A comprehensive method for calculating total body irradiation

PurposeTo provide means for calculating the dose received by various tissues of the patient, calculate lung shield, and verify received dose using a phantom as a tool for quality assurance for a planned Total Body Irradiation (TBI) procedure in radiotherapy.MethodUsing Microsoft Visual Basic, MATLAB, and Python, a program for Total Body Irradiation Calculation in Radiotherapy (TBICR) is constructed. It uses patient translation and beam zone method for total body irradiation calculations to compute the proper dose received by the patient and determine the lung shield thickness. There are three main user-friendly interfaces in the application. The first one allows the user to upload the TBI topography and estimate the distances needed for TBI calculations. The second one enables the user to count the number of beam zones needed for each point and estimate the effective area (A_eff) for each level. The third interface estimates the velocity required to deliver the relative dose depending on patient separation, Monitor Units (MU), couch speed and travel distance. It allows the user to compute the required lung shield thickness, read any patient's CT DICOM file and acquire dose in any distinct location using machine learning model to predict the dose.ResultsThe TBICR software has been successfully validated by reproducing all of the manual calculations in an exact and timely manner. TBICR generated more accurate results and confirmed the absorbed dose to patient through measurements on Anderson phantom.ConclusionsA computer program for the calculation of total body irradiation (TBI) is described in full. The dose received at each point on the patient, the calculation of lung shield and the determination of the velocity and time required for the couch movement are all made possible using the software. The ease of use, precision, data storage and printing are some important features of the present software.     

Higenamine as a Potential Pharmacologic Stress Agent in the Detection of Coronary Artery Disease

Myocardial perfusion imaging (MPI) is valuable for the diagnosis, prognosis, and management of coronary artery disease (CAD). The most commonly used pharmacologic stress agents at present are vasodilators and adrenergic agents. However, these agents have contraindications and may cause adverse effects in some patients. Thus, other stress agents feasible for more patients are required. Higenamine (HG) is a β-adrenergic receptor agonist currently approved for clinical trials as a stress agent for myocardial infarction. It also has a promising value in MPI for the detection of CAD in preclinical and clinical studies. This review summarizes the application of HG on MPI, including its mechanism of action, stress protocol, efficacy, and safety.     

Exosome-delivered miR-221/222 exacerbates tumor liver metastasis by targeting SPINT1 in colorectal cancer

MicroRNAs (miRNAs) are involved in the progression of many cancers through largely unelucidated mechanisms. The results of our present study identified a gene cluster, miR-221/222, that is constitutively upregulated in serum exosome samples of patients with colorectal carcinoma (CRC) with liver metastasis (LM); this upregulation predicts a poor overall survival rate. Using an in vitro cell coculture model, we demonstrated that CRC exosomes harboring miR-221/222 activate liver hepatocyte growth factor (HGF) by suppressing SPINT1 expression. Importantly, miR-221/222 plays a key role in forming a favorable premetastatic niche (PMN) that leads to the aggressive nature of CRC, which was further shown through in vivo studies. Overall, our results show that exosomal miR-221/222 promotes CRC progression and may serve as a novel prognostic marker and therapeutic target for CRC with LM.     

An observational study evaluating the impact on prostate patient outcomes and experiences when radiation therapists use a standard grading system tool to assess and document treatment-related toxicities and interventions

Background/PurposeMen undergoing radiation therapy (RT) treatment for prostate cancer (PC) often experience acute urinary, bowel, sexual, and hormonal toxicities. Timely screening, management, and documentation of these toxicities is an integral part of clinician practice, ensuring patients receive the care they require. Various screening tools, completed by either the patient or the clinician, are available, which allow clinicians to collect and respond to these toxicity outcomes; however there is a paucity of literature regarding the effective use and timing of these tools during RT treatment. This study aims to evaluate the feasibility of conducting comprehensive toxicity screening and symptom management using a toxicity screening tool in one of the busiest RT departments in Canada. Specifically, the use of a toxicity screening tool and its effect on the quality of toxicity documentation, operational impact, and patient reported outcomes (PRO).Methods90 consented patients were allocated to either the structured or non-structured arm. Patients in the structured arm were assessed weekly by radiation therapists for 13 toxicities across four domains (bladder, bowel, hormonal, and sexual), using an in-house developed structured questionnaire, known as the Grid, to complete the National Cancer Institute's Common Toxicity Criteria for Adverse Events v3 (CTCAEv3). Patients in the non-structured arm were assessed and had free text clinical documentation charted according to current department policy. The Expanded Prostate Cancer Index Composite (EPIC), a PRO tool to evaluate patient function and bother after prostate cancer treatment, was completed by all study patients on a weekly basis. Statistical analysis compared documentation completeness, EPIC scores, patient satisfaction, and operational impact between study arms, as well as evaluated optimal timing of toxicity assessments.ResultsAssessment of the non-structured arm for completeness revealed an inconsistent and insufficient amount of documentation for the bladder and bowel domains. As for both the sexual and hormonal domains, documentation was largely absent. There was no difference in EPIC scores and patient satisfaction scores between the structured arm and the non-structured arm. Evaluation of the timing of PROs showed significant week to week change for the bladder and bowel toxicities, but not the sexual and hormonal toxicities. Finally, the use of the Grid revealed no significant impact on daily operations, only increasing average treatment times by seven seconds, and did not create any additional workload for the oncologists.ConclusionsUse of the Grid increased documentation completeness without negatively impacting clinical flow or operations, despite the fact that PROs were not improved. Based on EPIC PRO scores, bladder and bowel toxicities should be evaluated on a weekly basis during RT treatment, while sexual and hormonal toxicities need only be evaluated monthly.     

Alcohol-induced changes in urinary aminolevulinic acid and porphyrins: Unrelated to liver disease

Urinary porphyrins and their metabolites aminolevulinic acid (ALA) and porphobilinogen (PBG) were determined in 15 normal volunteers and in 45 alcoholics, subdivided into three groups according to their liver function tests and histology: alcoholics exhibiting no evidence of hepatocellular damage; alcoholics with fatty liver and impaired function of liver enzymes; and alcoholics with proven liver cirrhosis. The dominant trend observed in those alcoholics devoid of any evidence of liver disease was increased ALA, PBG, and uroporphyrin. Coproporphyrinuria was shared by the patients exhibiting liver damage. The data shown enabled us to differentiate between the direct, primary effect of alcohol on the heme biosynthetic pathway and the secondary indirect effect, which is probably related to liver damage that follows alcohol consumption. Evaluation of the results led to the suggestion that urinary ALA could possibly serve as a marker of alcoholism. The specificity and sensitivity of the test were found to be 87A and 80%, respectively.     

Potentiation of microglial endocannabinoid signaling alleviates neuroinflammation in Alzheimer's disease

Alzheimer's disease (AD) isaprogressive neurodegenerative disorder characterized by chronic inflammation due to the presence of neurotoxic Aβ and tau proteins. Increased microglial activation and inflated immune response are the other factors to be considered in AD pathology. Microglial cells own biochemical machinery that synthesizes and release endocannabinoids. The exploitation of therapeutic actions of endocannabinoid system has newly emerged in the field of Alzheimer's disease. The activation of cannabinoid receptors/ cannabinoid system modulates inflammatory responses. This review assesses the association between the microglial endocannabinoid system and neuroinflammation in AD. The data supporting the anti-inflammatory role of pharmacological agents modulating cannabinoid system are also reviewed.     

中成药在美国寻求批准的现状及展望

Veregen^TM and Fulyzaq are the first two botanical drug products that were approved by the Food and Drug Administration （FDA） to market in the US in recent years. Additional herbal medicines, including Compound Danshen Dripping Pills （复方丹参滴丸）, Fuzheng Huayu Tablets （扶正化瘀片）, Xuezhikang Capsule （血脂康胶囊）, Guizhi Fuling Capsule （桂枝茯苓胶囊）, Kanglaite Capsule （康莱特胶囊） and Kanglaite Injection （康莱特注射液）, have filed the investigational new drug （IND） application to the FDA and are in phaseⅡ or phase Ⅲ clinical development. In order to gain better understanding of the process of botanical drug approval in the US, this article examines the aforementioned drugs by looking at their composition, indication, prior clinical experience and clinical development process, and summarizes key features that enabled IND filing and marketing approval by the FDA.     

GSK-3β as a target for apigenin-induced neuroprotection against Aβ 25–35 in a rat model of Alzheimer's disease

Glycogen synthase kinase-3 (GSK-3) is a critical molecule in Alzheimer's disease (AD) that modulates two histopathological hallmarks of AD: Amyloid beta (Aβ) plaques and neurofibrillary tangles composed of aberrant hyper-phosphorylation of tau protein. This study was performed to investigate the protective effect of flavone apigenin through inhibition of GSK-3 and the involvement of this kinase in the inhibition of BACE1 expression and hyperphosphorylation of tau protein in an AD rat model. 15 nM of aggregated amyloid-beta 25–35 was microinjected into the left lateral ventricle of an AD rat. Apigenin (50 mg/kg) was administered orally 45 min before the Aβ injection and continued daily for three weeks. Immunohistochemistry and western blot analysis showed that apigenin significantly reduced the hyperphosphorylation of tau levels in the hippocampus. Real-time PCR analysis revealed significant inhibition of the mRNA level of β secretase (BACE1) and GSK-3β, but Apigenin had no effect on the level of GSK-3α.The results demonstrate that apigenin has a protective effect against amyloid-beta 25–35 by decreasing the expression of GSK-3β with the consequence of lowering the hyperphosphorylation of tau protein and suppressing BACE1 expression.     

To see or not to see: Evaluation of magnetic resonance imaging sequences for use in MR Linac-based radiotherapy treatment

Background/PurposeThis work evaluated the suitability of MR derived sequences for use in online adaptive RT workflows on a 1.5 Tesla (T) MR-Linear Accelerator (MR Linac).Materials/MethodsNon-patient volunteers were recruited to an ethics approved MR Linac imaging study. Participants attended 1-3 imaging sessions in which a combination of DIXON, 2D and 3D volumetric T1 and T2 weighted images were acquired axially, with volunteers positioned using immobilisation devices typical for radiotherapy to the anatomical region being scanned.Images from each session were appraised by three independent reviewers to determine optimal sequences over six anatomical regions: head and neck, female and male pelvis, thorax (lung), thorax (breast/chest wall) and abdomen. Site specific anatomical structures were graded by the perceived ability to accurately contour a typical organ at risk. Each structure was independently graded on a 4-point Likert scale as ‘Very Clear’, ‘Clear’, ‘Unclear’ or ‘Not visible’ by observers, consisting of radiographers (therapeutic and diagnostic) and clinicians.ResultsFrom July 2019 to September 2019, 18 non-patient volunteers underwent 24 imaging sessions in the following anatomical regions: head and neck (n=3), male pelvis (n=4), female pelvis (n=5), lung/oesophagus (n=5) abdomen (n=4) and chest wall/breast (n=3). T2 sequences were the most preferred for perceived ability to contour anatomy in both male and female pelvis. For all other sites T1 weighted DIXON sequences were most favourable.ConclusionThis study has determined the preferential sequence selection for organ visualisation, as a pre-requisite to our institution adopting MR-guided radiotherapy for a more diverse range of disease sites.