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71.
K.-C. Sung D.-C. Seo S.-J. Lee M.-Y. Lee S.H. Wild C.D. Byrne 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(5):489-495
Background and aims
It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.Methods and results
As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women.Conclusions
In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes. 相似文献72.
Eduardo H. Umeoka Matheus C. Eiras Iara G. Viana Vanessa S. Giorgi Aline Bueno Débora C. Damasceno 《Systems biology in reproductive medicine》2019,65(1):87-94
Wistar Audiogenic Rat (WAR) strain is an animal model for epilepsy studies, the chronic multifactorial disease that affects millions of people worldwide. The animals of this strain are genetically predisposed to sound-induced seizures, called audiogenic seizures, and have been used for many years in studies to understand the mechanisms involved in the epilepsies and their neuropsychiatric comorbidities, as well as the screening of potential anti-convulsant agents. Nevertheless, little is known about the reproductive characteristics of these animals. The main goal of this study was to characterize the female reproductive performance and the fetal growth of WARs in comparison to the Wistar rats, obtaining important information for physiology and behavioral studies, as well as for the preservation of the strain. The results indicated few differences between WAR and Wistar regarding the female reproductive performance. There was no significant difference in the number of pregnant females by mating, number of live births per female, number of cells per blastocyst, and several characteristics related to reproductive performance, such as pre- and post-implantation losses. However, significant differences were observed in birth weight and weight gain until weaning, with WAR animals presenting a body weight below Wistar at birth and reduced body weight gain during the lactation period. In addition, the WAR females showed lower body weight on the day 20 of pregnancy and a larger number of corpora lutea, when compared with those of Wistar animals. Thus, we conclude that although Wistar and WAR strains have few differences in their reproductive performance, which might impact future physiological life challenges or others experimentally induced procedures, it still is a very viable strain regarding reproduction.
Abbreviations: CONCEA: National Council for the Control of Animal Experimentation; GEPR: genetically epilepsy-prone rats; WAR: Wistar Audiogenic Rat. 相似文献
73.
Otavio Berwanger Renato D. Lopes Diogo D.F. Moia Francisco A. Fonseca Lixin Jiang Shaun G. Goodman Stephen J. Nicholls Alexander Parkhomenko Oleg Averkov Carlos Tajer Germán Malaga Jose F.K. Saraiva Helio P. Guimaraes Pedro G.M. de Barros e Silva Lucas P. Damiani Renato H.N. Santos Denise M. Paisani Tamiris A. Miranda Jose C. Nicolau 《Journal of the American College of Cardiology》2019,73(22):2819-2828
BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088) 相似文献
74.
M. Tobias Heinrichs George L. Drusano David L. Brown Michael S. Maynard Sherwin K.B. Sy Kenneth H. Rand Charles A. Peloquin Arnold Louie Hartmut Derendorf 《International journal of antimicrobial agents》2019,53(3):275-283
Introduction
There is an urgent need for new anti-tuberculosis (TB) drugs and optimization of current TB treatment. Moxifloxacin and linezolid are valuable options for the treatment of drug-resistant TB; however, it is crucial to find a dose at which these drugs not only show high efficacy but also suppress the development of further drug resistance.Methods
Activity of moxifloxacin and linezolid against Mycobacterium tuberculosis was studied in the hollow-fiber infection model system in log-phase growth under neutral pH and slow growth in an acidic environment. Doses that achieved maximum bacterial kill while suppressing the emergence of drug resistance were determined. Through Monte Carlo simulations the quantitative output of this in vitro study was bridged to the human patient population to inform optimal dosage regimens while accounting for clinical minimum inhibitory concentration (MIC) distributions.Results and Discussion
Moxifloxacin activity was significantly decreased in an acidified environment. The loss of activity was compensated by accumulation of the drug in TB lung lesions; therefore, moderate efficacy can be expected. Moxifloxacin 800 mg/day is the dose that most likely leads to resistance suppression while exerting maximum bacterial kill. Linezolid demonstrated very good activity even at a reduced pH. Linezolid 900 mg once-daily (QD) is likely to achieve a maximum killing effect and prevent the emergence of drug resistance; 600 mg QD in a robust drug regimen may have similar potential. 相似文献75.
C. Ludes A. Labani F. Severac M.Y. Jeung P. Leyendecker C. Roy M. Ohana 《Diagnostic and interventional imaging》2019,100(2):85-93
Purpose
To qualitatively and quantitatively compare unenhanced ultra-low-dose chest computed tomography (ULD-CT) acquired at 80 kVp and 135 kVp.Materials and methods
Fifty-one patients referred for unenhanced chest CT were prospectively included. There were 29 men and 22 women, with a mean age of 64.7 ± 11.6 (SD) years (range: 35–91 years) and a mean body mass index of 26.2 ± 6.3 (SD) (range: 17–54.9). All patients underwent two different ULD-CT protocols (80 kVp-40 mA and 135 kVp-10 mA). Image quality of both ULD-CT examinations using a 5-level scale as well as assessability of 6 predetermined lung parenchyma lesions were blindly evaluated by three radiologists and compared using a logistic regression model. Image noise of the two protocols was compared with Wilcoxon signed-rank test.Results
The mean dose-length product at 80 kVp and at 135 kVp were 14.7 ± 1.8 (SD) mGy.cm and 15.6 ± 1.9 (SD) mGy.cm, respectively (P < 0.001). Image noise was significantly lower at 135 kVp (58.9 ± 12.4) than at 80 kVp (74.7 ± 14.5) (P < 0.001). For all readers and for all examinations, the 135 kVp protocol yielded better image quality than 80 kVp protocol, with a mean qualitative score of 4.5 ± 0.7 versus 3.9 ± 0.8 (P < 0.001). The 135 kVp protocol was significantly more often of diagnostic quality than the 80 kvp protocol (92.3% versus 77.8%, respectively) (P < 0.001) and was less prone to image quality deterioration in obese patients. Parenchymal lesions were never better depicted on the 80 kVp protocol than with the 135 kVp protocol.Conclusion
Unenhanced chest ULD-CT should be acquired at a high kilovoltage and low current, such as 135 kVp-10 mA, over a low kilovoltage and high current protocol. 相似文献76.
P. Herent B. Schmauch P. Jehanno O. Dehaene C. Saillard C. Balleyguier J. Arfi-Rouche S. Jégou 《Diagnostic and interventional imaging》2019,100(4):219-225
Purpose
The purpose of this study was to assess the potential of a deep learning model to discriminate between benign and malignant breast lesions using magnetic resonance imaging (MRI) and characterize different histological subtypes of breast lesions.Materials and methods
We developed a deep learning model that simultaneously learns to detect lesions and characterize them. We created a lesion-characterization model based on a single two-dimensional T1-weighted fat suppressed MR image obtained after intravenous administration of a gadolinium chelate selected by radiologists. The data included 335 MR images from 335 patients, representing 17 different histological subtypes of breast lesions grouped into four categories (mammary gland, benign lesions, invasive ductal carcinoma and other malignant lesions). Algorithm performance was evaluated on an independent test set of 168 MR images using weighted sums of the area under the curve (AUC) scores.Results
We obtained a cross-validation score of 0.817 weighted average receiver operating characteristic (ROC)-AUC on the training set computed as the mean of three-shuffle three-fold cross-validation. Our model reached a weighted mean AUC of 0.816 on the independent challenge test set.Conclusion
This study shows good performance of a supervised-attention model with deep learning for breast MRI. This method should be validated on a larger and independent cohort. 相似文献77.
78.
V. Jenkins I. Solis-Trapala H. Payne M. Mason L. Fallowfield S. May L. Matthews S. Catt 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):99-107
Aims
Delaying progression, ameliorating symptoms and maintaining quality of life (QoL) are primary aims of treatment for metastatic castrate-resistant prostate cancer (mCRPC). Real-world rather than clinical trial data about symptoms and side-effects are sparse. In EXTREQOL, patients' QoL, pain and information needs were recorded during treatment.Material and methods
Men with mCRPC from 20 UK cancer centres starting various systemic mCRPC treatments completed QoL, pain and information needs questionnaires at baseline, 3 and 6 months.Results
In total, 132 patients were recruited. Overall QoL declined significantly by 6 months (Functional Assessment of Cancer Therapy-Prostate [FACT-P] mean = –3.89, 95% confidence interval –6.7 to –1.05, P = 0.007; Trial Outcome Index [TOI] analysis mean = –3.10, 95% confidence interval –5.34 to –0.83, P = 0.007). Those who came off novel therapy and remained on luteinising hormone-releasing hormone agonist therapy alone had worse scores than patients receiving concomitant chemotherapy (Prostate Concerns Subscale mean difference = –4.45, 95% confidence interval –7.06 to –1.83, P = 0.001; TOI mean difference = –5.62, 95% confidence interval –10.97 to –0.26, P = 0.040). At 3 and 6 months, men who reported pain at baseline improved (43%, 40%), but for others pain levels remained the same (45%, 42%) or worsened (13%, 18%). Information regarding supportive care was lacking throughout the period of time on the study.Conclusion
Most mCRPC treated patients experience reduced QoL and inadequate pain control. More help with pain management and better information provision regarding supportive care is warranted. 相似文献79.
Edward J.A. Harris Steven Kao Brian McCaughan Takashi Nakano Nobuyuki Kondo Rebecca Hyland Anna K. Nowak Nicholas H. de Klerk Fraser J.H. Brims 《Journal of thoracic oncology》2019,14(2):288-293
Introduction
Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.Methods
Data were collected from subjects undergoing cytoreductive surgery for MPM from specialist centers in Hyõgo, Japan, and Sydney, Australia, between 1991 and 2016. The CART model was applied using the combination of clinical variables to stratify subjects into risk groups (1 through 4); survival characteristics were then compared.Results
Two hundred eighty-nine cases were included (205 from Australia, 84 from Japan). Overall median survival was 34.6 (interquartile range: 17.5–56.1) months; median age was 63.0 (interquartile range: 57.0–67.8) years, and 83.0% (n = 240) were male. There were no clinically meaningful differences between the two cohorts. Survival across the four risk groups was significantly different (p < 0.0001); the model stratified survival well with a Harrell's concordance statistic of 0.62 (95% confidence interval: 0.57–0.66) at 36 months. The group with the longest survival (median, 82.5 months) had: no weight loss, hemoglobin > 153 g/L and serum albumin > 43 g/L at time of referral to the surgical center.Conclusions
Using routinely available clinical variables, the CART model was able to stratify surgical patients into risk groups with statistically different survival characteristics with fair to good performance. Presence of weight loss, anemia, and low albumin should confer caution when considering surgical therapy for MPM. 相似文献80.
A. Glahn P. J. Proskynitopoulos S. Bleich T. Hillemacher 《Expert opinion on pharmacotherapy》2020,21(9):1083-1092
ABSTRACT