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AIM: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for patients with EGFR mutated non-small cell lung cancer as first-line treatment. However, treatment resistance inevitably emerges and may present as oligo-progressive disease (OPD) or systemic progressive disease (SPD). The incidence of OPD on first-line osimertinib is unknown. METHODS: We retrospectively analyzed patients who received first-line osimertinib at 13 Swiss centers. The rate of OPD (PD in ≤ 5 lesions) and treatment outcomes were analyzed. RESULTS: The median age of the 148 patients was 68.2 years (range. 38.0-93.3). There were 62 % females, 83 % with a PS ≤ 1, 59 % never smokers, 57 % of patients with an EGFR exon 19 deletion and 37 % with EGFR p.L858R exon 21. 77 % experienced OPD. Median overall survival (OS) was 51.6 months (95 % CI, 38.4-65.0). Median progression-free survival (PFS) was 19.2 (95 % CI, 14.3-23.5) and 8.7 (95 % CI, 2.8-15.6) months for patients with common and uncommon EGFR mutations. Patients with OPD compared to SPD had a significantly longer time to treatment failure and longer OS of (22.9 vs. 10.8 months, p < 0.001 and 51.6 vs. 26.4 months, p = 0.004, respectively). The most common organ sites of PD were lung (62 %), brain (30 %), lymph nodes (30 %), bone (27 %) and pleura (27 %). Twenty-six patients (45 %) with OPD received local ablative treatment (LAT). The OS of OPD patients with LAT was 60.0 (95 % CI, 51.6-NA) vs. 51.4 (95 % CI 38.4-65.3) months (p = 0.43) without LAT. CONCLUSION: The rate of OPD of patients receiving first line osimertinib was 77 %. Patients with OPD had a significantly better OS compared to patients with SPD (51.6 vs. 26.4 months). Patients with OPD receiving LAT had the longest median OS (60.0 months).
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estudos de Coortes , Estudos Retrospectivos , Suíça , Inibidores de Proteínas Quinases/farmacologia , Compostos de Anilina/uso terapêutico , Receptores ErbB/genética , MutaçãoRESUMO
BACKGROUND: Recent studies identify large quantities of inflammatory cellular debris within Fresh Frozen Plasma (FFP). As FFP is a mainstay of hemorrhagic shock resuscitation, we used a porcine model of hemorrhagic shock and ischemia/reperfusion to investigate the inflammatory potential of plasma-derived cellular debris administered during resuscitation. METHODS: The porcine model of hemorrhagic shock included laparotomy with 35 % hemorrhage (Hem), 45 min of ischemia from supraceliac aortic occlusion with subsequent clamp release (IR), followed by protocolized resuscitation for 6 h. Cellular debris (Debris) was added to the resuscitation phase in three groups. The four groups consisted of Hem + IR (n = 4), Hem + IR + Debris (n = 3), Hem + Debris (n = 3), and IR + Debris (n = 3). A battery of laboratory, physiologic, cytokine, and outcome data were compared between groups. RESULTS: As expected, the Hem + IR group showed severe time dependent decrements in organ function and physiologic parameters. All animals that included both IR and Debris (Hem + IR + Debris or IR + Debris) died prior to the six-hour end point, while all animals in the Hem + IR and Hem + Debris survived. Cytokines measured at 30-60 min after initiation of resuscitation revealed significant differences in IL-18 and IL-1ß between all groups. CONCLUSIONS: Ischemia and reperfusion appear to prime the immune system to the deleterious effects of plasma-derived cellular debris. In the presence of ischemia and reperfusion, this model showed the equivalency of 100 % lethality when resuscitation included quantities of cellular debris at levels routinely administered to trauma patients during transfusion of FFP. A deeper understanding of the immunobiology of FFP-derived cellular debris is critical to optimize resuscitation for hemorrhagic shock.
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Choque Hemorrágico , Humanos , Suínos , Animais , Transfusão de Sangue , Citocinas , Ressuscitação , IsquemiaRESUMO
BACKGROUND: Transcranial magnetic stimulation (TMS) is an FDA-approved therapeutic option for treatment resistant depression. However, exact mechanisms-of-action are not fully understood and individual responses are variable. Moreover, although previously suggested, the exact network effects underlying TMS' efficacy are poorly understood as of today. Although, it is supposed that DLPFC stimulation indirectly modulates the sgACC, recent evidence is sparse. METHODS: Here, we used concurrent interleaved TMS/fMRI and state-of-the-science purpose-designed MRI head coils to delineate networks and downstream regions activated by DLPFC-TMS. RESULTS: We show that regions of increased acute BOLD signal activation during TMS resemble a resting-state brain network previously shown to be modulated by offline TMS. There was a topographical overlap in wide spread cortical and sub-cortical areas within this specific RSN#17 derived from the 1000 functional connectomes project. CONCLUSION: These data imply a causal relation between DLPFC-TMS and activation of the ACC and a broader network that has been implicated in MDD. In the broader context of our recent work, these data imply a direct relation between initial changes in BOLD activity mediated by connectivity to the DLPFC target site, and later consolidation of connectivity between these regions. These insights advance our understanding of the mechanistic targets of DLPFC-TMS and may provide novel opportunities to characterize and optimize TMS therapy in other neurological and psychiatric disorders.
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Imageamento por Ressonância Magnética , Estimulação Magnética Transcraniana , Humanos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Córtex Pré-Frontal DorsolateralRESUMO
BACKGROUND: There is no standard for the treatment of functional aphakia in cases with a compromised capsular system. Retropupillary fixation of an Artisan iris-claw IOL ("Intraokularlinse") is one of the established procedures. OBJECTIVE: Aim of this study was the evaluation of indications, visual and refractive long-term results and complication rates after retropupillary implantation of an iris-claw lens. MATERIAL AND METHODS: This retrospective study comprised 366 eyes that received a retropupillary Artisan intraocular lens (IOL) in a single center between January 2009 and December 2019. The mean follow-up period was 249 days (8 months) ±516 days. RESULTS: IOL dislocation (68%) was the most common reason for a retropupillary iris-claw implantation. Previous vitrectomy was a significant preoperative risk factor for IOL dislocation (pâ¯= 0.0001). Best corrected visual acuity improved from 0.65⯱ 0.64 (logMAR) preoperatively to 0.57⯱ 0.51 (logMAR) 4-6 weeks after the surgery. The mean deviation from the planned refraction was +0.40⯱ 1.37â¯dpt and 73% of the patients had a deviation within ±1â¯dpt of the planned refraction. Relevant postoperative complications during the first 4 weeks were pupillary distortion (42%), ocular hypotony (15%) and transient hyphema (14%). Late complications (≥4 weeks after the surgery) included persistent pupillary distortion (20%), cystoid macular edema (13%) and iris-claw disenclavation (6%). CONCLUSION: The retropupillary Artisan implantation is an efficient method for treating aphakia without capsular support and provides good visual and refractive results with an acceptable surgical risk profile.
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Afacia Pós-Catarata , Lentes Intraoculares , Humanos , Implante de Lente Intraocular/efeitos adversos , Estudos Retrospectivos , Afacia Pós-Catarata/cirurgia , Refração OcularRESUMO
OBJECTIVE: To characterize the differences and correlations in osteophyte volumes between and within proximal tibial compartments, and to assess the correlations between osteophyte volumes and the femorotibial angle. DESIGN: CT scans of 73 knees with predominantly medial femorotibial osteoarthritis (21 K/L2, 28 K/L3, 24 K/L4) were retrospectively analyzed using a new, reproducible method measuring total and subregional osteophyte volumes in the medial and lateral compartments. Non-parametric statistics was used for comparison and correlation analyses. RESULTS: Total osteophyte volumes were larger in the medial than in the lateral compartment for all severity groups (p < 0.05). Additionally, statistically significant differences were observed among subregions of the lateral compartment in K/L3 and K/L4 knees. Statistically significant positive correlations were found between the medial and lateral total osteophyte volumes in K/L3 and K/L4 knees (ρ ≥ 0.44, p = 0.03), and among most subregional osteophyte volumes within each compartment in K/L3 knees. Markedly fewer statistically significant correlations were present in K/L2 and K/L4 knees. In K/L3 knees, the femorotibial angle was statistically significantly positively correlated with the total osteophyte volume in the medial compartment (ρ = 0.50, p = 0.01), with osteophyte volumes in most medial subregions, and with the osteophyte volume in the lateral posterior subregion (ρ = 0.40, p = 0.05). CONCLUSIONS: Quantitative assessment of osteophytes may bring insight on factors influencing their development. Positive correlations of osteophyte volumes found between and within compartments suggest the influence of biochemical mediators acting on the entire joint, while positive correlations between the femorotibial angle and osteophyte volumes suggest a role of mechanical factors. These hypotheses are to be further confirmed.
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Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Osteófito/diagnóstico por imagem , Idoso , Simulação por Computador , Estudos Transversais , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. It remains unresolved whether increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscle's disrupted contractile machinery. This knowledge has important implications for patients, as potential physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones. Recently we showed how burrowing dystrophic (dys-1) C. elegans recapitulate many salient phenotypes of DMD, including loss of mobility and muscle necrosis. Here, we report that dys-1 worms display early pathogenesis, including dysregulated sarcoplasmic calcium and increased lethality. Sarcoplasmic calcium dysregulation in dys-1 worms precedes overt structural phenotypes (e.g., mitochondrial, and contractile machinery damage) and can be mitigated by reducing calmodulin expression. To learn how dystrophic musculature responds to altered physical activity, we cultivated dys-1 animals in environments requiring high intensity or high frequency of muscle exertion during locomotion. We find that several muscular parameters (e.g., size) improve with increased activity. However, longevity in dystrophic animals was negatively associated with muscular exertion, regardless of effort duration. The high degree of phenotypic conservation between dystrophic worms and humans provides a unique opportunity to gain insight into the pathology of the disease as well as the initial assessment of potential treatment strategies.
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Distrofia Muscular Animal/terapia , Distrofia Muscular de Duchenne/terapia , Condicionamento Físico Animal , Esforço Físico/fisiologia , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos mdx , Contração Muscular/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/fisiopatologia , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/fisiopatologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/fisiopatologia , Esforço Físico/genéticaRESUMO
There is growing interest in using routinely collected data from health care databases to study the safety and effectiveness of therapies in "real-world" conditions, as it can provide complementary evidence to that of randomized controlled trials. Causal inference from health care databases is challenging because the data are typically noisy, high dimensional, and most importantly, observational. It requires methods that can estimate heterogeneous treatment effects while controlling for confounding in high dimensions. Bayesian additive regression trees, causal forests, causal boosting, and causal multivariate adaptive regression splines are off-the-shelf methods that have shown good performance for estimation of heterogeneous treatment effects in observational studies of continuous outcomes. However, it is not clear how these methods would perform in health care database studies where outcomes are often binary and rare and data structures are complex. In this study, we evaluate these methods in simulation studies that recapitulate key characteristics of comparative effectiveness studies. We focus on the conditional average effect of a binary treatment on a binary outcome using the conditional risk difference as an estimand. To emulate health care database studies, we propose a simulation design where real covariate and treatment assignment data are used and only outcomes are simulated based on nonparametric models of the real outcomes. We apply this design to 4 published observational studies that used records from 2 major health care databases in the United States. Our results suggest that Bayesian additive regression trees and causal boosting consistently provide low bias in conditional risk difference estimates in the context of health care database studies.
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Bases de Dados Factuais/estatística & dados numéricos , Estudos Observacionais como Assunto/estatística & dados numéricos , Resultado do Tratamento , Teorema de Bayes , Bioestatística , Causalidade , Simulação por Computador , Humanos , Aprendizado de Máquina , Modelos Estatísticos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pontuação de Propensão , Análise de Regressão , Estatísticas não ParamétricasRESUMO
BACKGROUND: Data on the social determinants of health can help primary care practices target improvement efforts, yet relevant data are rarely available. Our family practice located in Toronto, Ontario routinely collects patient-level sociodemographic data via a pilot-tested survey developed by a multi-organizational steering committee. We sought to use these data to assess the relationship between the social determinants and colorectal, cervical and breast cancer screening, and to describe the opportunities and challenges of using data on social determinants from a self-administered patient survey. METHODS: Patients of the family practice eligible for at least one of the three cancer screening types, based on age and screening guidelines as of June 30, 2015 and who had answered at least one question on a socio-demographic survey were included in the study. We linked self-reported data from the sociodemographic survey conducted in the waiting room with patients' electronic medical record data and cancer screening records. We created an individual-level income variable (low-income cut-off) that defined a poverty threshold and took household size into account. The sociodemographic characteristics of patients who were overdue for screening were compared to those who were up-to-date for screening for each cancer type using chi-squared tests. RESULTS: We analysed data for 5766 patients for whom we had survey data. Survey participants had significantly higher screening rates (72.9, 78.7, 74.4% for colorectal, cervical and breast cancer screening respectively) than the 13, 036 patients for whom we did not have survey data (59.2, 65.3, 58.9% respectively). Foreign-born patients were significantly more likely to be up-to-date on colorectal screening than their Canadian-born peers but showed no significant differences in breast or cervical cancer screening. We found a significant association between the low-income cut-off variable and cancer screening; neighbourhood income quintile was not significantly associated with cancer screening. Housing status was also significantly associated with colorectal, cervical and breast cancer screening. There was a large amount of missing data for the low-income cut-off variable, approximately 25% across the three cohorts. CONCLUSION: While we were able to show that neighbourhood income might under-estimate income-related disparities in screening, individual-level income was also the most challenging variable to collect. Future work in this area should target the income disparity in cancer screening and simultaneously explore how best to collect measures of poverty.
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Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/organização & administração , Neoplasias/epidemiologia , Atenção Primária à Saúde/normas , Autorrelato , Determinantes Sociais da Saúde/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Neoplasias/diagnóstico , Ontário/epidemiologia , Fatores Socioeconômicos , Adulto JovemRESUMO
Electron diffraction is a standard tool to investigate the atomic structure of surfaces, interfaces, and adsorbate systems. In particular, photoelectron diffraction is a promising candidate for real-time studies of structural dynamics combining the ultimate time resolution of optical pulses and the high scattering cross-sections for electrons. In view of future time-resolved experiments from molecular layers, we studied the sensitivity of photoelectron diffraction to conformational changes of only a small fraction of molecules in a monolayer adsorbed on a metallic substrate. 3,3',5,5'-tetra-tert-butyl-azobenzene served as test case. This molecule can be switched between two isomers, trans and cis, by absorption of ultraviolet light. X-ray photoelectron diffraction patterns were recorded from tetra-tert-butyl-azobenzene/Au(111) in thermal equilibrium at room temperature and compared to patterns taken in the photostationary state obtained by exposing the surface to radiation from a high-intensity helium discharge lamp. Difference patterns were simulated by means of multiple-scattering calculations, which allowed us to determine the fraction of molecules that underwent isomerization.
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PURPOSE: Many patients with thyroid nodules are presently referred to surgery for not only therapeutic but also diagnostic purposes. The aim of noninvasive diagnostic methods is to optimize the selection of patients for surgery. Strain elastography (SE) enables the ultrasound-based determination of tissue elasticity. The aim of the present study was to evaluate the value of SE for the differentiation of thyroid nodules in a prospective multicenter study. MATERIALS AND METHODS: The study was registered at clinicaltrials.gov and was approved by the local ethics committees of all participating centers. All patients received an ultrasound (US) of the thyroid gland including color Doppler US.âIn addition, all nodules were evaluated by SE (Hitachi Medical Systems) using qualitative image interpretation of color distribution (SE-ES), strain value and strain ratio. RESULTS: Overall, 602 patients with 657 thyroid nodules (567 benign, 90 malignant) from 7 centers were included in the final analysis. The sensitivity, specificity, NPV, PPV, +LR were 21â%, 73â%, 86â%, 11â%, 0.8, respectively, for color Doppler US; 69â%, 75â%, 94â%, 30â%, 2.9, respectively, for SE-ES; 56â%, 81â%, 92â%, 32â%, 2.9, respectively, for SE-strain value; and 58â%, 78â%, 92â%, 30â%, 2.6, respectively, for SE-strain ratio. The diagnostic accuracy was 71â% for both strain value and strain ratio of nodules. CONCLUSION: SE as an additional ultrasound tool improves the value of ultrasound for the work-up of thyroid nodules. It might reduce diagnostic surgery of thyroid nodules in the future.
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Técnicas de Imagem por Elasticidade/métodos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Alemanha , Bócio Nodular/diagnóstico por imagem , Bócio Nodular/patologia , Bócio Nodular/cirurgia , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Sociedades Médicas , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Ultrassonografia Doppler em Cores , Adulto JovemRESUMO
INTRODUCTION: The number of publications concerning mesenteric Doppler sonography (mesDS) is immense and does not correlate with the frequency of its use in clinical practice. This is astonishing since it provides real time blood flow (perfusion) information without side effects. Despite uncontrollable parameters like the technical limitations in some situations the optimization of (possibly) controllable parameters like standardization, production of normal values and reduction of the investigator variability by evaluating stable parameters could change the situation. PATIENTS AND METHODS: 10 investigators experienced in abdominal sonography ("DEGUM-Seminarleiter") performed mesenteric Doppler sonography in 5 healthy subjects with 5 different machines. RESULTS: The portal vein at the confluence and the common hepatic artery provide a significant portion of investigations with intromission angles of more than 60°. Values of diameter, resistance index and pulsatility index of the celiac trunc could be obtained with inter-observer variability values below 25â%. The proper and the common hepatic artery show no differences in inter-observer variability values, whereas the intrahepatic measure point of the portal vein showed a higher reproducibility. DISCUSSION: We define frame conditions for future mesenteric Doppler studies: the portal vein should be investigated at the intrahepatic measure point. Pathophysiological studies should refrain from velocity parameters except in the case of larger vessels running in a straight course towards the probe.
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Velocidade do Fluxo Sanguíneo/fisiologia , Artérias Mesentéricas/diagnóstico por imagem , Artérias Mesentéricas/fisiologia , Variações Dependentes do Observador , Ultrassonografia Doppler Dupla/métodos , Resistência Vascular/fisiologia , Adulto , Competência Clínica , Feminino , Humanos , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: The study of locomotion in vermiform animals has largely been restricted to animals crawling on agar surfaces. While this has been fruitful in the study of neuronal basis of disease and behavior, the reduced physical challenge posed by these environments has prevented these organisms from being equally successful in the study of neuromuscular diseases. Our burrowing assay allowed us to study the effects of muscular exertion on locomotion and muscle degeneration during disease (Beron et al., 2015), as well as the natural burrowing preference of diverse Caenorhabditis elegans strains (Vidal-Gadea et al., 2015). NEW METHOD: We describe a simple, rapid, and affordable set of assays to study the burrowing behavior of nematodes and other vermiform organisms which permits the titration of muscular exertion in test animals. RESULTS: We show that our burrowing assay design is versatile and can be adapted for use in widely different experimental paradigms. COMPARISON WITH EXISTING METHOD(S): Previous assays for the study of neuromuscular integrity in nematodes relied on movement through facile and homogeneous environments. The ability of modulating substrate density allows our burrowing assay to be used to separate animal populations where muscular fitness or health are not visible differentiable by standard techniques. CONCLUSION: The simplicity, versatility, and potential for greatly facilitating the study of previously challenging neuromuscular disorders makes this assay a valuable addition that overcomes many of the limitations inherent to traditional behavioral tests of vermiform locomotion.
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Comportamento Animal/fisiologia , Bioensaio/métodos , Fenômenos Magnéticos , Atividade Motora/fisiologia , Músculos/fisiologia , Nematoides/fisiologia , Esforço Físico/fisiologia , Animais , Bioensaio/instrumentação , Caenorhabditis elegans/fisiologiaRESUMO
PURPOSE: According to the German guidelines on colorectal cancer, unenhanced ultrasound is recommended for follow-up.âOn the other hand, ultrasound and radiology societies specify the use of contrast-enhanced ultrasound for ruling out liver metastases. Studies focusing on the follow-up of cancer patients are lacking. The goal of this multicenter study initiated by the German Ultrasound Society (DEGUM) was to determine the potential benefit of contrast-enhanced ultrasound in the follow-up of patients with colon cancer. MATERIALS AND METHODS: Follow-up patients with colon cancer (UICC > IIa) were investigated. As scheduled according to the German guidelines, unenhanced ultrasound was performed followed by contrast-enhanced ultrasound. All liver lesions were recorded. In case of additional metastases detected on contrast-enhanced ultrasound, contrast-enhanced CT, MRI or biopsy was performed to confirm additional liver metastases. RESULTS: A total of 45 liver metastases were detected in 26/290 patients (=â9â%) using unenhanced ultrasound. A further 28 metastases were detected on contrast-enhanced ultrasound in these 26 patients. In 18 patients showing no liver metastases, 40 additional metastases were detected on unenhanced ultrasound. This means that 44 patients with a total of 113 liver metastases were detected on contrast-enhanced ultrasound (pâ=â0.0006). CONCLUSION: Contrast-enhanced ultrasound should be recommended in the follow-up of patients with colon cancer in addition to unenhanced ultrasound - the up-to-date standard.
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Neoplasias do Colo/diagnóstico por imagem , Meios de Contraste , Aumento da Imagem/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Fosfolipídeos , Hexafluoreto de Enxofre , Idoso , Biópsia por Agulha , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Progressão da Doença , Feminino , Seguimentos , Fidelidade a Diretrizes , Humanos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Estadiamento de Neoplasias , Estudos Prospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada Espiral , UltrassonografiaRESUMO
This review article reports on evidence-based and clinical aspects of contrast-enhanced ultrasound of liver masses. The advanced possibilities of contrast-enhanced ultrasound to detect and characterise liver tumors are described as well as limitations and pitfalls of the method. The choice of the ultrasound device and contrast agents as well as the qualifications of the examiners according to guidelines are discussed.
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Meios de Contraste , Aumento da Imagem/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Fosfolipídeos , Polissacarídeos , Hexafluoreto de Enxofre , Ultrassonografia/métodos , Alemanha , HumanosRESUMO
Although the role of the ErbB2/HER2 oncogene in cancers has been extensively studied, how ErbB2 is regulated remains poorly understood. A novel microRNA, mir-4728, was recently found within an intron of the ErbB2 gene. However, the function and clinical relevance of this intronic miRNA are completely unknown. Here, we demonstrate that mir-4728 is a negative regulator of MAPK signaling through directly targeting the ERK upstream kinase MST4 and exerts numerous tumor-suppressive properties in vitro and in animal models. Importantly, our patient sample study shows that mir-4728 was under-expressed in breast tumors compared with normal tissue, and loss of mir-4728 correlated with worse overall patient survival. These results strongly suggest that mir-4728 is a tumor-suppressive miRNA that controls MAPK signaling through targeting MST4, revealing mir-4728's significance as a potential prognostic factor and target for therapeutic intervention in cancer. Moreover, this study represents a conceptual advance by providing strong evidence that a tumor-suppressive miRNA can antagonize the canonical signaling of its host oncogene.
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Neoplasias da Mama/genética , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Receptor ErbB-2/genética , Neoplasias da Mama/enzimologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Células HeLa , Humanos , Íntrons , MicroRNAs/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Receptor ErbB-2/metabolismo , Transdução de SinaisRESUMO
PURPOSE: To analyse the incidence of bleeding after percutaneous ultrasound guided diagnostic and therapeutic intraabdominal interventions in a prospective multicentre study (DEGUM percutaneous interventional ultrasound study). MATERIALS AND METHODS: Within a time period of 2 years diagnostic and therapeutic intraabdominal interventions (with the exclusion of ascites paracentesis) performed percutaneously under continuous ultrasound (US) guidance were prospectively assessed using a pseudonymized standardized web site entry form. Number and type of intervention, operator experience, patient characteristics, medication, lab data as well as technical aspects of the procedure and bleeding complications were analysed according to the interventional radiology standards. RESULTS: 8172 US-guided intraabdominal interventions (liver nâ=â5903; pancreas nâ=â501, kidney nâ=â434, lymph nodeâ=â272, biliary system nâ=â153, spleen nâ=â63, other abdominal organs and extra-organic targets nâ=â999) were analysed in 30 hospitals. The majority were diagnostic biopsies including 1780 liver parenchyma, 3400 focal liver lesions and 404 pancreatic lesions. 7525 interventions (92.1â%) were performed in hospitalized patients (mean age 62.6 years). Most operators were highly experienced in US-guided interventions (>â500 interventions prior to the study nâ=â5729; 70.1â%). Sedation was administered in 1131 patients (13.8â%). Needle diameter was ≥â1âmm in 7162 punctures (87.9â%) with main focus on core needle biopsies (18 G, nâ=â4185). Clinically relevant bleeding complications with need of transfusion (0.4â%), surgical bleeding control (0.1â%) and radiological coiling (0.05â%) were very rare. Bleeding complications with fatal outcome occurred in four patients (0.05â%). The frequency of major bleeding complications was significantly higher in patients with an INR >â1.5 (pâ<â0.001) and patients taking a medication potentially interfering with platelet function or plasmatic coagulation (pâ<â0.0333). CONCLUSION: This prospective multicentre study confirms the broad spectrum of percutaneous US-guided intraabdominal interventions. However diagnostic liver biopsies dominate with the use of core needle biopsies (18 G). Percutaneous US-guided interventions performed by experienced sonographers are associated with a low bleeding risk. Major bleeding complications are very rare. A pre-interventional INR <â1.5 and individual medication risk assessment are recommended.
Assuntos
Abdome/diagnóstico por imagem , Biópsia com Agulha de Grande Calibre/efeitos adversos , Hemoperitônio/epidemiologia , Ultrassonografia de Intervenção/efeitos adversos , Vísceras/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Competência Clínica , Estudos Transversais , Feminino , Hemoperitônio/etiologia , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Ultrassonografia de Intervenção/estatística & dados numéricos , Adulto JovemRESUMO
PURPOSE: Autoimmune pancreatitis (AIP) is an independent, underdiagnosed, rare form of chronic pancreatitis. The goal of this study is to document ultrasound findings in histologically confirmed AIP in order to determine the diagnostic value of ultrasound. MATERIALS AND METHODS: 6 of 74 DEGUM instructors for internal medicine (level 3 and 2) provided anonymized clinical and sonographic data from 17 patients with histologically confirmed AIP. RESULTS: 9/17 patients had diffuse AIP, 8/17 had focal AIP, 14/17 suffered from upper abdominal pain, 9/17 had jaundice, and 3/9 had an elevated IgG4 level. Ultrasound showed diffuse hypoechoic organ enlargement in 9/17 cases and a hypoechoic tumor with an unclear border in 8/17 cases. AIP was verified by ultrasound-guided percutaneous core biopsy in 14 cases, by biopsy of the bile duct in 1 case, and by surgical biopsy in 2 cases. Involvement of the hepatobiliary system was present in 7/17 patients and autoimmune cholangitis was verified in 5 cases. All patients experienced remission after immunosuppressive treatment. The pancreatic duct had a normal width in 11 cases, was dilated in 5 cases, and was stenosed over a long stretch in 3 cases. Contrast-enhanced ultrasound did not show uniform signal increase but also no significantly reduced or absent perfusion. CONCLUSION: Ultrasound can be diagnostically useful if the clinical manifestations of AIP are known. While the diffuse form allows an ad-hoc suspected diagnosis, the focal form can only be suspected in the case of additional extrapancreatic involvement. Contrast-enhanced ultrasound (CEUS) contributes greatly to the differentiation from ductal adenocarcinoma in the case of focal AIP.