Atkinssparks1118

OBJECTIVE To review the ongoing randomized trials of cytoreductive prostatectomy (CRP) in de novo hormone sensitive metastatic prostate cancer (HSPC) in order to identify their goals and assess their strengths and weaknesses. METHODS Pubmed, Medline and clinical trials websites searches were performed in order to identify currently ongoing trials of CRP in de novo HSPC. RESULTS Nine randomized clinical trials in CRP were identified and included SWOG 1802, SIMCAP, IP2-ATLANTA, TROMBONE, g-RAMPP, LOMP II, FUSCC-OMPCa and the Testing Radical Prostatectomy in Chinese Men with Prostate Cancer and oligoMetastases to the Bone study. Each study was different; assessing various primary outcome measures including overall survival, progression free survival and feasibility to randomize between standard therapy and CRP or between radiation therapy and CRP in the metastatic setting. In the oligometastatic setting, the trials assess OS, feasibility to randomize and time to castration. Similarly a number of secondary endpoints ranging from cancer specific outcomes to quality of life outcomes are being investigated. The inclusion criteria in these trials also varied in terms of volume of metastatic disease (oligo-metastatic to high volume metastatic disease), diagnosis of metastases (imaging based vs biopsy proven), imaging modalities used (conventional to newer modalities) as well as outcomes and follow-up regimes. CONCLUSION While there are differences in each protocol, each trial aims to address different aspects of CRP in de novo HSPC. Therefore the specific goals of each study and the limitations have to be taken into consideration when interpreting the results of these trials. This article is protected by copyright. All rights reserved.In radiation therapy, a Computed Tomography (CT) image is needed for an accurate dose calculation. To allow such a calculation, the CT image values have to be converted into relative electron densities. Thus, standard procedure is to calibrate the CT numbers to relative electron density (RED) by using a phantom with known composition inserts. This calibration curve is energy and CT dependent, therefore most radiotherapy CT acquisitions are obtained with 120 kVp, as each tube voltage needs an additional calibration curve. The commercially available DirectDensityTM (DD) reconstruction algorithm presents a reconstruction implementation without any dependence on the tube voltage. In comparison, it allows a calibration curve that is directly proportional to the RED, reducing the need of more than one calibration curve. This could potentially optimize CT acquisitions and reducing the dose given to the patient. Three different phantoms were used to evaluate the DirectDensityTM algorithm in simple and anthropomorphic Association of Physicists in Medicine.Flattening filter free (FFF) linear accelerators produce a fluence distribution that is forward peaked. Various dosimetric benefits, such as increased dose rate, reduced leakage and out of field dose has led to the growth of FFF technology in the clinic. The literature has suggested the idea of vendors offering dedicated FFF units where the flattening filter (FF) is removed completely and manipulating the beam to deliver conventional flat radiotherapy treatments. This work aims to develop an effective way to deliver modulated flat beam treatments, rather than utilizing a physical FF. This novel optimization model is an extension of the direct leaf trajectory optimization (DLTO) previously developed for volumetric modulated radiation therapy (VMAT) and is capable of accounting for all machine and multileaf collimator (MLC) dynamic delivery constraints, using a combination of linear constraints and a convex objective function. Furthermore, the tongue and groove (T&G) effect was also incorporated directly into obeam characteristics. © 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.Drug resistance is a fundamental clinical concern in pediatric acute lymphoblastic leukemia (pALL), and methotrexate (MTX) is an essential chemotherapy drug administered for the treatment. In the current study, the effect of iron in response to methotrexate and its underlying mechanisms were investigated in pALL cells. CCRF-CEM and Nalm6 cell lines were selected as T and B-ALL subtypes. Cells were pretreated with ferric ammonium citrate, exposed to the IC50 concentration of MTX and cell viability was assessed using MTT, colony formation, and flow cytometry assays. Iron-loaded cells were strongly resistant to MTX cytotoxicity. The inhibitory effect of N-acetyl cysteine to reverse the acquired MTX resistance was greater than that of the iron chelator, deferasirox, highlighting the importance of iron-mediated ROS in MTX resistance. Subsequently, the upregulation of BCL2, SOD2, NRF2, and MRP1 was confirmed using quantitative RT-PCR. Moreover, a positive correlation was demonstrated between the MRP1 expression levels and bone marrow iron storage in pALL patients. Further supporting our findings were the hematoxylin and eosin-stained histological sections showing that iron-treated nude mice xenografts demonstrated significantly more liver damage than those unexposed to iron. Overall, iron is introduced as a player with a novel role contributing to methotrexate resistance in pALL. Our findings suggest that the patients' bone marrow iron stores are necessary to be assessed during the chemotherapy, and transfusions should be carefully administrated. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This guideline is on the prevention of foot ulceration in persons with diabetes and updates the 2015 IWGDF prevention guideline. We followed the GRADE methodology to devise clinical questions and critically important outcomes in the PICO format, to conduct a systematic review of the medical-scientific literature, and to write recommendations and their rationale. Selleck Ruboxistaurin The recommendations are based on the quality of evidence found in the systematic review, expert opinion where evidence was not available, and a weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to the intervention. We recommend to screen a person at very low risk for ulceration annually for loss of protective sensation and peripheral artery disease and persons at higher risk at higher frequencies for additional risk factors. For preventing a foot ulcer, educate the at-risk patient about appropriate foot self-care and treat any pre-ulcerative sign on the foot.