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1.
Hand Surg Rehabil ; 41(5): 638-643, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35850181

RESUMO

Open carpal tunnel release (OCTR) under wide-awake local anesthesia with no tourniquet (WALANT) is a common outpatient procedure in hand surgery worldwide. In our clinic, WALANT has replaced intravenous regional anesthesia with a tourniquet (IVRA, or 'Bier block') as standard practice in OCTR. We therefore wondered what the optimal postoperative setting after OCTR under WALANT is. In this study, we compared patient satisfaction in two postoperative settings: immediate discharge (ID) after the operation, or short postoperative monitoring (PM) period in the outpatient clinic. Our hypothesis was that older patients would prefer a brief postoperative surveillance. We retrospectively analyzed patient satisfaction with the two settings using an adjusted questionnaire based on the standard Swiss grading system. We also assessed postoperative pain, satisfaction with the perioperative preparations and the reasons for unscheduled postoperative consultations, as secondary outcomes. One hundred and nine patients (ID, n = 63; PM, n = 46) were included in this single-center retrospective observational study. Patients were highly satisfied with both postoperative settings (Mean: ID 5.1/6; PM 5.5/6; p = 0.07). Even patients aged ≥80 years reported extremely high satisfaction with both settings (ID 5.6/6; PM 6.0/6; p = 0.08). Fifteen patients (ID, n = 11 [17.5%]; PM, n = 4 [8.7%], p = 0.72) unexpectedly consulted a doctor after surgery. OCTR under WALANT as an outpatient procedure with immediate discharge was associated with high patient satisfaction. However, detailed postoperative monitoring could contribute to the patient's well-being and education on how to cope with the postoperative course, and help with any questions.


Assuntos
Anestesia por Condução , Síndrome do Túnel Carpal , Anestesia por Condução/métodos , Anestesia Local/métodos , Síndrome do Túnel Carpal/cirurgia , Humanos , Estudos Retrospectivos , Torniquetes
2.
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
3.
Leukemia ; 34(4): 966-984, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32127639

RESUMO

The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Compostos de Anilina/uso terapêutico , Tomada de Decisão Clínica , Conferências de Consenso como Assunto , Dasatinibe/uso terapêutico , Gerenciamento Clínico , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Expressão Gênica , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Expectativa de Vida/tendências , Monitorização Fisiológica , Nitrilas/uso terapêutico , Pirimidinas/uso terapêutico , Qualidade de Vida , Quinolinas/uso terapêutico , Análise de Sobrevida
4.
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.
Arq. bras. med. vet. zootec. (Online) ; 71(2): 594-602, mar.-abr. 2019. tab
Artigo em Português | LILACS, VETINDEX | ID: biblio-1011288

RESUMO

O objetivo deste trabalho foi avaliar a concentração sérica de cálcio, cloretos, ferro, fósforo e magnésio, as características morfométricas ósseas e a deposição de cálcio e fósforo nas tíbias de frangos de corte recebendo dieta com zero, 0,25 ou 0,50% de bentonita. Um ensaio foi conduzido com 288 frangos de corte de 14 a 21 dias de idade, submetidos a três dietas experimentais: sem inclusão (0,0); com inclusão de 0,25 e com inclusão de 0,50% do adsorvente bentonita. Não foram observadas diferenças (P>0,05) no desempenho das aves, nos níveis séricos de cálcio, cloretos, ferro e magnésio, no entanto os níveis de fósforo foram reduzidos (P<0,05) nas aves que ingeriram dieta com 0,50% de bentonita. Em relação às tíbias, observou-se redução (P<0,05) na matéria mineral (g e %) e no teor de cálcio com a inclusão de 0,50% de bentonita. Houve redução (P<0,05) nos níveis de fósforo das tíbias com a inclusão de 0,25 e 0,50% de bentonita. Conclui-se que a inclusão de até 0,50% do adsorvente de micotoxinas bentonita na dieta de frangos de corte não altera o desempenho zootécnico das aves. A inclusão de 0,25% de bentonita, na dieta de frangos de corte, não altera a concentração dos minerais séricos e a deposição de minerais nas tíbias, entretanto a inclusão de 0,5% reduz os níveis séricos de fósforo, o teor de matéria mineral e a concentração de cálcio e fósforo ósseos, sem afetar as características morfométricas ósseas.(AU)


The aim of this study was to evaluate performance, serum concentration of calcium, chloride, iron, magnesium, phosphorus, and bone characteristics, ash, calcium, and phosphorus in tibias of broilers receiving diet with zero, 0.25 or 0.50% of bentonite. No differences were found on performance of poultry, on serum mineral calcium, chloride, iron, magnesium, however phosphorus levels of broilers fed on diets containing 0.5% bentonite was reduced. With respect to tibia, reduction was observed on mineral matter (g and %) and calcium levels with inclusion of 0.50% bentonite, and reduction on phosphorus levels with inclusion of 0.25 or 0.50% of bentonite on diet. We conclude that the inclusion of up to 0.50% of mycotoxin adsorbent bentonite in diet of broiler does not change broiler performance. The inclusion of 0.25% of bentonite in diet of broiler does not change serum mineral concentration and mineral deposition; however, the inclusion of 0.5% decrease serum levels of phosphorus, the content of bone mineral matter, with not effects on bone morphometric characteristics.(AU)


Assuntos
Animais , Masculino , Bentonita/administração & dosagem , Bentonita/uso terapêutico , Desenvolvimento Ósseo , Antitoxinas/administração & dosagem , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Aditivos Alimentares/uso terapêutico , Ração Animal , Minerais/análise , Minerais/sangue , Galinhas/microbiologia
7.
Sci Rep ; 9(1): 3274, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30824737

RESUMO

Lanthanum tungstate (LWO) and LWO with 20 at.% and 35 at.% molybdenum substituting tungsten were prepared by the Pechini method. Phase purity and successful Mo substitution inside these dense LWO membrane materials were confirmed by conventional and high resolution transmission electron microscopy techniques. The split of La2/W2 site by around 0.3 Å was proven. Extra reflections show up in the diffraction patterns from Mo-substituted LWO, and together with simulations, these reflections were recognized as forbidden reflections in a non-substituted LWO system, while the extinction rules are broken by Mo substitution due to the different scattering factors of W and Mo. Energy-dispersive X-ray chemical mapping allowed direct visualization of individual atomic columns, and revealed that all Mo is located at the W1 sites in the Mo-substituted LWO. Moreover, the diffuse scattering in diffraction patterns provides direct evidence of short range clustering of oxygen vacancies and could be further related to the oxygen conduction of the LWO membranes.

8.
Leukemia ; 33(4): 969-980, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30315239

RESUMO

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adenina/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cloridrato de Bendamustina/administração & dosagem , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Piperidinas , Prognóstico , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Rituximab/administração & dosagem , Taxa de Sobrevida , Adulto Jovem
10.
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
11.
Leukemia ; 32(2): 450-461, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28744014

RESUMO

The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found TP53 mutations in 50 cases (0.2-16.3% VAF), regardless of disease subtype, driver gene status and cytoreduction. Both therapy and TP53 mutations were strongly associated with older age. Over-time analysis showed that the mutations may be undetectable at diagnosis and slowly increase during disease course. Although three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type AML, we did not observe a significant age-independent impact on overall survival during the follow-up. Further, we showed that complete p53 inactivation alone led to neither blast transformation nor HU resistance. Altogether, we revealed patient's age as the strongest factor affecting low-burden TP53 mutation incidence in MPN and found no significant age-independent association between TP53 mutations and hydroxyurea. Mutations may persist at low levels for years without an immediate risk of progression.


Assuntos
Hidroxiureia/administração & dosagem , Janus Quinase 2/genética , Mutação/genética , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Progressão da Doença , Feminino , Frequência do Gene/efeitos dos fármacos , Frequência do Gene/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Estudos Retrospectivos , Adulto Jovem
12.
Leukemia ; 31(11): 2398-2406, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28804124

RESUMO

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Análise de Sobrevida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Auton Neurosci ; 206: 19-27, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28688831

RESUMO

Existing experimental studies of the effect of sympathetic nerve fibers on bone marrow cells are based on the systemic administration of neurotoxic 6-hydroxydopamine. The method of global chemical sympathectomy has some serious disadvantages and could lead to questionable results. We describe a new method of local chemical sympathectomy of rat femoral bone marrow using guanethidine (Ismelin) delivery using an osmotic mini pump. Local guanethidine treatment for 14days led to complete elimination of sympathetic fibers in femoral bone marrow in contrast to bone marrow of contralateral or naïve femurs. Ablation of sympathetic fibers was associated with a loss of rat endothelial cell marker (RECA) indicating immunophenotype changes in blood vessel endothelial cells, but no significant effect of guanethidine was found on the survival of endothelial cells and mesenchymal stem cells in vitro. Moreover, local guanethidine treatment also elicited a significant reduction of Nestin+/SDF1+ mesenchymal stem cells and c-Kit+/CD90+ hematopoietic stem cells in femoral bone marrow. Tissue-specific chemical sympathectomy of rat bone marrow by guanethidine overcomes some of the drawbacks of systemic administration of neurotoxic compounds like 6-hydroxydopamine and delivers unequivocal evidence on the effects of sympathetic innervation on the cell content of bone marrow.


Assuntos
Medula Óssea/inervação , Guanetidina/farmacologia , Simpatolíticos/farmacologia , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Fêmur/efeitos dos fármacos , Fêmur/inervação , Fêmur/metabolismo , Fêmur/patologia , Citometria de Fluxo , Imunofluorescência , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Modelos Animais , Ratos Wistar , Simpatectomia Química , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/patologia
14.
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
15.
Leukemia ; 31(9): 1944-1950, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28626220

RESUMO

The use of darbepoetin alfa to treat anemia in patients with lower-risk myelodysplastic syndromes (MDS) was evaluated in a phase 3 trial. Eligible patients had low/intermediate-1 risk MDS, hemoglobin ⩽10 g/dl, low transfusion burden and serum erythropoietin (EPO) ⩽500 mU/ml. Patients were randomized 2:1 to receive 24 weeks of subcutaneous darbepoetin alfa 500 µg or placebo every 3 weeks (Q3W), followed by 48 weeks of open-label darbepoetin alfa. A total of 147 patients were randomized, with median hemoglobin of 9.3 (Q1:8.8, Q3:9.7) g/dl and median baseline serum EPO of 69 (Q1:36, Q3:158) mU/ml. Transfusion incidence from weeks 5-24 was significantly lower with darbepoetin alfa versus placebo (36.1% (35/97) versus 59.2% (29/49), P=0.008) and erythroid response rates increased significantly with darbepoetin alfa (14.7% (11/75 evaluable) versus 0% (0/35 evaluable), P=0.016). In the 48-week open-label period, dose frequency increased from Q3W to Q2W in 81% (102/126) of patients; this was associated with a higher hematologic improvement-erythroid response rate (34.7% (34/98)). Safety results were consistent with a previous darbepoetin alfa phase 2 MDS trial. In conclusion, 24 weeks of darbepoetin alfa Q3W significantly reduced transfusions and increased rates of erythroid response with no new safety signals in lower-risk MDS (registered as EudraCT#2009-016522-14 and NCT#01362140).


Assuntos
Anemia/tratamento farmacológico , Darbepoetina alfa/administração & dosagem , Síndromes Mielodisplásicas/complicações , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , Darbepoetina alfa/uso terapêutico , Eritropoetina/sangue , Feminino , Hemoglobinas/análise , Humanos , Masculino , Risco
16.
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
17.
Leukemia ; 31(11): 2347-2354, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28322237

RESUMO

Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82-99%) as compared to CTX/ATRA (78%, 95% CI, 64-87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80-93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.


Assuntos
Arsenicais/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Óxidos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trióxido de Arsênio , Feminino , Humanos , Leucemia Promielocítica Aguda/etiologia , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/genética , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
18.
Mucosal Immunol ; 10(6): 1387-1399, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28145440

RESUMO

Intestinal macrophages (mφ) form one of the largest populations of mφ in the body and are vital for the maintenance of gut homeostasis. They have several unique properties and are derived from local differentiation of classical Ly6Chi monocytes, but the factors driving this tissue-specific process are not understood. Here we have used global transcriptomic analysis to identify a unique homeostatic signature of mature colonic mφ that is acquired as they differentiate in the mucosa. By comparing the analogous monocyte differentiation process found in the dermis, we identify TGFß as an indispensable part of monocyte differentiation in the intestine and show that it enables mφ to adapt precisely to the requirements of their environment. Importantly, TGFßR signaling on mφ has a crucial role in regulating the accumulation of monocytes in the mucosa, via mechanisms that are distinct from those used by IL10.


Assuntos
Colo/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Antígenos Ly/metabolismo , Diferenciação Celular , Células Cultivadas , Microambiente Celular , Feminino , Perfilação da Expressão Gênica , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Especificidade de Órgãos , Receptores de Fatores de Crescimento Transformadores beta/genética , Transdução de Sinais , Transcriptoma
19.
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
20.
Animal ; 11(8): 1344-1353, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28007043

RESUMO

Heat stress has a significant impact on all livestock and poultry species causing economic losses and animal well-being concerns. Providing shade is one heat-abatement strategy that has been studied for years. Material selected to provide shade for animals greatly influences the overall stress reduction provided by shade. A study was conducted to quantify both the environment and animal response, when cattle had no shade access during summertime exposure or were given access to shade provided by three different materials. A total of 32 Black Angus heifers were assigned to one of the four treatment pens according to weight (eight animals per pen). Each pen was assigned a shade treatment: No Shade, Snow Fence, 60% Aluminet Shade Cloth and 100% Shade Cloth. In the shaded treatment pens, the shade structure covered ~40% of the pen (7.5 m2/animal). Animals were moved to a different treatment every 2 weeks in a 4×4 Latin square design to ensure each treatment was applied to each group of animals. Both environmental parameters and physiological responses were measured during the experiment. Environmental parameters included dry-bulb temperature, relative humidity, wind speed, black globe temperature (BGT), solar radiation (SR) and feedlot surface temperature. Animal response measurements included manual respiration rate (RRm), electronic respiration rate (RRe), vaginal temperature (body temperature (BT)), complete blood count (CBC) and plasma cortisol. The environmental data demonstrated changes proportional to the quality of shade offered. However, the animal responses did not follow this same trend. Some of the data suggest that any amount of shade was beneficial to the animals. However, Snow Fence may not offer adequate protection to reduce BT. For some of the parameters (BT, CBC and cortisol), 60% Aluminet and 100% Shade Cloth offers similar protection. The 60% Aluminet lowered RRe the most during extreme conditions. When considering all parameters, environmental and physiological, 60% Aluminet Shade Cloth offered reductions of BGT, SR, feedlot surface temperature and the best (or equal to the best) overall protection for the animals (RRe, RRm, BT, blood parameters).


Assuntos
Doenças dos Bovinos/prevenção & controle , Bovinos/fisiologia , Transtornos de Estresse por Calor/veterinária , Animais , Temperatura Corporal , Peso Corporal , Doenças dos Bovinos/fisiopatologia , Feminino , Transtornos de Estresse por Calor/fisiopatologia , Transtornos de Estresse por Calor/prevenção & controle , Temperatura Alta , Taxa Respiratória , Estresse Fisiológico , Luz Solar
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