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1.
Nature ; 620(7976): 965-970, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37648757

RESUMO

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

3.
Sensors (Basel) ; 21(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803746

RESUMO

This paper proposes the use of a pseudo-3D ball-lattice artifact to characterize a handheld laser scanner from a metrological standpoint. The artifact allows the computation of local and global errors in measurement by using the reference-frame-independent parameters of size, form, and distance within the measuring volume of the scanner, and in a single point cloud, without the need for registration. A set of tests was performed using the whole measuring volume, and three acquisition parameters, namely the orientation of the sweeps during the scans, the exposure time, and the distance to the scanner were analyzed for their effects on the accuracy of the scan data. A composite error including the errors in measuring size, form, and distance was used as a single figure of merit to characterize the performance of the scanner in relation to the data-acquisition parameters. The orientation of sweeps did not have a considerable effect on the errors. The accuracy of the scan data was strongly affected by exposure time and its interaction with the distance at which the artifact was scanned. The errors followed a quadratic trend with respect to the distance of the artifact to the scanner. The tested scanner performed best at its manufacturer's recommended stand-off distance.

4.
Neoplasma ; 67(4): 939-945, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32567936

RESUMO

Monoclonal gammopathy of undetermined significance (MGUS) is a known precursor of more serious cancers, such as multiple myeloma (MM), Waldenström macroglobulinemia (MW) and other lymphoproliferative disorders. Using 18F-FDG PET/CT, we aimed to evaluate its benefit in early detection of various accompanying disorders and illnesses in MGUS patients. We prospectively analyzed the diagnostic relevance of 18F-FDG PET/CT in 390 newly diagnosed MGUS patients. On 18F-FDG PET/CT scans, the presence of focal or diffuse areas of detectable increased tracer uptake was recorded in 37 (9.5%) MGUS patients. The most frequent pathology was lymphadenopathy (3.8%), followed by thyroid diseases (2.1%), rheumatic diseases (1.8%), and other solid malignancies (1.5%). These results have major implications for confirmed associations of MGUS with numerous malignant and non-malignant disorders. We believe that 18F-FDG PET/CT imaging in newly diagnosed MGUS patients may be useful in early detection of other serious pathologies, not only in predicting progression of MGUS to active MM, and should be strongly recommended if available.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Adulto , Fluordesoxiglucose F18 , Humanos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico por imagem , Mieloma Múltiplo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons
5.
Neoplasma ; 67(3): 650-659, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32064883

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with aggressive behavior and poor prognosis. We present the first retrospective analysis mapping its incidence and therapeutic outcomes in patients diagnosed and treated from 2000 to 2017 in the Czech Republic. The cohort comprised 14 patients (10 males, 4 females) with a median age at diagnosis of 39 years (range, 5-68 years). Initially, skin involvement was noted in 10 (71%) patients and bone marrow infiltration was present in 9 (64%). The first complete remission was achieved in 6/14 (43%) patients after acute lymphoblastic leukemia/lymphoma induction therapy and in 3/14 (21%) patients after acute myeloid leukemia regimen. Nine patients underwent allogeneic hematopoietic cell transplantation, with two patients achieving the first complete remission only after allogeneic transplantation. Patients undergoing allogeneic hematopoietic cell transplantation had longer overall survival than those treated without transplantation (the median survival over the period 16.4 vs. 8.1 months). Relapse of the disease was a significant predictor of mortality (p=0.05). Over the study period, patients' survival ranged from 3.3 to 44.2 months, with a median overall survival of 13 months. Our results revealed an effectivity of allogeneic hematopoietic cell transplantation on complete remission achievement in refractory/relapsed disease. The study aimed to present the actual data from the Czech Republic and thus contribute to a global understanding of BPDCN.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , República Tcheca , Células Dendríticas/patologia , Feminino , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Estudos Retrospectivos , Adulto Jovem
6.
Schmerz ; 33(1): 49-56, 2019 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-29294211

RESUMO

BACKGROUND: Up to now, the investigation of joint pain in adolescents, especially in adolescent elite athletes, has been neglected. This is critical because the musculoskeletal system is still in growth and consecutive trauma and irreversible damage can result. OBJECTIVES: To shed light into the research area of joint pain in elite adolescent athletes, we studied the willingness to compete while having joint pain as part as the phenomenon of "playing hurt". Our aim was to describe which athletes are more willing to compete in spite of joint pain and which individual and sport-specific characteristics are associated with it. MATERIALS AND METHODS: We used data of the nationwide GOAL study which included 1138 adolescent athletes from 51 Olympic sports (56.1% male, 14-18 years of age). RESULTS: Altogether, 43.8% of the German elite adolescent athletes were willing to participate in competition in spite of joint pain. The willingness was higher among female athletes, athletes with a higher number of competitions, athletes living in a boarding school, and athletes in weight-dependent sports. CONCLUSIONS: The fact that more than four out of ten adolescent elite athletes are willing to compete despite joint pain is alarming because joint pain can have severe long-term health consequences. It is important that trainers, managers and physicians offer assistance in the treatment of joint pain and support them as much as possible in therapy and pain management. The overarching aim should be to prevent irreversible damage as well as a premature end of the sports career.


Assuntos
Atletas , Esportes , Adolescente , Artralgia , Traumatismos em Atletas , Feminino , Humanos , Masculino
7.
Ann Oncol ; 29(3): 707-714, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29253068

RESUMO

Background: Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods: Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results: Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions: Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov: NCT00790036.


Assuntos
Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante/métodos , Everolimo/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/mortalidade , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Everolimo/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Vincristina/uso terapêutico , Adulto Jovem
8.
Epidemiol Infect ; 146(12): 1550-1555, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29914582

RESUMO

Escherichia coli O157:H7 is the largest cause of hemolytic uremic syndrome (HUS). Previous studies proposed that HUS risk varies across the E. coli O157:H7 phylogenetic tree (hypervirulent clade 8), but the role of age in the association is unknown. We determined phylogenetic lineage of E. coli O157:H7 isolates from 1160 culture-confirmed E. coli O157:H7 cases reported in Washington State, 2004-2015. Using generalised estimating equations, we tested the association between phylogenetic lineage and HUS. Age was evaluated as an effect modifier. Among 1082 E. coli O157:H7 cases with both phylogenetic lineage and HUS status (HUS n = 76), stratified analysis suggested effect modification by age. Lineages IIa and IIb, relative to Ib, did not appear associated with HUS in children 0-9-years-old. For cases 10-59-years-old, lineages IIa and IIb appeared to confer increased risk of HUS, relative to lineage Ib. The association reversed in ⩾60-year-olds. Results were similar for clade 8. Phylogenetic lineage appears to be associated with HUS risk only among those ⩾10-years-old. Among children <10, the age group most frequently affected, lineage does not explain progression to HUS. However, lineage frequency varied across age groups, suggesting differences in exposure and/or early disease manifestation.


Assuntos
Infecções por Escherichia coli/microbiologia , Escherichia coli O157/isolamento & purificação , Síndrome Hemolítico-Urêmica/microbiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Infecções por Escherichia coli/epidemiologia , Feminino , Síndrome Hemolítico-Urêmica/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Filogenia , Estudos Retrospectivos , Washington/epidemiologia
9.
BMC Public Health ; 18(1): 189, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29378550

RESUMO

BACKGROUND: Evaluation and monitoring methods are often unable to identify crucial elements of success or failure of integrated community-wide approaches aiming to tackle childhood overweight and obesity, yet difficult to determine in complex programmes. Therefore, we aimed to systematically appraise strengths and weaknesses of such programmes and to assess the usefulness of the appraisal tools used. METHODS: To identify strengths and weaknesses of the integrated community-based approaches two tools were used: the Good Practice Appraisal tool for obesity prevention programmes, projects, initiatives and intervention (GPAT), a self-administered questionnaire developed by the WHO; and the OPEN tool, a structured list of questions based on the EPODE theory, to assist face-to-face interviews with the principle programme coordinators. The strengths and weaknesses of these tools were assessed with regard to practicalities, quality of acquired data and the appraisal process, criteria and scoring. RESULTS: Several strengths and weaknesses were identified in all the assessed integrated community-based approaches, different for each of them. The GPAT provided information mostly on intervention elements whereas through the OPEN tool information on both the programme and intervention levels were acquired. CONCLUSION: Large variability between integrated community-wide approaches preventing childhood obesity in the European region was identified and therefore each of them has different needs. Both tools used in combination seem to facilitate comprehensive assessment of integrated community-wide approaches in a systematic manner, which is rarely conducted. Nonetheless, the tools should be improved in line to their limitations as recommended in this manuscript.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Prestação Integrada de Cuidados de Saúde , Promoção da Saúde/métodos , Obesidade Infantil/prevenção & controle , Adolescente , Criança , Pré-Escolar , Europa (Continente) , Humanos , Lactente , Recém-Nascido , Avaliação de Programas e Projetos de Saúde , Adulto Jovem
10.
Br J Anaesth ; 118(3): 407-414, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28203729

RESUMO

Background: In children younger than 4 yr, it is difficult to distinguish the cause of postoperative distress, such as thirst, pain, and emergence delirium. This may lead to inappropriate treatment, such as administration of opioids. The aim of this study was to evaluate the influence of early postoperative oral fluid intake on the use of opioid analgesics and the incidence of postoperative vomiting (POV) after paediatric day case surgery. Methods: After ethics committee approval and with parental informed consent, planned day surgery patients aged 6 months to 4 yr were randomized to the liberal group (LG), in which apple juice (10 ml kg−1) was offered first if the Face Legs Activity Cry COnsolability (FLACC) score was ≥4 in the PACU, or to the control group (CG), in which children were treated after surgery according to the institutional opioid protocol, and drinking was allowed only upon the return to the ward. Bayesian statistical analysis was used to compare POV incidence and opioid use across groups. Results: Data from 231 patients were analysed. The incidence of POV in the LG and the CG was 11.40 and 23.93%, respectively. An opioid was needed in 14.04% (mean total dose: 0.18 mg kg−1) and 35.89% (mean total dose: 0.20 mg kg−1) of the patients in the LG and the CG. The PACU stay was 53.45 and 65.05 min in the LG and the CG, respectively (all differences were statistically significant). Conclusions: In our paediatric outpatient setting, early postoperative oral fluid intake was associated with a reduction in opioid use and POV incidence. These results deserve confirmation in other settings. Clinical trial registration: NCT02288650.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Analgésicos Opioides , Hidratação/métodos , Dor Pós-Operatória/prevenção & controle , Cuidados Pós-Operatórios/métodos , Náusea e Vômito Pós-Operatórios/prevenção & controle , Pré-Escolar , Feminino , Humanos , Masculino , Dor Pós-Operatória/tratamento farmacológico , Período Pós-Operatório
11.
Klin Onkol ; 30(3): 190-196, 2017.
Artigo em Tcheco | MEDLINE | ID: mdl-28612615

RESUMO

BACKGROUND: At the time of diagnosis, most patients with acute myeloid leukemia are older than 65 years of age. Treatment of this group of patients is challenging because they become less tolerant to aggressive chemotherapy with increasing age. Less than one-third of elderly patients are considered eligible for intensive treatment; nevertheless, the survival analysis for this population remains poor. Due to numerous comorbidities and an overall deteriorating condition, most elderly patients with acute myeloid leukemia receive only palliative or best supportive care, which are associated with a high mortality rate. New therapeutic approaches are expected to improve the overall survival and quality of life of this group of patients. These promising treatments include cell kinase inhibitors, cytotoxic agents, monoclonal antibodies, and epigenetic therapy including hypomethylating agents and inhibitors of isocitrate dehydrogenase and histone deacetylase. In monotherapy, these new drugs show lower levels of toxicity than those commonly used in chemotherapy; however, they do not lead to a better long-lasting treatment response. To enhance therapeutic efficacy, combinations of the above-mentioned treatments are often used, and, during clinical trials, combinations with standard cytostatics are also common. The promising results of these studies show that even low-toxicity therapies can lead to a better overall treatment response and to longer overall survival. AIM: This article provides a brief overview of new drugs that are evaluated for their mechanism of effect, efficacy and toxicity in therapy of patients suffering from acute myeloid leukemia.Key words: acute myeloid leukemia - elderly - FLT3 inhibitors - epigenetic therapy - monoclonal antibodies The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 11. 2016Accepted: 13. 12. 2016.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino
12.
Klin Onkol ; 30(Supplementum1): 163-165, 2017.
Artigo em Tcheco | MEDLINE | ID: mdl-28471196

RESUMO

BACKGROUND: Molecular pathogenesis of follicular lymphoma (FL) is characterized by substantial dysregulation of epigenetic regulators. Many cases of FL are associated with the aberrant expression of non-coding regulatory RNAs, namely microRNAs (miRNA). Here we studied changes in miRNA expression and their association with histological transformation of FL to diffuse large B-cell lymphoma (DLBCL). MATERIAL AND METHODS: To identify changes in miRNA levels during FL transformation we performed a global expression analysis of 377 miRNAs in 16 samples (8 pairs) from FL patients vs. transformed FL (tFL) (TLDA miRNA cards; Thermo Fisher Scientific). The association of miRNA expression with clinical-biological characteristics and target proteins were further analyzed in a cohort of 89 FL patients. RESULTS: The miRNA expression profiling of paired FL-tFL samples revealed statistically significant changes in the expression of five miRNAs (p < 0.05). Four of them were down-regulated and one was up-regulated in tFL compared to FL. Lower levels of one of these miRNA were also associated with higher proliferation rate of FL cells (Ki-67 > 20%), higher FLIPI score ( 3) and shorter overall survival of FL patients. Furthermore, we found that this miRNA regulates the levels of FOXP1 protein in FL. The patients with high-level FOXP1 expression (> 70% positive cells) had significantly shorter overall survival in comparison to those with low-level FOXP1 expression (< 30% positive cells). Moreover, FOXP1 protein levels were higher in most tFL samples compared to FL before transformation. CONCLUSION: We found miRNAs associated with the transformation of FL to a more aggressive DLBCL, and described that one of them could serve as a prognostic marker. We found that reduced expression of this tFL-associated miRNA results in increased levels of FOXP1 protein and we assume that the increased activity of FOXP1 proto-oncogene contributes to the histological transformation of FL.Key words: follicular lymphoma - microRNA - histological transformation This work was supported by Czech Ministry of Health registration No. 16-29622A. All rights reserved. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 5. 3. 2017Accepted: 26. 3. 2017.


Assuntos
Transformação Celular Neoplásica , Linfoma Folicular/genética , Linfoma Difuso de Grandes Células B/patologia , MicroRNAs/fisiologia , Fatores de Transcrição Forkhead/análise , Humanos , Linfoma Folicular/etiologia , Linfoma Folicular/patologia , MicroRNAs/análise , Proto-Oncogene Mas , Proteínas Repressoras/análise
13.
Epidemiol Infect ; 144(5): 1075-83, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26449886

RESUMO

Initial infection with the sentinel respiratory pathogen in children with cystic fibrosis (CF), Pseudomonas aeruginosa (Pa), is generally with environmental strains of this ubiquitous organism. The purpose of this study was to evaluate the associations between meteorological and geographical factors and risk of initial Pa acquisition in young children with CF. Using the U.S. Cystic Fibrosis Foundation Patient Registry from 2003 to 2009, 3463 patients met inclusion criteria, of which 48% (n = 1659) acquired Pa during follow-up. From multivariable Weibull regression, increased risk of Pa acquisition was associated with increasing temperature [hazard ratio (HR) per 1 °C: 1·13; 95% confidence interval (CI) 1·08-1·13], dew point (HR per 1 °C: 1·10, 95% CI 1·07-1·13), rainfall (HR per cm: 1·10, 95% CI 1·07-1·12), latitude (HR per 1 °C northing: 1·15, 95% CI 1·11-1·20), longitude (HR per 1 °C easting: 1·01, 95% CI 1·01-1·02) and elevation (HR per 100 m: 1·05, 95% CI 1·03-1·07). These results suggest that environmental factors may play a previously unrecognized role in the aetiology of initial Pa acquisition.


Assuntos
Fibrose Cística/epidemiologia , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/fisiologia , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Fibrose Cística/genética , Feminino , Geografia , Humanos , Lactente , Recém-Nascido , Masculino , Modelos de Riscos Proporcionais , Infecções por Pseudomonas/microbiologia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Tempo (Meteorologia)
14.
Unfallchirurg ; 119(5): 408-13, 2016 May.
Artigo em Alemão | MEDLINE | ID: mdl-27160727

RESUMO

BACKGROUND: Prosthetic replacement after amputation or loss of function of the upper extremity has gained therapeutic value over the last years. The control of upper arm prostheses has been refined by the use of selective nerve transfers, and the indication for prosthetic replacement has been expanded. OBJECTIVES: Overview regarding surgical, therapeutic and prosthetic options in upper extremity amputations or their loss of function. METHODS: Selective literature research including the authors' own experience in everyday clinical practice, as well as a review of medical records. RESULTS: Selective nerve transfers of the amputated nerves of the brachial plexus to the remaining stump muscles can create up to six myosignals for intuitive and simultaneous control of the different prosthetic joints. This way, an efficient and harmonious control of the prosthetic device is possible without the need to change between the different control levels. The prosthetic replacement, with consequent elective amputation, represents a new approach in the functional reconstruction of the upper extremity, especially in patients with a functionless hand after massive soft tissue or nerve damage.


Assuntos
Cotos de Amputação/cirurgia , Amputação Cirúrgica/reabilitação , Traumatismos do Braço/reabilitação , Traumatismos do Braço/cirurgia , Membros Artificiais , Robótica/instrumentação , Análise de Falha de Equipamento , Exoesqueleto Energizado , Desenho de Prótese , Robótica/métodos , Resultado do Tratamento
15.
Klin Onkol ; 29(6): 411-418, 2016.
Artigo em Tcheco | MEDLINE | ID: mdl-27951719

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a clinically complex and very heterogeneous disease at the molecular level. Conventional cytogenetic analysis and FISH (fluorescence in situ hybridization) tests provide important information about the biological and clinical background of the disease and enable the classification of AML patients into three risk groups. However, up to half of patients have normal cytogenetics. Determining prognosis and treatment strategies in this group of patients is challenging. The development of molecular genetic methods, including next generation sequencing in the last decade, has led to the discovery of a number of recurrent mutations that have contributed to increasing the accuracy of prognosis of those patients with cytogenetically normal AML. Besides the prognostic value of these mutations, they may also be used to monitor minimal residual disease during and after treatment of AML and additionally constitute potential targets for the development of new therapeutic agents. The importance of molecular genetic testing of all patients with AML is highlighted by the WHO classification of 2008 in which subgroups of AML are purely defined by molecular genetics markers. AIM: In this article, we provide an overview of the most significant mutations in patients with cytogenetically normal AML. We describe their significance for prognosis, their importance in monitoring minimal residual disease, and their potential for the development of new targeted therapies. Further, we briefly draw attention to the significance of gene mutation accumulation in clonal disease development and how it affects the time of AML relapse.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Biomarcadores , Análise Mutacional de DNA , Testes Genéticos , Humanos , Prognóstico , Recidiva
16.
Ann Oncol ; 26(10): 2155-61, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26216382

RESUMO

BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. PATIENTS AND METHODS: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.


Assuntos
Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Síndrome de Lise Tumoral/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Seguimentos , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Síndrome de Lise Tumoral/sangue , Ácido Úrico/sangue , Adulto Jovem
17.
Phys Rev Lett ; 115(7): 076402, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26317735

RESUMO

The origin of the martensitic transition in the magnetic shape memory alloy Ni-Mn-Ga has been widely discussed. While several studies suggest it is electronically driven, the adaptive martensite model reproduced the peculiar nonharmonic lattice modulation. We used femtosecond spectroscopy to probe the temperature and doping dependence of collective modes, and scanning tunneling microscopy revealed the corresponding static modulations. We show that the martensitic phase can be described by a complex charge-density wave tuned by magnetic ordering and strong electron-lattice coupling.

19.
Neoplasma ; 62(5): 787-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26278142

RESUMO

Mobilization of peripheral blood stem cells (PBSC) using the granulocyte colony-stimulating factor (G-CSF) has enabled the collection even from older donors and those with comorbidities. Several clinical parameters have been reported to predict the success of PBSC mobilization. The aim of our study was to evaluate the safety of PBSC donation in a cohort of 167 sibling donors after mobilization with G-CSF 16 µg/kg/day for 5 days during short- and long term follow-up and to analyse the efficacy, toxicity and factors influencing CD34+ mobilization capacity. All 167 sibling donors completed the established mobilization protocol. The median yield was 7.9x106 CD34 cells/kg per recipient weight. The optimal target dose of CD34 cells ≥ 4.0x106/kg was achieved in 140 donors (84%). Only in 4 donors (2%) was the CD34+ yield < 2x106/kg. No major toxicities occured.Factors associated with higher PBSC yields included age 51/µL (p 45.5 x 109/L (p = 0.003). Comorbidity score, performance status and donor weight did not significantly influence PBSC yields. Long-term follow-up was possible in 60% (101/167) of the donors. The median length of follow-up from PBSC donation was 11.9 years. Most of these donors reported good or very good general health (91%), and no hematological malignancies were observed.The mobilization of PBSC in sibling donors with G-CSF 16 µg/kg/day is an effective and safe procedure with no significant short- and long-term toxicities.

20.
J Assist Reprod Genet ; 32(8): 1187-93, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25724588

RESUMO

PURPOSE: Aim of this prospective observational study was to analyze fertility status of Hodgkin lymphoma (HL) patients treated with different types of chemotherapy while receiving GnRH analogues to preserve ovarian function. METHODS: Fertility status was assessed among 108 females in reproductive age treated by curative chemotherapy for freshly diagnosed HL between 2005 and 2010 in university-based tertiary fertility and oncology center. All patients received GnRH analogues during chemotherapy to preserve their ovarian function. Their reproductive functions were assessed by follicle-stimulating hormone (FSH) measurement and pregnancy achievement. Ovarian function was determined separately in three groups with increasing gonadotoxicity of chemotherapy. RESULTS: One year following the treatment, normal ovarian function was found in 89 (82.4%) of patients. Two years after chemotherapy, 98 (90.7%) of patients retained their ovarian function, and 23 (21.3%) achieved clinical pregnancy during the follow-up period. Average FSH after chemotherapy was 11.6 ± 17.9 IU/l 1 year after the treatment resp. 9.0 ± 13.8 at the 2 years interval. There were significantly more patients with chemotherapy induced diminished ovarian reserve (chDOR) among the group receiving escalated BEACOPP chemotherapy in comparison with the other types of treatment (58.1% vs. 87.9% resp. 95.5%). CONCLUSION: The rate of chDOR is significantly higher after EB poly-chemotherapy and there is no tendency for improvement in time. The 2 + 2 chemotherapy with GnRH-a required for more advanced HL retained ovarian function significantly better after 2 years. Another important advantage of GnRH-a co-treatment is the excellent control of patient's menstrual cycle.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Preservação da Fertilidade/métodos , Hormônio Liberador de Gonadotropina/análogos & derivados , Doença de Hodgkin/tratamento farmacológico , Ovário/fisiologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Hormônio Foliculoestimulante/sangue , Doença de Hodgkin/fisiopatologia , Humanos , Ovário/efeitos dos fármacos , Gravidez , Estudos Prospectivos , Adulto Jovem
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