Regression

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  • 文章类型: Journal Article
    广义线性模型(GLM)是生态学中不可或缺的工具。像一般的线性模型一样,GLM假设线性,这需要自变量和因变量之间的线性关系。然而,因为这个假设作用于GLM中的链接而不是自然尺度,它更容易被忽视。我们回顾了最近的生态学文献,以量化线性的使用。然后,我们使用两个案例研究,通过两个GLM拟合经验数据来面对线性假设。在第一个案例研究中,我们将GLM与适合哺乳动物相对丰度数据的广义加性模型(GAM)进行了比较。在第二个案例研究中,我们使用雀形目点数数据测试了占用模型的线性。我们回顾了过去5年在5个领先的生态学期刊上发表的162项研究,发现只有不到15%的人报告了线性测试。这些研究使用转化和GAM的频率比他们报道的线性测试更多。在第一个案例研究中,在建模相对丰度时,GAM强烈优于AIC测得的GLM,和GAMs有助于揭示食肉动物物种对景观发展的非线性响应。在第二个案例研究中,14%的物种特异性模型未能通过正式的线性统计检验。我们还发现线性和非线性之间的差异(即,具有转换后的自变量的那些)模型预测对于某些物种是相似的,而对于其他物种则不是,对推理和保护决策有影响。OurreviewsuggeststhatreportingtestsforlinearityarerareinrecentstudiesemployingGLM.Ourcasestudiesshowshowformallycomparingmodelsthatallowedfor非线性relationshipbetweenthedependentandindependentvariableshasthepotentialtoimpactinference.产生新的假设,并改变保护的含义。最后,我们建议生态研究报告线性测试,并使用正式方法解决GLM中违反线性假设的问题。
    Generalized linear models (GLMs) are an integral tool in ecology. Like general linear models, GLMs assume linearity, which entails a linear relationship between independent and dependent variables. However, because this assumption acts on the link rather than the natural scale in GLMs, it is more easily overlooked. We reviewed recent ecological literature to quantify the use of linearity. We then used two case studies to confront the linearity assumption via two GLMs fit to empirical data. In the first case study we compared GLMs to generalized additive models (GAMs) fit to mammal relative abundance data. In the second case study we tested for linearity in occupancy models using passerine point-count data. We reviewed 162 studies published in the last 5 years in five leading ecology journals and found less than 15% reported testing for linearity. These studies used transformations and GAMs more often than they reported a linearity test. In the first case study, GAMs strongly out-performed GLMs as measured by AIC in modeling relative abundance, and GAMs helped uncover nonlinear responses of carnivore species to landscape development. In the second case study, 14% of species-specific models failed a formal statistical test for linearity. We also found that differences between linear and nonlinear (i.e., those with a transformed independent variable) model predictions were similar for some species but not for others, with implications for inference and conservation decision-making. Our review suggests that reporting tests for linearity are rare in recent studies employing GLMs. Our case studies show how formally comparing models that allow for nonlinear relationships between the dependent and independent variables has the potential to impact inference, generate new hypotheses, and alter conservation implications. We conclude by suggesting that ecological studies report tests for linearity and use formal methods to address linearity assumption violations in GLMs.
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  • 文章类型: Journal Article
    背景:糖尿病前期是糖尿病发展之前的一种疾病,并且与许多并发症的风险增加有关。主要的管理模式被认为是生活方式的改变。药物治疗,如胰高血糖素样肽-1受体激动剂(GLP-1RAs),在文献中没有得到很好的解决,并且仅在有限样本量的试验中作为次要和探索性结局进行评估.这里,GLP-1RA被评估为糖尿病前期患者的综合治疗方法。
    方法:对WebofScience的全面搜索,Scopus,PubMed,和Cochrane于2023年5月5日进行,以检索随机对照试验(RCT),比较GLP-1RA与安慰剂和/或生活方式改变对糖尿病前期恢复到血糖正常的影响,预防明显的糖尿病,血糖控制,人体测量参数,和脂质分布。使用了ReviewManager(RevMan)5.4版。使用修订版本的Cochrane偏差风险工具评估随机对照试验的质量。进行评分以评估证据的确定性。
    结果:12项研究纳入了GLP-1RAs组2903例患者和对照组1413例患者的荟萃分析。低质量的证据表明,GLP-1RA显著增加了糖尿病前期恢复到正常血糖状态的发生率[RR=1.76,95%CI(1.45,2.13),P<0.00001]和中等质量的证据表明,GLP-1RA可以显著预防新发糖尿病[RR=0.28,95%CI(0.19,0.43),P<0.00001]。HbA1c显著降低,空腹血糖,体重,腰围,甘油三酯,在GLP-1RAs组中观察到LDL(P<0.05)。然而,GLP-1RAs组胃肠道疾病发生率较高(P<0.05).
    结论:GLP-1RAs联合生活方式改变被证明是治疗糖尿病前期患者的一种比单独的生活方式改变更有效的治疗方法。具有可容忍的安全性。未来的指南应考虑将GLP-1RA作为糖尿病前期患者管理中生活方式改变的辅助手段,以提供更好的管理并提高治疗依从性。
    BACKGROUND: Prediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is thought to be lifestyle modification. Pharmacological therapy, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), were not well addressed in the literature and were only evaluated in trials as secondary and exploratory outcomes with a limited sample size. Here, GLP-1RAs are evaluated as a comprehensive therapy approach for patients with prediabetes.
    METHODS: A comprehensive search of Web of Science, SCOPUS, PubMed, and Cochrane was performed on May 5, 2023, to retrieve randomized controlled trials (RCTs) comparing the effect of GLP-1RAs to placebo and/or lifestyle modification on prediabetes reversion to normoglycemia, prevention of overt diabetes, glycemic control, anthropometric parameters, and lipid profiles. Review Manager (RevMan) version 5.4 was used. The quality of RCTs was assessed using the revised version of the Cochrane Risk of Bias Tool. GRADE was performed to evaluate the certainty of evidence.
    RESULTS: Twelve trials involving 2903 patients in the GLP-1RAs group and 1413 in the control group were included in the meta-analysis. Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43), P < 0.00001]. Significant reductions in HbA1c, fasting plasma glucose, body weight, waist circumference, triglycerides, and LDL were observed in the GLP-1RAs arm (P < 0.05). However, higher incidences of gastrointestinal disorders were reported in the GLP-1RAs group (P < 0.05).
    CONCLUSIONS: GLP-1RAs combined with lifestyle modification proved to be a more effective therapy for managing prediabetic patients than lifestyle modification alone, with a tolerable safety profile. Future guidelines should consider GLP-1RAs as an adjunct to lifestyle modification in the management of prediabetic patients to provide better management and improve treatment adherence.
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  • 文章类型: Journal Article
    抗生素耐药性(AR)被认为是本世纪最大的全球威胁之一。只有当人类所有相互联系的区域,动物和环境被视为世界卫生组织(WHO)提出的“一个健康”概念的一部分。水和废水是AR源最重要的环境介质之一,其中现象通常是非线性的。因此,这项研究的目的是研究基于机器学习的方法(MLM)在水和废水中解决AR引起的问题的应用。为此,在1987年至2023年期间搜索了大多数相关数据库,以对应用程序进行系统分析和分类。因此,结果表明,在12个应用程序中,11(91.6%)用于浅层学习,1(8.3%)用于深度学习。在浅层学习类别中,n=6,50%的应用为回归,n=4,33.3%为分类,主要使用人工神经网络,决策树和贝叶斯方法实现以下目标:预测抗生素抗性细菌(ARB)的存活,确定影响参数对基于AR的分数的顺序,并确定抗生素抗性基因(ARGs)的主要来源。此外,只有一项研究(8.3%)被发现用于聚类,没有发现相关性研究.令人惊讶的是,深度学习仅在一项研究(8.3%)中用于预测ARGs序列。因此,研究AR的知识差距,特别是使用聚类,联想和深度学习方法,将是一个有希望的选择,以分析更多方面的相关问题。然而,还有很长的路要走,以考虑和应用MLM作为研究水和废水中AR的不同方面的独特方法。
    Antibiotic resistance (AR) is considered one of the greatest global threats in the current century, which can only be overcome if all interconnected areas of humans, animals and the environment are taken into account as part of the One Health concept proposed by the World Health Organization (WHO). Water and wastewater are among the most important environmental media of AR sources, where the phenomena are generally non-linear. Therefore, the aim of this study was to investigate the application of machine learning-based methods (MLMs) to solve AR-induced problems in water and wastewater. For this purpose, most relevant databases were searched in the period between 1987 and 2023 to systematically analyze and categorize the applications. Accordingly, the results showed that out of 12 applications, 11 (91.6%) were for shallow learning and 1 (8.3%) for deep learning. In shallow learning category, n = 6, 50% of the applications were regression and n = 4, 33.3% were classification, mainly using artificial neural networks, decision trees and Bayesian methods for the following objectives: Predicting the survival of antibiotic-resistant bacteria (ARB), determining the order of influencing parameters on AR-based scores, and identifying the major sources of antibiotic resistance genes (ARGs). In addition, only one study (8.3%) was found for clustering and no study for association. Surprisingly, deep learning had been used in only one study (8.3%) to predict ARGs sequences. Therefore, working on the knowledge gaps of AR, especially using clustering, association and deep learning methods, would be a promising option to analyze more aspects of the related problems. However, there is still a long way to go to consider and apply MLMs as unique approaches to study different aspects of AR in water and wastewater.
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  • 文章类型: Journal Article
    从仰卧或坐着到站立的姿势改变导致300至1000毫升的血液从身体的中央部分移位到下肢,导致心脏静脉回流减少,因此心输出量减少,导致血压下降.这可能会导致跌倒,晕厥,通常会降低日常活动的质量,尤其是老年人和患有神经系统疾病的人,如帕金森氏症或直立性低血压(OH)。在研究大脑功能的不同方式中,功能近红外光谱(fNIRS)是一种神经成像方法,可光学测量脑组织中的血液动力学反应。氧合血红蛋白(HbO2)和脱氧血红蛋白(HHb)的浓度变化与脑神经活动有关。与fMRI相比,fNIRS对运动伪影的耐受性明显更高,PET,和脑电图。同时,它是便携式的,具有简单的结构和用法,更安全,而且更经济。在这篇文章中,我们系统回顾了使用fNIRS监测体位突然变化引起的脑氧合变化的历史及其与血压变化的关系。首先,介绍了基于fNIRS的脑血流动力学监测原理及其优缺点。然后,描述了使用fNIRS对姿势变化导致的血压变化的研究。据观察,只有58%的参考文献得出结论,脑氧合变化与血压变化之间存在正相关。同时,3%呈负相关,39%没有显示它们之间的相关性。
    Postural change from supine or sitting to standing up leads to displacement of 300 to 1000 mL of blood from the central parts of the body to the lower limb, which causes a decrease in venous return to the heart, hence decrease in cardiac output, causing a drop in blood pressure. This may lead to falling down, syncope, and in general reducing the quality of daily activities, especially in the elderly and anyone suffering from nervous system disorders such as Parkinson\'s or orthostatic hypotension (OH). Among different modalities to study brain function, functional near-infrared spectroscopy (fNIRS) is a neuroimaging method that optically measures the hemodynamic response in brain tissue. Concentration changes in oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (HHb) are associated with brain neural activity. fNIRS is significantly more tolerant to motion artifacts compared to fMRI, PET, and EEG. At the same time, it is portable, has a simple structure and usage, is safer, and much more economical. In this article, we systematically reviewed the literature to examine the history of using fNIRS in monitoring brain oxygenation changes caused by sudden changes in body position and its relationship with the blood pressure changes. First, the theory behind brain hemodynamics monitoring using fNIRS and its advantages and disadvantages are presented. Then, a study of blood pressure variations as a result of postural changes using fNIRS is described. It is observed that only 58 % of the references concluded a positive correlation between brain oxygenation changes and blood pressure changes. At the same time, 3 % showed a negative correlation, and 39 % did not show any correlation between them.
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  • 文章类型: Journal Article
    暂无摘要。
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  • 文章类型: Review
    背景:子宫平滑肌瘤是激素依赖性良性肿瘤,通常在绝经后由于卵巢类固醇的减少而开始缩小。妊娠对子宫肌瘤大小的影响尚不清楚。这里,我们介绍了一个巨大子宫平滑肌瘤分娩后自发消退的病例。
    方法:一名40岁的女性,表现为多发性子宫平滑肌瘤,其中之一是巨大的子宫平滑肌瘤(直径约8厘米),分娩后逐渐缩小。产后两个多月时,大型肌层平滑肌瘤已经转化为粘膜下平滑肌瘤,产后3年多,粘膜下平滑肌瘤和多发性壁内平滑肌瘤均完全消退。
    结论:巨大子宫平滑肌在分娩后自发消退是罕见的。考虑到子宫平滑肌瘤消退,直到产后3年以上,在没有子宫肌瘤相关并发症的情况下,我们需要在产后观察子宫肌瘤的消退时间更长。此外,它将为未来子宫平滑肌瘤的治疗选择提供新的见解。
    BACKGROUND: Uterine leiomyomas are hormone-dependent benign tumors and often begin to shrink after menopause due to the reduction in ovarian steroids. The influence of pregnancy on uterine leiomyomas size remains unclear. Here, we present a case of spontaneous regression of a giant uterine leiomyoma after delivery.
    METHODS: A 40-year-old woman presented with multiple uterine leiomyomas, one of which is a giant uterine leiomyomas (approximately 8 cm in diameter) that gradually shrinked after delivery. At over two months postpartum, the large myometrial leiomyoma had transformed into a submucosal leiomyoma, and over 3 years postpartum, both the submucosal leiomyoma and multiple intramural leiomyomas completely regressed.
    CONCLUSIONS: Spontaneous regression of a giant uterine leiomyom is rare after delivery. Considering uterine leiomyoma regression until over 3 year postpartum,we need to observe the regression of uterine fibroid for a longer time postpartum in the absence of fibroid related complications. In addition, it will provide new insights for treatment options of uterine leiomyomas in the future.
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  • 文章类型: Meta-Analysis
    使用机器学习(ML)算法可以识别未破裂的颅内动脉瘤(UIA)。这可能是一个拯救生命的策略,尤其是高危人群。为了更好地理解ML算法在实践中的重要性和有效性,我们进行了系统评价和荟萃分析以预测脑动脉瘤破裂风险.PubMed,Scopus,WebofScience,直到2023年3月20日,Embase才被无限制地搜索。合格标准包括在DSA确认的脑动脉瘤患者中使用ML方法的研究,CTA,或MRI。在包括的35项研究中,33人是队列,11使用数字减影血管造影(DSA)作为参考成像模式。大脑中动脉(MCA)和大脑前动脉(ACA)是动脉瘤血管受累最常见的位置-51%和40%,分别。在48%的研究中,动脉瘤的形态是囊状的。37项研究中有10项(27%)使用了深度学习技术,如CNN和ANN。对17项研究进行了荟萃分析:敏感性为0.83(95%置信区间(CI),0.77-0.88);特异性为0.83(95%CI,0.75-0.88);阳性DLR为4.81(95%CI,3.29-7.02),阴性DLR为0.20(95%CI,0.14-0.29);诊断评分为3.17(95%CI,2.55-3.78);比值比为23.69(95%CI,12.75-44.01)。ML算法可以有效预测脑动脉瘤破裂的风险,具有良好的准确性,灵敏度,和特异性。然而,需要进一步的研究来提高其在预测IA破裂状态方面的诊断能力。
    It is possible to identify unruptured intracranial aneurysms (UIA) using machine learning (ML) algorithms, which can be a life-saving strategy, especially in high-risk populations. To better understand the importance and effectiveness of ML algorithms in practice, a systematic review and meta-analysis were conducted to predict cerebral aneurysm rupture risk. PubMed, Scopus, Web of Science, and Embase were searched without restrictions until March 20, 2023. Eligibility criteria included studies that used ML approaches in patients with cerebral aneurysms confirmed by DSA, CTA, or MRI. Out of 35 studies included, 33 were cohort, and 11 used digital subtraction angiography (DSA) as their reference imaging modality. Middle cerebral artery (MCA) and anterior cerebral artery (ACA) were the commonest locations of aneurysmal vascular involvement-51% and 40%, respectively. The aneurysm morphology was saccular in 48% of studies. Ten of 37 studies (27%) used deep learning techniques such as CNNs and ANNs. Meta-analysis was performed on 17 studies: sensitivity of 0.83 (95% confidence interval (CI), 0.77-0.88); specificity of 0.83 (95% CI, 0.75-0.88); positive DLR of 4.81 (95% CI, 3.29-7.02) and the negative DLR of 0.20 (95% CI, 0.14-0.29); a diagnostic score of 3.17 (95% CI, 2.55-3.78); odds ratio of 23.69 (95% CI, 12.75-44.01). ML algorithms can effectively predict the risk of rupture in cerebral aneurysms with good levels of accuracy, sensitivity, and specificity. However, further research is needed to enhance their diagnostic performance in predicting the rupture status of IA.
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  • 文章类型: Journal Article
    现代基因分型技术的出现彻底改变了动物育种中的基因组选择。大型标记数据集显示了传统基因组预测方法在灵活性方面的几个缺点,准确度,和计算能力。最近,机器学习模型在动物育种中的应用由于其巨大的灵活性和在大型嘈杂数据集中捕获模式的能力而获得了极大的兴趣。这里,我们对一些机器学习算法及其在基因组预测中的应用进行了概述,以提供其在基因组估计育种值估计中的性能的元图,基因型插补,和特征选择。最后,我们讨论了机器学习模型在发展中国家基因组预测中的潜在应用。审查的研究结果表明,机器学习模型在一些研究中确实在拟合大型嘈杂数据集和建模次要非加性效应方面表现良好。然而,有时传统方法优于机器学习模型,这证实了基因组预测没有通用的方法。总之,机器学习模型在从单核苷酸多态性数据集中提取模式方面具有巨大的潜力。尽管如此,由于数据限制,它们在动物育种中的采用水平仍然很低,复杂的遗传相互作用,缺乏标准化和可重复性,以及在使用生物数据进行训练时缺乏机器学习模型的可解释性。因此,在基因组预测中,与传统方法相比,机器学习方法没有显著的优势。因此,应该进行更多的研究,以发现可以增强牲畜育种计划的新见解。
    The advent of modern genotyping technologies has revolutionized genomic selection in animal breeding. Large marker datasets have shown several drawbacks for traditional genomic prediction methods in terms of flexibility, accuracy, and computational power. Recently, the application of machine learning models in animal breeding has gained a lot of interest due to their tremendous flexibility and their ability to capture patterns in large noisy datasets. Here, we present a general overview of a handful of machine learning algorithms and their application in genomic prediction to provide a meta-picture of their performance in genomic estimated breeding values estimation, genotype imputation, and feature selection. Finally, we discuss a potential adoption of machine learning models in genomic prediction in developing countries. The results of the reviewed studies showed that machine learning models have indeed performed well in fitting large noisy data sets and modeling minor nonadditive effects in some of the studies. However, sometimes conventional methods outperformed machine learning models, which confirms that there\'s no universal method for genomic prediction. In summary, machine learning models have great potential for extracting patterns from single nucleotide polymorphism datasets. Nonetheless, the level of their adoption in animal breeding is still low due to data limitations, complex genetic interactions, a lack of standardization and reproducibility, and the lack of interpretability of machine learning models when trained with biological data. Consequently, there is no remarkable outperformance of machine learning methods compared to traditional methods in genomic prediction. Therefore, more research should be conducted to discover new insights that could enhance livestock breeding programs.
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  • 文章类型: Systematic Review
    不必要的延长住院时间(LOS)会增加医院获得性并发症的风险,发病率,和全因死亡率,需要得到承认和积极解决。
    本系统评价旨在确定有效的预测变量和方法,用于预测所有住院患者,特别是普通医学(GenMed)住院患者的长期LOS风险。
    自2010年以来发布的LOS预测工具在五个主要研究数据库中被确定。主要结果是模型性能指标,预测变量,和验证级别。对已验证的模型进行Meta分析。使用PROBAST检查表评估偏倚风险。
    总的来说,确定了25项所有入院研究和14项GenMed研究。统计和机器学习方法在两组中几乎相等地使用。校准指标不经常报告,39项研究中只有2项进行了外部验证。所有入院验证研究的荟萃分析显示,曲线下面积的θ为0.596至0.798的95%预测间隔。重要的预测指标类别是合并症诊断和疾病严重程度风险评分,人口统计,和录取特点。由于数据处理和分析报告不佳,总体研究质量被认为较低。
    据我们所知,这是首次评估GenMed和所有入院组的住院LOS风险预测模型质量的系统评价.值得注意的是,机器学习和统计建模都表现出良好的预测性能,但模型很少经过外部验证,总体研究质量较差.往前走,在临床应用之前,需要通过采用现有指南和外部验证来关注质量方法.
    https://www.crd.约克。AC.英国/PROSPERO/,标识符:CRD42021272198。
    UNASSIGNED: Unwarranted extended length of stay (LOS) increases the risk of hospital-acquired complications, morbidity, and all-cause mortality and needs to be recognized and addressed proactively.
    UNASSIGNED: This systematic review aimed to identify validated prediction variables and methods used in tools that predict the risk of prolonged LOS in all hospital admissions and specifically General Medicine (GenMed) admissions.
    UNASSIGNED: LOS prediction tools published since 2010 were identified in five major research databases. The main outcomes were model performance metrics, prediction variables, and level of validation. Meta-analysis was completed for validated models. The risk of bias was assessed using the PROBAST checklist.
    UNASSIGNED: Overall, 25 all admission studies and 14 GenMed studies were identified. Statistical and machine learning methods were used almost equally in both groups. Calibration metrics were reported infrequently, with only 2 of 39 studies performing external validation. Meta-analysis of all admissions validation studies revealed a 95% prediction interval for theta of 0.596 to 0.798 for the area under the curve. Important predictor categories were co-morbidity diagnoses and illness severity risk scores, demographics, and admission characteristics. Overall study quality was deemed low due to poor data processing and analysis reporting.
    UNASSIGNED: To the best of our knowledge, this is the first systematic review assessing the quality of risk prediction models for hospital LOS in GenMed and all admissions groups. Notably, both machine learning and statistical modeling demonstrated good predictive performance, but models were infrequently externally validated and had poor overall study quality. Moving forward, a focus on quality methods by the adoption of existing guidelines and external validation is needed before clinical application.
    UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021272198.
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  • 文章类型: Review
    骨巨细胞瘤(GCT)是一种局部侵袭性原发性骨肿瘤,很少会转移。主要出现在年轻的成年人长骨的骨phy,肿瘤由与破骨细胞(OLGC)混合的单核细胞组成,其分别表达RANK配体和RANK。Denosumab是一种针对RANK配体的单克隆抗体,已被证明可以通过抑制RANKL引起骨溶解来减少肿瘤。本文介绍了11例接受denosumab治疗的GCT患者的组织学变化。
    本研究纳入了11例接受新辅助治疗的GCT患者的临床记录和切片。治疗前和治疗后GCT标本的评估由两名病理学家(RK和VM)进行。有4名男性和7名女性。他们的平均年龄是30岁。所有患者每周皮下接受120mg地诺塞马,在治疗的第8天和第15天额外接受120mg。回顾了组织学切片,并指出以下几点:1)骨化程度,2)纤维化,3)破骨细胞巨细胞丢失,4)单核细胞增殖,5)非典型性,6)恶性细胞对类骨质的渗透。
    在11例病例中,2例没有显示任何显著的组织学改善。7例巨细胞减少,纤维化增加,增强单核细胞增殖和骨化与病理反应一致。在2例表现为骨肉瘤的转化中发现了异型和类骨渗透。
    Denosumab治疗的巨细胞瘤显示出戏剧性的组织学变化。治疗后病变可能与治疗前病变没有相似之处。可能有完全缓解或可能与良性或恶性病变混淆。病理学家必须意识到这些变化以防止诊断陷阱,因为它具有治疗和预后意义。
    Giant cell tumor (GCT) of the bone is a locally aggressive primary bone tumor, that can rarely metastasize. Arising mostly in epiphysis of the long bones in young adults, the tumor is composed of mononuclear cells that are admixed with osteoclastic giant cells(OLGCs), which express RANK ligand and RANK respectively. Denosumab a monoclonal antibody against RANK ligand has been shown to reduce the tumor by causing bone lysis by inhibiting RANKL. Histological changes in 11 patients of GCT who were treated with denosumab are presented here.
    Clinical records and slides of 11 patients of GCT who had been administered neoadjuvant denosumab were included in the study. Evaluation of pre and post therapy GCT specimens was performed by two pathologists (RK and VM). There were 4 males and 7 females. Their mean age was 30 years. All the patients received 120 mg denosumab subcutaneously every week with additional 120 mg on days 8 and 15 of therapy. The histological slides were reviewed and following points noted: 1) degree of ossification,2) fibrosis,3) loss of osteoclastic giant cells,4) proliferation of mononuclear cells,5) atypia,6) Permeation of osteoid by malignant cells.
    Out of 11 cases, 2 cases did not show any significant histological improvement. 7 cases showed reduction in giant cells, increased fibrosis, enhanced mononuclear cell proliferation and ossification consistent with a pathological response. Atypia and osteoid permeation were noted in 2 cases which showed transformation to osteosarcoma.
    Denosumab treated giant cell tumor show dramatic histological changes. The post therapy lesions may bear no resemblance to pretherapy lesion. There may be complete resolution or may be confused with benign or malignant lesions Rarely they may show sarcomatous transformation. It is imperative that the pathologist is aware of these changes to prevent diagnostic pitfalls as it poses therapeutic and prognostic implications.
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