RESUMO
BACKGROUND AND RATIONALE: Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. METHODS/DESIGN: TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patient's cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patient's death. RESULTS: After 18 months and with 35 centers and researchers, the registry has 1128 patients. CONCLUSION: TESEO registry will provide clinical real-world evidence for prevention, treatment and complications of CAT in different scenarios that are under-represented in randomized clinical trials.
Assuntos
Neoplasias/complicações , Sistema de Registros/estatística & dados numéricos , Tromboembolia/epidemiologia , Inibidores da Angiogênese/uso terapêutico , Anticoagulantes/uso terapêutico , Progressão da Doença , Hemorragia/epidemiologia , Humanos , Imunoterapia , Oncologia , Terapia de Alvo Molecular , Neoplasias/terapia , Prognóstico , Recidiva , Insuficiência Renal/epidemiologia , Sociedades Médicas , Espanha/epidemiologia , Trombocitopenia/epidemiologia , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Resultado do Tratamento , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema de Registros , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Platina/administração & dosagem , Platina/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
INTRODUCTION: Our aim was to assess efficacy and safety and prognostic factors associated with TAS-102 in clinical practice. METHOD: Retrospective, multicenter, and observational study including patients with advanced refractory colorectal cancer who started TAS-102 between March 2016 and August 2018. The primary end point was overall survival (OS). Secondary end points included progression-free survival, toxicity and analyze prognostic factors present at the beginning of TAS-102. RESULT: 84 patients were evaluable. The median OS was 8.30 (95% CI 6.23-9.87) months and PFS was 2.62 (95% CI 2.36-3.05) months. In multivariate analysis, ECOG 0 and reduced dose combined with more cycles were associated with better prognosis. Patients with an ECOG > 0 had worse prognosis (HR 3.34, 95% CI 1.09-10.27, p = 0.035). 95.2% experienced some type of adverse effect and 45.2% had grade ≥ 3 toxicities. CONCLUSION: Results suggest reconsidering TAS-102 in patients with ECOG > 0, something that should be investigated in prospective randomized clinical trials.
Assuntos
Neoplasias do Colo/tratamento farmacológico , Pirrolidinas/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Trifluridina/uso terapêutico , Uracila/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Esquema de Medicação , Combinação de Medicamentos , Estudos de Viabilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Pirrolidinas/efeitos adversos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Timina , Resultado do Tratamento , Trifluridina/efeitos adversos , Uracila/efeitos adversos , Uracila/uso terapêuticoRESUMO
Despite the fact that thromboembolism is relatively common in oncology patients and that the interrelationship between thrombotic risk and specific mechanisms of tumorigenesis has long been known, many cardinal elements of prevention and treatment remain unresolved. Among the existing knowledge gaps, the need to validate the Ay scale and compare it to the Khorana index, develop, and standardize the use of predictive biomarkers for thrombotic risk, conduct clinical trials in thromboprophylaxis adapted to thrombotic risk, evaluate the efficacy and safety of direct anticoagulants, select patients who can benefit from anticoagulants for antitumor treatment, validate the EPIPHANY study decision tree to choose patients with low-risk pulmonary embolism, and accumulate more practical experience in special situations (rethrombosis, prolonged therapy beyond 6 months, etc.) are especially remarkable. These gray areas surrounding cancer-related thromboembolism explain why it continues to be a relatively common cause of serious events, at times interfering significantly with the development of new tumor-fighting strategies.
Assuntos
Anticoagulantes/uso terapêutico , Pesquisa Biomédica , Gerenciamento Clínico , Neoplasias/complicações , Trombose/tratamento farmacológico , Humanos , Trombose/etiologiaRESUMO
Since its publication more than 15 years ago, the MASCC score has been internationally validated any number of times and recommended by most clinical practice guidelines for the management of febrile neutropenia (FN) around the world. We have used an empirical data-supported simulated scenario to demonstrate that, despite everything, the MASCC score is impractical as a basis for decision-making. A detailed analysis of reasons supporting the clinical irrelevance of this model is performed. First, seven of its eight variables are "innocent bystanders" that contribute little to selecting low-risk candidates for ambulatory management. Secondly, the training series was hardly representative of outpatients with solid tumors and low-risk FN. Finally, the simultaneous inclusion of key variables both in the model and in the outcome explains its successful validation in various series of patients. Alternative methods of prognostic classification, such as the Clinical Index of Stable Febrile Neutropenia, have been specifically validated for patients with solid tumors and should replace the MASCC model in situations of clinical uncertainty.
Assuntos
Neutropenia Febril/classificação , Humanos , Medição de Risco , Índice de Gravidade de DoençaRESUMO
This work shows the results obtained on a copper mine tailing in the Antofagasta Region, Chile. The tailing was classified as saline-sodic with high concentrations of metals, especially Cu and Fe, with pH 8.4. Our objectives were to (1) compare the physicochemical properties of the tailing with surrounding soils of the mine under study, and (2) evaluate the effect of two amendments (CaCO3 and compost) and their mixtures on Cu(2+), Mn, Fe, Zn, Mg(2+), and K(+) and Ca(2+), SO4 (2-), NO3 (-), and PO4 (3-) leaching. The data obtained were submitted to variance and covariance analysis. The results from the comparison between both substrates showed that in general, the tailing presented greater content of metals. Regarding tailing leaching, pH, electrical conductivity (EC), and concentration of the elements of interest were measured. The statistical analysis showed that Cu(2+) leaching and immobilization of Fe occurred to the greatest extent with compost. The EC decreased throughout the experiment with irrigation and increased upon treatment with compost. The major interactions found among the chemical parameters were (1) tailings without treatment, Cu(2+)/Fe and NO3 (-)/SO4 (2-); (2) tailings treated with CaCO3, Cu(2+)/K(+); (3) tailings treated with compost, NO3 (-)/SO4 (-2) and EC/Cu(2+); and (4) tailings treated with both amendments, EC/Fe and Cu(2+)/Fe. The ANOVA showed that the number of irrigations and the amendments statistically significantly affected the copper mobility and the organic amendment significantly influenced the iron mobility.
Assuntos
Carbonato de Cálcio/química , Cobre/análise , Metais Pesados/análise , Poluentes do Solo/análise , Solo/química , Chile , Metais/análise , MineraçãoAssuntos
Distrofina/genética , Distrofia Muscular Animal/genética , Mutação Puntual , Processamento Alternativo/genética , Animais , Análise Mutacional de DNA , Modelos Animais de Doenças , Cães , Distrofina/deficiência , Força Muscular/genética , Força Muscular/fisiologia , Distrofia Muscular Animal/patologia , Distrofia Muscular Animal/fisiopatologiaRESUMO
In patients with sarcoglycan (SG) deficiency, a primary defect in any one of the four SG proteins usually leads to reduced expression of the whole SG complex. We report a limb-girdle muscular dystrophy type 2D family (LGMD2D), with variable phenotype, where a mutation in the alpha-SG gene resulted in the partial deficiency of alpha-SG alone. The normal expression of the other three SG proteins suggests that mutations close to the alpha-SG transmembrane domain might be less critical for complex integrity, and that weakness may occur despite its retention.
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Proteínas do Citoesqueleto/genética , Distrofina/genética , Saúde da Família , Glicoproteínas/genética , Glicoproteínas de Membrana/genética , Distrofias Musculares/genética , Adulto , Biópsia , Distrofina/análise , Glicoproteínas/análise , Humanos , Masculino , Músculo Esquelético/química , Músculo Esquelético/patologia , Distrofias Musculares/patologia , Mutação , Núcleo Familiar , Linhagem , Polimorfismo Conformacional de Fita Simples , SarcoglicanasRESUMO
The pattern of X inactivation in lymphocyte DNA was investigated in 107 Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) carriers (102 asymptomatic and 5 manifesting carriers) and 117 normal female controls of different ages, with the aim: a) to analyze the pattern of X inactivation in blood DNA of a large number of DMD/BMD carriers as compared to normal female controls; b) to determine if there is a decrease in serum creatine kinase (CK) levels with age in obligate DMD/BMD carriers; c) to determine if there is a correlation between X-chromosome inactivation and serum CK among asymptomatic DMD/BMD carriers of different ages or with different clinical manifestations in symptomatic carriers. A high proportion of females showed extremely skewed X inactivation (>90% of one X preferentially inactivated), which was almost the same among carriers and normal controls (19 and 24%, respectively). The mean serum CK was significantly greater among young (<20 years old) than adult (>20 years old) DMD/BMD carriers and it decreased significantly until age 20 with an apparent stabilization afterwards. No statistically significant correlation was found between the proportion of active X(DMD) in blood and serum CK activity in DMD/BMD carriers although it was higher among those less than 20 years old. Our observations suggest that highly skewed X-chromosome pattern in blood (with preferential inactivation of the X(N) chromosome) is not enough to predict that a young DMD carrier will develop muscular weakness.
Assuntos
Creatina Quinase/sangue , Mecanismo Genético de Compensação de Dose , Distrofias Musculares/genética , Cromossomo X/genética , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Feminino , Heterozigoto , Humanos , Lactente , Recém-Nascido , Distrofias Musculares/enzimologia , Distrofias Musculares/patologiaRESUMO
Duchenne dystrophy (DMD) is an X-linked lethal condition which affects 1 in 3,500 boys. The DMD gene is deleted in about 60-65% of patients while in the remaining 35-40% the condition is caused by point mutations, small insertions, or duplications. We have ascertained 967 DMD families (680 isolated and 287 familial cases). Screening for deletions showed a molecular deletion in 383 among 615 (62.3%) analyzed cases. However, 10 families were unusual: In 7 of them, 2 or more DMD patients were related through paternal lines while in 3 others, affected boys related through maternal lines carried different mutations or originated through independent new mutation events. The finding of 10 atypical genealogies, which represent about 1% of the sample (10/967) or about 3% of familial cases (10/287) is higher than we would expect by chance. Even so, it is an underestimate because screening of mutations in all the affected DMD relatives from each genealogy is not done in many of the familial cases. It suggests that other mechanisms (such as transposon-like elements, for example) could be responsible for a higher genomic instability leading to novel mutations as reported previously by us and others in DMD and in other genetic disorders such as hemophilia and inherited peripheral neuropathies. On the other hand, it shows the importance of testing all affected patients within each genealogy to prevent possible mistakes in carrier detection, genetic counseling, and prenatal diagnosis.
Assuntos
Distrofina/genética , Distrofias Musculares/genética , Mutação , Cromossomo X/genética , Criança , Pré-Escolar , Creatina Quinase/sangue , Elementos de DNA Transponíveis/genética , Pai , Ligação Genética , Testes Genéticos , Genótipo , Humanos , Masculino , Mães , Distrofias Musculares/diagnóstico , Núcleo Familiar , Linhagem , Deleção de SequênciaRESUMO
To enhance our understanding of the autosomal recessive limb-girdle muscular dystrophy (LGMD), patients from six genetically distinct forms (LGMD2A to LGMD2F) were studied with antibodies directed against four sarcoglycan subunits (alpha-, beta-, gamma-, delta-SG), dystrophin, beta-dystroglycan (beta-DG) and merosin. All patients with LGMD2A and 2B had a mild clinical course while those with a primary sarcoglycan mutation (LGMD2C to 2F) had a range of clinical severity. Dystrophin and merosin immunofluorescence pattern was positive in patients with all six AR LGMDs. The majority of patients with a severe Duchenne-like phenotype presented total absence of the SG complex. However, some exceptions were found in 13q linked patients, indicating that the presence of a certain labelling for components of the SG may not be prognostic for a milder phenotype. The observation that the primary absence of alpha-SG results in the total absence of beta- and delta-SG but not of gamma-SG suggests that the alpha-, beta- and delta-subunits of sarcoglycan may be more closely associated. A secondary reduction in dystrophin amount was seen in patients with primary sarcoglycan mutations, which was most marked in patients with primary beta-, gamma- and delta-SG deficiencies. In contrast, beta-DG staining was retained in all patients, suggesting that the association between SG and DG subcomplexes is not so strong. Based on the above findings, we have refined the model for the interaction among the known glycoproteins of the sarcoglycan complex, within the DGC.