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BACKGROUND: Tumor embolism is a very rare primary manifestation of cancers and the diagnosis is challenging, especially if located in the pulmonary arteries, where it can mimic nonmalignant pulmonary embolism. Intimal sarcoma is one of the least commonly reported primary tumors of vessels with only a few cases reported worldwide. A typical location of this malignancy is the pulmonary artery. Herein, we present a case report of an intimal sarcoma with primary manifestation in the pulmonary arteries. A 53-year-old male initially presented with dyspnea. On imaging, a pulmonary artery embolism was detected and was followed by thrombectomy of the right ventricular outflow tract, main pulmonary artery trunk, and right pulmonary artery after ineffective lysis therapy. Complementary imaging of the chest and abdomen including a PET-CT scan demonstrated no evidence of a primary tumor. Subsequent pathology assessment suggested an intimal sarcoma further confirmed by DNA methylation based molecular analysis. We initiated adjuvant chemotherapy with doxorubicin. Four months after the completion of adjuvant therapy a follow-up scan revealed a local recurrence without distant metastases. DISCUSSION: Primary pulmonary artery intimal sarcoma (PAS) is an exceedingly rare entity and pathological diagnosis remains challenging. Therefore, the detection of entity-specific molecular alterations is a supporting argument in the diagnostic spectrum. Complete surgical resection is the prognostically most important treatment for intimal cardiac sarcomas. Despite adjuvant chemotherapy, the prognosis of cardiac sarcomas remains very poor. This case of a PAS highlights the difficulty in establishing a diagnosis and the aggressive natural course of the disease. CONCLUSION: In case of atypical presentation of a pulmonary embolism, a tumor originating from the great vessels should be considered. Molecular pathology techniques support in establishing a reliable diagnosis.
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Artéria Pulmonar , Sarcoma , Trombose , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/patologia , Sarcoma/diagnóstico , Sarcoma/patologia , Túnica Íntima/patologia , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/patologia , Embolia Pulmonar/diagnóstico , Diagnóstico DiferencialRESUMO
The meltwater streams of the McMurdo Dry Valleys are hot spots of biological diversity in the climate-sensitive polar desert landscape. Microbial mats, largely comprised of cyanobacteria, dominate the streams which flow for a brief window of time (~10 weeks) over the austral summer. These communities, critical to nutrient and carbon cycling, display previously uncharacterized patterns of rapid destabilization and recovery upon exposure to variable and physiologically detrimental conditions. Here, we characterize changes in biodiversity, transcriptional responses and activity of microbial mats in response to hydrological disturbance over spatiotemporal gradients. While diverse metabolic strategies persist between marginal mats and main channel mats, data collected from 4 time points during the austral summer revealed a homogenization of the mat communities during the mid-season peak meltwater flow, directly influencing the biogeochemical roles of this stream ecosystem. Gene expression pattern analyses identified strong functional sensitivities of nitrogen-fixing marginal mats to changes in hydrological activities. Stress response markers detailed the environmental challenges of each microhabitat and the molecular mechanisms underpinning survival in a polar desert ecosystem at the forefront of climate change. At mid and end points in the flow cycle, mobile genetic elements were upregulated across all mat types indicating high degrees of genome evolvability and transcriptional synchronies. Additionally, we identified novel antifreeze activity in the stream microbial mats indicating the presence of ice-binding proteins (IBPs). Cumulatively, these data provide a new view of active intra-stream diversity, biotic interactions and alterations in ecosystem function over a high-flow hydrological regime.
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The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.
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Docentes de Medicina , Radioterapia (Especialidade) , Competência Clínica , Currículo , Alemanha , Humanos , Radioterapia (Especialidade)/educaçãoRESUMO
BACKGROUND: Soft tissue sarcomas (STS) account for less than 1% of all malignancies. Approximately 50% of the patients develop metastases with limited survival in the course of their disease. For those patients, palliative treatment aiming at symptom relief and improvement of quality of life is most important. However, data on symptom burden and palliative intervention are limited in STS patients. AIM: Our study evaluates the effectiveness of a palliative care intervention on symptom relief and quality of life in STS patients. DESIGN/SETTING: We retrospectively analysed 53 inpatient visits of 34 patients with advanced STS, admitted to our palliative care unit between 2012 and 2018. Symptom burden was measured with a standardised base assessment questionnaire at admission and discharge. RESULTS: Median disease duration before admission was 24 months, 85% of patients had metastases. The predominant indication for admission was pain, weakness and fatigue. Palliative care intervention led to a significant reduction of pain: median NRS for acute pain was reduced from 3 to 1 (p < 0.001), pain within the last 24 h from 5 to 2 (p < 0.001) and of the median MIDOS symptom score: 18 to 13 (p < 0.001). Also, the median stress level, according to the distress thermometer, was reduced significantly: 7.5 to 5 (p = 0.027). CONCLUSIONS: Our data underline that specialised palliative care intervention leads to significant symptom relief in patients with advanced STS. Further efforts should aim for an early integration of palliative care in these patients focusing primarily on the identification of subjects at high risk for severe symptomatic disease.
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Neoplasias , Sarcoma , Humanos , Cuidados Paliativos , Qualidade de Vida , Estudos Retrospectivos , Sarcoma/complicações , Sarcoma/terapia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT. METHODS: A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated nâ¯= 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40-50â¯Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models. RESULTS: GTV1 was found to have a mean of 154.4â¯ml (95%CI: 1.5-877) and GTV2 of 106.2â¯ml (95% CI: 0.5-589.5), resulting in an estimated reduction of 48.2â¯ml (pâ¯< 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12-6.75, pâ¯= 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9-2, pâ¯> 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0-69, 0.32-1.49, pâ¯> 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01-13.53, pâ¯= 0.04) per 300â¯ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50â¯ml reduced the HR by 0.8 (CI 0.64-0.99, pâ¯= 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2. CONCLUSION: Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.
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Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Europa (Continente) , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral/efeitos da radiaçãoRESUMO
Chronic exposure of humans to inorganic arsenic as a potential risk for the incidence of diabetes has received wide attention. However, the biological mechanism through which arsenic plays a role in the development of diabetes is still being evaluated. One of the hallmark of diabetes is the ß-cell dysfunction followed by the changes in the insulin secretion. Pancreatic duodenal homeobox 1 (PDX1) has been widely recognized to play crucial role in the ß-cell development, survival and its regulation of insulin gene expression. Many of the arsenic mediated cellular affects have been shown to be regulated by miR-2909 in vitro. Our present study provides evidence to reveal that arsenic affects miR-2909 expression in the pancreatic ß-cell and this novel miRNA regulates PDX1 transcriptional expression indirectly through genes coding for c-Jun, MafA, PI3K and directly at the translational level by targeting the PDX1 mRNA. We provide further evidence for this miR-2909 RNomics in pancreatic tissue obtained from NOD mice where the expression of miR-2909 was high compared to the control mice. Keeping in view the fact that arsenic is known to cause ß-cell dysfunction and most of the cellular effects of arsenic have been shown to be mediated through miR-2909 RNomics, our study revealed that arsenic employs miR-2909 (at low doses) and c-Jun (at high doses) to down regulate PDX1 in order to cause ß-cell dysfunction leading to diabetic state.
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Arsênio/farmacologia , MicroRNAs/metabolismo , Animais , Linhagem Celular Tumoral , Proteínas de Homeodomínio/metabolismo , Células Secretoras de Insulina , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Transativadores/metabolismoRESUMO
Background Frequent computed tomography (CT) follow-ups involve significant radiation related risks for patients with low-grade neuroendocrine tumors (NETs). Contrast agent (CA) application is essential for diagnostic evidence and has additional risks especially in patients with limited renal function. Purpose To investigate if a combination of dose and contrast agent (CA) reduction affects image quality and diagnostic evidence in neuroendocrine tumor (NET) patients. Material and Methods A total of 51 NET patients were enrolled in the study and 153 CT scans were analyzed. Patients underwent a baseline CT scan (A = 120 kVp, filtered back projection [FBP]) and two follow-up CTs (B = 120 kVp, adaptive statistical iterative reconstruction [ASIR] 40%; C1 = 100 kVp, ASIR 40%; C2 = 100 kVp, ASIR 60%; the latter two protocols were applied with a 30% reduction in CA volume). We evaluated image quality and applied dose. Results In C1/2, the combination of low kV (100 kVp) with ASIR 40%/60% reduced the mean applied dose significantly by 28% compared to B and by 57% compared to A. Signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR) of tumor to liver/muscle were significantly increased by using C1/2 compared to B and A. With respect to subjective image quality, a slight loss of diagnostic confidence in C1 could be counterbalanced by the higher ASIR blending in C2. Conclusion Combined dose reduction techniques can be used to reduce radiation dose and CA volume without sacrificing image quality and diagnostic confidence in staging CT of NET patients.
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Meios de Contraste/administração & dosagem , Tumores Neuroendócrinos/diagnóstico por imagem , Doses de Radiação , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Iohexol/administração & dosagem , Iohexol/análogos & derivados , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Razão Sinal-RuídoRESUMO
The global occurrence of prostate cancer with a range of patient outcome has prompted various investigators to explore novel molecular biomarkers that can precisely detect and track this type of cancer severity. Several studies suggest that micro-RNAs have emerged to act as a new largely unexplored class of biomarkers because of their inherent stability, resilience and recruitment into exosomes present in various human body fluids. With this study, we aim to reveal the nature of urinary-exosomal miR-2909 & miR-615-3p recruitment in patients suffering from either prostate cancer (n=90) or bladder cancer (n=60) as compared to that in either prostate disease-control subjects having benign prostate hyperplasia (n=10) or healthy subjects (n=50). Unlike miR-615-3p, the urinary- exosomal miR-2909 recruitment was not only observed conspicuously in subjects having prostate cancer in comparison to bladder cancer but also the extent of urinary exosomal miR-2909 recruitment showed characteristic variation as a function of prostate cancer aggressiveness as compared to that of either urinary- exosomal miR-615-3p level or existing widely recognised serum prostate specifics antigen (PSA) biomarker of this cancer. In summary, we propose that the extent of urinary exosomal miR-2909 recruitment may provide a potential non-invasive candidate diagnostic marker for the detection of prostate cancer and its aggressiveness.
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Biomarcadores Tumorais/urina , Exossomos/metabolismo , MicroRNAs/urina , Neoplasias da Próstata/metabolismo , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino , MicroRNAs/metabolismo , Antígeno Prostático Específico/sangue , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/urinaRESUMO
Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. AIM: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing PCR was performed to analyze the methylation status of these genes. Reverse transcription PCR and real time PCR was carried out to determine changes in the mRNA expression level of the genes due to hypermethylation. RESULTS: Hypermethylation of the 5´CpG islands of the CASP8, TMS1 and DAPK gene promoters was found in 3.2, 6.4, and 13.6% of 125 childhood ALL samples from north Indian population, respectively. There were significant differences in pattern of hypermethylation of TMS1 (p = 0.045) and DAPK (p < 0.001) between patients and healthy controls. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. CONCLUSIONS: The present study indicated the impact of hypermethylation-mediated inactivation of CASP8, TMS1 and DAPK genes, which is associated with risk of childhood ALL. This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL.
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Apoptose/genética , Metilação de DNA , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Regiões Promotoras Genéticas/genética , Sequência de Bases , Proteínas Adaptadoras de Sinalização CARD , Estudos de Casos e Controles , Caspase 8/genética , Criança , Pré-Escolar , Proteínas do Citoesqueleto/genética , Proteínas Quinases Associadas com Morte Celular/genética , Regulação para Baixo , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Índia , Lactente , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIM: To assess how adaptive statistical iterative reconstruction (ASIR) contributes to dose reduction and affects image quality of non-contrast cranial computed tomography (cCT) in children. MATERIALS AND METHODS: Non-contrast cranial CT acquired in 78 paediatric patients (age 0-12 years) were evaluated. The images were acquired and processed using four different protocols: Group A (control): 120 kV, filtered back projection (FBP), n=18; Group B: 100 kV, FBP, n=22; Group C: 100 kV, scan and reconstruction performed with 20% ASIR, n=20; Group D1: 100 kV, scan and reconstruction performed with 30% ASIR, n=18; Group D2: raw data from Group D1 reconstructed using a blending of 40% ASIR and 60% FBP, n=18. The effective dose was calculated and the image quality was assessed quantitatively and qualitatively. RESULTS: Compared to Group A, Groups C and D1/D2 showed a significant reduction of the dose-length product (DLP) by 34.4% and 64.4%, respectively. All experimental groups also showed significantly reduced qualitative levels of noise, contrast, and overall diagnosability. Diagnosis-related confidence grading showed Group C to be adequate for everyday clinical practice. Quantitative measures of Groups B and C were comparable to Group A with only few parameters compromised. Quantitative scores in Groups D1 and D2 were mainly lower compared to Group A, with Group D2 performing better than Group D1. Group D2 was considered adequate for follow-up imaging of severe acute events such as bleeding or hydrocephalus. DISCUSSION: The use of ASIR combined with low tube voltage may reduce radiation significantly while maintaining adequate image quality in non-contrast paediatric cCT.
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Encéfalo/diagnóstico por imagem , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Mapeamento Encefálico/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos TestesRESUMO
Donor-derived coccidioidomycosis has caused unexpected morbidity and mortality in transplant recipients. All proven or probable reports of donor-derived coccidioidomycosis to the Disease Transmission Advisory Committee between 2005 and August 2012 were reviewed. Six reports of proven or probable coccidioidomycosis were discovered. In four of six, the infection was first detected at autopsy in the recipient. In two cases it was first identified in the donor. Twenty-one recipients received organs from these six donors. Transmission occurred in 43% at a median of 30 days posttransplant with a mortality rate of 28.5%. Eleven recipients received preemptive antifungals, seven did not receive treatment, and treatment information was not reported for three recipients. Five of seven who did not receive prophylaxis/treatment died and all 11 who received early therapy survived. Six deaths occurred 14 to 55 days after transplant, with a median of 21 days. For exposed recipients, donor-derived coccidioidomycosis is a significant cause of morbidity and mortality. Evidence of infection in one recipient should prompt immediate evaluation for treatment of all other recipients from the same donor as preemptive treatment was effective. Further studies are needed to decide whether all donors from endemic areas should have routine serologic screening.
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Coccidioides/patogenicidade , Coccidioidomicose/transmissão , Transmissão de Doença Infecciosa , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos , Comitês Consultivos , Coccidioidomicose/epidemiologia , Coccidioidomicose/etiologia , Seleção do Doador , Humanos , Segurança do Paciente , Prognóstico , Medição de Risco , Obtenção de Tecidos e Órgãos , Transplantados , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The optimal treatment for respiratory syncytial virus (RSV) infection in adult immunocompromised patients is unknown. We assessed the management of RSV and other non-influenza respiratory viruses in Midwestern transplant centers. METHODS: A survey assessing strategies for RSV and other non-influenza respiratory viral infections was sent to 13 centers. RESULTS: Multiplex polymerase chain reaction assay was used for diagnosis in 11/12 centers. Eight of 12 centers used inhaled ribavirin (RBV) in some patient populations. Barriers included cost, safety, lack of evidence, and inconvenience. Six of 12 used intravenous immunoglobulin (IVIG), mostly in combination with RBV. Inhaled RBV was used more than oral, and in the post-stem cell transplant population, patients with lower respiratory tract infection (LRTI), graft-versus-host disease, and more recent transplantation were treated at higher rates. Ten centers had experience with lung transplant patients; all used either oral or inhaled RBV for LRTI, 6/10 treated upper respiratory tract infection (URTI). No center treated non-lung solid organ transplant (SOT) recipients with URTI; 7/11 would use oral or inhaled RBV in the same group with LRTI. Patients with hematologic malignancy without hematopoietic stem cell transplantation were treated with RBV at a similar frequency to non-lung SOT recipients. Three of 12 centers, in severe cases, treated parainfluenza and metapneumovirus, and 1/12 treated coronavirus. CONCLUSIONS: Treatment of RSV in immunocompromised patients varied greatly. While most centers treat LRTI, treatment of URTI was variable. No consensus was found regarding the use of oral versus inhaled RBV, or the use of IVIG. The presence of such heterogeneity demonstrates the need for further studies defining optimal treatment of RSV in immunocompromised hosts.
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Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Órgãos/efeitos adversos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Ribavirina/uso terapêutico , Administração Oral , Antivirais/uso terapêutico , Coleta de Dados , Humanos , Hospedeiro Imunocomprometido , Vírus Sincicial Respiratório Humano , Terapia Respiratória , Ribavirina/administração & dosagemRESUMO
PURPOSE: To assess how ASIR (adaptive statistical iterative reconstruction) contributes to dose reduction and affects image quality of non-contrast cranial computed tomography (cCT). MATERIALS AND METHODS: Non-contrast emergency CT scans of the head acquired in 177 patients were evaluated. The scans were acquired and processed using four different protocols: Group A (control): 120âkV, FBP (filtered back projection) nâ=â71; group B1: 120âkV, scan and reconstruction performed with 20â% ASIR (blending of 20â% ASIR and 80â% FBP), nâ=â86; group B2: raw data from group B1 reconstructed using a blending of 40â% ASIR and 60â% FBP, nâ=â74; group C1: 120âkV, scan and reconstruction performed with 30â% ASIR, nâ=â20; group C2: raw data from group C1 reconstructed using a blending of 50â% ASIR and 50â% FBP, nâ=â20. The effective dose was calculated. Image quality was assessed quantitatively and qualitatively. RESULTS: Compared to group A, groups B1/2 and C1/2 showed a significantly reduced effective dose of 40.4â% and 73.3â% (pâ<â0.0001), respectively. Group B1 and group C1/2 also showed significantly reduced quantitative and qualitative image quality parameters. In group B2, quantitative measures were comparable to group A, and qualitative scores were lower compared to group A but higher compared to group B1. Diagnostic confidence grading showed groups B1/2 to be adequate for everyday clinical practice. Group C2 was considered acceptable for follow-up imaging of severe acute events such as bleeding or subacute stroke. CONCLUSION: Use of ASIR makes it possible to reduce radiation significantly while maintaining adequate image quality in non-contrast head CT, which may be particularly useful for younger patients in an emergency setting and in follow-up. KEY POINTS: ASIR may reduce radiation significantly while maintaining adequate image quality.âcCT protocol with 20â% ASIR and 40â%ASIR/60â%FBP blending is adequate for everyday clinical use. cCT protocol with 30â% ASIR and 50â%ASIR/50â%FBP blending is adequate for follow-up imaging
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Encefalopatias/diagnóstico por imagem , Lesões Encefálicas/diagnóstico por imagem , Emergências , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada Multidetectores/métodos , Doses de Radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Arsenic biology has caught the imagination of scientists across the globe because of its unique association with degenerative diseases in general and cancer in particular. Recent findings have added a new dimension to arsenic biology by revealing that most of the arsenic epigenomic effects are mediated through its ability to induce cellular miR-2909 expression at low doses. The present study was addressed to explore the molecular link that might exist between arsenic exposure, miR-2909 RNomics involving immunomodulatory genes and effector IgA class switching, revealed that arsenic-exposed Balb/c mice exhibited predominant Th1 immune response coupled with effector IgA class switching thereby tailoring their immune system to ensure increased risk to infections and chronic diseases like cancer.
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Arsenitos/toxicidade , Biomarcadores Tumorais/genética , Imunidade Celular/imunologia , MicroRNAs/genética , Compostos de Sódio/toxicidade , Linfócitos T/imunologia , Células Th1/imunologia , Animais , Células Cultivadas , Inibidores Enzimáticos/toxicidade , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Voluntários Saudáveis , Humanos , Imunidade Celular/efeitos dos fármacos , Imunomodulação , Imunofenotipagem , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Células Th1/efeitos dos fármacos , Células Th1/metabolismoRESUMO
OBJECTIVE: To investigate whether dose reduction via adaptive statistical iterative reconstruction (ASIR) affects image quality and diagnostic accuracy in neuroendocrine tumor (NET) staging. METHODS: A total of 28 NET patients were enrolled in the study. Inclusion criteria were histologically proven NET and visible tumor in abdominal computed tomography (CT). In an intraindividual study design, the patients underwent a baseline CT (filtered back projection, FBP) and follow-up CT (ASIR 40%) using matched scan parameters. Image quality was assessed subjectively using a 5-grade scoring system and objectively by determining signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNRs). Applied volume computed tomography dose index (CTDIvol) of each scan was taken from the dose report. RESULTS: ASIR 40% significantly reduced CTDIvol (10.17±3.06mGy [FBP], 6.34±2.25mGy [ASIR] (p<0.001) by 37.6% and significantly increased CNRs (complete tumor-to-liver, 2.76±1.87 [FBP], 3.2±2.32 [ASIR]) (p<0.05) (complete tumor-to-muscle, 2.74±2.67 [FBP], 4.31±4.61 [ASIR]) (p<0.05) compared to FBP. Subjective scoring revealed no significant changes for diagnostic confidence (5.0±0 [FBP], 5.0±0 [ASIR]), visibility of suspicious lesion (4.8±0.5 [FBP], 4.8±0.5 [ASIR]) and artifacts (5.0±0 [FBP], 5.0±0 [ASIR]). ASIR 40% significantly decreased scores for noise (4.3±0.6 [FBP], 4.0±0.8 [ASIR]) (p<0.05), contrast (4.4±0.6 [FBP], 4.1±0.8 [ASIR]) (p<0.001) and visibility of small structures (4.5±0.7 [FBP], 4.3±0.8 [ASIR]) (p<0.001). CONCLUSION: In clinical practice ASIR can be used to reduce radiation dose without sacrificing image quality and diagnostic confidence in staging CT of NET patients. This may be beneficial for patients with frequent follow-up and significant cumulative radiation exposure.
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Processamento de Imagem Assistida por Computador/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Artefatos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Razão Sinal-RuídoAssuntos
Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/transmissão , Transplante de Órgãos , Anticorpos Antivirais/sangue , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Período de Incubação de Doenças Infecciosas , Programas de Rastreamento , Transplante de Órgãos/efeitos adversos , Doadores de TecidosRESUMO
The detection and management of potential donor-derived infections is challenging, in part due to the complexity of communications between diverse labs, organ procurement organizations (OPOs), and recipient transplant centers. We sought to determine if communication delays or errors occur in the reporting and management of donor-derived infections and if these are associated with preventable adverse events in recipients. All reported potential donor-derived transmission events reviewed by the Organ Procurement and Transplantation Network Ad Hoc Disease Transmission Advisory Committee from January 2008 to June 2010 were evaluated for communication gaps between the donor center, OPO and transplant centers. The impact on recipient outcomes was then determined. Fifty-six infection events (IEs; involving 168 recipients) were evaluated. Eighteen IEs (48 recipients) were associated with communication gaps, of which 12 resulted in adverse effects in 69% of recipients (20/29), including six deaths. When IEs and test results were reported without delay, appropriate interventions were taken, subsequently minimizing or averting recipient infection (23 IEs, 72 recipients). Communication gaps in reported IEs are frequent, occur at multiple levels in the communication process, and contribute to adverse outcomes among affected transplant recipients. Conversely, effective communication minimized or averted infection in transplant recipients.
Assuntos
Comunicação , Transmissão de Doença Infecciosa , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos , Humanos , Prognóstico , TransplantadosRESUMO
PURPOSE: The purpose of this study was to analyse the feasibility, safety, and long-term efficacy of linear accelerator-based fractionated stereotactic radiotherapy for meningiomas of the skull base. We evaluated the long-term clinical outcome of patients and identified prognostic factors after fractionated stereotactic radiotherapy. PATIENTS AND METHODS: Between 10/1995 and 03/2009, 136 patients with a median age of 57 years with skull base meningioma received fractionated stereotactic radiotherapy. A total of 34 patients had a grade I meningioma, in 102 cases no histology was obtained (grade 0). Fractionated stereotactic radiotherapy was delivered as primary treatment for 57 patients and postoperatively for 79. The patients received a mean total dose of 56.95 (min/max 32.4/63)Gy. RESULTS: Median follow-up was 44.9 months. Overall progression-free survival was 96.9% after 3 years, 93.8% after 5 years, and 91.5% after 10 years. Patients with unknown histology showed progression-free survival rates of 100%, 98.7%, and 93.5% at 3, 5, and 10 years and patients with biopsy-proven grade I meningioma showed rates of 100% after 3 years, 91.7% after 5 years and 85.9% after 10 years. Patients with adjuvant radiotherapy showed significantly worse progression-free survival rates than patients who had been treated with primary radiotherapy (P=0.043), progression-free survival rates were independent of tumour size. The most common acute grade I symptoms were headache, fatigue, and local alopecia. The most common chronic grade I symptoms were fatigue and headache. CONCLUSIONS: This large study showed that fractionated stereotactic radiotherapy is an effective and safe treatment modality with high progression-free survival rates for intracranial meningioma. We identified "prior surgery" as significant poor prognostic factor.
Assuntos
Meningioma/radioterapia , Radiocirurgia , Neoplasias da Base do Crânio/radioterapia , Cirurgia Assistida por Computador , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
We describe two cases of donor-derived methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that developed after transplantation of organs from a common donor who died from acute MRSA endocarditis. Both recipients developed recurrent MRSA infection despite appropriate antibiotic therapy, and required prolonged hospitalization and hospital readmission. Comparison of S. aureus whole genome sequence of DNA extracted from fixed donor tissue and recipients' isolates confirmed donor-derived transmission. Current guidelines emphasize the risk posed by donors with bacteremia from multidrug-resistant organisms. This investigation suggests that, particularly in the setting of donor endocarditis, even a standard course of prophylactic antibiotics may not be sufficient to prevent donor-derived infection.