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BACKGROUND: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis. METHODS: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. RESULTS: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. CONCLUSIONS: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 .
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Neoplasias da Mama , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Cognição , Exercício Físico , Fadiga/induzido quimicamente , Feminino , Humanos , Oxigênio , Consumo de Oxigênio , Qualidade de Vida , Resultado do TratamentoRESUMO
Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Transporte Ativo do Núcleo Celular , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Humanos , Hidrazinas , TriazóisRESUMO
Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied.
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Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Embolia Pulmonar/diagnóstico , Algoritmos , Biomarcadores/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tomografia Computadorizada Espiral , Resultado do TratamentoRESUMO
Essentials The value of compression therapy in acute phase of deep vein thrombosis is still unclear. Patients with deep vein thrombosis received acute compression hosiery, bandaging, or none. Acute compression reduces irreversible skin signs related to post thrombotic syndrome. Compression hosiery may be the preferred choice for the acute phase SUMMARY: Background The effectiveness of compression therapy in the acute phase of deep vein thrombosis (DVT) is not yet determined. Objectives To investigate the impact of compression therapy in the acute phase of DVT on determinants of the Villalta score, health-related quality of life (HRQOL), and costs. Patients/Methods Eight hundred and sixty-five patients with proximal DVT (substudy of the IDEAL DVT study) received, immediately after DVT diagnosis, either no compression, multilayer bandaging, or hosiery. In the acute phase and 3 months after diagnosis, HRQOL was determined by use of the EQ-5D, SF6D, and VEINES-QoL intrinsic method (VEINES-QoLint ). At 3 months, signs and symptoms were assessed for the total and separate items of the Villalta score, and healthcare costs were calculated. Results The compression groups had lower overall objective Villalta scores than the no-compression group (1.47 [standard deviation (SD) 1.570] and 1.59 [SD 1.64] versus 2.21 [SD 2.15]). The differences were mainly attributable to irreversible skin signs (induration, hyperpigmentation, and venectasia) and pain on calf compression. Subjective and total Villalta scores were similar across groups. Differences in HRQOL were only observed at 1 month; HRQOL was better for hosiery (EQ-5D 0.86 [SD 0.18]; VEINES-QoLint 0.66 [SD 0.18]) than for multilayer compression bandaging (EQ-5D 0.81 [SD 0.23; VEINES-QoLint 0.62 [SD 0.19]). Mean healthcare costs per patient were 417.08 (354.10 to 489.30) for bandaging, 114.25 (92.50 to 198.43) for hosiery, and 105.86 (34.63 to 199.30) for no compression. Conclusions Initial compression reduces irreversible skin signs, edema, and pain on calf compression. Multilayer bandaging is slightly more effective than hosiery, but has substantially higher costs, without a gain in HRQOL. From a patient and economic perspective, compression hosiery would be preferred when initial compression is applied. TRIAL REGISTRATION: IDEAL DVT study ClinicalTrials.gov number, NCT01429714.
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BACKGROUND: Advanced imaging techniques as magnetic resonance imaging (MRI) are increasingly performed in the diagnostic workup of patients. Incidentally, diffuse signal alterations of the bone marrow are detected because MRI visualises various components of the bone marrow. The clinical significance of these signal alterations is unknown. OBJECTIVE: The main goal of this study was to determine the diagnostic value of a bone marrow biopsy in patients with incidentally found diffuse signal alterations of the bone marrow. METHODS: We retrospectively examined all bone marrow biopsies performed from 1 January 2007 to 31 December 2013 (n = 1947). Patients were included when the biopsy was obtained following an MRI with a diffuse abnormal bone marrow signal. Patients who underwent MRI for suspected malignancy were excluded. Histological and cytological results of the bone marrow examinations were analysed. RESULTS: 15 of the 1947 bone marrow biopsies (0.77%) were performed because of diffuse signal alterations on MRI. In seven of these 15 bone marrow biopsies (47%) a clinically important haematological disorder was found. Eight patients had a normal bone marrow evaluation. CONCLUSION: Based on this retrospective study, a bone marrow examination in patients with incidentally detected diffuse signal alterations should be considered to exclude haematological pathology. Prospective studies have to be performed to further investigate the best diagnostic strategy.
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Biópsia , Medula Óssea/patologia , Doenças Hematológicas/patologia , Achados Incidentais , Imageamento por Ressonância Magnética , Adulto , Idoso , Feminino , Doenças Hematológicas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Hypereosinophilic syndrome is a heterogeneous group of disorders characterised by hypereosinophilia and organ involvement of varying intensity. We describe involvement of the heart in patients with hypereosinophilic syndrome,and the diagnostic and therapeutic clinical management of these patients.
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Cardiopatias/etiologia , Síndrome Hipereosinofílica/complicações , Corticosteroides/uso terapêutico , Humanos , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/patologia , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , TroponinaRESUMO
BACKGROUND: Post-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) affecting a large number of patients. Because of its potential debilitating effects, identification of patients at high risk for the development of this syndrome is relevant, and only a few predictors are known. OBJECTIVES: To assess the incidence and potential predictors of PTS. METHODS: We prospectively followed 111 consecutive patients for 2 years after a first episode of objectively documented DVT of the leg. With non-invasive venous examinations, residual thrombosis, valvular reflux, calf muscle pump function and venous outflow resistance were assessed at 6 weeks, 3 months, 6 months, 1 year, and 2 years. The Clinical, Etiologic, Anatomic, and Pathophysiologi classification was used to record the occurrence and severity of PTS. Regression analysis with area under the receiver operating characteristic (ROC) curve was performed to identify potential predictors. RESULTS: The cumulative incidence of PTS was 46% after 3 months, and the incidence and severity did not increase further. Men appeared to be at increased risk as compared with women (risk ratio [RR] 1.4, 95% confidence interval [CI] 0.9-2.2), as were patients over 50 years as compared with younger patients (RR 1.4%, 95% CI 0.9-2.1). Patients with thrombosis localized in the proximal veins at diagnosis had an increased risk of PTS as compared with patients with distal thrombosis (RR 2.3%, 95% CI 1.0-5.6). PTS developed in 32 of 52 patients (62%) with residual thrombosis in the proximal veins 6 weeks after diagnosis, as compared with 17 of 45 patients (38%) without residual proximal thrombosis, leading to a 1.6-fold increased risk (95% CI 1.0-2.5). The presence of valvular reflux in the superficial veins was also a predictor at 6 weeks, with a 1.6-fold increased risk as compared with patients without superficial reflux (95% CI 1.1-2.3). A multivariate analysis of these predictors yielded an area under the ROC curve of 0.72 (95% CI 0.62-0.82). CONCLUSIONS: PTS develops in half of all patients within 3 months, with no further increase being seen up to 2 years of follow-up. Male sex, age over 50 years, proximal localization of the thrombus at entry, residual proximal thrombosis and superficial valvular reflux at 6 weeks seem to be the most important predictors of PTS in patients with a first episode of DVT. Duplex scanning 6 weeks after diagnosis appears to be clinically useful for the identification of patients at risk of PTS.
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Síndrome Pós-Flebítica/etiologia , Trombose Venosa/complicações , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Trombose Venosa/fisiopatologiaRESUMO
BACKGROUND: Post-thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). OBJECTIVES: To determine the risk of PTS after DVT and to assess risk factors for PTS. METHODS: Patients were recruited from the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Consecutive patients who suffered a first DVT of the leg were included in a follow-up study. All patients completed a questionnaire and DNA was obtained. PTS was ascertained in a structured interview using a clinical classification score. RESULTS: The 1-year cumulative incidence of PTS was 25% and 7% for severe PTS. Elastic compression stockings were prescribed in 1412 (85%) patients. The majority used their stockings every day. Women were at an increased risk compared with men [risk ratio (RR) 1.5, 95% confidence interval (CI) 1.3-1.8]. Similarly, obese patients had a 1.5-fold increased risk of PTS compared with normal weight patients (RR 1.5, 95% CI 1.2-1.9), with a 1-year cumulative incidence of 34% compared with 22%. Patients who already had varicose veins had an increased risk (RR 1.5, 95% CI 1.2-1.8) of PTS. DVT in the femoral and iliac vein was associated with a 1.3-fold increased risk of PTS compared with popliteal vein thrombosis (RR 1.3, 95% CI 1.1-1.6). Patients over 60 years were less likely to develop PTS than patients below the age of 30 (RR 0.6, 95% CI 0.4-0.9). Malignancy, surgery, minor injury, plaster cast, pregnancy or hormone use did not influence the risk of PTS neither did factor (F)V Leiden nor the prothrombin 20210A mutation. CONCLUSIONS: PTS is a frequent complication of DVT, despite the widespread use of elastic compression stockings. Women, obese patients, patients with proximal DVT and those with varicose veins have an increased risk of PTS, whereas the elderly appeared to have a decreased risk.
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Síndrome Pós-Trombótica/etiologia , Trombose Venosa/complicações , Adulto , Fatores Etários , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade , Síndrome Pós-Trombótica/epidemiologia , Fatores de Risco , Fatores Sexuais , Meias de Compressão/estatística & dados numéricos , Inquéritos e Questionários , Varizes , Trombose Venosa/epidemiologiaRESUMO
OBJECTIVES: Diagnostic strategies in patients with suspected pulmonary embolism have been extensively studied in outpatients; their value in hospitalized patients has not been well established. Our aim was to determine the safety and clinical utility of a simple diagnostic strategy in hospitalized patients with suspected pulmonary embolism. DESIGN: Prospective management study. SETTING: Twelve teaching hospitals (five academic, seven general hospitals). SUBJECT: A total of 605 hospitalized patients with clinically suspected pulmonary embolism. All patients completed the study. INTERVENTIONS: First the clinical decision rule (CDR)-score was calculated. An unlikely CDR-score in combination with a normal D-dimer excluded pulmonary embolism. All other patients underwent helical computed tomography (CT). CT either diagnosed or excluded pulmonary embolism, in which case anticoagulants were started or withheld. All patients were instructed to report symptoms of venous thrombosis. Objective tests were performed to confirm venous thromboembolism. The primary outcome was the incidence of symptomatic venous thrombosis during 3-month follow-up. RESULTS: The combination of an unlikely CDR-score and a normal D-dimer excluded pulmonary embolism in 60 patients (10% of all patients); no venous thromboembolic event occurred during follow-up (0%; 95% CI 0-6.7%). CT excluded pulmonary embolism in 380 patients; during follow-up venous thromboembolism occurred in five patients (1.4%; 95% CI 0.4-3.1%). CONCLUSIONS: An unlikely CDR-score in combination with a normal D-dimer appears to exclude pulmonary embolism safely in hospitalized patients. Before clinical implementation it is important this safety is confirmed by others. CT testing was obviated in only 10% of patients. CT can safely exclude pulmonary embolism in hospitalized patients.