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1.
Rev. esp. cardiol. (Ed. impr.) ; 75(7): 595-603, jul. 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-205129

RESUMO

Introducción y objetivos: El lactato y su evolución se asocian con el pronóstico de los pacientes en shock, si bien es escasa la evidencia en aquellos asistidos con oxigenador extracorpóreo de membrana venoarterial (ECMO-VA). Nuestro objetivo es evaluar su valor pronóstico en shock cardiogénico asistido con ECMO-VA. Métodos: Estudio de pacientes tratados con ECMO-VA por shock cardiogénico de indicación médica entre julio de 2013 y abril de 2021. Se calculó el aclaramiento de lactato: (lactato inicial − lactato 6 h) / lactato inicial × tiempo exacto entre ambas determinaciones. Resultados: De 121 pacientes, 44 (36,4%) tenían infarto agudo de miocardio; 42 (34,7%), implante intraparada; 14 (11,6%), tromboembolia pulmonar, 14 (11,6%), tormenta arrítmica y 6 (5,0%), miocarditis fulminante. A los 30 días habían fallecido 60 pacientes (49,6%); la mortalidad fue mayor con el implante intraparada que con el implante en circulación espontánea (30 [71,4%] de 42 frente a 30 [38,0%] de 79; p=0,030). Se asociaron de manera independiente con la mortalidad a 30 días la alanina aminotransferasa (ALT) antes del implante y el lactato (tanto basal como a las 6 h y el aclaramiento). Los modelos de regresión que incluían el lactato presentaron mejor capacidad predictiva de la supervivencia que las puntuaciones ENCOURAGE y ECMO-ACCEPTS, con mayor área bajo la curva ROC en el modelo con lactato a las 6 h.Conclusiones: El lactato (basal y a las 6 h y el aclaramiento) es un predictor independiente para el pronóstico de los pacientes en shock cardiogénico asistidos con ECMO-VA que facilita una mejor estratificación del riesgo y tiene una capacidad predictiva superior (AU)


Introduction and objectives: Lactate and its evolution are associated with the prognosis of patients in shock, although there is little evidence in those assisted with an extracorporeal venoarterial oxygenation membrane (VA-ECMO). Our objective was to evaluate its prognostic value in cardiogenic shock assisted with VA-ECMO. Methods: Study of patients with cardiogenic shock treated with VA-ECMO for medical indication between July 2013 and April 2021. Lactate clearance was calculated: [(initial lactate − 6 h lactate) / initial lactate × exact time between both determinations]. Results: From 121 patients, 44 had acute myocardial infarction (36.4%), 42 implant during cardiopulmonary resuscitation (34.7%), 14 pulmonary embolism (11.6%), 14 arrhythmic storm (11.6%), and 6 fulminant myocarditis (5.0%). After 30 days, 60 patients (49.6%) died, mortality was higher for implant during cardiopulmonary resuscitation than for implant in spontaneous circulation (30 of 42 [71.4%] vs 30 of 79 [38.0%], P=.030). Preimplantation GPT and lactate (both baseline, at 6hours, and clearance) were independently associated with 30-day mortality. The regression models that included lactate clearance had a better predictive capacity for survival than the ENCOURAGE and ECMO-ACCEPTS scores, with the area under the ROC curve being greater in the model with lactate at 6 h. Conclusions: Lactate (at baseline, 6h, and clearance) is an independent predictor of prognosis in patients in cardiogenic shock supported by VA-ECMO, allowing better risk stratification and predictive capacity (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Choque Cardiogênico/sangue , Choque Cardiogênico/terapia , Ácido Láctico/sangue , Estudos Retrospectivos , Prognóstico
2.
ESMO Open ; 7(3): 100514, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35714478

RESUMO

BACKGROUND: Recommendations for research articles include the use of the term sex when reporting biological factors and gender for identities or psychosocial or cultural factors. There is an increasing awareness of incorporating the effect of sex and gender on cancer outcomes. Thus, these types of analyses for advanced gastroesophageal adenocarcinoma are relevant. PATIENTS AND METHODS: Patients with advanced gastroesophageal adenocarcinoma from the Spanish AGAMENON-SEOM registry treated with first-line combination chemotherapy were selected. Epidemiology, characteristics of the disease, treatment selection, and results were examined according to sex. RESULTS: This analysis included 3274 advanced gastroesophageal adenocarcinoma patients treated with combination chemotherapy between 2008 and 2021: 2313 (70.7%) men and 961 (29.3%) women. Tumors in females were more frequently HER2-negative (67.8% versus 60.8%; P < 0.0001), grade 3 (45.4% versus 36.8%; P < 0.001), diffuse (43.3% versus 26.5%; P < 0.0001), and signet ring cell histology (40.5 versus 23.9%; P < 0.0001). Peritoneal spread was more common in women (58.6% versus 38.9%; P < 0.0001), while liver burden was lower (58.9% versus 71.1%; P < 0.0001). There were no significant differences in treatment recommendation. Treatment doses, density, and duration were comparable between sexes. Women experienced more diarrhea (46% versus 37%; P < 0.0001), neutropenia (51% versus 43%; P < 0.0001), and anemia (62% versus 57%; P < 0.0001). After a median 59.6-month follow-up [95% confidence interval (CI) 54.5-70.8], there were no statistically significant differences between the sexes in progression-free survival [6.21 months (95% CI 5.8-6.5 months) versus 6.08 months (95% CI 5.8-6.3 months); log-rank test, χ2 = 0.1, 1 df, P = 0.8] or in overall survival [10.6 months (95% CI 9.8-11.1 months) versus 10.9 months (95% CI 10.4-11.4 months); log-rank test: χ2 = 0.6, 1 df, P = 0.5]. CONCLUSION: This sex analysis of patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry receiving first-line polychemotherapy found no differences in survival. Although women had worse prognostic histopathology, metastatic disease pattern, and greater toxicity, treatment allocation and compliance were equivalent.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Intervalo Livre de Progressão , Sistema de Registros , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/epidemiologia
3.
Sci Rep ; 12(1): 8547, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35595798

RESUMO

Only up to 25% of the cases in which there is a familial aggregation of breast and/or ovarian cancer are explained by germline mutations in the well-known BRCA1 and BRCA2 high-risk genes. Recently, the BRCA1-associated ring domain (BARD1), that partners BRCA1 in DNA repair, has been confirmed as a moderate-risk breast cancer susceptibility gene. Taking advantage of next-generation sequencing techniques, and with the purpose of defining the whole spectrum of possible pathogenic variants (PVs) in this gene, here we have performed a comprehensive mutational analysis of BARD1 in a cohort of 1946 Spanish patients who fulfilled criteria to be tested for germline pathogenic mutations in BRCA1 and BRCA2. We identified 22 different rare germline variants, being 5 of them clearly pathogenic or likely pathogenic large deletions, which account for 0.26% of the patients tested. Our results show that the prevalence and spectrum of mutations in the BARD1 gene might vary between different regions of Spain and expose the relevance to test for copy number variations.


Assuntos
Neoplasias da Mama , Variações do Número de Cópias de DNA , Neoplasias Ovarianas , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Proteína BRCA1/genética , Neoplasias da Mama/genética , Variações do Número de Cópias de DNA/genética , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Neoplasias Ovarianas/genética , Espanha/epidemiologia , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética
4.
Clin Transl Oncol ; 22(2): 187-192, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32006339

RESUMO

Cancer is one of the major public health problems in our society. It is estimated that more than 18 million new cases are diagnosed worldwide every year; 280,000 in Spain. Incidence in following a growing trend. This epidemic could be controlled with research into new treatments and, above all, with adequate prevention. Primary prevention could prevent avoid up to half of all cases. For many others, secondary prevention is essential, as it make diagnosis possible in the stages of the disease when it is easily curable. These guidelines present the scientific evidence regarding secondary prevention in tumors in which its use is well-accepted: breast, cervical, colorectal, prostate, lung, ovarian, melanoma, and gastric cancer.


Assuntos
Ensaios Clínicos como Assunto/normas , Neoplasias/terapia , Guias de Prática Clínica como Assunto/normas , Prevenção Secundária/métodos , Humanos , Oncologia , Sociedades Médicas
5.
Clin Transl Oncol ; 22(5): 734-750, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31385226

RESUMO

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 Jovem
6.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31676415

RESUMO

INTRODUCTION: Unstable forearm fractures may require surgical management by reduction and osteosynthesis with intramedullary needles. This fixation should be removed early if it has been left exposed, but this could increase the risk of refracture in a bone in the period of remodelling. As an alternative we can keep the needles, buried subcutaneously, for a longer time, to protect the bone callus. OBJECTIVE: To assess whether there are differences between using exposed needles with respect to burying them in paediatric patients with forearm fractures. Our hypothesis is that by burying the needles we keep them longer by reducing forearm refractures. MATERIAL AND METHODS: We present a cohort of 75 paediatric patients with a forearm fracture between 2010 and 2016. Demographic data, surgical technique, complications and patient follow-up were collected. RESULTS: The implants were left exposed in 50 patients and 25 buried. The average time of removal of the exposed implants was 6.8weeks and 17.6weeks in the buried ones. No significant differences were found in terms of consolidation (P=.19) or immobilization time (P=.22). Regarding refractures, a greater number was observed in the exposed osteosynthesis group (4patients) compared to only one case with buried osteosynthesis, but there were no significant differences (P=.49). No postsurgical complications were detected and the functionality was excellent at the end of the follow-up in both groups. CONCLUSION: Leaving implants buried in relation to skin exposed does not cause a decrease in the number of refractures or other complications, with adequate patient functionality in both cases.


Assuntos
Fixação Intramedular de Fraturas/métodos , Fraturas do Rádio/cirurgia , Prevenção Secundária/métodos , Fraturas da Ulna/cirurgia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fixação Intramedular de Fraturas/instrumentação , Consolidação da Fratura , Fraturas Fechadas/cirurgia , Fraturas Expostas/cirurgia , Humanos , Lactente , Masculino , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/prevenção & controle , Recidiva , Estudos Retrospectivos , Fraturas da Ulna/diagnóstico por imagem , Fraturas da Ulna/prevenção & controle
8.
Med Oral Patol Oral Cir Bucal ; 23(6): e716-e722, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30341268

RESUMO

BACKGROUND: The main objective of the present study is to evaluate the effects and possible benefits with regard to the postoperative period of lower third molar extractions, comparing the intraalveolar application of a bioadhesive gel of 0.2% chlorhexidine (CHX) to the use of a mouthwash with a super-oxidized solution, (SOS) Dermacyn® Wound Care (Oculus Innovative Sciences lnc., California, USA). MATERIAL AND METHODS: A randomized double-blind study was carried out in 20 patients with a split-mouth design, with a total of 40 extractions of symmetrically impacted bilateral lower third molars. Patients were divided into two groups, a control group (C = 20) and an experimental group (D = 20). Any infectious complications, wound healing, plaque accumulation in the stitches, and presence of trismus and inflammation were evaluated using the distance between different facial points, at three, eight, and fifteen days after extraction. Pain, swelling, and amount of analgesics taken were evaluated using the VAS scale throughout the 15 days following extraction. Tolerance to treatment was evaluated using a verbal scale. Results were statistically compared using the Student's t- and chi-squared tests. RESULTS: No statistically significant differences were found between the two groups with regard to infectious complications, swelling, or wound healing. Use of analgesics and self-reported pain levels were slightly lower in the experimental group than in the control group during days 6 and 7 of the study (p < 0.05). The global treatment tolerance was satisfactory and similar in both groups. CONCLUSIONS: Both CHX and SOS are effective at improving the postoperative period after extraction of lower third molars.


Assuntos
Clorexidina/administração & dosagem , Edema/prevenção & controle , Ácido Hipocloroso/uso terapêutico , Dente Serotino/cirurgia , Antissépticos Bucais/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Hipoclorito de Sódio/uso terapêutico , Extração Dentária , Cicatrização/efeitos dos fármacos , Adulto , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Géis , Humanos , Masculino , Mandíbula , Estudos Prospectivos
9.
Psychooncology ; 27(6): 1530-1537, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29498768

RESUMO

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.


Assuntos
Aconselhamento Genético/psicologia , Predisposição Genética para Doença/psicologia , Testes Genéticos/métodos , Neoplasias/psicologia , Adulto , Ansiedade/psicologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/prevenção & controle , Espanha
10.
Gastric Cancer ; 21(1): 96-105, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28393278

RESUMO

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sistema de Registros
11.
Fungal Biol ; 121(9): 825-833, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28800852

RESUMO

The ectomycorrhizal (ECM) fungus Amanita caesarea CECT 20127 was tested in vitro with two potentially mycorrhizal-promoting bacterial strains, Pseudomonas fluorescens CECT 844 and Bacillus cereus CECT 148. Although P. fluorescens showed spatial and temporal compatibility with A. caesarea, it did not affect growth of the fungus. Conversely, B. cereus exhibited no such compatibility and also inhibited fungal growth. The expression pattern of the A. caesarea gene AcMST-1 was analysed using real-time quantitative polymerase chain reaction (qPCR) at three time points. This gene displays a high degree of homology with two genes, possible orthologues to AcMST-1, previously described in Amanita muscaria (AmMST-1) and Laccaria bicolor (LbMST-1) and encoding monosaccharide transporter proteins. The transcription levels of AcMST1 increased shortly after initial contact between A. caesarea and B. cereus, but expression of the gene was inhibited in the presence of P. fluorescens. Our results show that A. caesarea may possess orthologous genes of similar ECM fungal species that would allow it to adapt in nature to optimize sugar uptake from the environment depending on the presence of different microorganisms.


Assuntos
Amanita/crescimento & desenvolvimento , Bacillus cereus/fisiologia , Micorrizas/fisiologia , Pseudomonas fluorescens/fisiologia , Amanita/genética , Bioensaio , Meios de Cultura , Liofilização , Proteínas Fúngicas/genética , Proteínas de Transporte de Monossacarídeos/genética , Micélio/crescimento & desenvolvimento , RNA Fúngico/química , RNA Fúngico/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Espanha
12.
Br J Cancer ; 116(12): 1526-1535, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28463962

RESUMO

BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Nomogramas , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/química , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patologia , Nível de Saúde , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Gradação de Tumores , Neutrófilos , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Trastuzumab/administração & dosagem , Carga Tumoral , População Branca , Adulto Jovem
13.
Clin Transl Oncol ; 18(8): 805-12, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26542177

RESUMO

PURPOSE: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. METHODS/PATIENTS: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. RESULTS: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. CONCLUSION: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos de Nitrosoureia/uso terapêutico , Compostos Organofosforados/uso terapêutico , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Feminino , Glioma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
Minerva Anestesiol ; 80(11): 1178-87, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24569356

RESUMO

BACKGROUND: Liver transplantation (LT) implies hemodynamic instability, making invasive monitoring of cardiac output (CO) mandatory. Intermittent thermodilution with pulmonary artery catheter (PAC) remains the clinical gold standard to measure CO. The agreement between PAC and new monitoring methods in LT needs to be further investigated. Our aim is to clarify whether cardiac index (CI) measurements with transpulmonary intermittent thermodilution, and continuous pulmonary thermodilution methods agree sufficiently with those performed intermittently with PAC to be considered interchangeable during LT. METHODS: We studied prospectively hemodynamic parameters of 72 consecutive patients undergoing LT. Each CI was obtained simultaneously with three different techniques: intermittent (PACi) and continuous (CCI) pulmonary artery thermodilution with PAC, and intermittent transpulmonary thermodilution (TPTD) with PiCCO2 in 8 time points of the procedure, obtaining 1350 paired measurements. Exclusion criteria was retransplantation. The statistical Bland Altman method for repeated measures was used to assess agreement, and polar plot methodology to evaluate trending ability. RESULTS: Analysis of agreement between PACi and TPTD measurements (N.=474 paired measurements) showed a bias of -0.42 L/min/m2, 95% limits of agreement (95%LoA) of ±1.5 L/min/m2 and percentage error of 45%. PACi-CCI comparisons (N.=431) showed bias of -0.02 L/min/m2, 95%LoA of ±1.96 L/min/m2, and percentage error of 64%. These results demonstrated questionable clinical agreement between PACi and TPTD, and no agreement between PACi and CCI. TPTD and CCI showed poor CO trending ability. CONCLUSION: Continuous pulmonary thermodilution with PAC is not an alternative monitoring method of CO. Transpulmonary thermodilution CO monitoring with PiCCO2 shows too questionable agreement with the clinical gold standard (PACi) being in the limit of acceptance to be considered interchangeable during liver transplantation.


Assuntos
Débito Cardíaco , Transplante de Fígado/métodos , Pulmão , Monitorização Intraoperatória/métodos , Termodiluição/métodos , Cateterismo de Swan-Ganz , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Clin Transl Oncol ; 16(3): 273-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23793813

RESUMO

PURPOSE: The standard adjuvant treatment for glioblastoma is temozolomide concomitant with radiotherapy, followed by a further six cycles of temozolomide. However, due to the lack of empirical evidence and international consensus regarding the optimal duration of temozolomide treatment, it is often extended to 12 or more cycles, even in the absence of residual disease. No clinical trial has shown clear evidence of clinical benefit of this extended treatment. We have explored the economic impact of this practice in Spain. MATERIALS AND METHODS: Spanish neuro-oncologists completed a questionnaire on the clinical management of glioblastomas in their centers. Based on their responses and on available clinical and demographic data, we estimated the number of patients who receive more than six cycles of temozolomide and calculated the cost of this extended treatment. RESULTS: Temozolomide treatment is continued for more than six cycles by 80.5 % of neuro-oncologists: 44.4 % only if there is residual disease; 27.8 % for 12 cycles even in the absence of residual disease; and 8.3 % until progression. Thus, 292 patients annually will continue treatment beyond six cycles in spite of a lack of clear evidence of clinical benefit. Temozolomide is covered by the National Health Insurance System, and the additional economic burden to society of this extended treatment is nearly 1.5 million euros a year. CONCLUSIONS: The optimal duration of adjuvant temozolomide treatment merits investigation in a clinical trial due to the economic consequences of prolonged treatment without evidence of greater patient benefit.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , Antineoplásicos Alquilantes/economia , Neoplasias Encefálicas/economia , Quimioterapia Adjuvante/economia , Quimioterapia Adjuvante/métodos , Análise Custo-Benefício , Dacarbazina/administração & dosagem , Dacarbazina/economia , Glioblastoma/economia , Humanos , Padrões de Prática Médica , Espanha , Inquéritos e Questionários , Temozolomida
19.
Mol Ecol Resour ; 13(4): 746-54, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23656704

RESUMO

Approaches and tools to differentiate between natural selection and genetic drift as causes of population differentiation are of frequent demand in evolutionary biology. Based on the approach of Ovaskainen et al. (2011), we have developed an R package (DRIFTSEL) that can be used to differentiate between stabilizing selection, diversifying selection and random genetic drift as causes of population differentiation in quantitative traits when neutral marker and quantitative genetic data are available. Apart from illustrating the use of this method and the interpretation of results using simulated data, we apply the package on data from three-spined sticklebacks (Gasterosteus aculeatus) to highlight its virtues. DRIFTSEL can also be used to perform usual quantitative genetic analyses in common-garden study designs.


Assuntos
Biologia/métodos , Biologia Computacional/métodos , Locos de Características Quantitativas , Seleção Genética , Smegmamorpha/genética , Animais
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