antonio (n = 391) en Miranda y los barrios Libertador (n = 441) y Olaya Herrera (n = 438) en el municipio de Patía. Cabe resaltar que, se encontraron 70 casas inspeccionadas con más de 15 pupas de Ae. aegypti al interior de la vivienda. El mayor número de especímenes detectados pertenecía a una casa del municipio de Piamonte, con 280 pupas  y Miranda  e inferior en Piamonte  entre la captura de pupas y adultos, lo que sugiere el uso del índice de adultos para la vigilancia entomológica. Además, se observó una autocorrelación espacial entre la presencia de viviendas con pupas positivas y una mayor densidad de adultos en las manzanas vecinas.Para la época lluviosa del muestreo, en el análisis de regresión espacial, se encontró una correlación positiva para los municipios. Específicamente con un coeficiente de determinación superior al 50% en los municipios de Patía  explicó el número de adultos de . Nuestro análisis local (LISA) observó agrupaciones espaciales heterogéneas alto-alto y bajo-bajo para cada temporada, principalmente en el barrio Olaya Herrera (marzo y octubre de 2021). Variables como la frecuencia de floreros positivos cuando las precipitaciones alcanzaron sólo 1 mm (octubre 2021), explicaron la densidad de mosquitos adultos sólo en un 15%; mientras que en el periodo de mayor precipitación , el contenedor tanques bajos explicó el 37% de la densidad de mosquitos adultos. Esta comparación resulta de interés teniendo en cuenta que el clima del municipio de Patía presenta un comportamiento bimodal con picos en los meses de abril y noviembre R2 del 56% y autocorrelación espacial positiva en la época de menor precipitación, aunque con alto porcentaje de humedad relativa, entre las variables productividad de pupas hembra y el número de mosquitos adultos. Se identificó también la presencia de autocorrelación positiva para las variables frecuencia de tanques bajos positivos y productividad de pupas. No obstante, para la época de mayor precipitación y menor humedad relativa se encontró autocorrelación espacial negativa en las variables evaluadas, es decir, con patrones de agrupación cercanos a la aleatoriedad  en un 18% con autocorrelación espacial bivariada positiva . En relación con los contenedores diversos menores a 20 L, barriles y tanques bajos presentaron autocorrelación positiva no significativa referente a los indicadores entomológicos y número de adultos, resultados que contrastan con la correlación entre el porcentaje de baldes positivos y la productividad de pupas  en la época seca del muestreo.En el caso de Piamonte para la época lluviosa, la variable productividad de pupas hembra explicaron el ajuste del modelo  las manzanas de los barrios donde esta tendencia ocurre, evidenciando un comportamiento estacional. Mientras que la correlación espacial vinculó la captura de pupas y adultos en el mismo espacio geográfico, la autocorrelación bivariada (IM) relacionó estas mismas variables, pero sin que coincidan necesariamente en la misma vivienda. Asimismo, entre municipios se observó una mayor autocorrelación espacial positiva entre pupas y adultos en Patía, especialmente cuando descienden las precipitaciones previo al inicio de la temporada de lluvia. Nuestros resultados son similares a otros estudios espacio-temporales relacionados con la densidad de mosquitos , 27. mostrando patrones heterogéneos de ocurrencia para cada territorio, con comportamientos estacionales que registran mayores tasas de infestación en temporadas de mayor pluviosidad.Los resultados sugieren que para la especie La base de datos y el mapa de distribución del vector proporcionan importantes recursos para el entendimiento de los patrones espaciales del vector y su relación con indicadores entomológicos y con criaderos, que podrían aumentar la transmisión del virus dengue en los municipios estudiados.Para mejorar la accesibilidad de estos datos, la base de datos ha sido incluida en el GBIF. Esta información será útil para realizar aproximaciones representativas de la densidad del mosquito, mapear zonas con elevados incrementos en la productividad de pupas, y relacionar otros determinantes ambientales, entomológicos o sociodemográficos que suministren información vital para generar estrategias innovadoras en prevención, control del vector y la gestión del dengue. Sugerimos a otros investigadores que hagan disponibles sus datos de manera similar. Upload additional filesDRR-202305-01/form/Data-Review-DRR-202305-01.docxReviewer name and names of any other individual's who aided in reviewer Christopher I HunterDo you understand and agree to our policy of having open and named reviews, and having your review included with the published papers. YesIs the language of sufficient quality?YesPlease add additional comments on language quality to clarify if needed
Are all data available and do they match the descriptions in the paper? YesAdditional CommentsMostly, although the dataset includes additional data that is not explicitly described in this manuscript.Are the data and metadata consistent with relevant minimum information or reporting standards? See GigaDB checklists for examples <a href="http://gigadb.org/site/guide" target="_blank">http://gigadb.org/site/guide</a>YesAdditional CommentsBut please note the later comment regarding lack of reporting of negative observations.Is the data acquisition clear, complete and methodologically sound?YesAdditional CommentsIs there sufficient detail in the methods and data-processing steps to allow reproduction?YesAdditional CommentsPlease note the comment below regarding my lack of expertise in the field to know if all the analysis methodology is sufficient.Is there sufficient data validation and statistical analyses of data quality? Not my area of expertiseAdditional CommentsIs the validation suitable for this type of data?YesAdditional CommentsIs there sufficient information for others to reuse this dataset or integrate it with other data?YesAdditional CommentsAny Additional Overall Comments to the AuthorMajor comments (Author action required):
 1 – The manuscript describes negative screening events that do no appear to be in the GBIF data? E.g. Table 2 gives the number of containers screened and the percentage +ve with pupae. Without a record of those negative results this summary tables are unreproducible. GBIF has the field “OccurenceStatus” specifically to enable negative observations to be recorded.

 Minor comments (Author action suggested):
 1 – Event dates are slightly mis-aligned. First event date in dataset is Feb 10th 2021, but the manuscript doesn’t mention any collection dates prior to March 2021. The Feb2021 events are adult occurrences, so it can be seen why there is the difference, but maybe it could be simple enough to add in collection months for the adult data to the manuscript.

 2 – Are sufficient methods and data available to reproduce analysis shown in Fig2 and Table3? Please refer to subject area expert reviewers on this matter.

 See Data-Review document attached for additional information.
RecommendationMinor Revision Upload additional filesDRR-202305-01/form/gx-DR-1683034334 (1).pdfReviewer name and names of any other individual's who aided in reviewer Mauricio dos Santos ConceiçãoDo you understand and agree to our policy of having open and named reviews, and having your review included with the published papers. YesIs the language of sufficient quality?YesPlease add additional comments on language quality to clarify if needed
Are all data available and do they match the descriptions in the paper? YesAdditional CommentsAre the data and metadata consistent with relevant minimum information or reporting standards? See GigaDB checklists for examples <a href="http://gigadb.org/site/guide" target="_blank">http://gigadb.org/site/guide</a>YesAdditional CommentsIs the data acquisition clear, complete and methodologically sound?YesAdditional CommentsIs there sufficient detail in the methods and data-processing steps to allow reproduction?YesAdditional CommentsIs there sufficient data validation and statistical analyses of data quality? Not my area of expertiseAdditional CommentsIs the validation suitable for this type of data?YesAdditional CommentsIs there sufficient information for others to reuse this dataset or integrate it with other data?YesAdditional CommentsAny Additional Overall Comments to the AuthorThe text is well written, methodology clear and reproducible. Some observations, in some moments of the text the specimen Aedes aegypti is not in italics, the authors, therefore, should make this small adjustment.RecommendationAccept Editor’s AssessmentThere’s a shortage of disease vector data available from across the world, and this data release presents a biological collection of Aedes aegypti mosquitoes (the main vector of human arbovirosis) from the department of Cauca, in the southwest of Colombia. In 2022 this group released the first adult mosquito data in GBIF from this region, and here is an update presenting another 160 biological records  of the immature stage (pupae) of Ae. Aegypti. Plus some new records (and improved metadata with absence information after feedback). All made publicly available under a CC0 waiver from the Instituto Nacional de Salud and GBIF.


As evidências que embasam o uso de inibidores do sistema-renina-angiotensina aldosterona (SRAA) e betabloqueadores para prevenção de cardiomiopatia induzida por antraciclinas são controversas. Realizamos uma metanálise para avaliar a eficácia desses medicamentos na prevenção da cardiotoxicidade. A metanálise incluiu estudos prospectivos e randomizados com adultos submetidos à quimioterapia com antraciclina e comparou o uso de terapias SRAA ou betabloqueadores versus placebo com seguimento de 6 a 18 meses. O desfecho primário foi alteração da fração de ejeção do ventrículo esquerdo (FEVE) durante a quimioterapia. Os desfechos secundários foram: a incidência de insuficiência cardíaca, mortalidade por todas as causas e alterações na medida do diâmetro diastólico final. A avaliação da heterogeneidade foi realizada por estratificação e meta-regressão. O nível de significância adotado foi p < 0,05. A busca resultou em 17 estudos, totalizando 1.530 pacientes. A variação (delta) da FEVE foi avaliada em 14 estudos. A terapia neuro-hormonal foi associada a um menor delta na FEVE pré-terapia versus pós-terapia  e maior FEVE final . O tratamento resultou em menor incidência de insuficiência cardíaca . Não houve efeito na mortalidade . Para a análise da FEVE, foi documentada heterogeneidade substancial, não explicada pelas variáveis exploradas no estudo. O uso de inibidores do SRAA e betabloqueadores para prevenção da cardiotoxicidade induzida por antraciclinas foi associado a redução menos pronunciada da FEVE, maior FEVE final e menor incidência de insuficiência cardíaca. Não foram observadas alterações na mortalidade. (CRD PROSPERO 42019133615) A prevenção envolve abordagens que minimizam a exposição da droga, resultando em menor risco de cardiotoxicidade potencial e na decisão de iniciar drogas cardioprotetoras. O uso de drogas cardiovasculares, como inibidores da enzima conversora de angiotensina (IECA), bloqueador do receptor de angiotensina (BRA), antagonista do receptor de mineralocorticoide (ARM) e betabloqueadores é baseado em poucos ensaios clínicos com resultados controversos. O uso de tratamento preventivo com IECA, BRA, ARM ou terapia com betabloqueadores em pacientes em quimioterapia com antraciclinas com baixo risco cardiovascular basal permanece incerto, e nenhuma recomendação pode ser feita atualmente.6 e outras intervenções como estatinas, dexrazoxano ou N-acetilcisteína,10 enquanto outros estudos incluíram apenas betabloqueadores15 ou apenas antagonistas do sistema renina-angiotensina-aldosterona (SRAA).17 Recentemente, Vaduganathan et al. publicaram uma metanálise avaliando IECA, BRA, ARM e betabloqueadores na prevenção da cardiotoxicidade relacionada à quimioterapia, incluindo antraciclina e trastuzumabe.18 Conforme estabelecido, os mecanismos cardiotóxicos das antraciclinas e terapias anti-HER2 são distintos, o que poderia ser um fator de confusão para o real impacto da prevenção da cardiotoxicidade por antagonistas neuro-hormonais.Existem poucas metanálises publicadas avaliando terapias com antagonistas neuro-hormonais na prevenção da cardiotoxicidade. Alguns estudos incluíram populações pediátricasDiante de evidências controversas que apoiam o uso de inibidores do sistema da angiotensina e betabloqueadores apenas para prevenção primária da cardiotoxicidade induzida por antraciclinas, realizamos uma revisão sistemática e metanálise para avaliar a eficácia desses agentes como drogas profiláticas para início precoce de cardiotoxicidade.19 Nosso protocolo de estudo pré-especificado foi registrado no International Prospective Register of Systematic Reviews (PROSPERO CRD 42019133615). Pesquisamos sistematicamente PubMed, EMBASE, ClinicalTrials.Gov e Cochrane Central Register of Controlled Trials para ensaios controlados randomizados de drogas cardioprotetoras, como betabloqueadores, IECA, BRA e ARM, em pacientes sob quimioterapia com antraciclina para avaliar a eficácia desses medicamentos na prevenção da cardiotoxicidade. A lista de termos utilizados na busca é apresentada no Material Suplementar. Limitamos a busca a artigos em inglês. Além disso, pesquisamos as referências de todos os artigos identificados. Incluímos todos os ensaios controlados randomizados usando medicamentos cardioprotetores no braço ativo  comparados com placebo ou tratamento usual, com seguimento de 6 a 18 meses, que relataram a função cardíaca avaliada por ecocardiograma ou ressonância magnética cardíaca, diâmetros cardíacos e/ou desfechos clínicos . Excluímos resumos, estudos com períodos de seguimento mais curtos, população pediátrica, estudos sem braço controle e estudos não randomizados. Nenhum paciente foi incluído, e todos os dados do estudo são anônimos; portanto, não foi necessária aprovação do comitê de ética ou conselho de revisão institucional.Seguimos a declaração Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), e a lista de verificação PRISMA é apresentada no Material Suplementar.Dois investigadores (M.S.A. e S.R.R.S.) extraíram dados de forma independente usando um formulário padronizado, incluindo características do estudo , características da intervenção (medicamento cardioprotetor), características do paciente  e desfechos. Para os desfechos, definimos a priori o desfecho primário de alteração (delta) na fração de ejeção do ventrículo esquerdo (FEVE) desde a linha de base até o final do estudo. Desfechos secundários definidos a priori incluíram mortes por todas as causas, insuficiência cardíaca e alterações (delta) na medição do diâmetro diastólico final por ecocardiografia.odds ratios para resultados dicotômicos e diferenças médias ponderadas para os desfechos contínuos. Para estudos que não relataram as diferenças longitudinais nas mudanças dos parâmetros ecocardiográficos ao longo do tempo, usamos as diferenças relatadas com desvios-padrão, erros-padrão ou intervalos de confiança. Para os estudos que não relataram nenhuma das medidas de dispersão para a alteração (delta), os erros-padrão foram derivados do desvio-padrão das pré- e pós-medidas, inserindo os valores das correlações entre o pré-teste e o pós-teste, com base na correlação derivada de outros estudos nos quais tivemos acesso a dados individuais do nível do paciente para derivar os coeficientes. A descrição dos resultados dos ensaios e os critérios de inclusão/exclusão estão detalhados no Material Suplementar.Realizamos uma síntese narrativa dos achados dos estudos incluídos, que compreendia descrição do tipo de tratamento, características da população, desfechos e conteúdo da intervenção. Fornecemos resumos dos efeitos da intervenção para cada estudo, calculando as 2 e o I2 era superior a 50%, indicando heterogeneidade substancial, realizávamos análises adicionais de acordo com a qualidade do estudo, data do estudo, tipo de medicamento usado para tratamento, dose de antraciclina e características dos pacientes incluídos no estudo. Esta análise foi realizada usando metanálises estratificadas para preditores categóricos e meta-regressão para preditores contínuos. Também avaliamos evidências de viés de publicação usando gráficos de funil. A análise estatística foi realizada no Stata 17.0 , e o nível de significância foi definido como p < 0,05.Imaginamos que um grande número de estudos com diferentes desfechos e intervenções pudesse resultar em uma alta heterogeneidade, assim, realizamos todas as análises usando modelos de efeitos aleatórios. Além disso, quando a heterogeneidade medida pelo teste χ20 As discordâncias foram resolvidas por consenso.Dois investigadores (M.S.A. e S.R.R.S.) avaliaram independentemente a qualidade dos estudos usando a ferramenta da Cochrane Collaboration para avaliar o risco de viés em ensaios randomizados.Dois investigadores (M.S.A. e S.R.R.S.) avaliaram a qualidade dos estudos usando a Ferramenta de Risco de Viés Cochrane. Em particular, a avaliação considerou: geração de sequência aleatória, ocultação de alocação, ocultação de participantes e da equipe, ocultação de desfecho e avaliação, avaliação de dados e outros vieses. A qualidade do estudo é detalhada no Material Suplementar.A busca sistemática resultou em 355 artigos potencialmente relevantes. Após a remoção dos ensaios que não atendiam aos critérios de inclusão, com período de seguimento inferior a 6 meses, ensaios não randomizados, sem controle com placebo e população pediátrica, foram incluídos 17 ensaios na análise. O diagrama para a seleção dos estudos é mostrado na 2 no grupo placebo e 286  no grupo dos medicamentos cardioprotetores.Todos os 17 estudos avaliaram a função ventricular esquerda, e 10 estudos analisaram o diâmetro diastólico final do ventrículo esquerdo (DDFVE) para a detecção de cardiotoxicidade por ecocardiografia. A doxorrubicina foi a quimioterapia com antraciclina mais frequentemente incluída nos ensaios, e a dose cumulativa mediana (faixa interquartil) foi de 241 (240 a 369) mg/m2 = 92,7%), embora os tamanhos de efeito fossem comparáveis para todos os medicamentos. Metarregressões adicionais usando idade, dose cumulativa de antraciclinas ou ano do estudo não foram capazes de identificar qualquer fator associado à heterogeneidade.Catorze estudos analisaram o delta da fração de ejeção. Os valores de FEVE e DDVE desde a linha de base até o final dos estudos estão resumidos na risk ratio 0,45; intervalo de confiança de 95% 0,28 a 0,72; p = 0,32; 2 = 11,18%), e nenhum viés de publicação potencial foi identificado. Os números absolutos de insuficiência cardíaca e morte são relatados no Material Suplementar.Doze estudos relataram a influência de drogas neuro-hormonais e betabloqueadores na incidência de insuficiência cardíaca e onze na morte. No entanto, após agrupar os resultados dos doze estudos, a presença de medicamentos cardioprotetores foi associada a menos sintomas de insuficiência cardíaca durante e após o uso de antraciclina , angiotensin receptor blocker (ARB), mineralocorticoid receptor antagonist (MRA), and beta-blockers are based on few clinical trials with controversial results. Use of preventive treatment with ACEI, ARB, MRA, or beta-blocker therapy in patients under anthracyclines chemotherapy with low cardiovascular baseline risk remains uncertain, and no recommendation can be made at this time.6 and other interventions such as statins, dexrazoxane, or N-acetylcysteine,10 whereas other studies include only beta-blockers15 or only renin-angiotensin-aldosterone system (RAAS) antagonists. 17 Recently, Vaduganathan et al. published a meta-analysis evaluating ACEI, ARB, MRA, and beta-blockers in preventing chemotherapy-related cardiotoxicity, including anthracycline and trastuzumab.18 As established, the cardiotoxicity mechanisms of anthracyclines and anti-HER2 therapies are distinct, which could be a confounding factor for the real impact of neurohormonal antagonist prevention of cardiotoxicity.There are few meta-analyses published evaluating neurohormonal antagonist therapies in preventing cardiotoxicity. Some studies included pediatric populationsIn face of controversial evidence supporting the use of angiotensin system inhibitors and beta-blockers for primary prevention of anthracycline-induced cardiotoxicity alone, we performed a systematic review and meta-analysis to assess the efficacy of these agents as prophylactic drugs for early onset of cardiotoxicity.19 Our prespecified study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD 42019133615). We systematically searched PubMed, EMBASE, ClinicalTrials.Gov, and the Cochrane Central Register of Controlled Trials for randomized controlled trials of cardioprotective drugs, such as beta-blockers, ACEI, ARB, and MRA, in patients under anthracycline chemotherapy to evaluate the efficacy of these drugs in preventing cardiotoxicity. The list of terms used in the search is shown in the Supplementary Material. We limited the search to articles in English. We additionally searched the references of all articles retrieved. We included all randomized controlled trials using cardioprotective drugs on the active arm  compared with placebo or usual care, with follow-up from 6 to 18 months, that reported cardiac function evaluated by echocardiogram or cardiac magnetic resonance, cardiac diameters and/or clinical outcomes . We excluded abstracts, studies with shorter follow-up, pediatric population, studies without control arm, and non-randomized studies. No patients were included, and all study data are anonymous; therefore, no ethics committee or institutional review board approval was needed.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the PRISMA checklist is presented in the Supplementary Material.Two investigators (M.S.A. and S.R.R.S.) independently abstracted data using a standardized form, including study characteristics , characteristics of the intervention (cardioprotective drug), patient characteristics , and outcomes. For the outcomes, we defined a priori the primary outcome of change (delta) in left ventricular ejection fraction (LVEF) from baseline to the end of study. Secondary outcomes defined a priori included all-cause deaths, heart failure, and changes (delta) in measurement of end diastolic diameter by echocardiography.We performed a narrative synthesis of the findings from the included studies, including description of the type of treatment, population characteristics, outcomes, and intervention content. We provided summaries of intervention effects for each study by calculating odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. For studies that did not report the longitudinal differences in the changes in echocardiographic parameters over time, we used the reported differences with standard deviations, standard errors, or confidence intervals. For the studies that did not report any of the measures of dispersion for the change (delta), the standard errors were derived from the standard deviation of the pre- and post-measurements, inputting the values of correlations between the pretest and posttest, based on the correlation derived from other studies in which we had access to individual patient level data to derive the coefficients. The description of outcomes of the trials and inclusion/exclusion criteria are detailed in the Supplementary Material.2 test and the I2 were greater than 50%, indicating substantial heterogeneity, we performed additional analyses according to study quality, study date, type of drug used for treatment, anthracycline dose, and characteristics of patients included in the study. This analysis was performed using stratified meta-analyses for categorical predictors and meta-regression for continuous predictors. We also assessed evidence of publication bias using funnel plots. The statistical analysis was performed using Stata 17.0 , and the level of significance was defined as p < 0.05.We expected that a large number of studies with different outcomes and interventions could result in a high heterogeneity. Thus, we performed all analysis using random effects models. Moreover, when the heterogeneity measured by χ20 Disagreements were resolved by consensus.Two investigators (M.S.A. and S.R.R.S.) independently assessed study quality using the Cochrane Collaboration’s tool for assessing risk of bias in randomized trials.Two investigators (M.S.A. and S.R.R.S.) assessed study quality using Cochrane Risk of Bias Tool. In particular, the assessment considered: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome and assessment, data evaluation, and other bias. Study quality is detailed in the Supplementary Material.The systematic search resulted in 355 potentially relevant articles. After removal of trials that did not meet the inclusion criteria, with fewer than 6 months of follow up, non-randomized trials, lack of placebo control, and pediatric study, 17 trials were included in analysis. The diagram for the study selection is shown in 2 in placebo group and 286 (254.2 to 383) in cardioprotective drug group.All the 17 studies assessed left ventricular function, and 10 studies analyzed left ventricular end-diastolic diameter (LVEDD) for the detection of cardiotoxicity via echocardiography. Doxorubicin was the most common anthracycline chemotherapy included in the trials and the median cumulative dose (interquartile range) was 241 (240 to 369) mg/mFourteen studies analyzed the delta of ejection fraction. Values of LVEF and LVEDD from baseline to the end of the studies are summarized in Twelve studies reported the influence of neurohormonal drugs and beta-blockers on the incidence of heart failure and eleven on death. However, after pooling the results from the twelve studies, the presence of cardioprotective drugs was associated with fewer symptoms of heart failure during and after anthracycline use (risk ratio 0.45, 95% confidence interval 0.28 to 0.72, p = 0.32, The present meta-analysis analyzed the protective effects of RAAS inhibitors and beta-blockers against anthracycline-induced cardiotoxicity. We selected 17 randomized trials and found a benefit of cardioprotective agents on changes in LVEF and symptoms of heart failure. Neurohormonal therapy was associated with a lower delta in LVEF and fewer symptoms of heart failure, and there was no effect on mortality. Despite the positive impact of neurohormonal drugs, we found a high heterogeneity between the studies; thus, interpretation of these findings needs to be contextualized, and a potential for publication bias should be considered.21 showed, in 2006, that use of carvedilol could prevent the decrease in ejection fraction and the increase in left ventricle diameters in patients using anthracyclines, without a significant change in mortality. In another important trial, Cardinale et al.22 showed that the use of ACEI could reduce the elevation in left ventricular systolic diameter and prevent cardiotoxicity, in patients who had higher troponin changes after the chemotherapy cycle.The field of cardio-oncology has been studied extensively in the last 15 years. Kalay et al.23 The most recent randomized trial published, the CECCY Trial, was a single-center, randomized trial that tested carvedilol as a cardiac protector in breast cancer patients undergoing chemotherapy with anthracyclines. It showed no significant difference in ventricular dysfunction, but it did show a benefit in left ventricular diastolic diameter and troponin in the carvedilol group.24More recently, the PRADA trial, a randomized, placebo-controlled study, evaluated use of candesartan, metoprolol, and combined use of both drugs in primary prevention of anthracycline cardiotoxicity. The study found benefit only with candesartan, demonstrating a smaller extracellular volume assessed by magnetic resonance imaging and attenuated reduction in LVEF.The analysis of the outcome of heart failure performed individually in each study showed no statistical difference. However, when we analyzed the total population of all studies, we observed a better outcome in the group using beta-blockers and RAAS inhibitors, with significant results.Heterogeneity differs between the analyzed outcomes. We observed significant heterogeneity in the assessment of the ejection fraction delta, which potentially reflects variation in study population due to differences in cardioprotective therapy, malignancy, and doses of anthracyclines. Regarding evaluation of the clinical outcome, we observed a low heterogeneity.11 Recently Caspani et al. published a meta-analysis that evaluated neurohormonal therapies in this scenario, including a smaller number of trials and sample size. They found benefit in preventing LVEF reduction in the drug arm, but did not find an impact of cardioprotective drug on heart failure.25 Vaduganathan et al. published a meta-analysis evaluating ACEI, ARB, MRA, and beta-blockers in preventing chemotherapy-related cardiotoxicity, including, anthracycline and trastuzumab. The authors concluded that neurohormonal therapies had a positive impact on reducing decline in left ventricular function with a high heterogeneity, which is consistent with our analysis. Nonetheless, the inclusion of a trial with trastuzumab could be a confounding factor, as the cardiotoxicity mechanism is different from anthracycline.18Some meta-analyses evaluated the impact of neurohormonal therapy on anthracycline-induced cardiotoxicity. Kheiri et al. evaluated the impact of carvedilol on the prevention of anthracycline-induced cardiotoxicity and demonstrated a possible benefit attenuating the decrease in the LVEF. However, this study did not include RAAS inhibitors.Our results reveal the need for studies with larger populations, with higher potential to show the real benefit of cardioprotective drugs in cardiotoxicity.2 dose. Moreover, as the studies included different anthracyclines, the doses were different between the trials. The limited sample sizes in some trials and missing data on cardiovascular risk factors could prevent subgroup analyses by cardiovascular risk.Our meta-analysis has several important limitations. The majority of the studies included evaluated LVEF using standard echocardiography, and few included left ventricular structure. Changes in LVEF are a very heterogeneous measurement, and inter-observer variability was not reported in all trials. Concerning the endpoint of heart failure, there are missing data in some articles, and this could compromise the results of this outcome. Regarding anthracycline dose, some articles reported total dose of anthracycline and did not report mg/mWe conclude that RAAS antagonists and beta-blockers for prevention of anthracycline-induced cardiotoxicity were associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. Significant heterogeneity was observed across the studies in the assessment of the ejection fraction delta, which potentially reflects variation in study population. It is necessary to conduct further studies with larger populations, with consistent and significant results demonstrating the benefit of cardioprotective drugs in cardiotoxicity.For additional information, please click here.


Cell Death & Disease 10.1038/s41419-023-06177-1, published online 27 October 2023Correction to: In this article the funding note needs to be added:“This work was supported by a grant from Spanish Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación and the European Regional Development Fund .”The original article has been corrected.