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BACKGROUND: With the increasing use of neoadjuvant treatment (NAT) for patients with early-stage breast cancer (ESBC), adequate clinical staging is essential to inform treatment. While the use of MRI with NAT has been proposed to help with accuracy of pre-treatment clinical staging, its impact in clinical practice remains controversial. METHODS: A prospective institutional database of patients with ESBC treated with NAT between May 2012 and December 2020 was analyzed in order to compare the management of patients who received an MRI prior to NAT to those who did not. The indications for MRI and correlation of MRI findings to conventional breast imaging were evaluated. The impact of MRI on management was compared between the MRI and non-MRI groups. RESULTS: A total of 530 patients met inclusion criteria. Of these, 186 (35.1%) had an MRI and 344 (64.9%) did not. The most frequent indication for MRI was the determination of disease extent (54.5%). Patients who had an MRI prior to neoadjuvant treatment were significantly more likely to be younger (47 years versus 57 years; p < 0.001) and have multifocal disease (32.3% versus 22.1%; p < 0.05). When compared to conventional imaging, MRI reported a greater extent of disease in the breast (37.6%), more nodal involvement (18.8%), and multifocal disease (15.1%). Additional diagnostic interventions were advised in 52.2% of patients who underwent MRI. Rates of mastectomies were greater in the MRI group (80.0% versus 58.9%; p < 0.05) in addition to more axillary dissections (28.0% versus 17.4%; p < 0.01). Rates of locoregional recurrences were low in both groups, with similar disease-free survival outcomes at 5 years. CONCLUSION: MRI identified significantly more disease in contrast to conventional imaging and lead to more aggressive surgical management. Prospective studies evaluating the role of MRI before NAT and its impact on long-term outcomes are needed.
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Neoplasias da Mama , Terapia Neoadjuvante , Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Estudos ProspectivosRESUMO
The simulated noise used to benchmark wavelet edge detection in this work was described incorrectly. The correct description is given here, and new results based on noise that matches the original description are provided. The results support our original conclusion, which is that wavelet edge detection outperforms thresholding in the presence of white noise and 1/fnoise.
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PURPOSE: Data exploring optimal sequencing of anthracyclines and taxanes as neoadjuvant chemotherapy (NACT) for breast cancer are limited and inconsistent. The objective of this study was to assess the real-world impact of sequence order on pathologic complete response (pCR) and clinical outcomes from NACT. METHODS: Patients with HER2-negative breast cancer treated with NACT from May 2012 to April 2020 were identified from a prospectively collected institutional database. The primary endpoint was to compare rates of pCR (ypT0/isN0) between patients who received anthracyclines followed by taxanes (AC-T) to those who received taxanes followed by anthracyclines (T-AC). Additional endpoints of interest included clinical complete response, downstaging, Neo-Bioscore, conversion to breast-conserving surgery eligibility, relapse-free survival, and overall survival between groups. RESULTS: Of the 283 patients who met eligibility criteria, 187 (66%) received AC-T and 96 (34%) received T-AC. Sequence order did not influence the primary endpoint of pCR rate (19% for AC-T vs. 21% for T-AC, p = 0.752). There were also no significant differences in secondary NACT efficacy outcomes between groups. In the overall cohort, pCR rate was higher in patients with triple-negative breast cancer (TNBC) (32% vs. 13% in hormone-positive cancer, p < 0.001) and grade 3 tumors (31% vs. 12% for grade 1-2 tumors, p < 0.001). CONCLUSIONS: In this real-world analysis of HER2-negative breast cancer patients, there was no differential impact on pCR rate or clinical outcomes from NACT with sequence order of anthracyclines and taxanes. This supports the current variation in prescribing practice.
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Neoplasias da Mama , Terapia Neoadjuvante , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/genética , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
Background: Studies in the adjuvant setting suggest that the timing of breast cancer diagnosis, surgery, and chemotherapy might affect outcomes. In the neoadjuvant setting, data exploring whether expeditious neoadjuvant chemotherapy (nac) after diagnosis improves the rate of pathologic complete response (pcr) in breast cancer are limited. Methods: Patients who received nac and completed treatment between May 2012 and December 2018 were identified from a prospectively collected database at BC Cancer. Time from diagnosis to start of nac was calculated. Patients were grouped into those who did and did not experience a pcr, and those who started nac within 28 days or after 28 days [time to nac (ttn)]. The association between pcr and ttn was tested using logistic regression. Results: In the time period studied, 482 patients who received nac were identified. After exclusions, 421 patients met the eligibility criteria. Median time from biopsy to chemotherapy was 33 days (range: 7-140 days). In 149 patients (35.4%), nac was received within 28 days of diagnosis (range: 7-28 days); in 272 patients (64.6%), it was received after more than 28 days (range: 29-140 days). The overall pcr rate was 31.8%. A trend toward a higher pcr rate, although not statistically significant, was observed in the group that initiated chemotherapy within 28 days (34.2% vs. 30.5%, p = 0.43). In the logistic regression model, rates of pcr were associated with receptor status, but not age, stage, or ttn. Conclusions: In the neoadjuvant setting, we observed no difference in the rate of pcr in patients who started nac within 28 days or after 28 days.
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Biópsia/métodos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos ProspectivosRESUMO
Background: The real-world impact of tyrosine kinase inhibitors (tkis) in clinical practice for gastrointestinal stromal tumour (gist) has not been extensively reported. We sought to assess how outcomes have changed over the eras and to evaluate the effect of access to imatinib and sunitinib on survival in patients with unresectable or metastatic gist in British Columbia. Methods: Patients with metastatic or unresectable gist were allocated to one of three eras: pre-2002, 2002-2007, and post-2007 based on treatment availability (pre-imatinib, post-imatinib, and post-sunitinib). Overall survival (os) and progression-free survival (pfs) were compared between eras. Univariate and multivariate analyses were performed to determine the effects of tumour, patient, and treatment characteristics on survival outcomes. Results: Of 657 patients diagnosed with gist throughout British Columbia during 1996-2016, 196 had metastatic disease: 23 in the pre-imatinib era, 67 in the post-imatinib era, and 106 in the post-sunitinib era. A significant increase in os, by 53.6 months (p = 0.0007), and pfs, by 29.1 months (p = 0.044), was observed after the introduction of imatinib. The introduction of sunitinib did not significantly affect os or pfs. Conclusions: Implementation of tkis has drastically improved survival outcomes for patients with metastatic gist by up to 4.55 years in the real-world setting. Our study demonstrates that implementation of tkis in clinical practice has outperformed their benefit predicted in clinical trials.
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Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacologia , Adulto JovemRESUMO
Background: The use of Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) testing has been shown to change treatment decisions in approximately 30% of breast cancer (bca) cases, but research on how Recurrence Score testing has affected the type of chemotherapy offered is limited. We sought to determine if the availability of Oncotype dx testing resulted in a change to the type and duration of chemotherapy regimens used in the treatment of early-stage hormone receptor-positive bca. Methods: In a population-based cohort study, patients treated in the 2 years before the availability of Oncotype dx testing were compared with patients treated in the 2 years after testing availability. Charts were audited and divided into 2 groups: pre-Oncotype dx and post-Oncotype dx. The groups were compared for differences in duration of chemotherapy (12 weeks vs. >12 weeks), types of agents used (anthracycline vs. non-anthracycline), and myelosuppressive potential of the chosen regimen. Results: Of 834 patients who fulfilled the enrolment criteria, 360 fell into the pre-Oncotype dx era, and 474, into the post-Oncotype dx era. An increase of 11.2 percentage points, to 69.5% from 58.3%, was observed in the proportion of patients receiving short-course compared with long-course chemotherapy (p = 0.068). The proportion of patients prescribed anthracycline-containing regimens declined in the post-Oncotype dx era (47.7% pre vs. 32.2% post, p = 0.016). The selection of more-myelosuppressive chemotherapy protocols increased in the post-Oncotype dx era (67.4% pre vs. 78.8% post, p = 0.044). Conclusions: In the present study, the availability of Oncotype dx testing was observed to influence the choice of chemotherapy type in the setting of early-stage bca.
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Neoplasias da Mama/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Medicina de Precisão , Estudos RetrospectivosRESUMO
Background: Soft-tissue sarcoma (sts) represents a rare group of mesenchymal neoplasms comprising more than 50 heterogeneous subtypes. Great efforts have been made to increase the understanding of the treatment of advanced sts (unresectable or metastatic disease). We set out to determine whether outcomes for patients with advanced sts have improved over time and to assess the current evidence for systemic therapy. Methods: In a scoping review, we evaluated the contemporary evidence for systemic treatment of advanced sts in adults (>18 years of age). Phase i, ii, and iii studies of systemic therapy for advanced sts published in the English language were included. After abstract and full-text review of seventy-seven studies, sixty-two trials met the inclusion criteria. Results: The number of clinical trials conducted and published in advanced sts has increased over the last 30 years. Although median overall survival has increased, attempts at improving first-line therapy through dose intensification, doublet chemotherapy, or alternative backbones have not been successful. The optimal therapy beyond anthracyclines remains a challenge, especially given the heterogeneity that grouping multiple sts subtypes within clinical trials creates. However, increasing numbers of agents are being studied, and several studies had shown isolated benefit in progression-free or overall survival. Summary: First-line systemic therapy with an anthracycline remains the standard of care for advanced sts. However, choice of subsequent therapy beyond anthracyclines remains challenging. Novel systemic therapies, use of molecular diagnostics to direct therapy, subtype-specific trials, and learnings from real-world retrospective data are all important for improving outcomes in patients with advanced sts.
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Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Feminino , Humanos , MasculinoRESUMO
Changing patterns of land use, temperature, and precipitation are expected to impact ecosystem services, including water quality and quantity, buffering of extreme events, soil quality, and biodiversity. Scenario analyses that link such impacts on ecosystem services to human well-being may be valuable in anticipating potential consequences of change that are meaningful to people living in a community. Ecosystem services provide numerous benefits to community well-being, including living standards, health, cultural fulfillment, education, and connection to nature. Yet assessments of impacts of ecosystem services on human well-being have largely focused on human health or monetary benefits (e.g. market values). This study applies a human well-being modelling framework to demonstrate the potential impacts of alternative land use scenarios on multi-faceted components of human well-being through changes in ecosystem services (i.e., ecological benefits functions). The modelling framework quantitatively defines these relationships in a way that can be used to project the influence of ecosystem service flows on indicators of human well-being, alongside social service flows and economic service flows. Land use changes are linked to changing indicators of ecosystem services through the application of ecological production functions. The approach is demonstrated for two future land use scenarios in a Florida watershed, representing different degrees of population growth and environmental resource protection. Increasing rates of land development were almost universally associated with declines in ecosystem services indicators and associated indicators of well-being, as natural ecosystems were replaced by impervious surfaces that depleted the ability of ecosystems to buffer air pollutants, provide habitat for biodiversity, and retain rainwater. Scenarios with increases in indicators of ecosystem services, however, did not necessarily translate into increases in indicators of well-being, due to covarying changes in social and economic services indicators. The approach is broadly transferable to other communities or decision scenarios and serves to illustrate the potential impacts of changing land use on ecosystem services and human well-being.
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AIMS: Due to the rarity and varied natural history of desmoid-type fibromatosis, evidence-based treatment standards for this disease remain lacking. This study evaluated outcomes in patients with desmoid-type fibromatosis managed at a Canadian institution over two decades. MATERIALS AND METHODS: Records of 227 patients with desmoid-type fibromatosis referred from 1990 to 2013 were retrospectively reviewed to investigate management strategies including active surveillance, surgery, radiation therapy, cryoablation, and systemic therapy, including tamoxifen and chemotherapy. RESULTS: Thirty-two per cent of cases were men, median age 40 years, median tumour size 5.4 cm. Initial treatments were surgery (79%), tamoxifen (13%), radiation therapy (5.0%), chemotherapy (1.8%) and cryoablation (1.2%). Active surveillance was used upfront in 26% of cases, most after 2005. At a median follow-up of 77 months, one patient died of disease, 13 died of unrelated causes and the remainder were alive with no evidence of disease (56%), stable/responding disease (33%) or progressive disease (4%). The recurrence rate was 25% after upfront surgery. Response rates and disease control rates were 40% and 76% for active surveillance; 68% and 96% for radiation therapy; 31% and 67% for tamoxifen; and 53% and 80% for chemotherapy. On univariable analysis, factors associated with a higher recurrence after initial surgery were young age (P = 0.012), male gender (P = 0.012) and extremity location (P = 0.005). On multivariable analysis, only young age was significantly associated with recurrence risk (P = 0.010). CONCLUSIONS: Active surveillance was associated with spontaneous regression and long-term disease control consistent with other studies. Primary radiation therapy appeared to provide a similar response and disease control compared with systemic treatments and may be a viable option for patients who are not candidates for surgery or active surveillance.
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Fibromatose Agressiva/terapia , Adulto , Colúmbia Britânica , Feminino , Fibromatose Agressiva/patologia , História do Século XX , História do Século XXI , Humanos , Masculino , Estudos RetrospectivosRESUMO
AIMS: Soil biosolarization (SBS) is a pest control technology that includes the incorporation of organic matter into soil prior to solarization. The objective of this study was to measure the impact of the initial soil microbiome on the temporal evolution of genes encoding lignocellulose-degrading enzymes during SBS. METHODS AND RESULTS: Soil biosolarization field experiments were completed using green waste (GW) as a soil amendment and in the presence and absence of compost activating inoculum. Samples were collected over time and at two different soil depths for measurement of the microbial community and the predicted lignocellulosic-degrading microbiome. Compost inoculum had a significant positive effect on several predicted genes encoding enzymes involved in cellulose, hemicellulose and lignin degradation. These included beta-glucosidase, endo-1,3(4)-beta-glucanase, alpha-galactosidase and laccase. CONCLUSION: Amendment of micro-organisms found in compost to soil prior to SBS enhanced the degradation potential of cellulose, hemicellulose and lignin found in GW. SIGNIFICANCE AND IMPACT OF THE STUDY: The type of organic matter amended and its biotransformation by soil micro-organisms impact the efficacy of SBS. The results suggest that co-amending highly recalcitrant biomass with micro-organisms found in compost improves biomass conversion during SBS.
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Compostagem/métodos , Recuperação e Remediação Ambiental/métodos , Lignina/metabolismo , Microbiota , Microbiologia do Solo , Biomassa , Microbiota/genética , Solo , Luz SolarRESUMO
BACKGROUND: The intranasal route is a minimally invasive method for rapidly delivering midazolam and fentanyl to provide short-term analgesia and sedation in infants. However, intranasal use of midazolam and fentanyl is not labeled for infants and safety data are sparse. The objective of this study is to evaluate the safety of intranasal midazolam and intranasal fentanyl in infants admitted to the Neonatal Intensive Care Unit (NICU). METHODS: We retrospectively identified all infants receiving intranasal midazolam or fentanyl in the NICU from 2009 to 2015. We recorded indication for use and vital signs and determined the proportion of infants experiencing the following adverse events: death within 24 hours, hypotension, bradycardia, worsening respiratory status, and chest wall rigidity. Vital signs 4 hours before and after each dose were compared using the Wilcoxon signed-rank test. RESULTS: We identified 17 infants (gestational ages 23- 41 weeks) receiving 25 intranasal doses. None of the infants died or developed hypotension, bradycardia, or chest wall rigidity. Intranasal delivery was most commonly used for sedation during magnetic resonance imaging studies. Other indications include analgesia or sedation for retinopathy of prematurity surgery, intubation, and peripherally inserted central catheter placement. One infant receiving intranasal midazolam experienced worsening respiratory status. Vital signs before and after dosing were not significantly different. CONCLUSIONS: Intranasal midazolam and fentanyl use in term and preterm infants appeared safe and well-tolerated in this small cohort of infants. Larger, prospective studies evaluating the safety and efficacy of intranasal midazolam and fentanyl use in infants are warranted.
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Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Dor Processual/prevenção & controle , Administração Intranasal , Analgésicos Opioides/uso terapêutico , Pressão Arterial , Bradicardia/epidemiologia , Cateterismo Periférico , Feminino , Fentanila/uso terapêutico , Humanos , Hipnóticos e Sedativos/uso terapêutico , Hipotensão/epidemiologia , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Intubação Intratraqueal , Imageamento por Ressonância Magnética , Masculino , Midazolam/uso terapêutico , Mortalidade , Procedimentos Cirúrgicos Oftalmológicos , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Taxa Respiratória , Retinopatia da Prematuridade/cirurgia , Estudos Retrospectivos , Fatores de Risco , Parede TorácicaRESUMO
Organ-on-a-chip platforms serve as cost-efficient testbeds for screening pharmaceutical agents, mimicking natural physiology, and studying disease. In the field of diabetes, the development of an islet-on-a-chip platform would have broad implications in understanding disease pathology and discovering potential therapies. Islet microphysiological systems are limited, however, by their poor cell survival and function in culture. A key factor that has been implicated in this decline is the disruption of islet-matrix interactions following isolation. Herein, we sought to recapitulate the in vivo peri-islet niche using decellularized extracellular matrix (ECM) hydrogels. Sourcing from porcine bladder, lung, and pancreas tissues, 3-D ECM hydrogels were generated, characterized, and validated using both rodent and human pancreatic islets. Optimized decellularization protocols resulted in hydrogels with distinctive viscoelastic properties that correlated to their matrix composition. The in situ 3-D encapsulation of human or rat islets within ECM hydrogels resulted in improved functional stability over standard culture conditions. Islet composition and morphology were also altered, with enhanced retention of islet-resident endothelial cells and the formation of cord-like structures or sprouts emerging from the islet spheroid. These supportive 3-D physiomimetic ECM hydrogels can be leveraged within microfluidic platforms for the long-term culture of islets.
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Células Imobilizadas/citologia , Matriz Extracelular/química , Hidrogéis/química , Ilhotas Pancreáticas/citologia , Alicerces Teciduais/química , Animais , Células Cultivadas , Células Imobilizadas/transplante , Elasticidade , Matriz Extracelular/transplante , Matriz Extracelular/ultraestrutura , Humanos , Transplante das Ilhotas Pancreáticas , Masculino , Ratos , Ratos Endogâmicos Lew , Suínos , ViscosidadeRESUMO
BACKGROUND: Pelareorep, a serotype 3 reovirus, has demonstrated preclinical and early clinical activity in breast cancer and synergistic cytotoxic activity with microtubule targeting agents. This multicentre, randomized, phase II trial was undertaken to evaluate the efficacy and safety of adding pelareorep to paclitaxel for patients with metastatic breast cancer (mBC). METHODS: Following a safety run-in of 7 patients, 74 women with previously treated mBC were randomized either to paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 4 weeks plus pelareorep 3 × 1010 TCID50 intravenously on days 1, 2, 8, 9, 15, and 16 every 4 weeks (Arm A) or to paclitaxel alone (Arm B). Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate, overall survival (OS), circulating tumour cell counts, safety, and exploratory correlative analyses. All comparisons used a two-sided test at an alpha level of 20%. Survival analyses were adjusted for prior paclitaxel. RESULTS: Final analysis was performed after a median follow-up of 29.5 months. Pelareorep was well tolerated. Patients in Arm A had more favourable baseline prognostic variables. Median adjusted PFS (Arm A vs B) was 3.78 mo vs 3.38 mo (HR 1.04, 80% CI 0.76-1.43, P = 0.87). There was no difference in response rate between arms (P = 0.87). Median OS (Arm A vs B) was 17.4 mo vs 10.4 mo (HR 0.65, 80% CI 0.46-0.91, P = 0.1). CONCLUSIONS: This first, phase II, randomized study of pelareorep and paclitaxel in previously treated mBC did not show a difference in PFS (the primary endpoint) or RR. However, there was a significantly longer OS for the combination. Further exploration of this regimen in mBC may be of interest.
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Neoplasias da Mama/tratamento farmacológico , Orthoreovirus Mamífero 3/genética , Terapia Viral Oncolítica/métodos , Paclitaxel/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/virologia , Canadá , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Receptor ErbB-2RESUMO
BACKGROUND: The use of neoadjuvant systemic therapy (nast) in the treatment of breast cancer is increasing, and the role of adjuvant radiation therapy (rt) in that setting is uncertain. We sought to review and report the use of nast, its trends over time, and its relationship with the prescribing patterns of locoregional rt in a provincial cancer system. METHODS: Patients with stages i-iii breast cancer diagnosed during 2007-2012 were identified using a provincial database. Patient, tumour, and treatment characteristics were extracted. Multivariable logistic regression analyses were used to assess associations with the use of nast. Kaplan-Meier and Cox regression were used for survival analyses. RESULTS: Of the 11,658 patients who met the inclusion criteria, 602 (5%) had received nast. Use of nast was more frequent in stage iii patients (53%) than in stages i and ii patients (2%). In clinically lymph-node positive patients, a pathology assessment was made approximately 50% of the time. Higher clinical tumour stage and increasing clinical nodal stage predicted for increasing use of nast and of nodal rt after nast, but pathologic nodal status after nast was not associated with use of nodal rt. A statistically significant survival difference was observed between patients in the nast and no-nast groups, but that significance disappeared in a multivariable Cox regression analysis. CONCLUSIONS: This population-based study demonstrated 5% use of nast for breast cancer. Most patients received nodal rt after nast, and nodal rt was not associated with pathologic stage after nast. Findings likely reflect the realities of clinical practice and show that reliance on clinical nodal staging results in outcomes similar to those reported in the literature.
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Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.
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Processamento Alternativo , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Farmacogenética , Variantes Farmacogenômicos , Análise de Sequência de RNA , Transcriptoma , Tecido Adiposo/metabolismo , Linhagem Celular , Bases de Dados Genéticas , Genótipo , Humanos , Rim/metabolismo , Fígado/metabolismo , Miocárdio/metabolismo , FenótipoRESUMO
The rapid expansion in unconventional gas development over the past two decades has led to concerns over the potential impacts on groundwater resources. Although numerical models are invaluable for assessing likelihood of impacts at particular sites, simpler analytical models are also useful because they help develop hydrological understanding. Analytical approaches are also valuable for preliminary assessments and to determine where more complex models are warranted. In this article, we present simple analytical solutions that can be used to predict: (1) the spatial extent of drawdown from horizontal wells drilled into the gas-bearing formation, and rate of recovery after gas production ceases; (2) the potential for upward transport of contaminants from the gas-bearing formation to shallow aquifers during hydraulic fracturing operations when pressures in the gas-bearing formation are greatly increased; and (3) the potential downward leakage of water from shallow aquifers during depressurization of gas-bearing formations. In particular, we show that the recovery of pressure after production ceases from gas-bearing shale formations may take several hundred years, and we present critical hydraulic conductivity values for intervening aquitards, below which the impact on shallow aquifers will be negligible. The simplifying assumptions inherent in these solutions will limit their predictive accuracy for site-specific assessments, compared to numerical models that incorporate knowledge of spatial variations in formation properties and which may include processes not considered in the simpler solutions.
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Água Subterrânea , Campos de Petróleo e Gás , Gás Natural , Poços de ÁguaRESUMO
Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.
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Humanos , Cardiotoxicidade/diagnóstico , Neoplasias/terapia , Antineoplásicos , Arritmias Cardíacas , Prevenção Primária , Radioterapia , Radioterapia/efeitos adversos , Trombose Coronária , Proteína C-Reativa , Biomarcadores , Cardiotônicos , Fatores de Risco , Isquemia Miocárdica , Disfunção Ventricular Esquerda , Imagem Cinética por Ressonância Magnética , Ecocardiografia Tridimensional , Troponina T , Peptídeo Natriurético Encefálico , Diagnóstico Precoce , Cardiotoxinas , Cardiotoxinas/efeitos adversos , Cardiotoxicidade , Hipertensão/terapia , Antineoplásicos/efeitos adversosRESUMO
AIM: To document the radiation exposure metrics, including fluoroscopic radiation time and radiation dose-area product, in children <18 years of age who undergo nasoenteral tube placement using fluoroscopic guidance with maximal dose-reduction techniques. MATERIALS AND METHODS: Following institutional review board approval, the age, gender, anatomical information, immediate procedure-related complications if any, fluoroscopy time, and radiation dose-area product were collected retrospectively in all paediatric patients who underwent fluoroscopically guided nasoenteral tube placement during a 5-year period. Three paediatric radiology faculty members, a radiologist assistant, and trainee residents during their paediatric radiology rotation performed the procedures on two different digital fluoroscopic machines using radiation-minimising techniques. Median values of the fluoroscopy time and radiation dose-area product were calculated and compared to values reported in the literature using the Wilcoxon procedure. RESULTS: There were 41 male and 33 female patients with a median age of 4 years and 6 months. Median fluoroscopy time used for placing a nasoenteral tube was 1.25 minutes with a median radiation exposure dose-area product of 0.245 Gy·cm(2). All patients had successful placement of nasoenteral tube without immediate procedure-related complications. CONCLUSION: Fluoroscopy-guided nasoenteral feeding tube placement can be performed successfully with minimal radiation exposure without compromising procedural success.