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Ichneumonidae, or Chilean Darwin wasps, are an important component of South American hymenopteran diversity, but the taxonomic and distributional knowledge on this insect is still deficient. Taking advantage of recently updated taxonomic knowledge, we assessed biogeographic relationships at the genus level and biodiversity spatial patterns along the latitudinal gradient. The results show the presence of 264 species in Chile, arranged in 102 genera and 22 subfamilies. Biogeographic relationships are based on six elements (cosmopolitan (n = 50; 36%), endemic (n = 29; 21%), Neotropical (n = 22; 16%), Holarctic-Oriental (n = 19; 14%), south-temperate (n = 16; 11%) and Australasian) and composed of just three genera: Anacis, Labena, and Meringops. Species and genera show a bimodal distribution along the latitudinal gradient: around 34° and 38° S. From an ecoregional perspective, richness is concentrated in the Valdivian temperate forests, but when assessed at a 0.5 × 0.5 cell scale, several outstanding cells are in the contact zone between the temperate forests and the Chilean Matorral. On the other hand, the Atacama Desert shows little or no presence of Darwin wasps. The results agree with Charles Porter, who identified a northern province composed of Neotropical and cosmopolitan genera with their own representatives in the far north (11 genera), a distributional gap in the core of the Atacama Desert, and around 128 genera in Porter's Neantarctic realm, covering all of Chile from 25° S to Cape Horn, including the Juan Fernandez islands. These results reinforce knowledge gaps and the need for more sampling and studies of available collections. Due to sampling gaps at this stage, identifying a continued increase or decrease in richness towards higher latitudes is not possible. More taxonomic and distributional information is also needed to assess potential threats to endemic genera and species.
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Asteraceae is the world's richest plant family and is found on all continents, in environments ranging from the coast to the highest mountains. The family shows all growth forms and, as in other angiosperm families, species richness is concentrated in tropical regions. South America has the highest diversity of Asteraceae in the world, yet taxonomic and distributional knowledge gaps remain. This study compiles an updated catalog of Asteraceae native to South America, based on national and regional checklists and ongoing large-scale flora projects. The resulting checklist includes a total of 6,940 species and 564 genera native to South America to date, which represent about a quarter of the family's global diversity. Countries already considered to be megadiverse show the greatest diversity, such as Brazil with 2,095 species, followed by Peru (1,588), Argentina (1,377), and Colombia (1,244), with this diversity mainly focused on the Brazilian Highlands and the Andes. Species endemism also peaks in Brazil, but Sørensen distances reveal the Chilean flora to be eminently different from the rest of the continent. Tribes better represented in the continent are Eupatorieae, Senecioneae and Astereae, also with a remarkably presence of entirely South American subfamilies representing earliest diverging lineages of the Asteraceae, such as Barnadesioideae, Wunderlichioideae, Famatinanthoideae, and Stifftioideae. It is estimated that the discovery and description curves have not yet stabilized, and the number of species is likely to increase by 5 to 10% in the coming years, posing major challenges to continental-scale conservation.
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OBJECTIVE: To describe the sociodemographic and clinical characteristics of imprisoned patients with epilepsy seen at Samaritana University Hospital (HUS) in Bogotá D.C., between January 2017 and November 2020. METHODS: Cross-sectional cohort study of inmate patients over 18 years of age seen at HUS between January 2017 and November 2020, with a discharge diagnosis of epilepsy. A descriptive univariate analysis of patient sociodemographic and clinical characteristics was carried out. RESULTS: Overall, 92 patients were included, 95.7% were males with a median age of 32 years (IQR: 26-44); 65% were assessed in the outpatient clinic; median hospital length of stay was 2 days (IQR: 0) and 7.6% required admission to the intensive care unit; 75% had focal onset epilepsy, 63.04% with undetermined etiology 31.52% with structural causes. Polytherapy was found in 53.3%, valproic acid being the most frequently used antiseizure medication in 59.78%; lack of adherence was reported in 15.22% and inadequate seizure control in 81.52%; status epilepticus occurred in 5.34%. A total of 31 EEG recordings and 53 brain images were performed, of which, 29% and 39.62%, respectively, were abnormal. Non-epileptic paroxysmal events were diagnosed in 5.34%, while organic or psychiatric comorbidities were found in 25%, and the use of psychoactive substances was documented in 17.39%. Upon discharge, 93.47% had no disability, and only 45.65% returned for outpatient follow-up. SIGNIFICANCE: The clinical profile was of men in the fourth decade of life with focal onset epilepsy characterized by high seizure frequency, most of whom were receiving antiseizure medication, with a high proportion of polytherapy. The results are a point of departure for prospective studies designed to identify points to intervene and improve healthcare for inmates with epilepsy. PLAIN LANGUAGE SUMMARY: Inmates are a vulnerable proportion of persons with epilepsy. In this group there are significant differences compared to the general population, especially with greater psychiatric comorbidity and worse control of epileptic seizures due to difficulties in accessing medical care, antiseizure medication and diagnostic tests. We found that the most characteristic population is made up of men in the fourth decade of life with a high frequency of seizures, most of whom were receiving multiple antiseizure medication This study is the first of its kind in Latin America and it is an initial approach to epilepsy in inmates.
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Anticonvulsivantes , Epilepsia , Humanos , Masculino , Estudos Transversais , Colômbia/epidemiologia , Adulto , Epilepsia/epidemiologia , Epilepsia/tratamento farmacológico , Feminino , Anticonvulsivantes/uso terapêutico , Prisioneiros/estatística & dados numéricos , Estudos de Coortes , Eletroencefalografia , Pessoa de Meia-Idade , Tempo de Internação , Adulto Jovem , Ácido Valproico/uso terapêuticoRESUMO
Heat stress is a major factor that negatively affects animal welfare and production systems. Livestock should adapt to tropical and subtropical areas and to meet this, composite breeds have been developed. This work aimed to evaluate gene expression profiles in the skin of Brangus cattle under heat stress using a case-control design, and to correlate this with skin histological characteristics. Two groups of bulls were set using rectal temperature as a criterion to define stress conditions: stressed (N = 5) and non-stressed (N = 5) groups. Skin transcriptomics was performed and correlations between breed composition, phenotypic and skin histological traits were evaluated. Results showed 4309 differentially expressed genes (P < 0.01), 2113 downregulated and 2196 upregulated. Enrichment and ontology analyses revealed 132 GO terms and 67 pathways (P < 0.01), including thermogenesis, glycolysis, gluconeogenesis, mitochondrial activity, antioxidant and immune response, and apoptosis. The identity of the terms and pathways indicated the diversity of mechanisms directed to relieve the animals' suffering, acting from simple passive mechanisms (conduction, convection and radiation) to more complex active ones (behavioural changes, evaporation, vasodilation and wheezing). Furthermore, significant differences between phenotypic and skin histological traits and correlations between pairs of traits suggested a direction towards heat dissipation processes. In this sense, number of vessels was positively correlated with number of sweat glands (P < 0.001) and both were positively correlated with zebuine genetic content (P < 0.05 and P < 0.01, respectively), gland size was positively correlated with epidermal thickness and negatively with hair length (P < 0.05), and epidermal thickness was negatively correlated with gland-epidermis distance (P < 0.0005). These results support the notion that response to heat stress is physiologically complex, producing significant changes in the expression of genes involved in several biological pathways, while the animal's ability to face it depends greatly on their skin features.
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Resposta ao Choque Térmico , Pele , Transcriptoma , Animais , Bovinos/genética , Bovinos/fisiologia , Resposta ao Choque Térmico/genética , Masculino , Pele/metabolismo , Perfilação da Expressão Gênica , Transtornos de Estresse por Calor/veterinária , Transtornos de Estresse por Calor/genética , Transtornos de Estresse por Calor/metabolismoRESUMO
OBJECTIVES: To identify differences in the mean vitamin D concentrations in samples obtained from a private laboratory in Quito and to explore their relationship with the pre-pandemic and pandemic periods spanning from 2018 to 2022. DESIGN: A combination of an interrupted time series design and a retrospective cross-sectional approach. SETTING AND PARTICIPANTS: The study involved 9285 participants who had their 25-hydroxyvitamin D (25(OH)D) levels tested at a well-known private laboratory in Quito, Ecuador, from 2018 to 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: The 25(OH)D levels were analysed and assessed for correlations with age, and the year the measurements were taken. RESULTS: The mean 25(OH)D level was 27.53 ng/mL (± 14.11). Approximately 68.8% of participants had serum 25(OH)D levels of less than 30 ng/mL, and 0.6% showed potential harm from excess 25(OH)D, with levels over 100 ng/mL. The analysis indicated a significant monthly increase of 0.133 units in 25(OH)D levels (p=0.006). However, the period after March 2020, compared with before, saw a non-significant decrease of 1.605 units in mean 25(OH)D levels (p=0.477). CONCLUSIONS: The study's findings indicate a significant prevalence of 25(OH)D deficiency, underscoring the necessity for preventative measures. However, the increasing trend in high 25(OH)D levels is concerning, emphasising the importance of prudent vitamin D supplement prescriptions and public education against self-medication. For efficient resource allocation and targeting of those with higher risks, it may be advantageous to concentrate vitamin D testing on specific population groups.
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Análise de Séries Temporais Interrompida , Deficiência de Vitamina D , Vitamina D , Vitamina D/análogos & derivados , Humanos , Equador/epidemiologia , Estudos Transversais , Vitamina D/sangue , Feminino , Adulto , Masculino , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/sangue , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Estudos Retrospectivos , Idoso , Criança , Pré-Escolar , Cidades , COVID-19/epidemiologia , COVID-19/sangue , LactenteRESUMO
The aim of this study was to investigate the growth and development of animals produced from demi-embryos and compare them with whole embryos from fetus to adult life. To achieve this, calves produced from fresh demi-embryos and whole embryos were individually transferred and monitored from 60 days of pregnancy until slaughter at 550 days. Ultrasound scans were conducted on fetuses at 60 and 90 days to evaluate the biparietal, abdominal, umbilical cord, orbital, and aorta diameters. Subsequently, morphological traits of newborn calves were measured at 0, 7, and 21 days (N = 18). Live weight was recorded at birth, weaning, and every 30 days thereafter until slaughter at 550 days. The growth curve of each group was modeled using logistic regression, and the factors of the respective functions were compared. As early as 60 days of pregnancy, ultrasound evaluations revealed no morphometric differences between fetuses produced from demi-embryos and those from whole embryos. This lack of differentiation persisted in the morphometric evaluations of newborns up to 21 days of age, as well as in live weight and the growth curve from birth to slaughter. Moreover, there were no significant differences between the groups in terms of rib eye area and fat thickness evolution. Consequently, individuals from demi-embryos exhibited no discernible disparities to those whole embryos in growth and development from 60 days of gestation, through birth, and into adulthood.
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Animais Recém-Nascidos , Animais , Bovinos/embriologia , Feminino , Gravidez , Desenvolvimento Fetal/fisiologia , Transferência Embrionária/veterinária , Ultrassonografia Pré-Natal/veterinária , Fertilização in vitro/veterinária , Desenvolvimento Embrionário/fisiologiaRESUMO
One of the limitations of implementing animal breeding programs in small-scale or extensive production systems is the lack of production records and genealogical records. In this context, molecular markers could help to gain information for the breeding program. This study addresses the inclusion of molecular data into traditional genetic evaluation models as a random effect by molecular pedigree reconstruction and as a fixed effect by Bayesian clustering. The methods were tested for lactation curve traits in 14 dairy goat herds with incomplete phenotypic data and pedigree information. The results showed an increment of 37.3% of the relationships regarding the originals with MOLCOAN and clustering into five genetic groups. Data leads to estimating additive variance, error variance, and heritability with four different models, including pedigree and molecular information. Deviance Information Criterion (DIC) values demonstrate a greater fitting of the models that include molecular information either as fixed (genetic clusters) or as random (molecular matrix) effects. The molecular information of simple markers can complement genetic improvement strategies in populations with little information.
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Cabras , Lactação , Feminino , Animais , Linhagem , Teorema de Bayes , Lactação/genética , Fenótipo , Cabras/genética , Modelos Genéticos , LeiteRESUMO
BACKGROUND: Individuals with Parkinson's Disease (IwPD) often fail to adjust their voice in different situations, without awareness of this limitation. Clinicians use self-report questionnaires that are typically designed for individuals with General Voice Disorders (GVD) in the vocal assessment of IwPD. However, these instruments may not consider that IwPD have a reduced self-perception of their vocal deficits. This study aimed to compare self-reported vocal symptoms and voice loudness between IwPD and GVD. METHODS: 28 IwPD and 26 with GVD completed the Voice Symptom Scale (VoiSS) questionnaire to evaluate their voice self-perception. Vocal loudness (dB) was also assessed. Univariate and multivariate analyses were used to compare the outcomes from these measures between the two groups. Principal Component Analysis and Hierarchical Clustering Analysis were applied to explore data patterns related to voice symptoms. RESULTS: IwPD reported significantly fewer vocal symptoms than those with GVD in all VoiSS questionnaire domains. Multivariate principal component analysis found no significant correlations between VoiSS scores and participant similarities in voice measures. Despite experiencing hypophonia, IwPD scored lower in all VoiSS domains but still fell in the healthy voice range. Hierarchical Clustering Analysis grouped participants into three distinct categories, primarily based on age, vocal loudness, and VoiSS domain scores, distinguishing between PD and GVD individuals. CONCLUSIONS: IwPD reported fewer vocal symptoms than GVD. The voice self-assessment seems to be unreliable to assess vocal symptoms in IwPD, at least regarding loudness. New self-report instruments tailored to PD individuals are needed due to their particular voice characteristics.
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Doença de Parkinson , Distúrbios da Voz , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Masculino , Feminino , Idoso , Distúrbios da Voz/etiologia , Distúrbios da Voz/diagnóstico , Distúrbios da Voz/fisiopatologia , Pessoa de Meia-Idade , Autoavaliação (Psicologia) , Inquéritos e Questionários , Autoavaliação Diagnóstica , Autorrelato , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE. METHODS: The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding. RESULTS: In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group. CONCLUSION: The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.
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Anticoagulantes , Dalteparina , Inibidores do Fator Xa , Hemorragia , Neoplasias , Pirazóis , Piridonas , Recidiva , Tromboembolia Venosa , Humanos , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Dalteparina/efeitos adversos , Dalteparina/uso terapêutico , Hemorragia/induzido quimicamente , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Feminino , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Masculino , Pessoa de Meia-Idade , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fatores de Tempo , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Resultado do Tratamento , AdultoRESUMO
INTRODUCTION: We aimed to determine if advanced BRAF-mutant NSCLC has a higher thromboembolic events (TEE) rate than the expected. METHODS: Between 2008 and 2021, 182 patients with BRAF-mutant advanced NSCLC (BRAF V600E, n = 70; BRAF non-V600E, n = 112) were retrospectively identified from 18 centers in Spain. Patients received chemotherapy (n = 147), immunotherapy (n = 69), targeted therapy (n = 42), and immunotherapy + chemotherapy (n = 26). RESULTS: Incidence rate of TEE was 26.4 % (95%CI: 19.9 %-32.9 %). A total of 72 TEE were documented among 48 patients, as 18 patients (37.5 %) developed more than one event. Median time to TEE onset was 2 months, 69 % of TEE occurred in the peridiagnostic period (+/- 90 days from cancer diagnosis), and in 16 pts. (33 %) TEE was the form of lung cancer presentation. Although most TEE were only venous (82 %; PE, n = 33; DVT, n = 16), arterial events were reported in 31 % and occurred earlier, or TEE presented in atypical locations (13.9 %). TEE were related to high hospitalization rate (59 %), recurrence (23 %), and mortality (10.4 %) despite appropriate anticoagulant/antiaggregant treatment. Median OS in patients without-TEE was 19.4 months (95%CI: 4.6-34.1), and significantly shorter in patients with arterial-TEE vs venous-TEE vs both of them: 9.9 months (95%CI: 0-23.5) vs 41.7 months (95%CI: 11.3-72.2 m) vs 2.7 months (95%CI: 2.1-3.3), p = 0.001. Neither clinical or molecular features (BRAF V600E/non-V600E), nor cancer treatment was associated to TEE occurrence. Khorana score underperformed to predict thrombosis at cancer diagnosis, as only 19.2 % of patients were classified as high-risk. CONCLUSIONS: Thrombotic events represent a new clinical feature of BRAF-mutant lung cancer. Patients with almost a 30 % incidence of TEE should be offered systematic anticoagulation.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Tromboembolia , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Incidência , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Tromboembolia/etiologia , Tromboembolia/genéticaRESUMO
Introducción: El personal sanitario de emergencia se encuentra extremadamente expuesto a situaciones estresantes. El trastorno de estrés post traumático es una patología emergente en el personal sanitario durante los últimos años y es reconocida únicamente como enfermedad mental de carácter laboral. Objetivos: Establecer la prevalencia y síntomas asociados al trastorno de estrés post traumático obtenidos del tamizaje con lista de verificación del trastorno de estrés post traumático para DSM-5 aplicado al personal sanitario de la unidad de emergencia de un hospital terciario durante la pandemia por SARS-CoV-2. Material y Métodos: Estudio retrospectivo, de cohorte observacional, transversal, unicéntrico en los (5) estamentos profesional y no profesional, entre el periodo abril 2021 a diciembre 2022. Resultados: Participaron 241 funcionarios (69.45% de esta unidad de emergencia). Donde, un 19.9% presentó síntomas de estrés post traumático, desagregados en; 36.0% auxiliar de servicio, 26.7% kinesiología, 26.1% técnico en enfermería nivel superior, 13.3% enfermería y un 9.8% médicos. La mayor sintomatología correspondió a recuerdos intrusivos, malestar psicológico intenso, comportamiento imprudente-autodestructivo e hipervigilancia. Asimismo, a mayor antigüedad laboral y los estamentos auxiliares, kinesiología incrementan la probabilidad de puntaje alto en el tamizaje (variables de riesgo), mientras que a mayor edad disminuye (variable protector). El 29.46% fue vinculado a una atención en salud mental posterior al tamizaje. Discusión y conclusión: El estudio identificó y caracterizó a un grupo representativo de la unidad de emergencia presentó síntomas de estrés post traumático durante la pandemia SARS-CoV-2. Una red de apoyo psicológico permanente podría ser una intervención efectiva de promoción en salud mental (AU)
Introduction: Emergency medical personnel are extremely exposed to stressful situations. Post-traumatic stress disorder is an emerging pathology in health personnel in recent years and is only recognized as a mental illness of an occupational nature. Objective: To establish the prevalence and symptoms associated with post-traumatic stress disorder obtained from the screening with the checklist of post-traumatic stress disorder for DSM-5 applied to health personnel from the emergency unit of a tertiary hospital during the SARS-CoV-pandemic. 2. Material and Method: Retrospective, observational, cross-sectional, single-center study in the (5) professional and non-professional levels, between the period April 2021 to December 2022. Results: 241 officials participated (69.45% of this emergency unit). Where, 19.9% presented symptoms of post-traumatic stress, broken down into 36.0% service assistant, 26.7% kinesiology, 26.1% higher level nursing technician, 13.3% nursing and 9.8% doctors. The greatest symptomatology corresponded to intrusive memories, intense psychological discomfort, reckless-self-destructive behavior and hypervigilance. Likewise, the higher the job seniority and the auxiliary levels, kinesiology increase the probability of a high score in the screening (risk variables), while at an older age it decreases (protective variable). 29.46% were linked to mental health care after the screening. Discussion: The study identified and characterized a representative group from the emergency unit who presented post-traumatic stress symptoms during the SARS-CoV-2 pandemic. A permanent psychological support network could be an effective promotion intervention in mental health. (AU)
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Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/epidemiologia , /psicologia , Saúde Mental , Estudos Retrospectivos , Estudos Transversais , Estudos de Coortes , Prevalência , Pessoal de Saúde/psicologia , ChileRESUMO
BACKGROUND: Apixaban and rivaroxaban are two direct-acting oral anticoagulants (DOACs) recommended for thromboprophylaxis in cancer patients treated with chemotherapy in an ambulatory setting. We aimed to assess the cost-utility of thromboprophylaxis with apixaban and rivaroxaban vs no thromboprophylaxis in ambulatory cancer patients starting chemotherapy with an intermediate-to-high risk of venous thromboembolism (VTE), Khorana score ≥ 2 points. METHODS: A cost-effectiveness analysis was performed from the perspective of Spain's National Health System (NHS) using an analytical decision model in the short-term (180 days) and a Markov model in the long-term (5 years). Transition probabilities were obtained from randomized, double-blind, placebo-controlled clinical trials of apixaban and rivaroxaban in adult ambulatory patients with cancer at risk for VTE, treated with chemotherapy (AVERT and CASSINI trials). The costs (2,021) were taken from Spanish sources. The utilities of the model were obtained through the EQ-5D questionnaire. Deterministic (base case) and probabilistic (second-order Monte Carlo simulation) analyses were conducted. RESULTS: In the probabilistic sensitivity analysis, apixaban generated a cost per patient of 1,082 ± 187, with a 95% confidence interval (CI) of 713-1,442, while no prophylaxis produced a cost per patient of 1,146 ± 218, with a 95% CI of 700-1,491, with a saving of 64 per patient and a gain of 0.008 QALYs. Likewise, rivaroxaban provided a cost per patient of 993 ± 133, with a 95% CI of 748-1,310, while no prophylaxis produced a cost per patient of 872 ± 152, with a 95% CI of 602-1,250, with an additional expense of 121 per patient and a gain of 0.008 QALYs. CONCLUSIONS: In thromboprophylaxis of cancer patients, the use of apixaban and rivaroxaban generated similar costs compared to non-prophylaxis, without the difference found being statistically significant, with a clinically insignificant QALY gain.
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Neoplasias , Tromboembolia Venosa , Adulto , Humanos , Anticoagulantes , Análise Custo-Benefício , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Espanha , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Anti-cancer treatment is considered an independent risk factor for emergent bleeding during anticoagulant treatment in patients with cancer-associated thrombosis. This increased bleeding risk is perceived as major concern particularly when tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial derived growth factor receptor (VEGFR-TKIs) are co-administered with anticoagulants. We evaluated the effects of the combined administration of a VEGF-TKI and the oral direct anticoagulant (apixaban) or the low-molecular weight-heparin dalteparin in a sub-analysis of the Caravaggio study in patients with a diagnosis of cancer patients with venous thromboembolism. The rate of major bleeding was 4.2% in the 668 patients who received any type of anti-cancer treatment and 3.5% in the 487 patients who did not receive any anti-cancer treatment. The relative risk for patients treated with a VEGF-TKI was 1.58 (95% CI: 0.69-3.68), compared to patients treated with anticancer agents other than a VEGF-TKI and 1.73 (95% CI: 0.73-4.07) compared to patients who did not receive any anticancer treatment. The administration of a VGEF-TKI did not have any impact on the recurrence rate of venous thromboembolism. We observed a numerically not statistically significant increase in major bleeding events in patients on concurrent VEGF-TKI and therapeutic anticoagulation with no excess in those who received apixaban. Further prospective well-designed studies are needed to evaluate whether the concomitant administration of VGEF-TKI and anticoagulant agents may result in an increase of bleeding in patients with a diagnosis of cancer treated for venous thromboembolism.
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75Cancer research has found in the recent years a formidable ally in liquid biopsy, a noninvasive technique that allows the study of circulating tumor cells (CTCs) and biomolecules involved in the dynamics of cancer spread like cell-free nucleid acids or tumor-derived extracellular vesicles. However, single-cell isolation of CTCs with high viability for further genetic, phenotypic, and morphological characterization remains a challenge. We present a new approach for single CTC isolation in enriched blood samples using a liquid laser transfer (LLT) process, adapted from standard laser direct write techniques. In order to completely preserve the cells from direct laser irradiation, we used an ultraviolet laser to produce a blister-actuated laser-induced forward transfer process (BA-LIFT). Using a plasma-treated polyimide layer for blister generation, we completely shield the sample from the incident laser beam. The optical transparency of the polyimide allows direct cell targeting using a simplified optical setup, in which the laser irradiation module, standard imaging, and fluorescence imaging share a common optical path. Peripheral blood mononuclear cells (PBMCs) were identified by fluorescent markers, while target cancer cells remained unstained. As a proof of concept, we were able to isolate single MDA-MB-231 cancer cells using this negative selection process. Unstained target cells were isolated and culture while their DNA was sent for single-cell sequencing (SCS). Our approach appears to be an effective approach to isolate single CTCs, preserving cell characteristics in terms of cell viability and potential for further SCS.
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INTRODUCTION: Patients with cancer and venous thromboembolism (VTE) show a high risk of VTE recurrence during anticoagulant treatment. This study aimed to develop a predictive model to assess the risk of VTE recurrence within 6 months at the moment of primary VTE diagnosis in these patients. MATERIALS AND METHODS: Using the EHRead® technology, based on Natural Language Processing (NLP) and machine learning (ML), the unstructured data in electronic health records from 9 Spanish hospitals between 2014 and 2018 were extracted. Both clinically- and ML-driven feature selection were performed to identify predictors for VTE recurrence. Logistic regression (LR), decision tree (DT), and random forest (RF) algorithms were used to train different prediction models, which were subsequently validated in a hold-out data set. RESULTS: A total of 16,407 anticoagulated cancer patients with diagnosis of VTE were identified (54.4 % male and median age 70). Deep vein thrombosis, pulmonary embolism and metastases were observed in 67.2 %, 26.6 %, and 47.7 % of the patients, respectively. During the study follow-up, 11.4 % of the patients developed a recurrent VTE, being more frequent in patients with lung cancer. Feature selection and model training based on ML identified primary pulmonary embolism, deep vein thrombosis, metastasis, adenocarcinoma, hemoglobin and serum creatinine levels, platelet and leukocyte count, family history of VTE, and patients' age as predictors of VTE recurrence within 6 months of VTE diagnosis. The LR model had an AUC-ROC (95 % CI) of 0.66 (0.61, 0.70), the DT of 0.69 (0.65, 0.72) and the RF of 0.68 (0.63, 0.72). CONCLUSIONS: This is the first ML-based predictive model designed to predict 6-months VTE recurrence in patients with cancer. These results hold great potential to assist clinicians to identify the high-risk patients and improve their clinical management.
Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Humanos , Idoso , Lactente , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Anticoagulantes/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Aprendizado de Máquina , Recidiva , Fatores de RiscoRESUMO
Herpes simplex virus type 2 (HSV-2) is a human infectious agent with significant impact on public health due to its high prevalence in the population and its ability to elicit a wide range of diseases, from mild to severe. Although several antiviral drugs, such as acyclovir, are currently available to treat HSV-2-related clinical manifestations, their effectiveness is poor. Therefore, the identification and development of new antiviral drugs against HSV-2 is necessary. Seaweeds are attractive candidates for such purposes because they are a vast source of natural products due to their highly diverse compounds, many with demonstrated biological activity. In this study, we evaluated the in vitro antiviral potential of red algae extracts obtained from Agarophyton chilense, Mazzaella laminarioides, Porphyridium cruentum, and Porphyridium purpureum against HSV-2. The phycocolloids agar and carrageenan obtained from the macroalgae dry biomass of A. chilense and M. laminarioides and the exopolysaccharides from P. cruentum and P. purpureum were evaluated. The cytotoxicity of these extracts and the surpluses obtained in the extraction process of the agar and carrageenans were evaluated in human epithelial cells (HeLa cells) in addition to their antiviral activity against HSV-2, which were used to calculate selectivity indexes (SIs). Several compounds displayed antiviral activity against HSV-2, but carrageenans were not considered as a potential antiviral therapeutic agent when compared to the other algae extracts with a SI of 23.3. Future assays in vivo models for HSV-2 infection should reveal the therapeutic potential of these algae compounds as new antivirals against this virus.
RESUMO
Venous thromboembolism (VTE) is a common and impactful complication of cancer. Several clinical prediction rules have been devised to estimate the risk of a thrombotic event in this patient population, however they are associated with limitations. We aimed to develop a predictive model of cancer-associated VTE using machine learning as a means to better integrate all available data, improve prediction accuracy and allow applicability regardless of timing for systemic therapy administration. A retrospective cohort was used to fit and validate the models, consisting of adult patients who had next generation sequencing performed on their solid tumor for the years 2014 to 2019. A deep learning survival model limited to demographic, cancer-specific, laboratory and pharmacological predictors was selected based on results from training data for 23,800 individuals and was evaluated on an internal validation set including 5,951 individuals, yielding a time-dependent concordance index of 0.72 (95% CI = 0.70-0.74) for the first 6 months of observation. Adapted models also performed well overall compared to the Khorana Score (KS) in two external cohorts of individuals starting systemic therapy; in an external validation set of 1,250 patients, the C-index was 0.71 (95% CI = 0.65-0.77) for the deep learning model vs 0.66 (95% CI = 0.59-0.72) for the KS and in a smaller external cohort of 358 patients the C-index was 0.59 (95% CI = 0.50-0.69) for the deep learning model vs 0.56 (95% CI = 0.48-0.64) for the KS. The proportions of patients accurately reclassified by the deep learning model were 25% and 26% respectively. In this large cohort of patients with a broad range of solid malignancies and at different phases of systemic therapy, the use of deep learning resulted in improved accuracy for VTE incidence predictions. Additional studies are needed to further assess the validity of this model.
RESUMO
Up to 15-20% of cancer patients experience one or more episodes of venous thromboembolism during cancer disease. Approximately 80% of all cancer-associated venous thromboembolic events occur in non-hospitalized patients. Routine thromboprophylaxis for outpatients with cancer who start new anticancer treatment is currently not recommended by the international guidelines due to the high heterogeneity of these patients in terms of VTE or bleeding risks, the difficulties in selecting patients at high risk, and the uncertainty of duration of prophylaxis. Although the international guidelines endorsed the Khorana score for estimating the thrombotic risk in ambulatory cancer patients, the discriminatory performance of this score is not completely convincing and varies according to the cancer type. Consequently, a minority of ambulatory patients with cancer receive an accurate screening for primary prophylaxis of VTE. The aim of this review is to provide support to physicians in identifying those ambulatory patients with cancer for whom thromboprophylaxis should be prescribed and those that should not be candidate to thromboprophylaxis. In absence of high bleeding risk, primary thromboprophylaxis should be recommended in patients with pancreatic cancer and, probably, in patients with lung cancer harboring ALK/ROS1 translocations. Patients with upper gastrointestinal cancers are at high risk of VTE, but a careful assessment of bleeding risk should be made before deciding on antithrombotic prophylaxis. Primary prevention of VTE is not recommended in cancer patients at increased risk of bleeding as patients with brain cancer, with moderate-to-severe thrombocytopenia or severe renal impairment.