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1.
Sci Rep ; 14(1): 9665, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671061

RESUMO

This study clinically implemented a ready-to-use quantitative perfusion (QP) cardiovascular magnetic resonance (QP CMR) workflow, encompassing a simplified dual-bolus gadolinium-based contrast agent (GBCA) administration scheme and fully automated QP image post-processing. Twenty-five patients with suspected obstructive coronary artery disease (CAD) underwent both adenosine stress perfusion CMR and an invasive coronary angiography or coronary computed tomography angiography. The dual-bolus protocol consisted of a pre-bolus (0.0075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) and a main bolus (0.075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) at an infusion rate of 3 ml/s. The arterial input function curves showed excellent quality. Stress MBF ≤ 1.84 ml/g/min accurately detected obstructive CAD (area under the curve 0.79; 95% Confidence Interval: 0.66 to 0.89). Combined visual assessment of color pixel QP maps and conventional perfusion images yielded a diagnostic accuracy of 84%, sensitivity of 70% and specificity of 93%. The proposed easy-to-use dual-bolus QP CMR workflow provides good image quality and holds promise for high accuracy in diagnosis of obstructive CAD. Implementation of this approach has the potential to serve as an alternative to current methods thus increasing the accessibility to offer high-quality QP CMR imaging by a wide range of CMR laboratories.


Assuntos
Meios de Contraste , Doença da Artéria Coronariana , Fluxo de Trabalho , Humanos , Meios de Contraste/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Angiografia Coronária/métodos , Imagem de Perfusão do Miocárdio/métodos , Gadolínio/administração & dosagem
2.
Lung Cancer ; 187: 107440, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38104353

RESUMO

OBJECTIVES: Nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA-4) is a new first-line treatment combination for patients with pleural mesothelioma. Nivolumab-ipilimumab improved the survival, however, 30.3% of the patients suffered from grade 3-4 treatment related adverse events (TRAE's) and TRAE's led to discontinuation in 23.0% of all patients. Here, we present the first real-world data of nivolumab plus ipilimumab in patients with malignant mesothelioma treated in two mesothelioma expert centers. METHODS: Clinical data of patients with mesothelioma treated with nivolumab and ipilimumab were prospectively collected. Clinical parameters were obtained every visit, CT scans were evaluated every 12 weeks and adverse events were assessed continuously during the treatment. Data on grade 2-5 TRAE's and activity (overall response rate (ORR), duration of response (DOR), disease control rate (DCR), median progression-free survival (mPFS) and median overall survival (mOS) were reported. RESULTS: Between January 2021 and August 2022, 184 patients were treated with nivolumab plus ipilimumab. The median follow-up was 12.1 months (95 %CI 11.1 - 13.1). Grade 3-4 TRAEs were seen in 27.7 % of the patients and 25.0 % discontinued immunotherapy treatment early because of TRAE's. ORR was 21.7 % (95 % CI 15.7-27.7), median DOR was 5.7 months (IQR 3.2-8.7) and DCR at 12 weeks 56.0 % (95 % CI 48.8-63.2). The mPFS was 5.5 months (95 %CI 4.1-6.9), mOS was 14.1 months (95 % CI 11.1-18.2). CONCLUSIONS: Nivolumab plus ipilimumab had an equal efficacy in a real-world comparable population but also a high risk of TRAE's, leading to discontinuation of treatment in 25% of the patients.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Humanos , Nivolumabe/efeitos adversos , Ipilimumab/efeitos adversos , Mesotelioma Maligno/tratamento farmacológico , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
3.
Nat Commun ; 14(1): 5346, 2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660083

RESUMO

Chimeric antigen receptor (CAR) T cells have transformed the treatment landscape for hematological malignancies. However, CAR T cells are less efficient against solid tumors, largely due to poor infiltration resulting from the immunosuppressive nature of the tumor microenvironment (TME). Here, we assessed the efficacy of Lewis Y antigen (LeY)-specific CAR T cells in patient-derived xenograft (PDX) models of prostate cancer. In vitro, LeY CAR T cells directly killed organoids derived from androgen receptor (AR)-positive or AR-null PDXs. In vivo, although LeY CAR T cells alone did not reduce tumor growth, a single prior dose of carboplatin reduced tumor burden. Carboplatin had a pro-inflammatory effect on the TME that facilitated early and durable CAR T cell infiltration, including an altered cancer-associated fibroblast phenotype, enhanced extracellular matrix degradation and re-oriented M1 macrophage differentiation. In a PDX less sensitive to carboplatin, CAR T cell infiltration was dampened; however, a reduction in tumor burden was still observed with increased T cell activation. These findings indicate that carboplatin improves the efficacy of CAR T cell treatment, with the extent of the response dependent on changes induced within the TME.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias da Próstata , Masculino , Animais , Humanos , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Microambiente Tumoral , Linfócitos T , Neoplasias da Próstata/tratamento farmacológico , Modelos Animais de Doenças
4.
Ann Oncol ; 34(6): 507-519, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36924989

RESUMO

Radiotheranostics is a field of rapid growth with some approved treatments including 131I for thyroid cancer, 223Ra for osseous metastases, 177Lu-DOTATATE for neuroendocrine tumors, and 177Lu-PSMA (prostate-specific membrane antigen) for prostate cancer, and several more under investigation. In this review, we will cover the fundamentals of radiotheranostics, the key clinical studies that have led to current success, future developments with new targets, radionuclides and platforms, challenges with logistics and reimbursement and, lastly, forthcoming considerations regarding dosimetry, identifying the right line of therapy, artificial intelligence and more.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Medicina de Precisão , Inteligência Artificial , Radioisótopos/uso terapêutico , Neoplasias da Próstata/patologia , Radiometria , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Compostos Radiofarmacêuticos/uso terapêutico
5.
PLoS One ; 14(5): e0216223, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31071155

RESUMO

Satellite telemetry is an increasingly utilized technology in wildlife research, and current devices can track individual animal movements at unprecedented spatial and temporal resolutions. However, as we enter the golden age of satellite telemetry, we need an in-depth understanding of the main technological, species-specific and environmental factors that determine the success and failure of satellite tracking devices across species and habitats. Here, we assess the relative influence of such factors on the ability of satellite telemetry units to provide the expected amount and quality of data by analyzing data from over 3,000 devices deployed on 62 terrestrial species in 167 projects worldwide. We evaluate the success rate in obtaining GPS fixes as well as in transferring these fixes to the user and we evaluate failure rates. Average fix success and data transfer rates were high and were generally better predicted by species and unit characteristics, while environmental characteristics influenced the variability of performance. However, 48% of the unit deployments ended prematurely, half of them due to technical failure. Nonetheless, this study shows that the performance of satellite telemetry applications has shown improvements over time, and based on our findings, we provide further recommendations for both users and manufacturers.


Assuntos
Animais Selvagens/fisiologia , Ecossistema , Monitoramento Ambiental , Sistemas de Informação Geográfica , Astronave , Telemetria , Animais
6.
World J Urol ; 37(7): 1255-1261, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30374609

RESUMO

The heterogeneity of prostate cancer has made imaging modalities of crucial importance in this disease. Accurate diagnosis and staging of the volume and extent of disease, especially in advanced and metastatic prostate cancer, can help to tailor the timing and modalities of treatment. While MRI has been effective in the detection of significant prostate cancer, its use in the identification and quantification of extraprostatic disease is limited. This gap is now being filled by PSMA PET. PSMA PET scans have now been shown to have a role in all stages in the prostate cancer journey. Emerging evidence has shown its promise in primary staging, restaging and theranostics. In this paper, we review the evidence for the use of PSMA PET in the various stages of prostate cancer, from initial diagnosis to advanced metastatic disease where other systemic treatments have failed.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Dipeptídeos/uso terapêutico , Isótopos de Gálio , Radioisótopos de Gálio , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Lutécio , Masculino , Glicoproteínas de Membrana , Metástase Neoplásica , Compostos Organometálicos , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos , Nanomedicina Teranóstica
7.
Anaesthesia ; 73(12): 1524-1530, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30284241

RESUMO

Cardiac events are a common cause of peri-operative morbidity. Cardiopulmonary exercise testing can objectively assess risk, but it does not quantify myocardial ischaemia. With appropriate dietary preparation to suppress basal myocardial glucose uptake, positron emission tomography with 18 F-fluorodeoxyglucose can identify post-ischaemic myocardium, providing an attractive complement to exercise testing. We aimed to investigate the feasibility of this diagnostic algorithm. Patients referred for cardiopulmonary exercise testing before major cancer surgery were prospectively recruited. Exercise testing and positron emission tomography imaging were performed after a high fat-low carbohydrate meal. Protocol feasibility (primary end-point) included compliance with pre-test diet instructions and the completion of tests. Stress myocardial perfusion imaging was performed if either exercise testing or positron emission tomography was equivocal or positive for ischaemia. We recorded cardiac complications for 30 postoperative days. We enrolled 26 participants, 20 of whom completed protocol. Twenty-one participants proceeded to surgery: myocardial injury or infarction was diagnosed in three participants, two of whom had positive or equivocal positron emission tomography but negative myocardial perfusion imaging. We have shown that pre-operative cardiac positron emission tomography after cardiopulmonary exercise testing is feasible; protocol deviations were minor and did not affect image quality. Our findings warrant further investigation to compare the diagnostic utility of cardiac positron emission tomography imaging with standard pre-operative stress tests.


Assuntos
Teste de Esforço/métodos , Coração/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Cuidados Pré-Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/métodos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Circulação Coronária , Dieta com Restrição de Carboidratos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/diagnóstico por imagem , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/diagnóstico por imagem , Imagem de Perfusão do Miocárdio , Projetos Piloto
8.
Neth J Med ; 75(6): 241-246, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28741583

RESUMO

BACKGROUND: Very little information is available on the prevalence and clinical outcome of elderly patients with atypical presentations of illness in the emergency department. The objective was to determine the prevalence and clinical outcome of elderly patients seen in the emergency department with an atypical presentation. METHODS: A monocentric retrospective observational study on 355 elderly patients presenting to the emergency department. Patients of 80 years and older were included. Data were extracted from the electronic medical file. RESULTS: A total of 355 patients were included, with a mean age of 86 years; 53% of these elderly patients had an atypical presentation of illness. Mostly this was due to a fall (71%). A total of 15% of the patients with an atypical presentation reported no specific symptoms of the underlying disease. Patients with atypical presentation were more likely to have a longer stay in hospital (p < 0.001), to be discharged to a care institution (p = 0.000), and to have a higher delirium observation score (p < 0.001). There was no significant difference in one-year survival (p = 0.056). CONCLUSION: Atypical presentation of illness in elderly patients is highly prevalent in the emergency department. Falling accidents are the most important reason for this. Patients with an atypical presentation have a worse clinical outcome. Accurate training of emergency staff is necessary to recognise this group of patients to ensure proper clinical monitoring and timely treatment.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Avaliação Geriátrica/estatística & dados numéricos , Acidentes por Quedas/estatística & dados numéricos , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos Retrospectivos
9.
Orthop Traumatol Surg Res ; 103(2): 171-176, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27940250

RESUMO

BACKGROUND AND HYPOTHESIS: The aim of this study was to address the inconsistency regarding the operative treatment of Rockwood type III acromioclavicular joint separation. We compared results after single- and double TightRope® reduction with results after acromioclavicular transfixation via K-wires only and additional ligament augmentation in acute acromioclavicular (AC) joint separations graded Rockwood type III, and hypothesized that the TightRope® technique leads to better clinical and radiological results. MATERIALS AND METHODS: We conducted a retrospective clinical cohort study and included 42 consecutive patients (mean age 43 years [24-66]) diagnosed and operatively treated between 2004 and 2012 (mean follow-up was 54.6 months [15-118]). Specific shoulder scores as well as scores reflecting the patients' overall mental and physical health status were used. Radiological evaluation was also performed. RESULTS: The SF12 test revealed comparability between all subgroups. Specific shoulder tests and a visual analogue scale demonstrated comparable results. Radiographic measurements showed a significant reduction in the AC distance and CC distance after surgery in all subgroups. The early complication rate was 9.5% for all patients, while late complications occurred in 14.3% of all cases. CONCLUSIONS: Compared to the established methods, the operative TightRope® procedures represent a safe alternative in Rockwood III injuries. All investigated techniques predominantly led to good and excellent clinical results in acute Rockwood type III AC joint instabilities. Avoidance of material removal and shorter hospital stays appear to speak in favour for the TightRope® technique. LEVEL OF EVIDENCE: IV.


Assuntos
Articulação Acromioclavicular/cirurgia , Fios Ortopédicos , Luxações Articulares/cirurgia , Articulação Acromioclavicular/diagnóstico por imagem , Adulto , Idoso , Feminino , Seguimentos , Humanos , Luxações Articulares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Radiografia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Eur J Trauma Emerg Surg ; 42(6): 741-747, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26555727

RESUMO

PURPOSE: The aim of this study was to compare the demographics, injury patterns, and outcomes following major trauma between Alpine skiing, snowboarding, and sledding winter sports. METHODS: An international population-based prospective trauma database (TraumaRegister DGU®) was analyzed for demographic data, types and severity of injuries [body regions, Injury Severity Score (ISS)], early physiology [Glasgow Coma Scale (GCS), blood pressure, body temperature], rescue modality, surgical care, length of stay, and major complications (shock, multiple organ failure mortality). Participating countries included Germany, Austria, Switzerland, Finland, Slovenia, Belgium, Luxembourg, and The Netherlands. RESULTS: A total of 243 winter sport athletes with major trauma were identified (1993-2012), and subjects were divided into Alpine skiers (n = 174), snowboarders (n = 29), and sledders (n = 40). Athletes were predominantly male and presented hypothermic at emergency room arrival, despite a large proportion of air rescue (77 %). Alpine skiing was associated with higher injury severity (ISS 20.8 ± 14.0, p = 0.010) when compared with snowboarding (ISS 18.7 ± 14.0) and sledding (ISS 13.8 ± 9.5). Snowboarding was associated with the highest pre-hospital intubation rate (40.9 %, p = 0.007), despite comparable GCS values and prevalence of loss of consciousness at scene. The injury patterns were different between the three groups. Skiing was associated with head (47.1 %), chest (40.2 %, p = 0.047), and spinal injuries (40.9 %, p = 0.022). Snowboarding was associated with the highest percentage of upper extremity trauma. Sledders had the highest prevalence of facial and lower extremity trauma. CONCLUSIONS: Alpine skiing, snowboarding, and sledding result in different injury patterns and affect various age groups. Our data suggest an increased risk for chest and spinal injuries in Alpine skiers. Due to high-energy injury mechanisms, all three winter sports involve a risk of severe multiple trauma. While all athlete groups required a high rate of emergency surgery procedures, the observed in-hospital mortality from winter sports remains low.


Assuntos
Traumatismos em Atletas/epidemiologia , Bases de Dados Factuais , Adulto , Temperatura Baixa , Feminino , Humanos , Masculino , Sistema de Registros , Estações do Ano
11.
Knee ; 22(6): 535-41, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26004197

RESUMO

BACKGROUND: Acute quadriceps tendon tears are infrequent injuries requiring surgical treatment. Improved stability after surgical repair may allow for earlier weight-bearing and range of motion. Therefore, a new implant was tested and compared with the "gold standard", using transosseous sutures. METHODS: Quadriceps tendon tears were constructed using a cadaveric model of 12 fresh matched-pair specimens (aged 61-97; mean age: 82 years). The biomechanical testing compared non-absorbable suture anchors (Polyvinylidene fluoride) versus transosseous absorbable sutures (Polydioxanon). Following anatomic reconstruction, the repaired specimens were loaded until they failed (testing machine: Hounsfield H10KM, Redhill, United Kingdom; maximum force: 1000 N; load speed: 25 mm/min; maximum test length: 150 mm; pre-load: 5 N). Values for load until tear displacement, maximum load until complete failure of the construct (pullout or breakage of the sutures or anchors) and stiffness of the reconstruction were recorded. RESULTS: The stiffness found in the Polyvinylidene fluoride reconstruction (mean 9.83 N/mm) (standard deviation (SD) 7.75) showed a significant increase compared to the Polydioxanon reconstruction (mean 6.66 N/mm (SD 3.32); P=0.045). Transosseous fixation showed comparable results to the suture anchor system. There was no significant difference found in the maximum load to tear displacement (PVDF: 290.88 N (SD 106.01) vs. PDS: 266.75 N (SD 82.61); P=0.358). CONCLUSIONS: Using the Polyvinylidene fluoride thread showed comparable results to the established method in reconstruction of ruptured quadriceps tendon. Stiffness of the Polyvinylidene fluoride thread reconstruction was even greater than Polydioxanon thread. CLINICAL RELEVANCE: Improved stiffness may facilitate healing and is suggested as clinical relevance in reconstruction.


Assuntos
Parafusos Ósseos , Patela/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Polivinil/farmacologia , Músculo Quadríceps/lesões , Técnicas de Sutura/instrumentação , Traumatismos dos Tendões/cirurgia , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Cadáver , Humanos , Membranas Artificiais , Pessoa de Meia-Idade , Músculo Quadríceps/cirurgia , Ruptura , Suturas , Traumatismos dos Tendões/fisiopatologia
12.
Eur J Nucl Med Mol Imaging ; 41(10): 1831-44, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24844348

RESUMO

PURPOSE: To review the response and outcomes of (177)Lu-DOTA-octreotate chemoradionuclide therapy (LuTate PRCRT) in patients with neuroendocrine tumour (NET) expressing high levels of somatostatin receptors with uncontrolled symptoms or disease progression. METHODS: A total of 68 patients (39 men; 17 - 76 years of age) who had completed an induction course of at least three cycles of LuTate PRCRT between January 2006 and June 2010 were reviewed. Ten patients were treated for uncontrolled symptoms and 58 had disease progression despite conventional treatment. The majority had four induction LuTate cycles (median treatment duration 5 months and cumulative activity 31 GBq), and 63 patients had concomitant 5-FU radiosensitizing infusional chemotherapy. Factors predicting overall survival were assessed using the log-rank test and Cox proportional hazards regression. RESULTS: Of those treated for uncontrolled symptoms, 70 % received benefit maintained for at least 6 months after treatment. Among patients with progressive disease 68 % showed stabilization or regression on CT, 67 % on molecular imaging and 56 % biochemically up to 12 months after treatment; 32 patients died. Overall survival rates at 2 and 5 year were 72.1 % and 52.1 %, respectively. Median overall survival was not estimable at a median follow-up of 60 months (range 5 - 86 months). Nonpancreatic primary sites, dominant liver metastases, lesion size <5 cm and the use of 5-FU chemotherapy were statistically significantly associated with objective response. A disseminated pattern and a high disease burden (whole-body retention index) were associated with an increased risk of death. Objective biochemical, molecular imaging and CT responses were all associated with longer overall survival. CONCLUSION: A high proportion of patients with progressive NET or uncontrolled symptoms received therapeutic benefit from LuTate with concomitant 5-FU chemotherapy. The achievement of objective biochemical, molecular or CT responses within 12 months was associated with improved overall survival. Patients with a primary pancreatic site and larger lesions (>5 cm) appeared to have lower objective response rates and may need a more aggressive treatment approach.


Assuntos
Antineoplásicos/uso terapêutico , Tumores Neuroendócrinos/terapia , Octreotida/análogos & derivados , Compostos Radiofarmacêuticos/uso terapêutico , Adolescente , Adulto , Idoso , Quimiorradioterapia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico , Octreotida/uso terapêutico , Receptores de Somatostatina/metabolismo , Análise de Sobrevida , Resultado do Tratamento
13.
Mol Imaging Biol ; 16(4): 469-77, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24430291

RESUMO

PURPOSE: Quantification of positron emission tomography/magnetic resonance imaging (PET/MRI) studies is hampered by inaccurate MR-based attenuation correction (MR-AC). To date, most studies on MR-AC have been performed using PET/MR systems without time of flight (TOF). Maximum likelihood reconstruction of attenuation and activity (MLAA), however, has the potential to improve MR-AC by exploiting TOF. The purpose of this study is to assess the impact of MR-AC on PET image quantification for TOF-PET/MR systems and to evaluate PET accuracy when using TOF in combination with MLAA (TOF-MLAA). PROCEDURES: Simulations were designed to evaluate (1) the impact of MR-AC on PET quantification for different TOF windows (667, 500, 333 and 167 ps) and (2) use of TOF-MLAA for improving PET quantification. TOF-ordered subset expectation maximisation (OSEM) and TOF-MLAA reconstructions using MR-AC were compared with those obtained using TOF-OSEM with computed tomography-based AC (CT-AC). RESULTS: OSEM reconstructions without TOF showed a negative MR-AC-induced bias of -50 % in the bone. TOF-OSEM was able to reduce this bias down to -15 %, with more accurate results for better TOF. TOF-MLAA was able to reduce the bias to within 5 % but at the cost of a ∼40 % increase in image variance. CONCLUSIONS: TOF-MLAA can improve quantitative PET accuracy of PET/MR studies. Further improvements are anticipated with improving TOF performance.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Simulação por Computador , Humanos , Funções Verossimilhança , Imagens de Fantasmas , Fatores de Tempo
14.
Z Rheumatol ; 73(3): 269-76, 2014 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-24166363

RESUMO

As a pro-inflammatory cytokine, the 21-kDa glycoprotein interleukin-6 (IL-6) plays a crucial role in the initiation of acute inflammation, as well in the perpetuation of a chronic inflammatory immune response. Thus, IL-6 might be involved in the pathogenesis of various autoimmune diseases. So far, the IL-6-rezeptor-antibody tocilizumab (TCZ, RoActemtra®) is the only approved drug for the treatment of IL-6-mediated disease, including rheumatoid arthritis (RA), systemic juvenile idiopathic (sJIA) and polyarticular juvenile arthritis (pJiA), as well as Castleman's disease (in Japan only). In recent years, an emerging number of case reports and small uncontrolled case series have reported on the successful treatment of various other chronic inflammatory diseases, which has resulted in the idea of a broad therapeutic potential for IL-6 blockade. Numerous IL-6 targets are currently in phase II/III study programs for RA as well as for other indications. This review focuses on the development of tocilizumab and other IL-6 targets as a therapeutic option for various diseases in rheumatology.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologia , Animais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/imunologia , Desenho de Fármacos , Medicina Baseada em Evidências , Humanos , Modelos Imunológicos , Doenças Reumáticas/diagnóstico , Resultado do Tratamento
15.
Eur J Neurol ; 21(2): 245-52, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24112523

RESUMO

BACKGROUND AND PURPOSE: A substantial proportion of patients with Parkinson's disease (PD) suffer from cognitive deficits, although there is a large variability in the severity of these impairments. Whilst the cognitive deficits are often attributed to monoaminergic changes, there is evidence that alterations in structural brain volume also play a role. The aim of our study was to gain more insight into the variability of cognitive performance amongst PD patients by examining the relation between regional gray matter (GM) volume and cognitive performance. METHODS: Linear regression analyses were performed between task performance and GM volume for six neuropsychological tasks within a group of 93 PD patients; they were additionally compared at a group level with matched healthy controls, using voxel-based morphometry. RESULTS: Our most important findings were positive correlations between GM volume and cognitive performance for (i) parahippocampal gyrus and verbal memory, (ii) medial temporal lobe and putamen and visuospatial memory, and (iii) middle temporal gyrus and frontal lobe and verbal fluency. In addition, decreased GM volume was found in the frontal, parietal and temporal cortices of PD patients compared with matched healthy controls. CONCLUSIONS: It is argued that the large variability in cognitive function across PD patients is partly mediated by GM volume differences in the implicated areas. Volume differences in these brain regions do not discriminate between patients and controls but explain cognitive variation within the patient population.


Assuntos
Encéfalo/patologia , Cognição/fisiologia , Fibras Nervosas Amielínicas/patologia , Doença de Parkinson/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/psicologia
16.
Br J Cancer ; 109(2): 312-7, 2013 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-23807169

RESUMO

BACKGROUND: The usefulness of positron emission tomography with computed tomography (PET-CT) in the surveillance of patients with diffuse large B-cell lymphoma (DLBCL) in complete metabolic remission after primary therapy is not well studied. METHODS: We performed a retrospective review of our database between 2002 and 2009 for patients with de novo DLBCL who underwent surveillance PET-CT after achieving complete metabolic response (CMR) following primary therapy. RESULTS: Four-hundred and fifty scans were performed in 116 patients, with a median follow-up of 53 (range 8-133) months from completion of therapy. Thirteen patients (11%) relapsed: seven were suspected clinically and six were subclinical (all within first 18 months). The positive predictive value in patients with international prognostic index (IPI) <3 was 56% compared with 80% in patients with IPI ≥3. Including indeterminate scans, PET-CT retained high sensitivity 95% and specificity 97% for relapse. CONCLUSION: Positron emission tomography with computed tomography is not useful in patients for the majority of patients with diffuse large B-cell lymphoma in CMR after primary therapy, with the possible exception of patients with baseline IPI ≥3 in the 18 months following completion of primary therapy. This issue could be addressed by a prospective clinical trial.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Monitorização Fisiológica/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/estatística & dados numéricos , Imagem Multimodal/estatística & dados numéricos , Terapia Neoadjuvante , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Adulto Jovem
17.
J Colloid Interface Sci ; 404: 91-101, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23719415

RESUMO

CpTiCl3/SiO2/MAO (Cp=cyclopentadienyl, MAO - methylaluminoxane) catalysts, where the Al:Ti varies from 20:1 to 500:1, were used in styrene polymerization. Atactic - syndiotactic polystyrene blends (aPS-sPS) were obtained in situ, the morphology of which was investigated by means of scanning electron microscopy. The blends morphology changed according to the kind of catalytic centers: cationic and syndiotactic on the catalyst surface, which create individually atactic or syndiotactic polystyrenes forming specific blends containing nano or micro-forms: when the Al:Ti ranges from 50:1 and to 100:1 in the blends, there occur nano-sPS particles 40-120 nm in size, if the Al:Ti≥300:1, the filament of δ-sPS polymorph, is produced where the filament size ranged from 30 to 10 nm. A decay of this form leads to the formation of spherical sPS forms several hundreds of nm in size. When the Al:Ti ranges 20:1-50:1, blend rods of several dozen micrometers were obtained.

18.
Eur J Surg Oncol ; 38(1): 64-71, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21906907

RESUMO

AIMS: To assess the clinical utility of peptide receptor chemoradionuclide therapy (PRCRT) using (177)Lu-octreotate (LuTate) with concurrent 5FU chemotherapy in patients with inoperable primary pancreatic and duodenal neuroendocrine tumours (NETs). METHODS: Between December 2006 and October 2009, five patients with progressive inoperable pancreatic and duodenal NETs without distant metastatic disease or with a potentially resectable solitary distant metastasis were treated with PRCRT; in combination with external beam radiotherapy in one case. Patients were followed up three months post-treatment with somatostatin receptor scintigraphy, radiology, biochemical markers and clinical assessment. Radiological response classification was defined by Response Evaluation Criteria in Solid Tumours (RECIST) with the addition of a minor response (MR; 10-30% size reduction) classification. Long-term follow up was performed until July 2011. RESULTS: At three months post-treatment, all five patients had a scintigraphic response, four had a radiological response and three of the four symptomatic patients responded clinically. All five patients had an ongoing treatment response beyond three months including one where further tumour shrinkage facilitated curative surgery. All five patients are alive with 12-42 months of follow-up post-treatment. CONCLUSION: PRCRT can be effective in inoperable pancreatic and duodenal neuroendocrine tumours and may play a role as neoadjuvant therapy in this patient group.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Duodenais/radioterapia , Fluoruracila/uso terapêutico , Lutécio/uso terapêutico , Tumores Neuroendócrinos/radioterapia , Neoplasias Pancreáticas/radioterapia , Radioisótopos/uso terapêutico , Idoso , Neoplasias Duodenais/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Receptores de Peptídeos/efeitos dos fármacos , Indução de Remissão , Projetos de Pesquisa , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Eur J Trauma Emerg Surg ; 38(3): 253-60, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26815956

RESUMO

INTRODUCTION: The organization of trauma care has different perspectives that depend on regional aspects. Among these, geographical peculiarities, historical developments regarding development of medical subspecialties and resident education appear to be the most relevant factors. METHODS: We performed a structured literature search on PubMed. RESULTS AND CONCLUSION: This manuscript deals with the differences of several trauma systems in certain European countries, the USA and Australia. It aims to provide an overview of the peculiarities and influences of these systems on the clinical management. However, the effect of differences in organization in different countries on patient outcome is difficult to assess. There appears to be consensus on the fact that structured treatment for acute trauma care is beneficial for trauma patients. Thus, any kind of organization contributes to improved patient outcome.

20.
Versicherungsmedizin ; 63(3): 137-42, 2011 Sep 01.
Artigo em Alemão | MEDLINE | ID: mdl-21922716

RESUMO

Rehabilitation treatment, which is necessary in the majority of polytrauma patients, is long-lasting and even after several years the final result is frequently not reached yet. Our study is the first in which a population of 510 patients were followed up for 10 years and more and in which many clinical and social parameters were determined. Our study showed that even after a period of 10 years and more the quality of life in several patients is still obviously impaired, according to the parametes "financial losses", "decreased net income", "loss of social services", "credit loan" and "loss of friends". In our study, differences according to financial and professional perspectives between injuries of the lower and upper extremities or combination injuries of the extremities were statistically significant. For the everyday clinic it is important to reintegrate children and young patients into a strong social network because there is a higher percentage of young patients who are socially impaired, even many years after trauma. Adult patients should get strong support to return to their original profession and financial status.


Assuntos
Traumatismo Múltiplo/reabilitação , Adolescente , Adulto , Traumatismos do Braço/epidemiologia , Traumatismos do Braço/psicologia , Traumatismos do Braço/reabilitação , Criança , Pré-Escolar , Estudos Transversais , Avaliação da Deficiência , Seguimentos , Alemanha , Humanos , Renda , Escala de Gravidade do Ferimento , Traumatismos da Perna/epidemiologia , Traumatismos da Perna/psicologia , Traumatismos da Perna/reabilitação , Pessoa de Meia-Idade , Traumatismo Múltiplo/epidemiologia , Traumatismo Múltiplo/psicologia , Qualidade de Vida/psicologia , Reabilitação Vocacional , Ajustamento Social , Apoio Social , Adulto Jovem
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