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Clostridioides difficile (C. difficile) is widely distributed in the intestinal tract of humans, animals, and in the environment. It is the most common cause of diarrhea associated with the use of antimicrobials in humans and among the most common healthcare-associated infections worldwide. Its pathogenesis is mainly due to the production of toxin A (TcdA), toxin B (TcdB), and a binary toxin (CDT), whose genetic variants may be associated with disease severity. We studied genetic diversity in 39 C. difficile isolates from adults and children attended at two Mexican hospitals, using different gene and genome typing methods and investigated their association with in vitro expression of toxins. Whole-genome sequencing in 39 toxigenic C. difficile isolates were used for multilocus sequence typing, tcdA, and tcdB typing sequence type, and phylogenetic analysis. Strains were grown in broth media, and expression of toxin genes was measured by real-time PCR and cytotoxicity in cell-culture assays. Clustering of strains by genome-wide phylogeny matched clade classification, forming different subclusters within each clade. The toxin profile tcdA+/tcdB+/cdt+ and clade 2/ST1 were the most prevalent among isolates from children and adults. Isolates presented two TcdA and three TcdB subtypes, of which TcdA2 and TcdB2 were more prevalent. Prevalent clades and toxin subtypes in strains from children differed from those in adult strains. Toxin gene expression or cytotoxicity was not associated with genotyping or toxin subtypes. In conclusion, genomic and phenotypic analysis shows high diversity among C. difficile isolates from patients with healthcare-associated diarrhea. IMPORTANCE: Clostridioides difficile is a toxin-producing bacterial pathogen recognized as the most common cause of diarrhea acquired primarily in healthcare settings. This bacterial species is diverse; its global population has been divided into five different clades using multilocus sequence typing, and strains may express different toxin subtypes that may be related to the clades and, importantly, to the severity and progression of disease. Genotyping of children strains differed from adults suggesting toxins might present a reduced toxicity. We studied extensively cytotoxicity, expression of toxins, whole genome phylogeny, and toxin typing in clinical C. difficile isolates. Most isolates presented a tcdA+/ tcdB+/cdt+ pattern, with high diversity in cytotoxicity and clade 2/ST1 was the most prevalent. However, they all had the same TcdA2/TcdB2 toxin subtype. Advances in genomics and bioinformatics tools offer the opportunity to understand the virulence of C. difficile better and find markers for better clinical use.
Assuntos
Toxinas Bacterianas , Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Diarreia , Variação Genética , Tipagem de Sequências Multilocus , Filogenia , Humanos , Clostridioides difficile/genética , Clostridioides difficile/classificação , Clostridioides difficile/isolamento & purificação , Diarreia/microbiologia , Diarreia/epidemiologia , México/epidemiologia , Criança , Toxinas Bacterianas/genética , Adulto , Infecções por Clostridium/microbiologia , Infecções por Clostridium/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Proteínas de Bactérias/genética , Enterotoxinas/genética , Masculino , Pré-Escolar , Feminino , Prevalência , Adolescente , Sequenciamento Completo do Genoma , Fenótipo , Genoma Bacteriano/genética , Lactente , Pessoa de Meia-Idade , GenômicaRESUMO
OBJECTIVE: To describe the main retinal alterations detected by non-mydriatic retinal camera screening and to evaluate factors related to referral to ophthalmology in a population at high cardiovascular risk in Palmira, Colombia. MATERIALS AND METHODS: Cross-sectional observational study, which included 11,983 photographic imaging records of patients with hypertension and diabetes mellitus from Gesencro's S.A.S. comprehensive chronic disease care program between 2018 and 2020. Risk factors associated to referral to ophthalmology were evaluated with logistic regression, and crude and adjusted ORs (odds ratios) were obtained. RESULTS: A total of 11,880 records were analyzed; 67.7±12years old, and 69.5% were women. Among the retinal alterations were patients with diabetic retinopathy classified as more than mild in 10% and gradeI hypertensive retinopathy in 54.9% right eye, 51.9% left eye. Macular edema was also identified. Only 2069 patients (17.4%) required referral to ophthalmology, and for imaging control 82.6%. In the multivariate analysis, the risk factors associated with the probability of being referred were male gender, age 60years and older, glycosylated hemoglobin out-of-target, advanced chronic kidney disease and the microalbumin-to-creatinine ratio moderate to severely elevated. CONCLUSION: This study makes it possible to determine the importance of screening with a non-mydriatic retinal camera in patients at high cardiovascular risk to detect retinal abnormalities and assess risk factors associated with referral to ophthalmology. Early documentation of ocular compromise in these patients could prevent and avoid visual impairment and blindness.
Assuntos
Doenças Cardiovasculares , Retinopatia Diabética , Oftalmologia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Oftalmologia/métodos , Estudos Transversais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Programas de Rastreamento/métodos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Fatores de Risco de Doenças Cardíacas , Encaminhamento e ConsultaRESUMO
Objetivo: el trastorno de déficit de atención e hiperactividad (TDAH) ha sido descrito como el trastorno del neurodesarrollo más común en la infancia. Esta condición se asocia a un significativo deterioro en calidad de vida, múltiples comorbilidades y, a largo plazo, a menores logros académicos y laborales. A pesar de que se ha evidenciado que en los pacientes de ascendencia latina se presenta un posible subdiagnóstico, que en Colombia se han estimado prevalencias mayores a las descritas en el planeta, y que los efectos de la pandemia por Covid-19 han podido exacerbar esta problemática, el volumen de estudios con estimaciones reproducibles sobre las características, tratamientos recibidos y control de síntomas de estos pacientes aún requiere ampliarse. Este estudio busca establecer los factores sociodemográficos, clínicos y del tratamiento asociados al control de los síntomas nucleares de este trastorno, que consisten en patrones persistentes y generalizados de inatención, impulsividad e hiperactividad. Metodología: estudio descriptivo con intención analítica en una cohorte retrospectiva de pacientes pediátricos con trastorno de déficit de atención e hiperactividad seguidos durante seis meses en un centro especializado de Medellín, Colombia, entre 2018 y 2019. Resultados: se identificó una incidencia de control de síntomas de 46,7% que se asoció de manera significativa con la adherencia al tratamiento y con historia familiar de TDAH. Conclusiones: puede afirmarse que, en pacientes pediátricos con TDAH, estos factores podrían aumentar la probabilidad de lograr el control de los síntomas nucleares.
Objective: Attention Deficit Hyperactivity Disorder (ADHD) has been described as the most common neurodevelopmental disorder in childhood. This condition is associated with significant deterioration in the quality of life, multiple comorbidities and, in the long term, lower academic and work achievements. Despite the fact that it has been shown that patients of Latin descent present a possible underdiagnosis, that in Colombia higher prevalence has been estimated than those described worldwide, and that the effects of the Covid-19 pandemic have been able to exacerbate this problem, the volume of studies with reproducible estimates on the characteristics, treatments received, and symptom control of these patients still needs to be expanded. This study seeks to establish the sociodemographic, clinical and treatment factors associated with the control of the core symptoms of this disorder, which consist of persistent and generalized patterns of inattention, impulsivity and hyperactivity. Methodology: Descriptive study with analytical intent in a retrospective cohort of pediatric patients with attention deficit hyperactivity disorder followed up for 6 months in a specialized center in Medellín, Colombia, between 2018 and 2019. Results: An incidence of symptom control of 46.7% was identified, which was significantly associated with adherence to treatment and with a family history of ADHD. Conclusions: It can be affirmed that, in pediatric patients with ADHD, these factors could increase the probability of achieving control of nuclear symptoms.
Objetivo: o transtorno dedéficit de atenção e hiperatividade (TDAH) tem sido descrito como o transtorno do neurodesenvolvimento mais comum na infância. Esta condição está associada a uma deterioração significativa na qualidade de vida, múltiplas comorbidades e, a longo prazo, menores rendimentos acadêmicos e profissionais. Apesar de ter sido demonstrado que os pacientes de ascendência latina apresentam um possível subdiagnóstico, e que na Colômbia foram estimadas prevalências mais altas do que as descritas no planeta e que os efeitos da pandemia de Covid-19 foram capazes de exacerbar esse problema, o volume de estudos com estimativas reprodutíveis sobre as características, tratamentos recebidos e controle de sintomas desses pacientes ainda precisam ser ampliados. Este estudo busca estabelecer os fatores sociodemográficos, clínicos e de tratamento associados ao controle dos sintomas centrais desse transtorno, que consistem em padrões persistentes e generalizados de desatenção, impulsividade e hiperatividade. Metodologia: estudo descritivo com intenção analítica em uma coorte retrospectiva de pacientes pediátricos com transtorno de déficit de atenção e hiperatividade acompanhados por seis meses em um centro especializado em Medellín, Colômbia, entre 2018 e 2019.Resultados: identificou-se uma incidência de controle dos sintomas de 46,7%, signifi-cativamente associada à adesão ao tratamento e ao histórico familiar de TDAH.Conclusões: Pode-se afirmar que, em pacientes pediátricos com TDAH , esses fatores podem aumentar a probabilidade de controle dos sintomas nucleares.
Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade , Transtornos do Neurodesenvolvimento , Cooperação e Adesão ao TratamentoRESUMO
Several plants of the Fabaceae family have been assessed regarding their high nutritional value and anthelmintic properties. The ovicidal effect of the hydroalcoholic extract (Bm-HAE) and subfractions from the aerial parts of Brongniartia montalvoana (Fabaceae) against a mixed strain of gastrointestinal nematodes (GIN) (Haemonchus spp., Trichostrongylus spp. and Oesophagostomum spp.) resistant to albendazole sulfoxide, ivermectin and levamisole was evaluated by the egg hatch test (EHT). The Bm-HAE was subjected to liquid-liquid chemical separation with ethyl acetate giving two fractions, an aqueous (Bm-Aq) and an organic (Bm-EtOAct). The purification of the bioactive fraction (Bm-EtOAct) through chromatographic separation resulted in four bioactive subfractions (BmR6, BmR7, BmR8 and BmR10). The treatments were designed as follows: Bm-HAE at 800, 1,500, 3,000 and 6,000 µg/mL, and Bm-Aq, Bm-EtOAct and subfractions (BmR6, BmR7, BmR8 and BmR10) at 100, 200, 400 and 800 µg/mL. Two properly negative controls (distilled water and 2% methanol) and thiabendazole (100 µg/mL) as a positive control were used for each bioassay. The chemical identification of the extract, fractions and subfractions was performed through chromatographic processes like open column chromatography, thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC-PDA). Additionally, the GIN eggs exposed to the bioactive compounds were observed through confocal laser scanning microscopy (CLSM). The Bm-HAE showed 99.5% egg hatching inhibition (EHI) at 6,000 µg/mL with a lethal concentration (LC50) of 1110 µg/mL. The Bm-EtOAc fraction displayed 99.1% EHI at 800 µg/mL with LC50 = 180 µg/mL. The ovicidal activity of the four subfractions was similar at 800 µg/mL: BmR6 (92% EHI); BmR7 (100% EHI); BmR8 (97.8%); and BmR10 (99.1%). The HPLC-PDA analysis of the bioactive subfractions allowed identification of p-coumaric acid, ferulic acid and coumarin derivatives as major compounds. The CLSM analysis allowed observation of morphological alterations in unhatched larvae caused by bioactive compounds present in the Bm-EtOAc and BmR10. In addition, the flavonoids eriodyctiol, luteolin and cynaroside were described for the first time for B. montalvoana.
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Anti-Helmínticos , Fabaceae , Haemonchus , Nematoides , Animais , Anti-Helmínticos/uso terapêutico , Larva , Extratos Vegetais/química , RuminantesRESUMO
Introduction: The SARS-CoV-2 pandemic has been affecting the world since January 2020. Although its pathogenesis is primarily directed to the respiratory tract, other organs may be affected, including the nervous system. It has also been shown that the social context (confinement, lack of treatment) has affected neurological patients during this period. The aim of the study it was to assess the subjective worsening of neurological/psychiatric diseases in the context of the SARS-Cov-2 pandemic. Methods: Three groups of neurological/psychiatric patients were included: Patients who had symptomatic COVID-19 (nâ¯=â¯89), patients who had asymptomatic COVID-19 (nâ¯=â¯40), and a control group (nâ¯=â¯47), consisting of neurological/psychiatric patients without a history of SARS-Cov-2 infection. Results: 30.7% of the included individuals considered that their basal pathology had worsened during the study period. This feeling was significantly more frequent (Pâ¯=â¯0.01) in patients with symptomatic COVID-19 (39.3%) than in patients of the other 2 groups (21.8%). Worsening was not related to the severity of COVID-19. The neurological conditions that significantly worsened after COVID-19, comparing symptomatic COVID-19 with the other 2 groups, were demyelinating and degenerative diseases. Conclusions: These results confirmed the impact of the SARS-Cov-2 pandemic on patients with neurological/psychiatric diseases. Confinement, lack of medical care, and the threat of diagnosis are surely contributing factors. Although the finding of a higher frequency of worsening in symptomatic COVID-19 patients may be related to greater anxiety/depression in this group of patients, we cannot exclude the role of direct affectation of the nervous system by the virus or damage due to neuroinflammation.
Introducción: La pandemia por SARS-CoV-2 afecta al mundo desde enero de 2020. Aunque su patogenia se dirige principalmente a las vías respiratorias, otros órganos pueden verse afectados, incluido el sistema nervioso. También se ha demostrado que el contexto social (confinamiento, falta de tratamiento) ha afectado a los pacientes neurológicos durante este periodo. El objetivo del estudio fue evaluar el empeoramiento subjetivo de enfermedades neurológicas/psiquiátricas en el contexto de la pandemia por SARS-Cov-2. Métodos: Se incluyeron tres grupos de pacientes neurológicos/psiquiátricos: pacientes que tenían COVID-19 sintomático (nâ¯=â¯89), pacientes que tenían COVID-19 asintomático (nâ¯=â¯40) y un grupo control (nâ¯=â¯47), formado por pacientes neurológicos/psiquiátricos sin antecedentes de infección por SARS-Cov-2. Resultados: El 30,7% de los individuos incluidos consideró que su patología basal había empeorado durante el período de estudio. Este sentimiento fue significativamente más frecuente (pâ¯=â¯0,01) en pacientes con COVID-19 sintomático (39,3%) que en pacientes de los otros 2 grupos (21,8%). El empeoramiento no estuvo relacionado con la gravedad de COVID-19. Las condiciones neurológicas que empeoraron significativamente después de la COVID-19, comparando la COVID-19 sintomática con los otros 2 grupos, fueron las enfermedades desmielinizantes y degenerativas. Conclusiones: estos resultados confirmaron el impacto de la pandemia del SARS-Cov-2 en pacientes con enfermedades neurológicas/psiquiátricas. El encierro, la falta de atención médica y la amenaza del diagnóstico son seguramente factores contribuyentes. Aunque el hallazgo de una mayor frecuencia de empeoramiento en pacientes sintomáticos de COVID-19 puede estar relacionado con una mayor ansiedad/depresión en este grupo de pacientes, no podemos excluir el papel de la afectación directa del sistema nervioso por el virus o el daño por neuroinflamación.
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The effect of including partially dehulled sunflower seeds in the diet of grazing chickens in meat quality was evaluated. Two hundred and forty, one-day-old, Ross 308 chickens were used, randomly distributed into four treatments with six replicates of 10 birds each. Seventy-two birds were slaughtered at seven weeks of age, 18 per treatment, extracting the Pectoralis major muscle to analyze meat quality. The treatments were completely randomized in a 2x2 factorial arrangement, where type of rearing (confinement or grazing) and diet (base diet or base diet substituting 10% soybean meal for partially dehulled sunflower seeds) were the independent variables. The grazing chickens spent 8 hours a day in a white clover (Trifolium repens) paddock. Including sunflower seeds improved (p<0.05) the color and crude protein (CP) in breast meat (p<0.05), while grazing increased (p<0.05) CP, dry mater (DM), and shear force (SF), and the percentage of breast fat decreased (p<0.05) by up to 50%. Additionally, grazing increased (p<0.05) saturated fatty acids (SFA) and reduced (p<0.05) lipid oxidation by up to 50%. Partially replacing soybean meal with partially dehulled sunflower seeds in the diet of grazing chickens with white clover improves the physicochemical characteristics and nutritional quality of the breast meat; it also decreases lipid oxidation, extending the shelf life of the meat.(AU)
Assuntos
Animais , Sementes , Helianthus , Carne/análise , Pastagens , Galinhas/fisiologia , Ingestão de Alimentos/fisiologia , Ração Animal/efeitos adversosRESUMO
Iron oxide nanoparticles (FeONPs) prepared with plant extracts have been emerging as green and sustainable materials. FeONPs are usually amorphous due to the chelation of the tea polyphenols (TPs) to the iron, and the real nature of the iron compounds is not completely understood. The main goal of this study was to investigate the behavior of the green FeONPs synthesized from an Fe3+ salt and Cammelia sinensis (black tea) extract upon thermal treatment, in order to remove TPs and enable the formation of crystalline materials suitable for a thorough characterization and with the potential for diverse applications. The as-prepared FeONPs were assigned as mixed-valence Fe(III) oxyhydroxides and Fe(II)/Fe(III) ions bound to TPs. A detailed description of the phase transformation upon heating revealed the formation of the rare nano ß-Fe2O3 phase at 400 °C, followed by a transformation to α-Fe2O3 as the temperature increased. Above 600 °C, the unprecedented formation of FePO4 and Fe3PO7 was observed, produced from the reaction of Fe2O3 and free phosphate ions present in the black tea leaves, Fe3PO7 being the major phase obtained at 900 °C. Finally, the catalytic potential of the FeONPs to treat the azo dye methyl orange through a heterogeneous Fenton-like system was investigated.
Assuntos
Camellia sinensis/química , Compostos Férricos/química , Fosfatos/síntese química , Extratos Vegetais/química , Polifenóis/química , Compostos Férricos/síntese química , Tamanho da Partícula , Fosfatos/química , TemperaturaRESUMO
In the area of health there are scales that allow collecting and analyzing conditions objectively. Its validation process includes translation from another language, semantic adaptation, and its application to measure its validity and reliability in an environment other than the original one. The objective of this review was to identify the instruments validated in Hispanics America in the literature and to know the psychometric properties in the field of neurorehabilitation. An exploratory review was carried out in the PubMed, PeDro, Scholar, Science Direct and LILACS databases, using combinations with «evaluation¼, «physical therapy¼, «rehabilitation¼, «Neurology¼. Of the 18,355 records retrieved, 105 received a full title and abstract reading; where finally 25 were included in the qualitative synthesis and critically appreciated. It is concluded that the scales presented here have good psychometric characteristics that allow their adoption in clinical and therapeutic processes.
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Reabilitação Neurológica , Hispânico ou Latino , Humanos , Psicometria , Reprodutibilidade dos Testes , TraduçõesRESUMO
RESUMEN Introducción: Las enfermedades cardiovasculares representan la primera causa de muerte en el mundo. La estimación del Riesgo Cardiovascular (RCV) podría disminuir la carga de la enfermedad y mejorar la calidad de vida de los pacientes. Objetivo: Estimar el RCV en pacientes sin sospecha de cifras tensionales elevadas en una Clínica de Medicina Familiar en la Ciudad de México. Métodos: Estudio transversal descriptivo, participaron 101 pacientes de sexo masculino y femenino, de 40 a 69 años, sin diagnóstico previo de Hipertensión Arterial (HTA), pero que presentaron cifras tensionales altas al momento del estudio. Para diagnosticar HTA se utilizaron los criterios de la Asociación Americana del Corazón-2017. El RCV se evaluó con el ASCVD-Risk Estimator Plus. Resultados: En la muestra la HTA estuvo presente en el 55.4 %, 44.6 % manifestaron presión arterial elevada. Respecto al RCV, 54.4 % presentaron bajo riesgo, 11.8 % riesgo límite, 25.7 % intermedio y 7.9 % alto. Los factores de RCV con mayor prevalencia fueron diabetes mellitus tipo 2 (DM2), sobrepeso, obesidad y elevación de cifras tensionales. Discusión: Un porcentaje importante de participantes presentó RCV en sus diferentes categorías. Se requiere ser más estrictos en los parámetros utilizados para definir la HTA; pues sin intervenciones oportunas las enfermedades cardiovasculares continuarán incrementándose. Conclusión: Cerca de la mitad de los casos presentaron un RCV de límite a alto. Existió alta prevalencia de factores de riesgo individuales como DM2, HTA y dislipidemia. Se deben fortalecer búsquedas intencionadas de pacientes con características similares a las de este estudio para prevenir el desarrollo de enfermedades cardiovasculares.
ABSTRACT Introduction: Cardiovascular diseases are the main cause of death in the world. The estimation of the Cardiovascular Risk (CVR) could both reduce the burden of the illness and improve the quality of life of the patients. Objective: To estimate the CVR in adult patients without a suspicion of having high pressure readings in a Clinic of Family Medicine in Mexico City. Methods: This is a descriptive and transversal study with a sample of 101 male and female patients in the range of 40 to 69 years old, who did not have a previous hypertension diagnosis but who, at the moment of this study, showed high tension readings. The American Heart Association 2017 criteria were used. The cardiovascular risk was assessed using the ASCVD-Risk Estimator Plus. Results: Arterial hypertension readings were found in 55.4 % of the sample. 54.4 % of the sample met the criteria for low risk, 11.8 % for limit risk, 25.7 % for medium risk, and 7.9 % for high risk. The most prevalent factors associated with cardiovascular risk were type 2 diabetes mellitus, overweight, obesity, and hypertension. Discussion: An important percentage of the sample showed cardiovascular risk to some degree, suggesting that perhaps using stricter parameters to define hypertension could prompt more timely interventions. Conclusion: Considering both the high percentage of participants who demonstrated having a cardiovascular risk of concern and the high prevalence of risk factors such as Type 2 Diabetes Mellitus, hypertension, and overweight, timely monitoring interventions should be promoted in order to prevent the development of cardiovascular diseases.
RESUMO Introdução: As doenças cardiovasculares representam a principal causa de morte a nível mundial. A estimativa do risco cardiovascular (RCV) poderia diminuir o peso da doença e melhorar a qualidade de vida dos pacientes. Objetivo: Estimar o RCV em pacientes sem suspeita de tensão arterial elevada em uma Clínica de Medicina Familiar na Cidade do México. Métodos: Um estudo descritivo transversal envolvendo 101 pacientes do sexo masculino e feminino com idades entre os 40 - 69 anos, sem diagnóstico prévio de hipertensão (HTA), mas com tensão arterial elevada no momento do estudo. Os critérios da American Heart Association-2017 foram utilizados para diagnosticar o HTA. O RCV foi avaliado utilizando o ASCVD-Risk Estimator Plus. Resultados: Na amostra, a HTA esteve presente em 55,4 %, 44,6 % reportou tensão arterial elevada. Em relação à RCV, 54,4 % apresentavam baixo risco, 11,8 % risco limite, 25,7 % risco intermédio e 7,9 % alto risco. Os fatores de RCV mais prevalentes foram a diabetes melito tipo 2 (DM2), excesso de peso, obesidade e tensão arterial elevada. Discussão: Uma percentagem significativa de participantes tinha RCV em diferentes categorias. Há necessidade de ser mais rigoroso nos parâmetros utilizados para definir a HTA; sem intervenções atempadas, as doenças cardiovasculares continuarão aumentando. Conclusão: Quase metade dos casos tinham um limite de RCV elevado. Havia uma elevada prevalência de fatores de risco individuais tais como DM2, hipertensão e dislipidemia. A procura intencional de pacientes com características semelhantes às deste estudo deve ser reforçada para prevenir o desenvolvimento de doenças cardiovasculares.
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BACKGROUND: Despite major advances, multiple myeloma remains an incurable disease. Epidemiological data from high-quality population-based registries are needed to understand the heterogeneous landscape of the disease. METHODS: Incidence, mortality and survival in multiple myeloma were comprehensively analyzed in the Girona and Granada population-based cancer registries, over a 23-year study (1994-2016), divided into three periods (1994-2001, 2002-2009 and 2010-2016). Joinpoint regression analysis was used to estimate the annual percentage change in incidence and mortality. Age-standardized net survival was calculated with the Pohar-Perme method. RESULTS: 1957 myeloma patients were included in the study, with a median age of 72 years. Age-standardized incidence and mortality rates decreased over time in both sexes and both rates were higher in males. Five-year age-standardized net survival by period was 27.4% (1994-2001), 38.8% (2002-2009), and 47.4% (2010-2016). Survival improved for all age groups: 32.4%, 74.1% and 78.5% for patients aged 15-49; 27.5%, 44.6%, and 58.5% for those aged 50-69; finally, 24.8%, 25.5%, and 26.3% for the older group. CONCLUSION: Incidence remained overall stable throughout the study, with only a small increase for men. Mortality was progressively decreasing in both sexes. Both incidence and mortality were higher in men. Age plays a critical role in survival, with impressive improvement in patients younger than 70 years, but only a minor benefit in those older than 70.