RESUMO
BACKGROUND AND AIMS: The prevalence of lower extremity artery disease (LEAD) is increasing worldwide and sex-related differences are a current matter of debate. METHODS: We analysed claims data on unselected patients with in-patient treatment for LEAD with intermittent claudication (IC; Rutherford grade 1-3) from 01.01.2014 to 31.12.2015. Data files included diagnostic and procedural information from two years before index, and a five-year follow-up. RESULTS: Our analysis comprised 42,197 IC patients, thereof 28,520 (68%) male. Male patients were younger (median: 66.4 years vs. 72.6 years) but presented with higher frequency of cardiovascular risk factors such as diabetes (40% female vs. 46% male), atrial fibrillation (13% vs. 17%), chronic coronary syndrome (41% vs. 53%), chronic heart failure (23% vs. 27%), or chronic kidney disease (29% vs. 32%; all p < 0.001; age adjusted). Revascularisation applied in 80% of patients, thereof endovascular approach predominantly in female and surgery in male patients. Concomitant pharmacotherapy with statins (74% at 2 years) and platelet inhibitors (75% respectively) were long lasting below guideline recommendation, under-use being more pronounced in women. Two years after index, one-third of IC patients had subsequent revascularisation, one-quarter progressed to chronic limb threatening ischemia (CLTI), and 2% underwent amputation. Male sex was an independent risk factor for long-term mortality (female HR 0.75; 95%-CI 0.72-0.79; p < 0.001) and CLTI (female HR 0.89; 95%-CI 0.86-0.92; p < 0.001) during follow-up. CONCLUSIONS: The majority of in-patient treated patients for IC are male, presenting with worse cardiovascular risk profiles. In view of a general under-supply with statins and platelet inhibitors, women received somewhat less often preventive medication. Despite low LEAD stages at index, serious prognosis was observed in the long term. Particularly male patients were at high risk for all-cause mortality and the combined endpoint CLTI and death.
Assuntos
Procedimentos Endovasculares , Doença Arterial Periférica , Idoso , Amputação Cirúrgica , Feminino , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/epidemiologia , Claudicação Intermitente/terapia , Isquemia , Extremidade Inferior , Masculino , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/terapia , Fatores de Risco , Resultado do TratamentoRESUMO
DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/uso terapêutico , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Citarabina/uso terapêutico , Análise Citogenética , Daunorrubicina/uso terapêutico , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Análise de SobrevidaRESUMO
The purpose of this study was to evaluate whether the serum level of interleukin 6 (IL-6) could be used to identify the persistence of infection after the first stage of a two-stage revision for periprosthetic joint infection. Between 2010 and 2011, we prospectively studied 55 patients (23 men, 32 women; mean age 69.5 years; 36 to 86) with a periprosthetic joint infection. Bacteria were identified in two intra-operative tissue samples during re-implantation in 16 patients. These cases were classified as representing persistent infection. To calculate a precise cut-off value which could be used in everyday clinical practice, a 3 x 2 contingency table was constructed and manually defined. We found that a serum IL-6 ≥ 13 pg/mL can be regarded as indicating infection: its positive-predictive value is 90.9%. A serum IL-6 ≤ 8 pg/mL can be regarded as indicating an absence of infection: its negative predictive value is 92.1%. The serum IL-6 level seems to be a reasonable marker for identifying persistent infection after the first stage of a revision joint arthroplasty and before attempting re-implantation.
Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Interleucina-6/sangue , Infecções Relacionadas à Prótese/sangue , Infecções Relacionadas à Prótese/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Artroplastia de Quadril/métodos , Artroplastia do Joelho/métodos , Biomarcadores/sangue , Estudos de Coortes , Intervalos de Confiança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Infecções Relacionadas à Prótese/diagnóstico , Curva ROC , Reoperação/métodos , Medição de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Rhabdoid tumors mainly affect infants and other very young children with a marked vulnerability towards intensive therapy such as invasive surgery, high dose chemotherapy (HDCT) and dose intense radiotherapy. Radiotherapy (RT) is a promising option in rhabdoid tumors but its application in infants remains controversial. Neurocognitive and vascular side effects occur even long after completion of therapy. Therapeutic recommendations suggested by the European Rhabdoid Registry including RT, high dose chemotherapy (HDCT) and methotrexate (MTX) were developed by a consensus committee. Unique to our EU-RHAB database is the ability to analyze data of 64 of 81 registered infants (under one year of age) separate from older children. 20 (age at diagnoses 2-12 months) of these had received radiotherapy. To our knowledge, this is the first report specifically analyzing treatment data of infants suffering from malignant rhabdoid tumors. Our results suggest that radiotherapy significantly increases the mean survival time as well as the 3 year overall survival in infants. We detected a doubling of survival times in infants who received RT. Overall, our results suggest that infants benefit from RT with tolerable acute side effects. Severe long term sequelae likely due to intraventricular MTX and/or RT were reported in 4 patients (leukoencephalopathy). No differences in chemotherapy-related toxicity were observed between infants and children. We suggest that a nihilistic therapeutic approach towards young infants is not warranted and that RT may not be a priori rejected as a therapeutic option in infants.
Assuntos
Sistema de Registros , Tumor Rabdoide/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Dactinomicina/administração & dosagem , Dactinomicina/efeitos adversos , Estudos de Viabilidade , Alemanha , Humanos , Lactente , Recém-Nascido , Infusões Intraventriculares , Comunicação Interdisciplinar , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Dosagem Radioterapêutica , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/mortalidade , Taxa de SobrevidaRESUMO
UNLABELLED: Differentiated thyroid carcinomas (DTC) have an excellent prognosis, with 10-year overall survival rates over 90%. In addition, DTC patients benefit from their lifelong medical surveillance. The AIM of the study was to compare the patients' overall survival with that of a matched general population. PATIENTS AND METHODS: We have analyzed 1497 consecutive patients with DTC, who underwent radioiodine therapy in Münster, Germany, according to international standards. We classified our patients according to the current 7th edition of the UICC (Union Internationale Contre le Cancer) classification and we compared the overall survival of the patients with the expected survival based on age and sex of the general population as provided by the Federal Statistical Office, Germany. RESULTS: There were no significant differences in overall survival rates between DTC patients of the cohort in stages I to IVa compared to the expected survival based on age and sex of the general population. However, patients in stage IVc showed a significantly worse overall survival rate using the log-rank test (p < 0.0001). CONCLUSION: Patients with DTC showed excellent overall survival rates in stages I, II, III and IVa. All patients, except for those in stage IVc (M1 ≥ 45 years), had overall survival rates similar to the general population.
Assuntos
Radioisótopos do Iodo/uso terapêutico , Lesões por Radiação/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/radioterapia , Distribuição por Idade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Compostos Radiofarmacêuticos/uso terapêutico , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida , Resultado do TratamentoRESUMO
After allo-SCT, analysis of CD34(+) lineage-specific donor cell chimerism (DCC) is a sensitive method for monitoring minimal residual disease in patients with AML or myelodysplastic syndrome (MDS) with CD34 expression. To substantiate evidence of whether immune interventions in patients with impending relapse, defined by incomplete lineage-specific DCC, may prevent hematological relapse, we performed a retrospective nested case control study. Unsorted and lineage-specific DCC were measured in 134 patients. Forty-three patients had an incomplete CD34(+)-DCC with no other evidence of relapse. After immediate tapering of immunosuppressive treatment (30 patients) and/or infusion of donor lymphocytes (10 patients), 21 patients remained in remission (conversion to complete lineage-specific DCC) and 22 relapsed. Relapse-free survival at 3 years of the 91 patients with stable DCC and of the 43 patients with incomplete DCC was 74% (95% confidence interval (CI), 64-83%) and 40% (95% CI, 24-58%), respectively. OS rates were 79% (95% CI, 70-88%) and 52% (95% CI, 35-69%), respectively. These results, with 49% of patients with impending relapse successfully treated with immune intervention, highly suggest that analysis of CD34(+)-DCC is an important tool for monitoring and the management of AML and MDS patients after allo-SCT.
Assuntos
Antígenos CD34/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/imunologia , Leucemia Mieloide Aguda/cirurgia , Síndromes Mielodisplásicas/cirurgia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Quimerismo , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/imunologia , Recidiva , Estudos Retrospectivos , Quimeras de Transplante , Transplante Homólogo , Adulto JovemRESUMO
Peripheral artery disease is a progressive disease. Primary ischemic leg symptoms are muscle fatigue, discomfort or pain during ambulation, known as intermittent claudication. The most severe manifestation of peripheral artery disease is critical limb ischemia (CLI). The long-term safety of gene therapy in peripheral artery disease remains unclear. This four center peripheral artery disease registry was designed to evaluate the long-term safety of the intramuscular non-viral fibroblast growth factor-1 (NV1FGF), a plasmid-based angiogenic gene for local expression of fibroblast growth factor-1 versus placebo in patients with peripheral artery disease who had been included in five different phase I and II trials. Here we report a 3-year follow-up in patients suffering from CLI or intermittent claudication. There were 93 evaluable patients, 72 of them in Fontaine stage IV (47 NV1FGF versus 25 placebo) and 21 patients in Fontaine stage IIb peripheral artery disease (15 NV1FGF versus 6 placebo). Safety parameters included rates of non-fatal myocardial infarction (MI), stroke, death, cancer, retinopathy and renal dysfunction. At 3 years, in 93 patients included this registry, there was no increase in retinopathy or renal dysfunction associated with delivery of this angiogenic factor. There was also no difference in the number of strokes, MI or deaths, respectively, for NV1FGF versus placebo. In the CLI group, new cancer occurred in two patients in the NV1FGF group. Conclusions that can be drawn from this relatively small patient group are limited because of the number of patients followed and can only be restricted to safety. Yet, data presented may be valuable concerning rates in cancer, retinopathy, MI or strokes following angiogenesis gene therapy in the absence of any long-term data in angiogenesis gene therapy. It may take several years until data from larger patient populations will become available.
Assuntos
Fator 1 de Crescimento de Fibroblastos/genética , Vetores Genéticos/administração & dosagem , Doença Arterial Periférica/genética , Doença Arterial Periférica/terapia , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Feminino , Fator 1 de Crescimento de Fibroblastos/metabolismo , Seguimentos , Terapia Genética , Vetores Genéticos/efeitos adversos , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Neoplasias/complicações , Doença Arterial Periférica/complicações , Doença Arterial Periférica/mortalidade , Acidente Vascular Cerebral/complicações , Análise de SobrevidaRESUMO
Although BCR-ABL+ stem cells in chronic myeloid leukemia (CML) resist elimination by targeted pharmacotherapy in most patients, immunological graft-versus-leukemia effects can cure the disease. Besides cytotoxic T cells, natural killer (NK) cells may have a role in immune control of CML. Here, we explored the functionality of NK cells in CML patients and in a transgenic inducible BCR-ABL mouse model. Compared with controls, NK-cell proportions among lymphocytes were decreased at diagnosis of CML and did not recover during imatinib-induced remission for 10-34 months. Functional experiments revealed limited in vitro expansion of NK cells from CML patients and a reduced degranulation response to K562 target cells both at diagnosis and during imatinib therapy. Consistent with the results in human CML, relative numbers of NK1.1+ NK cells were reduced following induction of BCR-ABL expression in mice, and the defects persisted after BCR-ABL reversion. Moreover, target-induced degranulation by expanded BCR-ABL+ NK cells was compromised. We conclude that CML is associated with quantitative and functional defects within the NK-cell compartment, which is reproduced by induced BCR-ABL expression in mice. Further work will aim at identifying the mechanisms of NK-cell deficiency in CML and at developing strategies to exploit NK cells for immunotherapy.
Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Células Matadoras Naturais/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Antineoplásicos/farmacologia , Benzamidas , Degranulação Celular/genética , Degranulação Celular/imunologia , Criança , Modelos Animais de Doenças , Humanos , Mesilato de Imatinib , Células K562 , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Adulto JovemRESUMO
AIM: Duplication of 7q34 resulting in generation of BRAF-KIAA1549 fusion transcripts is a characteristic event in pilocytic astrocytoma that may also aid distinction from diffuse astrocytic tumours. As data on BRAF-KIAA1549 fusion transcript status remain mainly limited to children, we aimed to examine the diagnostic value of BRAF-KIAA1549 fusion transcripts across all age groups. METHODS: BRAF-KIAA1549 fusion transcript status was examined using reverse transcription polymerase chain reaction on formalin-fixed paraffin-embedded samples of 105 primary pilocytic astrocytomas [median patient age: 17 years (1-74 years)]. RESULTS: Informative results (distinct wildtype BRAF bands detectable) were obtained in 105/124 cases (85%). Fusion transcripts were detected in 53 of cases (51%). They were more often encountered in tumours of infratentorial location [42/67 (63%) vs. 11/38 (29%)] and comprised KIAA1549-Ex16_BRAF-Ex9 (32 cases), KIAA1549-Ex15_BRAF-Ex9 (14 cases) and KIAA1549-Ex16_BRAF-Ex11 (seven cases). Fusion transcripts were present in 79% of tumours diagnosed in the first decade of life, but only in 51% of patients aged 11-20 years, 42% of patients aged 21-30 years, 30% of patients aged 31-40 years and 7% of patients older than 40 years. On multivariate logistic regression analysis, the association of fusion transcript status and age was confirmed adjusting for tumour location (P = 0.006). CONCLUSIONS: The frequency of BRAF-KIAA1549 fusion transcripts is significantly lower in adult patients with pilocytic astrocytoma, weakening the sensitivity of this specific diagnostic marker in that age group.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Proteínas de Fusão Oncogênica/genética , Adolescente , Adulto , Fatores Etários , Idoso , Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-IdadeRESUMO
PURPOSE: To distinguish between benign and malignant mediastinal lymph nodes in patients with NSCLC by comparing 2D and semi-automated 3D measurements in FDG-PET-CT. PATIENTS, MATERIAL, METHODS: FDG-PET-CT was performed in 46 patients prior to therapy. 299 mediastinal lymph-nodes were evaluated independently by two radiologists, both manually and by semi-automatic segmentation software. Longest-axial-diameter (LAD), shortest-axial-diameter (SAD), maximal-3D-diameter, elongation and volume were obtained. FDG-PET-CT and clinical/FDG-PET-CT follow up examinations and/or histology served as the reference standard. Statistical analysis encompassed intra-class-correlation-coefficients and receiver-operator-characteristics-curves (ROC). RESULTS: The standard of reference revealed involvement in 87 (29%) of 299 lymph nodes. Manually and semi-automatically measured 2D parameters (LAD and SAD) showed a good correlation with mean intraclass coefficients of .80 and .72, respectively. Semi-automated prediction revealed the highest areas-under-the-ROC-curve for volume (.75, 95%CI: .69-81) and SAD (.75, 95%CI: .70-.81). AUC for LAD and maximal-3D diameter were about .68. Substantially lower accuracies were found for elongation (.57, 95%CI: .50-.64). CONCLUSION: Optimized semi-automated three dimensional parameters by CT cannot approximate reported data on FDG-PET-CT for lymph node assessment in NSCLC. SAD remains the most accurate and at the same time simple to achieve anatomical criterion for definition of NSCLC target lesions.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Fluordesoxiglucose F18 , Metástase Linfática/diagnóstico por imagem , Idoso , Automação , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Curva ROC , Radiografia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Medical research suggests benefits of vitamin E supplementation in treatment or prevention of cardiovascular disease, inflammatory joint diseases and cancer. Regardless of these benefits in a recently published meta analysis the authors drew the conclusion that high dose supplementation may cause a slight increase in mortality of the treated patients. The purpose of the present paper is to re-analyse the association of vitamin E supplementation and mortality. By means of augmented data sources as well as additional methodological approaches the results of the above mentioned meta analysis is to be either confirmed or called into question. In the above mentioned meta analysis 19 clinical trials comprising a total of 135967 participants were included. The dosages of vitamin E supplementation ranged from 16.5 to 2000 IU/d. In the present paper this data source was augmented and 10 additional trials were included (2495 additional participants receiving vitamin E doses from 136 to 5000 IU/d). Moreover in 2 of the originally included trials updated results of mortality at longer periods of follow-up were available. The present paper yields contradictory results regarding the association of vitamin E supplementation and mortality. Hierarchical logistic regression analyses confirm the former results showing an increased mortality of patients receiving high dose vitamin E. Furthermore a traditional methodological approach of meta-regression was applied to the same data source. Contrary to the former result it showed that the increased mortality odds ratio in certain trials is not due to the higher dose of vitamin E supplementation. Rather it can be explained by a higher proportion of male patients that were included in these trials compared to other trials. The causal relationship of vitamin E supplementation and increased mortality is questionable. Different methodological approaches of meta analysis yield contradictory results. Thus none of these results can be regarded to supply evidence in a statistical sense. In particular high dose vitamin E supplementation can not be regarded proved to increase mortality.
Assuntos
Suplementos Nutricionais/efeitos adversos , Metanálise como Assunto , Mortalidade , Vitamina E/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Razão de Chances , Fatores Sexuais , Vitamina E/administração & dosagemRESUMO
Compelling evidence indicates that microvessel density (MVD) is a prognostic marker in early nonsmall cell lung cancer (NSCLC). However, its role in lymph node metastases in stage III NSCLC receiving multimodality treatment is unknown. Lymph nodes of 142 patients with stage III NSCLC, treated in a trial of the German Lung Cancer Cooperative group, were evaluated for MVD. Median follow-up was 7.39 yrs. MVD was correlated with demographic and tumour-related variables and survival. MVD (median 33.9) did not correlate with survival. However, in multimodality-treated stage IIIA patients receiving tumour resection with negative margins (R0), those with a high MVD had significantly prolonged overall survival with a median of 4.96 yrs compared with 1.99 yrs for those with low MVD (p = 0.041). Cox regression analysis revealed that MVD was a prognostic factor in R0-resected stage IIIA (hazard ratio 0.417). Furthermore, a significant correlation of MVD to stage was observed, with significantly lower MVD in stage IIIA than IIIB (p = 0.0062), and a significant correlation of MVD to histological subtype was observed, with adenocarcinoma revealing the highest scores (p = 0.0001). Increased angiogenesis within lymph node metastases is a prognostic indicator for better survival in NSCLC patients. Thus, measurement of MVD might be useful in selecting patients for future neoadjuvant treatment decisions.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Neovascularização Patológica/patologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Terapia Combinada , Feminino , Alemanha , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
BACKGROUND: A novel urine test for early detection of prostate cancer (PCA), distributed and marketed by the company DiaPat, is advertised by the statement "correct analysis in 9 of 10 cases." PATIENTS AND METHODS: The test separates urinary polypeptides by means of capillary electrophoresis and characterizes the peptides in a time-of-flight mass spectrometer. The DiaPat test was performed on the urine of 18 men prior to multiple ultrasound-guided prostate biopsies. RESULTS: Sixteen of the 18 samples met the requirements for sample quality as established by the manufacturer. Eight of these 16 urine samples had been collected from patients in whom biopsies consecutively detected PCA; the remaining eight patients had benign biopsy results. Among the eight patients with detected PCA, the urine test yielded a low probability for PCA in three cases and a high probability in five. Within the group of eight patients with benign biopsy results, the urine test predicted a high probability for PCA in five men and a low probability in three. For the given PCA incidence of 50% within the investigated population, the DiaPat test correctly predicted biopsy results in one half of the population, whereas prediction in the remaining half was incorrect. CONCLUSION: Unless reliable validation of the DiaPat urine test for PCA is available, no clinical consequences should be drawn from the test results.
Assuntos
Biomarcadores Tumorais/urina , Proteínas de Neoplasias/urina , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/urina , Urinálise/métodos , Idoso , Eletroforese Capilar/métodos , Humanos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeAssuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Imunossupressores/uso terapêutico , Condicionamento Pré-Transplante , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Europa (Continente) , Saúde da Família , Humanos , Lactente , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Retrospectivos , Transplante HomólogoRESUMO
Angiogenesis plays an important role in solid tumors and hematologic malignancies. The angiopoietins act as essential regulators in this process. We investigated the impact of circulating angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and soluble Tie2 (sTie2) on overall survival in patients with acute myeloid leukemia (AML). Ang-1, Ang-2 and sTie2 were measured in plasma samples from 68 AML patients and 11 controls using enzyme-linked immunosorbent assay. Circulating levels of Ang-2 and sTie2 (median (range): 1098.0 (361.4-4147.6) pg/ml and 3.40 (1.21-10.00) ng/ml, respectively) were significantly elevated in AML patients as compared to controls (307.9 (199.7-1225.0) pg/ml and 2.88 (1.71-3.29) ng/ml; P<0.001 and P=0.014). In a univariate Cox proportional hazards model, higher levels of Ang-2 and sTie2 were predictive of poor survival. In multivariate analyses, Ang-2 and cytogenetics proved to be independent prognostic factors, with a relative risk of 4.07 (95% confidence interval (CI) 1.88-8.81) and 2.70 (95% CI 1.25-5.81), respectively. The 3-year survival rate for AML patients with Ang-2 levels>/=1495.6 pg/ml was only 14.7% compared to 64.7% for those with Ang-2 levels<1495.6 pg/ml. These data provide evidence that circulating Ang-2 represents an independent prognostic factor in AML and may be used as a prognostic tool in the risk-adapted management of AML.
Assuntos
Angiopoietina-2/sangue , Biomarcadores Tumorais/sangue , Leucemia Mieloide/sangue , Leucemia Mieloide/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiopoietina-1/sangue , Feminino , Humanos , Leucemia Mieloide/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Receptor TIE-2/sangue , Fatores de Risco , SolubilidadeRESUMO
The presence of histological variants of haemangioblastoma is well established, but data on the prognostic implications of histological subtyping are missing. We thus characterized clinical factors associated with histological subtypes, that is, of the cellular and reticular variant of haemangioblastoma, in a series of 88 consecutive primary haemangioblastomas of the central nervous system. Ten haemangioblastomas were classified as 'cellular' according to Cushing and Bailey. As compared to the more common 'reticular' variant (n = 78), the proportion of tumours containing glial fibrillary acidic protein-positive tumour cells (80% vs. 7%), as well as median Ki67 (MIB1) proliferation indices [4% (quartiles: 1-8%) vs. < 1% (<1-2%)], was significantly higher in cellular haemangioblastomas (P < 0.01). Recurrences were more frequent in the cellular variant [2/8 (25%) vs. 4/51 (8%)]. Kaplan-Meier analysis confirmed a significantly higher probability of recurrence in the cellular variant (Log-Rank test P < 0.01). Cox regression analysis not only confirmed the well established association of von Hippel-Lindau disease with tumour recurrence (P < 0.01), but also revealed an independent effect of histological subtype on the probability of recurrence (P < 0.05), whereas no significant influence of age, sex or tumour location was observed. To conclude, the results from this retrospective study suggest that histological subtyping of haemangioblastomas has prognostic implications and might contribute to identify patients at risk for recurrence.
Assuntos
Neoplasias Cerebelares/patologia , Hemangioblastoma/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Coluna Vertebral/patologia , Adolescente , Adulto , Idoso , Neoplasias Cerebelares/epidemiologia , Intervalo Livre de Doença , Feminino , Seguimentos , Hemangioblastoma/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Coluna Vertebral/epidemiologiaRESUMO
OBJECTIVE: Testosterone-containing gels have improved testosterone substitution therapy, but they are associated with the risk of interpersonal transfer. Therefore, we tested a new hydroalcoholic 2.5% testosterone gel (TGW), which was removed by washing 10 min after administration. DESIGN: The gel was applied to scrotal or non-scrotal skin in comparison to two 2.5 mg Androderm patches in a randomised, three-arm, parallel-group, controlled multicentre trial over a period of 24 weeks. We included symptomatic hypogonadal men whose morning testosterone levels were <10 nmol/l. Either 1 g TGW was applied to scrotal skin (n = 54) or 5 g to non-scrotal skin (n = 56) once daily; the patch group (n = 52) applied two patches/day. Dose titration was allowed. RESULTS: Whereas serum testosterone levels and the pre-post changes of the areas under the curve of testosterone and free testosterone between weeks 0 and 24 indicated equivalent treatment success for the patch and scrotal groups, the dermal gel group was significantly superior to the other two groups. Questionnaires on sexual function, mood and quality of life did not differ significantly between study groups, nor were prostate volume, prostate-specific antigen (PSA) levels and prostate symptoms different. However, tolerability was much better in the gel groups than the patch group. CONCLUSION: Efficacy, safety and tolerability suggest TGW as a favourable treatment for hypogonadal patients.