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PURPOSE: To assess radiation therapy (RT)-induced vasculitis in patients with non-small cell lung cancer (NSCLC) by examining changes in the uptake of 18F-fluoro-D-deoxyglucose ([18F]FDG) by positron emission tomography/computed tomography (PET/CT) images of the ascending aorta (AA), descending aorta (DA), and aortic arch (AoA) before and after proton and photon RT. METHOD: Thirty-five consecutive locally advanced NSCLC patients were definitively treated with proton (n = 27) or photon (n = 8) RT and concurrent chemotherapy. The patients were prospectively enrolled to undergo [18F]FDG-PET/CT imaging before and 3 months after RT. An adaptive contrast-oriented thresholding algorithm was applied to generate mean standardized uptake values (SUVmean) for regions of interest (ROIs) 3 mm outside and 3 mm inside the outer perimeter of the AA, DA, and AoA. These ROIs were employed to exclusively select the aortic wall and remove the influence of blood pool activity. SUVmeans before and after RT were compared using two-tailed paired t-tests. RESULTS: RT treatments were associated with increased SUVmeans in the AA, DA, and AoA-1.9%, 0.3%, and 1.3% for proton and 15.8%, 9.5%, and 15.5% for photon, respectively. There was a statistically significant difference in the ∆SUVmean (post-RT SUVmean - pre-RT SUVmean) in patients treated with photon RT when compared to ∆SUVmean in patients treated with proton RT in the AA (p = 0.043) and AoA (p = 0.015). There was an average increase in SUVmean that was related to dose for photon patients (across structures), but that was not seen for proton patients, although the increase was not statistically significant. CONCLUSION: Our results suggest that patients treated with photon RT for NSCLC may exhibit significantly more RT-induced inflammation (measured as ∆SUVmean) in the AA and AoA when compared to patients who received proton RT. Knowledge gained from further analyses in larger cohorts could aid in treatment planning and help prevent the significant morbidity and mortality associated with RT-induced vascular complications. TRIAL REGISTRATION: NCT02135679.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Lesões por Radiação , Vasculite , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Prótons , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
Background: Anti-HER2 therapies are associated with a risk of increased cardiac toxicity, particularly when part of anthracycline-containing regimens. We report cardiac safety of pertuzumab, trastuzumab, and chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer. Patients and methods: BERENICE (NCT02132949) is a nonrandomized, phase II, open-label, multicenter, multinational study in patients with normal cardiac function. In the neoadjuvant period, cohort A patients received four cycles of dose-dense doxorubicin and cyclophosphamide, then 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles. Cohort B patients received four standard fluorouracil/epirubicin/cyclophosphamide cycles, then four docetaxel cycles with four standard trastuzumab and pertuzumab cycles. The primary end point was cardiac safety during neoadjuvant treatment, assessed by the incidence of New York Heart Association class III/IV heart failure and of left ventricular ejection fraction declines (≥10 percentage-points from baseline and to a value of <50%). The main efficacy end point was pathologic complete response (pCR, ypT0/is ypN0). Results are descriptive. Results: Safety populations were 199 and 198 patients in cohorts A and B, respectively. Three patients [1.5%; 95% confidence interval (CI) 0.31% to 4.34%] in cohort A experienced four New York Heart Association class III/IV heart failure events. Thirteen patients (6.5%; 95% CI 3.5% to 10.9%) in cohort A and four (2.0%; 95% CI 0.6% to 5.1%) in cohort B experienced at least one left ventricular ejection fraction decline. No new safety signals were identified. pCR rates were 61.8% and 60.7% in cohorts A and B, respectively. The highest pCR rates were in the HER2-enriched PAM50 subtype (75.0% and 73.7%, respectively). Conclusion: Treatment with pertuzumab, trastuzumab, and common anthracycline-containing regimens for the neoadjuvant treatment of early breast cancer resulted in cardiac and general safety profiles, and pCR rates, consistent with prior studies with pertuzumab. Clinical Trial Information: NCT02132949.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/epidemiologia , Quimioterapia Adjuvante/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Cardiotoxicidade/etiologia , Quimioterapia Adjuvante/métodos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Receptor ErbB-2/genética , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversosRESUMO
Patients undergoing peripheral venoarterial extracorporeal membrane oxygenation have a high risk of lower limb ischemia. In general, regular controls are carried out based on clinical and laboratory parameters in order to quickly detect and treat complications. These controls are challenging due to states of shock, nonpulsatile flow and vasopressor therapy. As additional monitoring the use of near-infrared spectroscopy (NIRS) is described in the literature as being very successful in detecting ischemia. The present article describes the use and possible limitations of NIRS for the diagnostics of peripheral ischemia.
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Oxigenação por Membrana Extracorpórea/métodos , Extremidades/irrigação sanguínea , Perfusão/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cardiomiopatias/fisiopatologia , Cardiomiopatias/cirurgia , Cardiomiopatias/terapia , Feminino , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/terapia , Oximetria , Choque/etiologiaRESUMO
Alkali metal alkoxides were studied as catalysts for the addition of CS2 to epoxides. A screening of several commercially available alkoxides revealed lithium tert-butoxide as an active and selective catalyst for this reaction. The influence of different reaction parameters as well as the substrate scope under optimized reaction conditions has been studied. Terminal and highly substituted epoxides as well as thiiranes were converted. In total 28 products were prepared and isolated in yields up to 95%. Notably, the reactions were performed under mild conditions without additional solvents. The regio- and stereoselectivity of the reaction has been studied e.g. by converting (R)-styrene and (R)-propylene oxide. Moreover, the test reaction was monitored by (13)C NMR and a plausible mechanism for the conversion of terminal and internal epoxides is given. This proposal is in agreement with the observed regio- and stereoselectivity of the reaction.
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OBJECTIVE: Respiratory physiotherapy is an integral part of the care of patients in intensive care units (ICU) after cardiac surgery. One of the most commonly used techniques in ICU to prevent pulmonary complications are mechanical vibrations, which can be applied with a tool called Vibrax.The aim of this study was to investigate the effects of Vibrax (mechanical vibrations) on the arterial blood gases of patients in ICU during the 1. or 2. day after cardiac surgery. METHODS: A randomized controlled pilot study was conducted with 23 patients. The participants of the control group (CG) received a cardiovascular training with mobilization to the edge of the bed and active breathing exercises. On the patients of the intervention group (IG) additionally Vibrax was applied for 5 minutes. As primary outcome parameter the PaO2/FiO2 ratio was measured. RESULTS: In the CG no significant changes over time were observed (pâ≥â0.06). The IG showed a significant (pâ=â0.009) increase in the PaO2/FiO2 ratio from before the physiotherapy intervention (Mâ=â296.52, SEâ=â34.94âmmHg) to 60 minutes after completion of the physiotherapy intervention (Mâ=â331.39, SEâ=â48.14âmmHg). There was no significant difference between the CG and IG at any measuring time (pâ≥â0.09). CONCLUSION: The results of this pilot study indicate that the application of Vibrax has positive effects on the arterial blood gases of patients in ICU on the 1. or 2. day after cardiac surgery. But whether the effects are clinically relevant could not be clarified.
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Gasometria , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/reabilitação , Modalidades de Fisioterapia/instrumentação , Insuficiência Respiratória/prevenção & controle , Vibração/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Biotic plant-soil interactions and land-use intensity are known to affect plant individual fitness as well as competitiveness and therefore plant-species abundances in communities. Therefore, a link between soil biota and land-use intensity on local abundance of plant species in grasslands can be expected. In two greenhouse experiments, we investigated the effects of soil biota from grassland sites differing in land-use intensity on three grass species that vary in local abundances along this land-use gradient. We were interested in those soil-biota effects that are associated with land-use intensity, and whether these effects act directly or indirectly. Therefore, we grew the three plant species in two separate experiments as single individuals and in mixtures and compared their performance. As single plants, all three grasses showed a similar performance with and without soil biota. In contrast, in mixtures growth of the species in response to the presence or absence of soil biota differed. This resulted in different soil-biota effects that tend to correspond with patterns of species-specific abundances in the field for two of the three species tested. Our results highlight the importance of indirect interactions between plants and soil microorganisms and suggest that combined effects of soil biota and plant-plant interactions are involved in structuring plant communities. In conclusion, our experiments suggest that soil biota may have the potential to alter effects of plant-plant interactions and therefore influence plant-species abundances and diversity in grasslands.
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Biota , Pradaria , Poaceae/crescimento & desenvolvimento , Microbiologia do Solo , Biodiversidade , Ecossistema , Alemanha , Especificidade da EspécieRESUMO
BACKGROUND: The German hospital reimbursement system (G-DRG) is incomplete for endoscopic interventions and fails to differentiate between complex and simple procedures. This is caused by outdated methods of personnel-cost allocation. METHODS: To establish an up-to-date service catalogue 50 hospitals made their anonymized expense-budget data available to the German-Society-of-Gastroenterology (DGVS). 2.499.900 patient-datasets (2011-2013) were used to classify operation-and-procedure codes (OPS) into procedure-tiers (e.g. colonoscopy with biopsy/colonoscopy with stent-insertion). An expert panel ranked these tiers according to complexity and assigned estimates of physician time. From June to November 2014 exact time tracking data for a total 38.288 individual procedures were collected in 119 hospitals to validate this service catalogue. RESULTS: In this three-step process a catalogue of 97 procedure-tiers was established that covers 99% of endoscopic interventions performed in German hospitals and assigned validated mean personnel-costs using gastroscopy as standard. Previously, diagnostic colonoscopy had a relative personnel-cost value of 1.13 (compared to gastroscopy 1.0) and rose to 2.16, whereas diagnostic ERCP increased from 1.7 to 3.62, more appropriately reflecting complexity. Complex procedures previously not catalogued were now included (e.g. gastric endoscopic submucosal dissection: 16.74). DISCUSSION: This novel service catalogue for GI-endoscopy almost completely covers all endoscopic procedures performed in German hospitals and assigns relative personnel-cost values based on actual physician time logs. It is to be included in the national coding recommendation and should replace all prior inventories for cost distribution. The catalogue will contribute to a more objective cost allocation and hospital reimbursement - at least until time tracking for endoscopy becomes mandatory.
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Catálogos como Assunto , Grupos Diagnósticos Relacionados/economia , Endoscopia Gastrointestinal/classificação , Endoscopia Gastrointestinal/economia , Gastroenterologia/economia , Custos Hospitalares/classificação , Alocação de Custos/economia , Alocação de Custos/métodos , Tabela de Remuneração de Serviços/economia , Alemanha , Reembolso de Seguro de Saúde/economiaRESUMO
Baroreceptor stimulators are novel implantable devices that activate the carotid baroreceptor reflex. This results in a decrease in activity of the sympathetic nervous system and inhibition of the renin-angiotensin-aldosterone system. In patients with drug-resistant hypertension, permanent electrical activation of the baroreceptor reflex results in blood pressure reduction and cardiac remodeling. For correct intraoperative electrode placement at the carotid bifurcation, the baroreceptor reflex needs to be activated several times. Many common anesthetic agents, such as inhalation anesthetics and propofol dampen or inhibit the baroreceptor reflex and complicate or even prevent successful placement. Therefore, a specific anesthesia and pharmacological management is necessary to ensure successful implantation of baroreceptor reflex stimulators.
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Eletrodos Implantados , Pressorreceptores , Implantação de Prótese/métodos , Anestesia , Barorreflexo , Terapia por Estimulação Elétrica , HumanosRESUMO
Pigmentation is a rapidly evolving trait that is under both natural and sexual selection in many organisms. In the quinaria group of Drosophila, nearly all of the 30 species have an abdomen that is light in color with distinct markings; D. tenebrosa is the exception in that it has a completely melanic abdomen with no visible markings. In this study, we use a combination of quantitative genetic and candidate gene approaches to investigate the genetic basis of abdominal pigmentation in D. tenebrosa. We find that abdominal pigmentation is invariant across wild-caught lines of D. tenebrosa and is not sexually dimorphic. Quantitative genetic mapping utilizing crosses between D. tenebrosa and the light-colored D. suboccidentalis indicates that two genomic regions together underlie abdominal pigmentation, including the X-chromosome and an autosome (Muller Element C/E). Further support for their central importance in pigmentation is that experimental introgression of one phenotype into the other species, in either direction, results in introgression of these two genomic regions. Finally, the expression of the X-linked gene yellow in the pupae exactly foreshadows the adult melanization pattern in the abdomen of both species, suggesting that changes in the regulation of yellow are important for the phenotypic divergence of D. tenebrosa from the rest of the quinaria group. These results contribute to a body of work that demonstrates how changes in expression of highly conserved genes can cause substantial phenotypic differences even between closely related species.
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Drosophila/genética , Genoma , Pigmentação/genética , Abdome/anatomia & histologia , Animais , Ligação Genética , Genótipo , Dados de Sequência MolecularRESUMO
The management of papillary microcarcinoma (PMC) of the thyroid is controversial, especially after partial thyroid resection for benign thyroid disease. In order to detect prognostic factors for PMC, we analyzed 116 patients with PMC for encapsulation status and lymph node metastases. Between 10/1992 and 12/2010, 116 patients with PMC have been operated in our department (87 females, 29 males, median age 49 years). Eighty per cent of PMCs were diagnosed postoperatively. Seventy-six patients (66%) received a more extended resection with either thyroidectomy, near total thyroidectomy, or Dunhill operation either primarily or after completion operation, whereas 40 patients (34%) had only partial resection. Fifty patients (43%) received radioiodine (RIA) ablation. Lymph node metastases were found in 21 patients (18%). Univariate analysis showed four risk factors to be significantly associated with the risk of lymph node metastasis (p<0.05): male gender, younger age, age group<50 years and nonencapsulation of the tumor. Multivariate analysis demonstrated statistical significance for gender and tumor capsulation status. The tumor capsulation status also correlated with tumor multifocality. Our data show that the risk of lymph node metastases is significantly higher in partially or nonencapsulated PMC than in encapsulated specimens. We therefore suggest that the WHO classification should be extended to a compulsory notification of the encapsulation status in PMC.
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Carcinoma Papilar/patologia , Metástase Linfática/patologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Biópsia por Agulha Fina , Carcinoma Papilar/genética , Carcinoma Papilar/terapia , Criança , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Fatores de Risco , Fatores Sexuais , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/terapia , TireoidectomiaRESUMO
Prostate cancer (PCa) currently stands as the most common malignancy and the second most common cause of death in men worldwide. Dr. C. Huggins revolutionized the field of PCa treatment through his work investigating the therapeutic effects of androgen deprivation. These early surgical castration methods were expanded upon by integrating reversible pharmacologic castration via biologic agonists. Following this, intermittent ADT (iADT) became a medical substitute for its continuous counterpart. This data synthesis aims to highlight and assess the pertinent adverse effects of ADT, to compare mortality for PCa treatment plans, and consequently provide direction for clinicians in choosing the suitable systemic ADT approach. We performed a thorough systematic search across the PubMed database to identify prospective randomized clinical trials (RCTs) comparing continuous and intermittent androgen deprivation therapy (cADT and iADT). Our qualitative analysis aimed to evaluate the potential of iADT as an alternative treatment approach, emphasizing recent clinical outcomes. The analysis of randomized control trials in the literature revealed no discernable statistical difference in PCa-specific mortality in comparison of iADT and cADT treatments. Further, in the analysis of mortality due to non-PCa causes, iADT patients fared more favorably compared to cADT. Due to iADT's characteristics of being more cost-efficient and less likely to cause undesirable side effects, urologic healthcare professionals should be made aware of these findings when counseling patients on the optimal form of ADT and consulting for future treatment guidelines.
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INTRODUCTION: Patient satisfaction surveys, used as a quality indicator, play a role in determining reimbursement. Quality-based payments have been used by Medicare for physician reimbursement since 2015. Numerous papers report a scoring bias associated with nonmodifiable patient demographics, such as age or gender. Our systematic review across multiple specialties determines if patient age influences patient satisfaction scores. METHODS: A focused literature search using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using the PubMed database. Odds ratios (ORs), fixed-effects modeling, and presence of publication bias were calculated for an overall summary. RESULTS: Out of 387 reviewed papers, 12 articles were selected for this systematic review resulting in a total of 174,558 patients. Selected studies included hospital level and surgical specialty data of patient satisfaction scores of their physician providers only. Overall, our analysis revealed an OR of 1.36 (95% CI 1.23-1.50; I2 = 99.4%; P < .0001). The inpatient setting showed an OR of 1.18 (1.07-1.30; I2 = 99.1%; P < .001). The outpatient setting showed an OR of 1.38 (1.24-1.55; I2 = 99.5%; P < .001). Funnel plot and bias test did not show publication bias in both the inpatient and outpatient settings (P = .242, and .139, respectively). CONCLUSIONS: A positive and statistically significant relationship exists between patient age and satisfaction scores with their physicians, meaning that older patients are more satisfied with their physician providers. This relationship was more pronounced in the outpatient setting.
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Satisfação do Paciente , Humanos , Fatores EtáriosRESUMO
PURPOSE: Prostate Imaging-Reporting and Data System (PI-RADS) assists in evaluating lesions on multiparametric magnetic resonance imaging (mpMRI), but there are still ongoing efforts in improving the predictive value for the presence of clinically significant PCa (csPCa) with a Gleason grade group ≥ 2 on Fusion-Biopsy. This pilot study intends to propose an easily implementable method for augmenting predictability of csPCa for PI-RADS. METHODS: A cohort of 151 consecutive patients underwent mpMRI Fusion and random US Biopsy as a result of having at least one PI-RADS lesion grade 3-5 between January 1, 2019 and December 31, 2022. A single radiologist reads all films in this study applying PI-RADS V2. RESULTS: Of the 151 consecutive patients, 49 had a highest lesion of PI-RADS 3, 82 had a highest lesion of PI-RADS 4, and 20 had a highest lesion of PI-RADS 5. For each respective group, 12, 42, and 18 patients had proven csPCa. Two predictive models for csPCa were created by employing a logistical regression with parameters readily available to providers. The models had an AUC of 0.8133 and 0.8206, indicating promising effective models. CONCLUSION: PI-RADS classification has relevant predictability problems for grades 3 and 4. By applying the presented risk calculators, patients with PI-RADS 3 and 4 are better stratified, and thus, a significant number of patients can be spared biopsies with potential complications, such as infection and bleeding. The presented predictive models may be a valuable diagnostic tool, adding additional information in the clinical decision-making process for biopsies.
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Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Humanos , Masculino , Idoso , Neoplasias da Próstata/patologia , Medição de Risco , Pessoa de Meia-Idade , Biópsia Guiada por Imagem/métodos , Projetos Piloto , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are prevalent urological ailments in elderly males. Numerous clinical studies have revealed an invert association between BPH/prostate size and PCa growth. This study investigates the association between prostate size and total glandular tissue volume of the peripheral zone (GVPZ) using a unique blend of magnetic resonance imaging (MRI) and histo-anatomical imaging technique. MATERIALS AND METHODS: Patients were selected who underwent both radical prostatectomy and preoperative MRI scans. MRI scans provided quantitative measurements of prostatic zone dimensions, while histo-anatomical slides yielded quantitative data on glandular density of the peripheral zone (PZ) using imaging software. Integration of MRI and histopathology enabled the assessment of the GVPZ. Statistical analysis identified relationships between total prostate volume (TPV) and GVPZ. RESULTS: Seventy-two patients were selected and 40 cc was determined to be the optimal cutoff for small-to-moderate versus large prostates. Once the two subgroups in TPV were formed, the relationship between TPV and GVPZ was found to be highly significant (p<0.001). CONCLUSIONS: The combination of MRI and histopathology offers a novel approach for precise quantification of glandular tissue within the prostatic PZ. This study corroborates the hypothesis of PZ compression via an enlarging transition zone in larger BPH prostates, resulting in PZ glandular atrophy. Given that most PCa originates in the PZ, these results shed light on the potential protective role of larger BPH prostates against PCa growth.
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Imageamento por Ressonância Magnética , Próstata , Hiperplasia Prostática , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/diagnóstico por imagem , Idoso , Tamanho do Órgão , Hiperplasia Prostática/patologia , Hiperplasia Prostática/diagnóstico por imagem , Pessoa de Meia-Idade , ProstatectomiaRESUMO
To further investigate the inhibition of Pseudomonas aeruginosa's in vitro growth and biofilm formation by an organo-selenium-incorporated polyurethane (PU) catheter material. P. aeruginosa, Staphylococcus aureus, and Candida albicans were incubated in vitro with organo-selenium and control polyurethane catheter materials in the presence of glutathione. Growth was evaluated by a colony-forming-unit (CFU) count and visualized with confocal laser scanning microscopy. Two different PU catheter materials were used. Using tin-catalyzed PU catheter material, complete inhibition of S. aureus was seen at 1% selenium (Se), whereas no inhibition was seen for P. aeruginosa at up to 3.0% Se. Whereas, using a thermoplastic PU catheter material, 1.5% Se and 2% Se organo-selenium caused several logs of growth inhibition of P. aeruginosa, and 2.5% selenium, incorporation showed complete inhibition (8 logs). Samples with lower than 1.5% selenium did not show adequate growth inhibition for P. aeruginosa. Similar in vitro growth inhibition was achieved against a multidrug-resistant C. albicans strain. It was concluded that optimal inhibition of P. aeruginosa in vitro growth and biofilm formation occurs with 2.5% selenium incorporated as organo-selenium in a thermoplastic PU catheter material. These results suggest that reduced incidence of CAUTIs (catheter associated urinary tract infections) with P. aeruginosa and other bacteria and fungi can be achieved by using organo-selenium-incorporated catheters.
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The availability of the complete genomic sequence of yeast now enables elucidation of molecular mechanisms governing gene expression patterns. New results from the yeast genome and recent advances in predicting and finding human promoters support the use of similar combinatorial approaches to study genome-wide transcriptional regulation in humans.
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Regiões Promotoras Genéticas , Saccharomyces cerevisiae/genética , Sítios de Ligação , Regulação Fúngica da Expressão Gênica , Genoma Fúngico , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
INTRODUCTION: Androgen deprivation therapy first became the treatment of choice for advanced prostate cancer in the 1940s with Charles Huggins' discoveries. Eight decades later, androgen deprivation therapy has significantly evolved, and yet is still utilized in various ways to treat certain forms of prostate cancer. For local recurrence after failed primary treatment and for locally advanced and metastatic disease, continuous androgen deprivation therapy has been standard of treatment. However, intermittent androgen deprivation therapy has emerged as a therapeutic alternative to continuous androgen deprivation therapy. The purpose of this meta-analysis is to provide an update on mortality, specifically prostate cancer-specific and nonprostate cancer causes, in order to offer some guidance when selecting the appropriate form of systemic androgen deprivation therapy. METHODS: The PubMed database was searched for prospective randomized clinical trials. Inclusion and exclusion criteria were defined. Using statistical software, we analyzed random-effects models with the assumption that the data were randomly sampled, estimated the pooled log risk ratio, assessed heterogeneity, and created funnel plots to evaluate publication bias. RESULTS: A total of 12 randomized clinical trials met all inclusion criteria for final analysis. There was no statistically significant difference in prostate cancer-specific mortality between intermittent androgen deprivation therapy and continuous androgen deprivation therapy (RR=1.10 [0.85-1.42]). The analysis of nonprostate cancer mortality favored intermittent androgen deprivation therapy over continuous androgen deprivation therapy, but the difference was statistically insignificant (RR=0.94 [0.76-1.17]). CONCLUSIONS: These 2 treatment modalities can be considered as equivalent in long-term treatment outcomes. As intermittent androgen deprivation therapy is more cost-efficient and less likely to yield adverse side effects, future treatment guidelines should consider these advantages over continuous androgen deprivation therapy.
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Antagonistas de Androgênios , Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Estudos Prospectivos , Neoplasias da Próstata/tratamento farmacológico , UrologistasRESUMO
PURPOSE: Catheter-associated urinary tract infections are of significant medical burden in cost, morbidity, and mortality. Experimental selenium-coated medical devices have demonstrated non-toxic in vitro and in vivo antimicrobial activity. While antimicrobial-coated catheters have shown efficacy in preventing CAUTIs, selenium has not been tested in this context. The purpose of this in vitro study is to evaluate selenium-incorporated urinary catheters for inhibition of uropathogenic bacterial growth and biofilm formation. METHODS: Urinary catheters incorporated with 1% organo-selenium and standard (uncoated) catheters were incubated in vitro with E. coli, K. pneumoniae, P. aeruginosa, H. influenzae, and combinations of these bacteria. Growth was evaluated by colony-forming unit count and visualized with confocal laser and scanning electron microscopy. Organo-selenium catheter material integrity was also tested by soaking the tubing in phosphate-buffered saline for 12 weeks at 37 °C. RESULTS: Organo-selenium-incorporated catheters demonstrated total reduction (100%) of in vitro bacterial growth and biofilm formation for E. coli, K. pneumoniae, H. influenzae, and a combination of these species when compared to control. P. aeruginosa growth was inhibited by approximately 4 logs (99.99%). Complete inhibition of E. coli growth was maintained after long-term phosphate-buffered saline soaking. CONCLUSION: The results demonstrate that organo-selenium was stably incorporated into catheter tubing and inhibited bacterial attachment, growth, and biofilm formation for multiple uropathogenic organisms. Furthermore, long-term soaking of organo-selenium tubing in phosphate-buffered saline did not show any decline in bacterial growth inhibition or biofilm formation. These findings suggest that organo-selenium-incorporated catheters may be advantageous in preventing catheter-associated urinary tract infections and warrant further in vivo and clinical evaluation.
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Anti-Infecciosos , Selênio , Infecções Urinárias , Humanos , Cateteres Urinários/microbiologia , Escherichia coli , Pseudomonas aeruginosa , Biofilmes , Infecções Urinárias/prevenção & controle , Bactérias , FosfatosRESUMO
PURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent urologic diseases affecting elderly men. An inverse relationship between BPH/prostate size and PCa incidence is well documented in the current literature, but the precise mechanism is poorly understood. This study aims to investigate the effect of total prostate volume on total glandular tissue volume of the peripheral zone via a novel combination of magnetic resonance imaging (MRI) and histo-anatomical imaging. METHODS: 42 male patients between ages 53-79 years underwent both radical prostatectomy and pre-operative MRI scans. Prostate sizes ranged from 14.8-133.3cc. Quantitative measurements of surgical capsule thickness and glandular epithelial cell density within the peripheral zone (PZ) were obtained on histo-anatomical slides using computer-based imaging software. Quantitative prostatic zonal measurements were obtained from MRI scans. Combining MRI- and histopathology-obtained parameters allowed measurement of the total glandular tissue volume of the PZ (GVPZ). Statistical analysis was performed to identify associations between total prostate volume (TPV) and GVPZ. RESULTS: The Mann-Whitney U-test showed significant decreases in GVPZ in larger prostates when compared to smaller prostates. CONCLUSIONS: Combined MRI and histopathology techniques provide a novel method for accurate measuring of glandular tissue content within the prostatic PZ. The findings of this pilot study support the hypothesis of PZ compression by an expanding transition zone in large BPH prostates, leading to atrophy of PZ glandular tissue. As the majority of PCa originates in the PZ, this dynamic process may explain the protective effect of large BPH prostates against PCa development.
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Hiperplasia Prostática , Neoplasias da Próstata , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Próstata/patologia , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/patologia , Projetos Piloto , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
Chemically ordered 5 nm-thick L10 FePtCu films with strong perpendicular magnetic anisotropy were post-patterned by nanoimprint lithography into a dot array over a 3 mm-wide circumferential band on a 3 inch Si wafer. The dots with a diameter of 30 nm and a center-to-center pitch of 60 nm appear as single domain and reveal an enhanced switching field as compared to the continuous film. We demonstrate successful recording on a single track using shingled writing with a conventional hard disk drive write/read head.