小剂量阿替普酶治疗急性脑梗死患者的临床疗效及安全性评价

目的:探讨急性脑梗死患者静脉溶栓使用小剂量(0.6 mg/kg)阿替普酶的临床疗效及安全性。方法:将2016年1月至2019年12月我院神经内科收治的溶栓时间窗内40例急性脑梗死患者随机分为标准剂量组(0.9 mg/kg)和小剂量组(0.6 mg/kg),每组20例,分别在溶栓前、溶栓后1小时对患者进行美国国立卫生研究院卒中量表(NIHSS)评分,溶栓前和溶栓后24小时做头颅CT排除脑出血,密切监测不良反应。结果:标准剂量组有效率为80.00%,小剂量组有效率为75.00%,两组比较差异无统计学意义(P0.05)。治疗前两组NIHSS评分比较差异无统计学意义(P0.05),治疗后两组NIHSS评分均降低,与治疗前相比差异有统计学意义(P0.05),治疗后两组NIHSS评分差异无统计学意义(P0.05)。标准剂量组总不良反应发生率为40.00%,高于小剂量组的20.00%,差异无统计学意义(P0.05)。结论:阿替普酶可有效改善急性脑梗死患者的神经功能,小剂量(0.6 mg/kg)与标准剂量(0.9 mg/kg)溶栓效果相当,安全性较好,出血事件发生率较低,可根据患者情况酌情选用小剂量。     

Geometric and dosimetric quality assurance using logfiles and a 3D helical diode detector for Dynamic WaveArc

PurposeTo conduct patient-specific geometric and dosimetric quality assurance (QA) for the Dynamic WaveArc (DWA) using logfiles and ArcCHECK (Sun Nuclear Inc., Melbourne, FL, USA).MethodsTwenty DWA plans, 10 for pituitary adenoma and 10 for prostate cancer, were created using RayStation version 4.7 (RaySearch Laboratories, Stockholm, Sweden). Root mean square errors (RMSEs) between the actual and planned values in the logfiles were evaluated. Next, the dose distributions were reconstructed based on the logfiles. The differences between dose-volumetric parameters in the reconstructed plans and those in the original plans were calculated. Finally, dose distributions were assessed using ArcCHECK. In addition, the reconstructed dose distributions were compared with planned ones.ResultsThe means of RMSEs for the gantry, O-ring, MLC position, and MU for all plans were 0.2°, 0.1°, 0.1 mm, and 0.4 MU, respectively. Absolute means of the change in PTV D_99% were 0.4 ± 0.4% and 0.1 ± 0.1% points between the original and reconstructed plans for pituitary adenoma and prostate cancer, respectively. The mean of the gamma passing rate (3%/3 mm) between the measured and planned dose distributions was 97.7%. In addition, that between the reconstructed and planned dose distributions was 99.6%.ConclusionsWe have demonstrated that the geometric accuracy and gamma passing rates were within AAPM 119 and 142 criteria during DWA. Dose differences in the dose-volumetric parameters using the logfile-based dose reconstruction method were also clinically acceptable in DWA.     

Ecological indicators for assessing ecological success of forest restoration: a world review

Restoration is increasingly being used to reverse degradation and destruction of forest ecosystems. With increasing investment in restoration, there is an urgent need to develop effective programs to assess treatment efficacy and effects. We conducted a global review of forest restoration assessments, in order to identify geographic trends in the locations where assessments have been implemented and the specific ecological attributes (ecosystem composition, structure, and function) and indicators being used to measure effects. We found that the number of forest restoration assessments varied by region and was not related to degree of degradation or restoration need. Some regions, like Africa, which have experienced high rates of forest loss and degradation, had few assessments. The majority (43%) of assessments included indicators for only two of three key ecological attributes (composition‐structure or composition‐function) and assessments on average used fewer than three indicators per attribute. The most commonly employed indicators for composition were richness and abundance of plant species and for structure were height and diameter of trees, variables that are generally relatively easy to measure. The use of functional indicators has been increasing over time and they are now more commonly used than structural indicators. The most common functional indicators were soil functions. Most investigators evaluated treatment effects for 6–10 years after implementation. Our findings related to gaps in analysis of ecological indicators can serve as a guide for developing monitoring and assessment protocols for current global forest restoration initiatives by 2020–2030.     

Continual reassessment method for partial ordering

Summary Much of the statistical methodology underlying the experimental design of phase 1 trials in oncology is intended for studies involving a single cytotoxic agent. The goal of these studies is to estimate the maximally tolerated dose, the highest dose that can be administered with an acceptable level of toxicity. A fundamental assumption of these methods is monotonicity of the dose–toxicity curve. This is a reasonable assumption for single‐agent trials in which the administration of greater doses of the agent can be expected to produce dose‐limiting toxicities in increasing proportions of patients. When studying multiple agents, the assumption may not hold because the ordering of the toxicity probabilities could possibly be unknown for several of the available drug combinations. At the same time, some of the orderings are known and so we describe the whole situation as that of a partial ordering. In this article, we propose a new two‐dimensional dose‐finding method for multiple‐agent trials that simplifies to the continual reassessment method (CRM), introduced by O'Quigley, Pepe, and Fisher (1990, Biometrics 46 , 33–48), when the ordering is fully known. This design enables us to relax the assumption of a monotonic dose–toxicity curve. We compare our approach and some simulation results to a CRM design in which the ordering is known as well as to other suggestions for partial orders.     

The formation of DNA single-strand breaks and alkali-labile sites in human blood lymphocytes exposed to 365-nm UVA radiation

The potency of UVA radiation, representing 90% of solar UV light reaching the earth׳s surface, to induce human skin cancer is the subject of continuing controversy. This study was undertaken to investigate the role of reactive oxygen species in DNA damage produced by the exposure of human cells to UVA radiation. This knowledge is important for better understanding of UV-induced carcinogenesis. We measured DNA single-strand breaks and alkali-labile sites in human lymphocytes exposed ex vivo to various doses of 365-nm UV photons compared to X-rays and hydrogen peroxide using the comet assay. We demonstrated that the UVA-induced DNA damage increased in a linear dose-dependent manner. The rate of DNA single-strand breaks and alkali-labile sites after exposure to 1 J/cm² was similar to the rate induced by exposure to 1 Gy of X-rays or 25 μM hydrogen peroxide. The presence of either the hydroxyl radical scavenger dimethyl sulfoxide or the singlet oxygen quencher sodium azide resulted in a significant reduction in the UVA-induced DNA damage, suggesting a role for these reactive oxygen species in mediating UVA-induced DNA single-strand breaks and alkali-labile sites. We also showed that chromatin relaxation due to hypertonic conditions resulted in increased damage in both untreated and UVA-treated cells. The effect was the most significant in the presence of 0.5 M Na⁺, implying a role for histone H1. Our data suggest that the majority of DNA single-strand breaks and alkali-labile sites after exposure of human lymphocytes to UVA are produced by reactive oxygen species (the hydroxyl radical and singlet oxygen) and that the state of chromatin may substantially contribute to the outcome of such exposures.     

Overview of commercial treatment planning systems for targeted radionuclide therapy

IntroductionTargeted Radionuclide Therapy (TRT) is a branch of cancer medicine dealing with the therapeutic use of radioisotopes associated with biological vectors accumulating in the tumors/targets, indicated as Molecular Radiotherapy (MRT), or directly injected into the arteries that supply blood to liver tumour vasculature, indicated as Selective RT (SRT). The aim of this work is to offer a panoramic view on the increasing number of commercially-available TRT treatment planning systems (TPSs).Materials and methodsA questionnaire was sent to manufacturers' representatives. Academic software were not considered. Questions were grouped as follows: general information, clinical workflow, calibration procedure, image processing/reconstruction, image registration and segmentation tools, time-activity curve (TAC) fitting and absorbed dose calculation.ResultsAll software reported have CE-marking. TPSs were divided between SRT-dedicated software [4] and MRT [5] dosimetry software. In SRT, since no kinetic process is involved, absorbed dose calculation does not require TAC fitting, and image registration is not fully developed in all TPS. All software requires a radionuclide-specific calibration. In SRT, a relative image calibration can be obtained by scaling the counts to a known activity. Automated VOI contouring and rigid/deformable propagation between different acquisitions time-points is implemented in most TPSs, although DICOM export is rare. Different TAC fits are available depending on the number of time-points. Voxel S-value and Local deposition methods are the most frequent dosimetric approaches; dose-voxel kernel convolution and semi-Monte Carlo method are also available.ConclusionsAvailable TPSs allows performing personalized dosimetry in clinical practice. Individual variations in methodology/algorithms must be considered in the standardisation/harmonization processes.     

Integral dose based inverse optimization objective function promises lower toxicity in head-and-neck

PurposeThe voxels in a CT data sets contain density information. Besides its use in dose calculation density has no other application in modern radiotherapy treatment planning. This work introduces the use of density information by integral dose minimization in radiotherapy treatment planning for head-and-neck squamous cell carcinoma (HNSCC).Materials and methodsEighteen HNSCC cases were studied. For each case two intensity modulated radiotherapy (IMRT) plans were created: one based on dose-volume (DV) optimization, and one based on integral dose minimization (Energy hereafter) inverse optimization. The target objective functions in both optimization schemes were specified in terms of minimum, maximum, and uniform doses, while the organs at risk (OAR) objectives were specified in terms of DV- and Energy-objectives respectively. Commonly used dosimetric measures were applied to assess the performance of Energy-based optimization. In addition, generalized equivalent uniform doses (gEUDs) were evaluated. Statistical analyses were performed to estimate the performance of this novel inverse optimization paradigm.ResultsEnergy-based inverse optimization resulted in lower OAR doses for equivalent target doses and isodose coverage. The statistical tests showed dose reduction to the OARs with Energy-based optimization ranging from ∼2% to ∼15%.ConclusionsIntegral dose minimization based inverse optimization for HNSCC promises lower doses to nearby OARs. For comparable therapeutic effect the incorporation of density information into the optimization cost function allows reduction in the normal tissue doses and possibly in the risk and the severity of treatment related toxicities.     

Dose calculation accuracy in proximity of a pacemaker: A multicenter study with threecommercial treatment planning systems

This study compares Treatment Planning System (TPS) out of field dose calculation on a pacemaker (PMK) during external beam radiotherapy treatment. We consider four TPSs (Elekta-Monaco, Oncentra- Masterplan and two Philips-Pinnacle3) commissioned for two linacs (Elekta Sinergy and Varian Clinac) delivering two test beams (a highly modulated one and a square field) and two clinical breast plans. To calculate and measure dose to a PMK we built a Real Water3 phantom with a PMK embedded in it. Measures are performed with thermo-luminescent dosimeters and Mosfet dosimeters. We evaluate differences between TPS calculated values for the dose to the PMK (both point dose and dose-volume histogram parameters) when the PMK is positioned in the first 10 cm outside the radiation fields. TPS calculation accuracy is evaluated comparing such values with measures. Differences in TPS calculations are on average 3.5 cGy Gy^-1 for the modulated beam, and always lower than 2 cGy Gy^-1 for the square beam. TPS dose calculation depends mostly on the TPS algorithm and model rather than the linac commissioned. TPSs considered show different degrees of calculation accuracy. In the first 4 cm to the field edge three out of four TPSs are in good agreement with measurements in the square beam, but only one keeps the agreement in the modulated beam: the others show over and underestimations up to +20% −40%. The same accuracy is found considering a homogeneous phantom. Our results confirm what reported in previous studies and highlight the impact of TPS commissioning.