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INTRODUCTION: Renal transplant recipients are at increased risk of keratinocyte skin cancers with a tendency to have multiple, aggressive and difficult to treat tumours. The eye and the skin share the same embryological ectoderm. Iris pattern has recently been reported as a predictive risk factor for skin cancer in non-immunosuppressed Southern European (Grigore et al., J Eur Acad Dermatol Venereol, 2018, 1662) and Irish populations (Ridge et al., J Eur Acad Dermatol Venereol, 2022, e542). AIMS: To analyse if an individual's iris pattern is an independent risk factor for the development of keratinocyte skin cancers in renal transplant recipients. METHODS: Iris patterns of 110 renal transplant recipients were evaluated using the Simionescu visual three-step technique (iris periphery, colarette and iris freckling [Simionescu et al., Ann Res Rev Biol, 2014, 2525]). Established risk factors for skin cancer in transplant patients were recorded as confounding factors. RESULTS: Observational cross-sectional study including 110 renal transplant population. Thirty-one participants had skin cancer. In the skin cancer group, iris periphery was blue/grey in 74.3% (p = 0.053, OR 2.5), the colarette was light brown in 57.1% (p < 0.0043) and iris freckles were present in 55%(p = 0.044). Dark brown and blue colarettes were observed in controls. Binary Logistic Regression analysis showed light brown colarette is a significant independent risk factor for skin cancer (OR 4.54, p < 0.02, CI 1.56-10.57). CONCLUSION: Within this renal transplant population a blue iris periphery, light brown colarette and presence of freckling confers an independent risk for keratinocyte skin cancer. Iris pattern is a useful tool for identification of transplant patients at risk of keratinocyte skin cancer and an easy-to-use technique for risk evaluation in this cohort. This is the first study looking at iris pattern and keratinocyte skin cancer risk in renal transplant population.
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Transplante de Rim , Melanose , Neoplasias Cutâneas , Humanos , Estudos Transversais , Iris/patologia , Transplante de Rim/efeitos adversos , Melanose/complicações , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologiaRESUMO
We present a co-axial acoustic-based optical coherence vibrometry probe (CoA-OCV) for vibro-acoustic resonance quantification in biological tissues. Sample vibrations were stimulated via a loudspeaker, and pre-compensation was used to calibrate the acoustic spectrum. Sample vibrations were measured via phase-sensitive swept-source optical coherence tomography (OCT). Resonance frequencies of corneal phantoms were measured at varying intraocular pressures (IOP), and dependencies on Young´s Modulus (E), phantom thickness and IOP were observed. Cycling IOP revealed hysteresis. For E = 0.3 MPa, resonance frequencies increased with IOP at a rate of 3.9, 3.7 and 3.5 Hz/mmHg for varied thicknesses and 1.7, 2.5 and 2.8 Hz/mmHg for E = 0.16 MPa. Resonance frequencies increased with thickness at a rate of 0.25 Hz/µm for E = 0.3 MPa, and 0.40 Hz/µm for E = 0.16 MPa. E showed the most predominant impact in the shift of the resonance frequencies. Full width at half maximum (FWHM) of the resonance modes increased with increasing thickness and decreased with increasing E. Only thickness and E contributed to the variance of FWHM. In rabbit corneas, resonance frequencies of 360-460 Hz were observed. The results of the current study demonstrate the feasibility of CoA-OCV for use in future OCT-V studies.
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Pressão Intraocular , Vibração , Animais , Coelhos , Acústica , Tomografia de Coerência Óptica/métodosRESUMO
Our study investigated whether pre-operative screening and treatment for anaemia and suboptimal iron stores in a patient blood management clinic is cost effective. We used outcome data from a retrospective cohort study comparing colorectal surgery patients admitted pre- and post-implementation of a pre-operative screening programme. We applied propensity score weighting techniques with multivariable regression models to adjust for differences in baseline characteristics between groups. Episode-level hospitalisation costs were sourced from the health service clinical costing data system; the economic evaluation was conducted from a Western Australia Health System perspective. The primary outcome measure was the incremental cost per unit of red cell transfusion avoided. We compared 441 patients screened in the pre-operative anaemia programme with 239 patients not screened; of the patients screened, 180 (40.8%) received intravenous iron for anaemia and suboptimal iron stores. The estimated mean cost of screening and treating pre-operative anaemia was AU$332 (£183; US$231; 204) per screened patient. In the propensity score weighted analysis, screened patients were transfused 52% less red cell units when compared with those not screened (rate ratio = 0.48, 95%CI 0.36-0.63, p < 0.001). The mean difference in total screening, treatment and hospitalisation cost between groups was AU$3776 lower in the group screened (£2080; US$2629; 2325) (95%CI AU$1604-5947, p < 0.001). Screening elective patients pre-operatively for anaemia and suboptimal iron stores reduced the number of red cell units transfused. It also resulted in lower total costs than not screening patients, thus demonstrating cost effectiveness.
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Anemia/diagnóstico , Anemia/terapia , Cirurgia Colorretal/economia , Análise Custo-Benefício/métodos , Ferro/sangue , Cuidados Pré-Operatórios/métodos , Anemia/economia , Estudos de Coortes , Análise Custo-Benefício/economia , Análise Custo-Benefício/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/economia , Transfusão de Eritrócitos/economia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Ferro/economia , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/economia , Estudos Retrospectivos , Austrália OcidentalRESUMO
INTRODUCTION: This report presents a synopsis of a three-part, cross-sector, seminar series held at the George Washington University (GWU) in Washington, DC from February-April, 2018. The overarching goal of the seminar series was to provide a neutral forum for diverse stakeholders to discuss and critically evaluate approaches to address added sugar intake, with a key focus on the role of low-calorie sweeteners (LCS). METHODS: During three seminars, twelve speakers from academic institutions, federal agencies, non-profit organizations, and the food and beverage industries participated in six interactive panel discussions to address: 1) Do Farm Bill Policies Impact Population Sugar Intake? 2) What is the Impact of Sugar-sweetened Beverage (SSB) Taxes on Health and Business? 3) Is Sugar Addictive? 4) Product Reformulation Efforts: Progress, Challenges, and Concerns? 5) Low-calorie Sweeteners: Helpful or Harmful, and 6) Are Novel Sweeteners a Plausible Solution? Discussion of each topic involved brief 15-minute presentations from the speakers, which were followed by a 25-minute panel discussion moderated by GWU faculty members and addressed questions generated by the audience. Sessions were designed to represent opposing views and stimulate meaningful debate. Given the provocative nature of the seminar series, attendee questions were gathered anonymously using Pigeonhole™, an interactive, online, question and answer platform. RESULTS: This report summarizes each presentation and recapitulates key perspectives offered by the speakers and moderators. CONCLUSIONS: The seminar series set the foundation for robust cross-sector dialogue necessary to inform meaningful future research, and ultimately, effective policies for lowering added sugar intakes.
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Few studies have investigated if, and how, red cell transfusion and anaemia interact. We analysed 60,955 admissions to three metropolitan hospitals in Western Australia between 2008 and 2017 to determine whether the relationship between red cell transfusion and outcomes in surgical patients differed by lowest (nadir) level of haemoglobin. At levels above 100 g.l-1 , in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratios (ORs) (95%CI) being 8.80 (4.43-17.45) p < 0.001 and 3.68 (1.93-7.02) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.83 (1.28-2.61) p = 0.001, respectively. Likewise, between 90 g.l-1 and 99 g.l-1 , in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratio (95%CI) being 3.76 (2.23-6.34) p < 0.001 and 1.96 (1.23-3.12) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.34 (1.05-1.70) p = 0.017, respectively. Length of stay was longer with transfusion at nadir haemoglobin levels above 100 g.l-1 and in the following ranges: 90-99 g.l-1 , 80-89 g.l-1 , 70-79 g.l-1 and 60-69 g.l-1 , the adjusted rate ratio (95%CI) being 1.38 (1.25-1.53) p < 0.001, 1.18 (1.10-1.27) p < 0.001, 1.17 (1.13-1.22) p < 0.001, 1.07 (1.02-1.12) p = 0.003 and 1.24 (1.13-1.36) p < 0.001, respectively. Mortality was higher with red cell transfusion at haemoglobin levels greater than 90 g.l-1 , whereas at all levels below 90 g.l-1 mortality was not significantly higher or lower. Length of stay was longer with transfusion at nadir haemoglobin levels of 60 g.l-1 or above. Our results suggest that nadir haemoglobin modified the relationship between red cell transfusion and outcomes and adds to the evidence recommending caution before transfusing red cells.
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Transfusão de Eritrócitos/mortalidade , Hemoglobinas/análise , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Operatórios/mortalidade , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Austrália Ocidental/epidemiologiaRESUMO
Adult Mesenchymal Stem Cells (MSCs) have a well-established tumor-homing capacity, highlighting potential as tumor-targeted delivery vehicles. MSCs secrete extracellular vesicle (EV)-encapsulated microRNAs, which play a role in intercellular communication. The aim of this study was to characterize a potential tumor suppressor microRNA, miR-379, and engineer MSCs to secrete EVs enriched with miR-379 for in vivo therapy of breast cancer. miR-379 expression was significantly reduced in lymph node metastases compared to primary tumor tissue from the same patients. A significant reduction in the rate of tumor formation and growth in vivo was observed in T47D breast cancer cells stably expressing miR-379. In more aggressive HER2-amplified HCC-1954 cells, HCC-379 and HCC-NTC tumor growth rate in vivo was similar, but increased tumor necrosis was observed in HCC-379 tumors. In response to elevated miR-379, COX-2 mRNA and protein was also significantly reduced in vitro and in vivo. MSCs were successfully engineered to secrete EVs enriched with miR-379, with the majority found to be of the appropriate size and morphology of exosomal EVs. Administration of MSC-379 or MSC-NTC cells, or EVs derived from either cell population, resulted in no adverse effects in vivo. While MSC-379 cells did not impact tumor growth, systemic administration of cell-free EVs enriched with miR-379 was demonstrated to have a therapeutic effect. The data presented support miR-379 as a potent tumor suppressor in breast cancer, mediated in part through regulation of COX-2. Exploiting the tumor-homing capacity of MSCs while engineering the cells to secrete EVs enriched with miR-379 holds exciting potential as an innovative therapy for metastatic breast cancer.
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Neoplasias da Mama/terapia , Sistemas de Liberação de Medicamentos/métodos , Vesículas Extracelulares/metabolismo , Terapia Genética/métodos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , MicroRNAs/administração & dosagem , Células-Tronco Adultas/transplante , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Células Cultivadas , Composição de Medicamentos/métodos , Vesículas Extracelulares/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Metástase Neoplásica , Terapias em Estudo/métodos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Background: Alveolar soft part sarcoma (ASPS) is an orphan malignancy associated with a rearrangement of transcription factor E3 (TFE3), leading to abnormal MET gene expression. We prospectively assessed the efficacy and safety of the MET tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic ASPS. Patients and methods: Eligible patients with reference pathology-confirmed ASPS received oral crizotinib 250 mg bd. By assessing the presence or absence of a TFE3 rearrangement, patients were attributed to MET+ and MET- sub-cohorts. The primary end point was the objective response rate (ORR) according to local investigator. Secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate, overall survival (OS) and safety. Results: Among 53 consenting patients, all had a centrally confirmed ASPS and 48 were treated. A total of 45 were eligible, treated and assessable. Among 40 MET+ patients, 1 achieved a confirmed partial response (PR) that lasted 215 days and 35 had stable disease (SD) as best response (ORR: 2.5%, 95% CI 0.6% to 80.6%). Further efficacy end points in MET+ cases were DCR: 90.0% (95% CI 76.3% to 97.2%), 1-year PFS rate: 37.5% (95% CI 22.9% to 52.1%) and 1-year OS rate: 97.4% (95% CI 82.8% to 99.6%). Among 4 MET- patients, 1 achieved a PR that lasted 801 days and 3 had SD (ORR: 25.0%, 95% CI 0.6% to 80.6%) for a DCR of 100% (95% CI 39.8% to 100.0%). The 1-year PFS rate in MET- cases was 50% (95% CI 5.8% to 84.5%) and the 1-year OS rate was 75% (95% CI 12.8% to 96.1%). One patient with unknown MET status due to technical failure achieved SD but stopped treatment due to progression after 17 cycles. The most common crizotinib-related adverse events were nausea [34/48 (70.8%)], vomiting [22/48 (45.8%)], blurred vision [22/48 (45.8%)], diarrhoea (20/48 (41.7%)] and fatigue [19/48 (39.6%)]. Conclusion: According to European Organization for Research and Treatment of Cancer (EORTC) efficacy criteria for soft tissue sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged ASPS MET+ patients. Clinical trial number: EORTC 90101, NCT01524926.
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Antineoplásicos/uso terapêutico , Crizotinibe/uso terapêutico , Sarcoma Alveolar de Partes Moles/tratamento farmacológico , Adolescente , Adulto , Idoso , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Feminino , Rearranjo Gênico , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêutico , Sarcoma Alveolar de Partes Moles/genética , Sarcoma Alveolar de Partes Moles/mortalidade , Adulto JovemRESUMO
BACKGROUND: Clear-cell sarcoma (CCSA) is an orphan malignancy, characterized by a specific t(12;22) translocation, leading to rearrangement of the EWSR1 gene and overexpression of MET. We prospectively investigated the efficacy and safety of the tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic CCSA. PATIENTS AND METHODS: Patients with CCSA received oral crizotinib 250 mg twice daily. Primary end point was objective response rate (ORR), secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate (PFR), overall survival (OS), OS rate and safety. The study design focused on MET+ disease with documented rearrangement of the EWSR1 gene by fluorescence in situ hybridization. RESULTS: Among 43 consenting patients with the local diagnosis of CCSA, 36 had centrally confirmed CCSA, 28 of whom were eligible, treated and assessable. Twenty-six out of the 28 patients had MET+ disease, of whom one achieved a confirmed partial response and 17 had stable disease (SD) (ORR 3.8%, 95% confidence interval: 0.1-19.6). Further efficacy end points in MET+ CCSA were DCR: 69.2% (48.2% to 85.7%), median PFS: 131 days (49-235), median OS: 277 days (232-442). The 3-, 6-, 12- and 24-month PFR was 53.8% (34.6-73.0), 26.9% (9.8-43.9), 7.7% (1.3-21.7) and 7.7% (1.3-21.7), respectively. Among two assessable MET- patients, one had stable disease and one had progression. The most common treatment-related adverse events were nausea [18/34 (52.9%)], fatigue [17/34 (50.0%)], vomiting [12/34 (35.3%)], diarrhoea [11/34 (32.4%)], constipation [9/34 (26.5%)] and blurred vision [7/34 (20.6%)]. CONCLUSIONS: The PFS with crizotinib in MET+ CCSA is similar to results achieved first-line in non-selected metastatic soft tissue sarcomas with single-agent doxorubicin. The PFS is similar to results achieved with pazopanib in previously treated sarcoma patients. CLINICAL TRIAL NUMBER: EORTC 90101, EudraCT number 2011-001988-52, NCT01524926.
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Proteínas Proto-Oncogênicas c-met/genética , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Sarcoma de Células Claras/tratamento farmacológico , Sarcoma de Células Claras/enzimologia , Adolescente , Adulto , Estudos de Coortes , Crizotinibe , Feminino , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Proteína EWS de Ligação a RNA/genética , Sarcoma de Células Claras/genética , Adulto JovemAssuntos
Doenças do Cão/microbiologia , Hemorragia/veterinária , Pneumonia Bacteriana/veterinária , Streptococcus equi/isolamento & purificação , Doença Aguda , Animais , Cães , Evolução Fatal , Hemorragia/microbiologia , Irlanda , Tipagem de Sequências Multilocus/veterinária , Pneumonia Bacteriana/microbiologiaRESUMO
Myxoid liposarcomas (MLS) are a subgroup of soft-tissue sarcomas which have a propensity for extra-pulmonary metastases. Conventional radiological staging of soft-tissue sarcomas consists of chest radiographs (CXR) and thoracic computed tomography (CT) for possible chest metastases, supplemented by magnetic resonance imaging (MRI) for local disease. The optimal radiological modality to detect extra-pulmonary metastases for systemic staging has not been proven. We reviewed the efficacy of Whole-Body MRI (WBMRI) for this purpose. 33 WBMRI and simultaneous CT scans were performed in 28 patients suffering from MLS between 2007 and 2015. 38 metastases were identified in seven patients via WBMRI. Osseous lesions predominated (spine, pelvis, chest-wall and long bones), followed by soft-tissue and abdominal lesions. Of the 29 soft-tissue or osseous metastases that were within the field-of-view of the simultaneous CT scans, five soft-tissue and zero osseous metastases were identified using CT. Metastatic disease was detected in three patients solely using WBMRI, which directly influenced their management. WBMRI is a useful adjunct in the detection of extra-pulmonary metastatic disease, which directly alters patient management. WBMRI has demonstrated an ability to identify more sites of metastatic disease compared to CT. WBMRI should be used in two situations. Firstly, at diagnosis where ablative treatment will be required e.g. amputation, when the diagnosis of occult metastasis would change treatment planning. Secondly, at diagnosis of relapse to confirm if it is a solitary site of relapse prior to consideration of metastectomy.
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Neoplasias Ósseas/secundário , Lipossarcoma Mixoide/diagnóstico , Imageamento por Ressonância Magnética/métodos , Neoplasias de Tecidos Moles/patologia , Imagem Corporal Total/métodos , Neoplasias Ósseas/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Lipossarcoma Mixoide/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Sporadic Burkitt lymphoma (BL), characterised by translocation-associated C-MYC upregulation is a rare, aggressive lymphoma with a cure rate up to 90 % using the R-CODOX-M/R-IVAC (RCRI) protocol. RCRI is active in HIV-associated BL in combination with HAART. The WHO classification system defines lymphomas intermediate between DLBCL and BL, in which lymphomas with t(14;18)(q32;q21) and C-MYC-carrying translocation, i.e. 'double-hit' are included (BL-DH), and these patients are conventionally treated with RCRI. RESULT: We describe the SJH experience of 25 patients with BL, BL + HIV and BL-DH treated with RCRI between 2002 and 2011. Twelve BL patients (8M/4F), median age 49.1 years (range 20-73 years); of whom 9 had extensive disease, including 8 with marrow and 2 with CNS involvement. Eleven patients remain in remission at 80.5 months (range 37-147 months) from completion of treatment and one died of progressive BL giving an OS of 91.6 % at 1 year with no late relapses. Eight patients with BL + HIV were treated (6M/2F) with a median age 40.25 years (range 24-64). Five remain in complete remission (CR) at 65 months (range 13-109 months), three patients died, two of progressive disease and one of treatment-associated hepatotoxicity in CR. Five patients with BL-DH were included; (3M/2F), age 47.8 years (range 42-55 years); and all patients died of progressive disease, 4 on RCRI therapy and a further patient despite an allogeneic transplantation. CONCLUSION: These results confirm that RCRI is an effective treatment in adults with BL and BL + HIV and remains the gold standard against which other regimens should be compared. We confirm the poor prognosis found in BL-DH, indicating new treatment approaches are needed for this sub-group which should be identified at diagnosis by FISH analysis.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT. PATIENTS AND METHODS: Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor. RESULTS: A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40 years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms. CONCLUSION: Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.
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Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Sarcoma/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Masculino , PrognósticoRESUMO
BACKGROUND/PURPOSE: Vascular abnormalities play an acute role in the pathogenesis of psoriasis. In order to characterize vascular involvement in psoriasis and its regular clinical assessment in vivo, non-invasive high speed imaging with high resolution and high sensitivity is needed. METHODS: The correlation mapping optical coherence tomography (cmOCT) technique was used for in vivo microcirculation imaging of human forearm under normal and psoriatic conditions. The cmOCT technique developed by our group uses dense scanning OCT image acquisition and post-processing software based on correlation statistics. The frequency domain OCT system was used for imaging which acquires a 3D volume of 1024 × 1024 A-scans, each of 512 pixels deep in approximately 70 s. The cmOCT technique processes the resulting OCT volume within 116 s using a 7 × 7 kernel. RESULTS: 3D structural and functional (microcirculation) maps of the healthy tissue and the psoriatic plaque were obtained using the cmOCT technique. The presented results indicate that cmOCT allows not only the identification of the microvessels, but also produces more detailed microvascular networks showing how the blood vessels relate to each other in healthy tissue and within the plaque. The microcirculation pattern within the plaque is totally different from the healthy tissue. The distinct changes are also observed in vessel density, tortuosity, and orientation. CONCLUSION: The cmOCT provides high sensitivity and imaging speed for in vivo microcirculation imaging within the human skin under normal and diseased conditions.
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Dermoscopia/métodos , Interpretação de Imagem Assistida por Computador/métodos , Microvasos/patologia , Psoríase/patologia , Pele/irrigação sanguínea , Pele/patologia , Tomografia de Coerência Óptica/métodos , Adulto , Algoritmos , Feminino , Humanos , Aumento da Imagem/métodos , Reconhecimento Automatizado de Padrão/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
AIM: Brostallicin is a DNA minor groove binder that has shown activity in patients with soft tissue sarcoma (STS) failing first-line therapy. The present study assessed the safety and efficacy of first-line brostallicin in patients with advanced or metastatic STS >60 years or not fit enough to receive combination chemotherapy. A prospective explorative pharmacogenetic analysis was undertaken in parallel. METHODS: Patients were randomised in a 2:1 ratio between IV brostallicin 10mg/m(2) and doxorubicin 75 mg/m(2) once every 3 weeks for a maximum of six cycles. Disease stabilisation at 26 weeks (primary end-point) was considered a 'success'. Further testing of brostallicin was warranted if ≥ 35 'successes' were observed in the first 72 eligible patients treated with brostallicin. In addition, patients were genotyped for glutathione S transferase (GST) polymorphisms. RESULTS: One hundred and eighteen patients were included (79 brostallicin and 39 doxorubicin). Brostallicin was well tolerated in comparison to doxorubicin with less grade 3-4 neutropenia (67% versus 95%), grade 2-3 systolic dysfunction (0% versus 11%), alopecia (17% versus 61%) and grade 2-3 mucositis (0% versus 18%). For brostallicin versus doxorubicin, 'successes' were observed in 5/77 versus 10/36, progression free survival at 1 year was 6.5% versus 15.6%, objective response rate was 3.9% versus 22.2% and overall survival at 1 year was 50.5% versus 57.9%, respectively. Only GSTA1 genotype was significantly associated with success rate of doxorubicin treatment. CONCLUSION: Brostallicin cannot be recommended at this dose and schedule in this patient population as first-line therapy. GSTA1 genotype may be predictive for doxorubicin efficacy but warrants further study.
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Neoplasias Ósseas/tratamento farmacológico , Doxorrubicina/uso terapêutico , Guanidinas/uso terapêutico , Pirróis/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Intervalo Livre de Doença , Esquema de Medicação , Europa (Continente) , Frequência do Gene , Genótipo , Glutationa Transferase/genética , Humanos , Isoenzimas/genética , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Farmacogenética , Polimorfismo Genético , Sarcoma/genética , Sarcoma/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Despite advances in the management of and changes in clinical practice, little is known about the epidemiology, patterns of care and outcomes of gastrointestinal stromal tumour (GIST) patients in the UK. Patient registries are receiving increasing attention as they can provide important information on clinical practice and patient outcomes. The rationale and study design of the GIST Epidemiology and Management (GEM) Registry, which forms part of the routine clinical practice for GISTs in several UK centres, are described. METHODS: The GEM Registry is a secure web-based registry system designed around a Microsoft Access core using SQL interface. Demographic, surgical, histopathological and clinical data will be captured including treatment outcomes and survival. The registry was piloted in six centres and following further fine tuning of the data sets, ethical committee submission and approval was completed. RESULTS: The GEM National Registry is the first of its kind to be implemented in rare cancers in UK. The registry is being rolled out initially in selected centres with the aim to expand to other centres. The first publication reporting analyses of the central data set is anticipated for the summer of 2013. CONCLUSION: GEM Registry will enable us to obtain a clear picture of incidence/prevalence of GISTS in UK. Clinicians will be able to review the prognostic and predictive value of variables in a large prospective data set. The data can be used for planning the delivery and improving the quality of care. This information is likely to inform clinical practice and, in years to come, guide the development and implementation of clinical trials for novel tyrosine kinase inhibitors. The results will not only benefit the GIST community, but also serve as a basis for the study of other rare tumour types.
Assuntos
Bases de Dados Factuais , Tumores do Estroma Gastrointestinal/epidemiologia , Sistema de Registros , Adulto , Coleta de Dados , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Incidência , Masculino , Prevalência , Resultado do Tratamento , Reino Unido/epidemiologiaRESUMO
AIM: To determine the frequency, time course and sites of recurrence following surgical resection of gastrointestinal stromal tumours (GIST) and to evaluate the performance of a risk-based surveillance protocol in detection of recurrence. METHODS: Eighty-one patients on surveillance following complete resection of GIST were included. Patients were stratified into risk groups according to accepted histopathological criteria. Computed tomography (CT) examinations were retrospectively reviewed to determine rates, sites and imaging characteristics of recurrence and to assess compliance with the local follow-up protocol. RESULTS: The median time of follow-up was 41 months. Nineteen patients suffered recurrence, all of whom were in the high-risk group. Fifty-eight percent of relapses occurred within 1 year and 84% within 3 years. Even within the high-risk group, patients with relapse had significantly larger (mean 15 versus 10.4 cm, p < 0.05) and more mitotically active primary tumours (mean 33.7 versus 5.6 mitoses per 50 high-power fields; p < 0.05) than those with no relapse. Relapse was to the liver in 12 cases (63%) and to the omentum and mesentery in nine cases (47%), and was asymptomatic in three-quarters of patients. CONCLUSIONS: The high incidence of GIST recurrence in the high-risk group in the first 3 years after surgery supports the use of intensive imaging surveillance in this period. Relapse is often asymptomatic and commonly occurs to the liver, omentum and mesentery. Stratification by tumour factors may enable improved tailoring of surveillance protocols within the high-risk group in the future.