Asunto(s)
Leucemia Mieloide Aguda , Proteína Tumoral p73 , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/genética , Pronóstico , Proteína Tumoral p73/genética , Proteína Tumoral p73/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Anciano , Regulación Leucémica de la Expresión Génica , AdultoRESUMEN
PURPOSE: Coronary artery calcium (CAC) is a frequent incidental finding on computed tomography pulmonary angiogram (CTPA) in the evaluation of pulmonary embolism (PE) in the emergency department (ED); however, its prognostic value is unclear. In this study, we interrogate the prognostic value of CAC identified on CTPA in predicting adverse outcomes in the evaluation of PE in the ED. MATERIALS AND METHODS: In this retrospective cohort study, we identified 610 patients presenting to the ED in 2013 and evaluated with CTPA for suspected PE. Ordinal CAC scores were evaluated as absent (0), mild (1), moderate (2), or severe (3) in each of the 4 main coronary arteries. Composite CAC scores were subsequently compared against adverse clinical outcomes, defined as intensive care unit admission, hospital stay longer than 72 hours, or death during hospital course or at 6-month follow-up, using univariate and multivariate logistic regression analyses. Relevant exclusion criteria included a history of cardiovascular disease. RESULTS: In all, 365 patients met the inclusion criteria (231 women, mean age 56±16 y) with 132 patients (36%) having some degree of CAC and 16 (4%) having severe CAC. Known malignancy was present in 151 (41%) patients and composite adverse clinical outcomes were observed in 98 patients (32%). Age, presence of acute PE, malignancy, and presence of CAC were significant predictors of adverse outcomes on both univariate and multivariate analyses. CAC was not an independent predictor of short-term adverse outcomes on multivariate analysis ( P =0.06) when all patients were considered. However, when patients with known malignancy were excluded, CAC was an independent predictor of short-term adverse outcomes (odds ratio=2.5, confidence interval=1.1-5.5, P =0.03) independent of age and presence of PE. CONCLUSION: The presence of CAC on CT PA was predictive of adverse outcomes in patients without known cardiac disease presenting to the ED with suspected PE.
Asunto(s)
Neoplasias , Embolia Pulmonar , Adulto , Anciano , Angiografía , Calcio , Angiografía por Tomografía Computarizada/métodos , Vasos Coronarios , Servicio de Urgencia en Hospital , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Embolia Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
The objective of the study was to assess functional outcomes and quality of life of patients treated for tibial tubercle avulsion fractures (TTAFs). Retrospective study of patients under 18 years of age treated from June 2011 to May 2018. Demographic data included age, gender, mechanism of injury, side, fracture classification, associated injuries, predisposing factors, and type of treatment. Clinical results included knee range of motion, pain, return to sports, overall satisfaction, functional outcomes, and complications. At final follow-up, Tegner Lysholm Knee Scoring Scale, and Kidscreen-10 were applied. Ten patients were included, all males, with a median age of 15 years. Mechanism of injury: football (three patients), basketball (two patients), running (two patients), handball (one patient), gymnastics (one patient), and fall (one patient). Nine were treated surgically with reduction and fixation with cannulated screws or Kirschner wires, plus treatment of associated injuries (three patellar tendon avulsions, one contralateral proximal tibia epiphyseal fracture, and two prophylactic fasciotomies). One patient developed mild recurvatum and two presented minor decreased knee flexion. Eight patients returned to their previous level of sports activity. Median Tegner Lysholm Knee Score was 100/100 and Kidscreen-10 was 50/50. With appropriate treatment, nearly 100% of TTAFs have good functional outcomes and low impact on quality of life.
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Fracturas por Avulsión , Fracturas de la Tibia , Adolescente , Fijación Interna de Fracturas , Fracturas por Avulsión/diagnóstico por imagen , Fracturas por Avulsión/cirugía , Humanos , Masculino , Calidad de Vida , Estudios Retrospectivos , Tibia , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/cirugía , Resultado del TratamientoRESUMEN
In the fight against the Varroa destructor mite, selective breeding of honey bee (Apis mellifera L.) populations that are resistant to the parasitic mite stands as a sustainable solution. Selection initiatives indicate that using the suppressed mite reproduction (SMR) trait as a selection criterion is a suitable tool to breed such resistant bee populations. We conducted a large European experiment to evaluate the SMR trait in different populations of honey bees spread over 13 different countries, and representing different honey bee genotypes with their local mite parasites. The first goal was to standardize and validate the SMR evaluation method, and then to compare the SMR trait between the different populations. Simulation results indicate that it is necessary to examine at least 35 single-infested cells to reliably estimate the SMR score of any given colony. Several colonies from our dataset display high SMR scores indicating that this trait is present within the European honey bee populations. The trait is highly variable between colonies and some countries, but no major differences could be identified between countries for a given genotype, or between genotypes in different countries. This study shows the potential to increase selective breeding efforts of V. destructor resistant populations.
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Leucemia Promielocítica Aguda/sangre , Leucemia Promielocítica Aguda/mortalidad , Adolescente , Adulto , Anciano , Niño , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Promielocítica Aguda/terapia , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Neoplasia Residual , Tasa de SupervivenciaRESUMEN
Pinewood nematode (PWN), Bursaphelenchus xylophilus, is the causal agent of pine wilt disease, a serious threat to global forest populations of conifers, especially Pinus spp. A time-course study of the essential oils (EOs) of 2-year-old Pinus halepensis, Pinus pinaster, Pinus pinea and Pinus sylvestris following inoculation with the PWN was performed. The constitutive and nematode inoculation induced EOs components were analyzed at both the wounding or inoculation areas and at the whole plant level. The enantiomeric ratio of optically active main EOs components was also evaluated. External symptoms of infection were observed only in P. pinaster and P. sylvestris 21 and 15 days after inoculation, respectively. The EO composition analysis of uninoculated and unwounded plants revealed the occurrence of chemotypes for P. pinaster, P. halepensis and P. sylvestris, whereas P. pinea showed a homogenous EO composition. When whole plants were evaluated for EO and monoterpene hydrocarbon enantiomeric chemical composition, no relevant qualitative and quantitative differences were found. Instead, EO analysis of inoculated and uninoculated wounded areas revealed an increase of sesquiterpenes and diterpenic compounds, especially in P. pinea and P. halepensis, comparatively to healthy whole plants EOs.
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Aceites Volátiles/análisis , Pinus/química , Animales , Monoterpenos/análisis , Nematodos/patogenicidad , Infecciones por Nematodos/metabolismo , Aceites Volátiles/química , Enfermedades de las Plantas/parasitología , Terpenos/análisisRESUMEN
The KMT2E (MLL5) gene encodes a histone methyltransferase implicated in the positive control of genes related to haematopoiesis. Its close relationship with retinoic acid-induced granulopoiesis suggests that the deregulated expression of KMT2E might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of KMT2E expression on the prognosis of 121 APL patients treated with ATRA and anthracycline-based chemotherapy. Univariate analysis showed that complete remission (P = 0·006), 2-year overall survival (OS) (P = 0·005) and 2-year disease-free survival (DFS) rates (P = 0·037) were significantly lower in patients with low KMT2E expression; additionally, the 2-year cumulative incidence of relapse was higher in patients with low KMT2E expression (P = 0·04). Multivariate analysis revealed that low KMT2E expression was independently associated with lower remission rate (odds ratio [OR]: 7·18, 95% confidence interval [CI]: 1·71-30·1; P = 0·007) and shorter OS (hazard ratio [HR]: 0·27, 95% CI: 0·08-0·87; P = 0·029). Evaluated as a continuous variable, KMT2E expression retained association with poor remission rate (OR: 10·3, 95% CI: 2·49-43·2; P = 0·001) and shorter survival (HR: 0·17, 95% IC: 0·05-0·53; P = 0·002), while the association with DFS was of marginal significance (HR: 1·01; 95% CI: 0·99-1·02; P = 0·06). In summary, low KMT2E expression may predict poor outcome in APL patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proteínas de Unión al ADN/metabolismo , Leucemia Promielocítica Aguda/tratamiento farmacológico , Adolescente , Adulto , Antraciclinas/administración & dosificación , Estudios de Casos y Controles , Femenino , Humanos , Leucemia Promielocítica Aguda/metabolismo , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Tretinoina/administración & dosificación , Adulto JovenRESUMEN
TP73 encodes for two proteins: full-length TAp73 and DeltaNp73, which have little transcriptional activity and exert dominant-negative function towards TP53 and TAp73. We compared TATP73 and DeltaNTP73 expression in acute myeloid leukaemia (AML) samples and normal CD34(+) progenitors. Both forms were more highly expressed in leukaemic cells. Amongst AML blasts, TATP73 was more expressed in AML harbouring the recurrent genetic abnormalities (RGA): PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11, whereas higher DeltaNTP73 expression was detected in non-RGA cases. TP53 expression did not vary according to DeltaNTP73/TATP73 expression ratio. Leukaemic cells with higher DeltaNTP73/TATP73 ratios were significantly more resistant to cytarabine-induced apoptosis.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Citarabina/uso terapéutico , Proteínas de Unión al ADN/genética , Genes p53/genética , Leucemia Mieloide Aguda/genética , Proteínas Nucleares/genética , Proteínas Supresoras de Tumor/genética , Apoptosis/efectos de los fármacos , Aberraciones Cromosómicas , Resistencia a Antineoplásicos , Expresión Génica , Reordenamiento Génico , Humanos , Reacción en Cadena de la Polimerasa , RecurrenciaRESUMEN
The use of all trans-retinoic acid (ATRA) is the basis of treatment of acute promyelocytic leukemia (APL) and represents the paradigm of differentiation therapy. In general, ATRA is well-tolerated but may be associated with a potentially lethal side-effect, referred to as retinoic acid or differentiation syndrome (DS). The cellular and molecular mechanisms of DS are poorly understood and involve changes in the adhesive qualities and cytokine secretion of leukemic cells during ATRA-induced differentiation. As leukocyte extravasation is a key event in DS pathogenesis, we analyzed the association between the polymorphisms at Exon 4 (G241R) and Exon 6 (E469K) of ICAM-1 and Exon 3 (L125V) of PECAM-1 genes with DS development in APL patients treated with ATRA and anthracyclines. DS was diagnosed in 23/127 (18.1%) APL patients at an average of 11.5 days after the start of ATRA. All patients presented respiratory distress associated with increased ground-glass opacity in chest radiographies. Other accompanying symptoms were: fever not attributable to infection (65.2%), generalized edema (37.5%), weight gain (37.5%), and impairment of renal function (8.6%). We detected an association between development of DS and the AA genotype at Codon 469 of ICAM-1 (odds ratio of 3.5; 95% confidence interval: 1.2-10.2). Conversely, no significant association was detected between G241R or L125V polymorphisms at Exon 4 of ICAM-1 and Exon 3 of PECAM-1, respectively. Our results suggest that susceptibility to DS in APL patients may be influenced by genetic variation in adhesion molecule loci.