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Richard Kim Elaine Tan Emily Wang Amit Mahipal Dung-Tsa Chen Biwei Cao Fadzai Masawi Cindy Machado James Yu Dae Won Kim 《The oncologist》2020,25(12):e1893-e1899
Lessons Learned
- The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
- Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
- The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.
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Enrique Luengo Izaskun Buendia Cristina Fernndez‐Mendívil Paula Trigo‐Alonso Pilar Negredo Patrycja Michalska Borja Hernndez‐García Cristina Snchez‐Ramos Juan A. Bernal Tsuneya Ikezu Rafael Len Manuela G. Lpez 《Journal of pineal research》2019,67(1)
Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTauP301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTauP301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD. 相似文献
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Maria Gonzalez-Cao Cristina Carrera Juan Francisco Rodriguez Moreno Pedro Rodríguez-Jiménez Mónica Antoñanzas Basa Rosa Feltes Ochoa Teresa Puertolas Eva Muñoz-Couselo José Luis Manzano Ivan Marquez-Rodas Juan Martín-Liberal Ainara Soria Pilar Lopez Criado Almudena Garcia-Castaño Aram Boada Pablo Ayala de Miguel Susana Puig Guillermo Crespo Alfonso Berrocal 《Journal of the American Academy of Dermatology》2021,84(5):1412-1415
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Willy Baccaglini Felipe A. Glina Cristiano Linck Pazeto Luis G. Medina Fernando Korkes Wanderley M. Bernardo Rene Sotelo Sidney Glina Giancarlo Marra Marco Moschini Xavier Cathelineau Rafael Sanchez-Salas 《Clinical genitourinary cancer》2021,19(1):3-11.e1
This meta-analysis focuses on the accuracy of upgrading to clinically significant prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted biopsy (MRI-TB) versus systematic biopsy (SB). We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Literatura Latino Americana em Ciências da Saúde databases through January 2020 for comparative, retrospective/prospective, paired-cohort, and randomized clinical trials with paired comparisons. The population consisted of patients with low-risk PCa in active surveillance with at least 1 index lesion on imaging. We evaluated the quality of evidence by using the Quality Assessment of Diagnostic Accuracy Studies-2 score. Group comparisons considered the differences between the area under the curve summary receiver operating characteristic curve in a 2-tailed method. We also compared the positive predictive value of the best single method (MRI-TB or SB) and the referral study test (combined biopsy, a combination of MRI-TB and SB). The meta-analysis included 6 studies enrolling 741 patients. The pooled sensitivity for the 2 groups was 0.79 (95% confidence interval, 0.74-0.83; I2 = 75%) and 0.67 (95% confidence interval, 0.63-0.74; I2 = 55.4%), respectively. The area under the curve for the MRI-TB and SB groups were 0.99 and 0.92 (P < .001), respectively. The positive predictive value for the MRI-TB and combined biopsy groups were similar. The accumulated evidence suggests better results for MRI-TB compared with SB. Therefore, use of MRI-TB alone may be preferable in patients in active surveillance harboring low-risk PCa. 相似文献
7.
Del Lama Rafael Silva Candido Raquel Mariana Chiari-Correia Natália Santana Nogueira-Barbosa Marcello Henrique de Azevedo-Marques Paulo Mazzoncini Tinós Renato 《Journal of digital imaging》2022,35(3):446-458
Journal of Digital Imaging - Vertebral Compression Fracture (VCF) occurs when the vertebral body partially collapses under the action of compressive forces. Non-traumatic VCFs can be secondary to... 相似文献
8.
Stefan Scholz Florian Koerber Kinga Meszaros Rosa Maya Fassbender Bernhard Ultsch Robert R. Welte Wolfgang Greiner 《Vaccine》2019,37(12):1692-1701
Introduction
Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.Method
A bottom-up, model-based costing approach has been used to calculate the diagnose- and age-specific yearly lifetime costs of a hypothetical cohort of MenB-related IMD cases. Direct costs contain the treatment cost for the acute phase of the disease, long-term sequelae, costs for rehabilitation, and public health response. Indirect costs are calculated for the human-capital approach and the friction-cost approach considering productivity losses of patients or parents for the acute phase and long-term sequelae. Publicly available databases from the Federal Statistical Office, the SOEP panel data set, literature, and expert opinion were used as data sources. All future costs beyond the reference year of 2015 were discounted at 3%.Results
The total costs for the hypothetical cohort (343 patients) from a societal perspective are €19.6 million (€57,100/IMD case) using the friction-cost approach and €58.8 million (€171,000/IMD case) using the human-capital approach. Direct costs amount to €18.6 million or €54,300 €/case. Sequelae are responsible for 81% of the direct costs/case.Discussion
The elevated costs/MenB-related IMD case reflect the severity of the disease. The total costs are sensitive to the productivity-loss estimation approach applied. MenB is an uncommon but severe disease; The costs/case reflect the severity of the disease and is within the same magnitude as for human papilloma virus infections. The available literature on sequelae is due to the uncommonness limited and heterogeneous. 相似文献9.