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Longitudinal strain analysis allows the identification of subclinical deterioration of right ventricular function in patients with cancer therapy-related left ventricular dysfunction. 纵向应变分析可以识别与癌症治疗相关的左心室功能障碍患者的右心室功能亚临床恶化。
Pub Date : 2019-06-27 DOI: 10.15190/d.2019.7
Diana Alexandra Cherata, Ionuț Donoiu, Rodica Diaconu, Adina Glodeanu, Doina Cârstea, Constantin Militaru, Octavian Istrătoaie

Background: This study was designed to assess right ventricular systolic function in cancer patients.

Methods and results: 68 consecutive patients receiving potentially cardiotoxic agents were followed for 6 months in a single-center, observational, cohort-study. Left ventricle and free-wall right ventricular longitudinal strain were analyzed prior and after 6 months of treatment, using a vendor-independent software, together with left ventricle ejection fraction, tricuspid annulus plane systolic excursion and right ventricular fractional area change. Cancer therapy-related cardiac dysfunction was defined as a left ventricle ejection fraction drop of >10% to <53%. Both left ventricle ejection fraction (59±7% vs. 55±8%, p<0.0001) and left ventricle longitudinal strain (-19.7±2.5% vs. -17.1±2.6%, p<0.0001) were reduced at follow up, along with free-wall right ventricular longitudinal strain (-24.9±4.5% vs. -21.6±4.9%, p<0.0001). Cancer therapy-related cardiac dysfunction was detected in 20 patients (29%). In 15 out of these 20 patients (75%), a concomitant relative reduction in free-wall right ventricular longitudinal strain magnitude by 17±7% was detected. Moreover, there was a significant correlation between left ventricle and free-wall right ventricular longitudinal strain at follow-up examinations (r=0.323, p<0.0001). A relative drop of right ventricular longitudinal strain >17% had a sensitivity of 55% and a specificity of 70% (AUC=0.75, 0.7-0.8, 95% CI) to identify patients with cancer treatment related cardiac dysfunction. Neither tricuspid annulus plane systolic excursion (24±5 vs. 23±4 mm, p=0.07), nor right ventricular fractional area change (45±8% vs. 44±7%, p=0.6) showed any significant change between examinations.

Conclusions: Longitudinal strain analysis allows the identification of subclinical right ventricular dysfunction appearing in the course of cancer treatment when conventional indices of right ventricular dysfunction function are unaffected.

背景:本研究旨在评估癌症患者的右心室收缩功能。方法和结果:在一项单中心、观察性、队列研究中,对68例连续接受潜在心脏毒性药物治疗的患者进行了为期6个月的随访。使用独立于供应商的软件分析治疗前后6个月左心室和自由壁右心室纵向应变,以及左心室射血分数、三尖瓣环平面收缩偏移和右心室分数面积变化。癌症治疗相关心功能障碍定义为左心室射血分数下降>10%至17%,识别癌症治疗相关心功能障碍患者的敏感性为55%,特异性为70% (AUC=0.75, 0.7-0.8, 95% CI)。三尖瓣环平面收缩偏移(24±5 vs. 23±4 mm, p=0.07)和右心室分数面积变化(45±8% vs. 44±7%,p=0.6)在两次检查之间均无显著变化。结论:纵向应变分析可以在常规右室功能指标未受影响的情况下识别癌症治疗过程中出现的亚临床右室功能障碍。
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引用次数: 11
Immunomodulatory Drugs in Melanoma Brain Metastases. 黑色素瘤脑转移中的免疫调节药物。
Pub Date : 2019-06-26 DOI: 10.15190/d.2019.6
Gil Nuno Castro Fernandes

Brain metastases are about ten times more frequent than a brain primary tumor, being present in 20-40% of adults with systemic cancer. Together with lung cancer and breast cancer, skin cancers such as melanoma are top primary tumors which metastasizes to the brain. Advanced melanoma is well known for its propensity to metastasize to the brain, with 80% of patients presenting brain metastasis at the autopsy. However, current therapies are not very efficient and brain metastases are in most of the cases lethal. Treatment of melanoma brain metastases with surgery and/or radiation therapy results in a median overall survival of only about four months after diagnosis. New immunotherapies such as targeted or immunomodulatory drugs, many in clinical trials, have shown promise, with some immunomodulatory drugs being able to at least double the overall survival rates for patients with melanoma brain metastases. This review focuses on the recent advances and future potential of using immunotherapy, such as the newly developed immunomodulatory drugs, for melanoma brain metastases therapy. Immunomodulatory drugs bring a great promise as new tools for melanoma treatment in particular and for the treatment of other types of malignancies in general.

脑转移的发生率约为脑原发肿瘤的 10 倍,20%-40% 的成人全身性癌症患者都会发生脑转移。与肺癌和乳腺癌一样,黑色素瘤等皮肤癌也是转移到脑部的首要原发肿瘤。众所周知,晚期黑色素瘤容易转移到脑部,80%的患者在尸检时会出现脑转移。然而,目前的疗法并不十分有效,在大多数情况下,脑转移是致命的。通过手术和/或放疗治疗黑色素瘤脑转移瘤,确诊后的中位总生存期仅为四个月左右。新的免疫疗法,如靶向药物或免疫调节药物(许多已进入临床试验阶段),已显示出良好的前景,其中一些免疫调节药物可使黑色素瘤脑转移患者的总生存率至少提高一倍。本综述将重点介绍使用免疫疗法(如新开发的免疫调节药物)治疗黑色素瘤脑转移的最新进展和未来潜力。免疫调节药物作为治疗黑色素瘤以及其他类型恶性肿瘤的新工具,具有广阔的前景。
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引用次数: 0
A case study for the use of medical cannabis in generalized anxiety disorder. 在广泛性焦虑症中使用医用大麻的案例研究。
Pub Date : 2019-06-12 DOI: 10.15190/d.2019.5
Chad Walkaden

Despite the increasing prevalence and acceptance of the medical cannabis use among the general public, the evidence required by physicians to use cannabis as a treatment is generally lacking. Research on the health effects of cannabis and cannabinoids has been limited worldwide, leaving patients, health care professionals, and policymakers without the evidence they need to make sound decisions regarding the use of cannabis and cannabinoids. This case study outlines an intervention that involved a patient integrating medical cannabis into her treatment to better manage a generalized anxiety disorder and the debilitating symptoms of vertigo. This case demonstrates how the patient drastically improved her quality of life and reinforces the need for more rigorous testing on the use of medical cannabis to support patients and better manage the symptoms associated with their medical conditions.

尽管公众对医用大麻的使用越来越普遍和接受,但医生使用大麻作为一种治疗手段所需的证据普遍缺乏。在世界范围内,关于大麻和大麻素对健康影响的研究一直有限,这使得患者、卫生保健专业人员和政策制定者没有必要的证据,无法就大麻和大麻素的使用做出合理的决定。本案例研究概述了一项干预措施,该干预措施涉及患者将医用大麻纳入其治疗,以更好地管理广泛性焦虑症和眩晕的衰弱症状。这一案例表明,患者的生活质量得到了极大的改善,因此有必要对医用大麻的使用进行更严格的测试,以支持患者并更好地管理与其医疗状况相关的症状。
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引用次数: 0
Immunotherapy for Breast Cancer: First FDA Approved Regimen. 乳腺癌免疫治疗:FDA批准的首个方案
Pub Date : 2019-03-31 DOI: 10.15190/d.2019.4
Georgiana R Soare, Costin A Soare

1 in 8 women will be affected by breast cancer, which is the most diagnosed malignancy among women. Although breast cancer was regarded as "immunologically cold", recent studies demonstrate that immunotherapy can be successful employed in combination regimens for the treatment of triple negative breast cancer, an aggressive type of breast cancer without many treatment options available. In March 2019, the US Food and Drug Administration granted accelerated approval for the first immunotherapy-based regimen comprising atezolizumab in combination with protein-bound paclitaxel for patients with advanced metastatic TNBC, expressing programmed cell death-ligand 1 (PD-L1) and without previous systemic treatment for metastatic disease. This immunotherapy-based regimen is not only a promising therapy for the TNBC patients, but it also represents an inspiring proof of concept for the development of more efficient advanced immunotherapy-based strategies for breast cancer treatment in the future.

每8名女性中就有1人会患乳腺癌,这是女性中诊断最多的恶性肿瘤。虽然乳腺癌被认为是“免疫冷淡”,但最近的研究表明,免疫疗法可以成功地用于治疗三阴性乳腺癌的联合方案,三阴性乳腺癌是一种侵袭性乳腺癌,没有许多治疗方案可供选择。2019年3月,美国食品和药物管理局(fda)加速批准了首个基于免疫治疗的方案,该方案包括atezolizumab与蛋白结合紫杉醇联合用于晚期转移性TNBC患者,表达程序性细胞死亡配体1 (PD-L1),先前未接受转移性疾病的全身治疗。这种基于免疫疗法的方案不仅对TNBC患者是一种有希望的治疗方法,而且它也代表了一个鼓舞人心的概念证明,为未来开发更有效的基于免疫疗法的乳腺癌治疗策略。
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引用次数: 19
Therapy-induced cardiotoxicity in breast cancer patients: a well-known yet unresolved problem. 乳腺癌患者治疗引起的心脏毒性:一个众所周知但尚未解决的问题。
Pub Date : 2019-03-31 DOI: 10.15190/d.2019.2
Diana Ruxandra Florescu, Diana Elena Nistor

Breast cancer is the second most commonly diagnosed cancer, being one of the main health issues that needs to be addressed worldwide. New therapies have led to a remarkable increase in survival rates, which is unfortunately overshadowed by their negative impact on cardiac structure and function in disease-free patients. Since anthracyclines and trastuzumab cause the most undesired outcome in breast cancer patients - cardiac-related mortality, they have been widely studied. However, other therapies (such as hormonal therapy, tyrosine kinase inhibitors, anti-VEGF drugs etc.) can also affect the cardiovascular system and lead to ischemia, hypertension or vascular thromboembolism. Even though excessive research has been conducted in thepast decades, there are still no guidelines regarding the most adequate methods neither to detect and prevent severe cardiotoxicity that can finally lead to heart failure and ultimately death nor for the further management of patients after cardiotoxicity is detected. Biomarkers of ischemia (troponins T and I) and of overload (BNP and NT-proBNP) in association with periodic echocardiographies (assessment of the global longitudinal strain) are two of the most important means used by physicians in the evaluation of cardiac disease in this group of patients. Given that no internationally accepted guidelines for screening and surveillance of different populations exist, the cardio-oncology team is crucial in the management of these patients, their collaboration resulting in individualized treatment regimens. After careful evaluation of different variables (treatment effects, malignancy status, and the patient's pre-existing conditions), a decision is made to either reduce the dosage or rate of administration, change the medication or interrupt the treatment and initiate the cardioprotective therapeutic associations. Consequently, it is an absolute necessity the development of customized treatment guidelines and the conduction of multiple clinical studies in order to demonstrate their effect on long-term survival.

乳腺癌是第二大最常诊断出的癌症,也是全世界需要解决的主要健康问题之一。新疗法使患者的存活率显著提高,但不幸的是,这些疗法对无病症患者的心脏结构和功能造成的负面影响却掩盖了这一成果。由于蒽环类和曲妥珠单抗会导致乳腺癌患者最不希望出现的结果--与心脏相关的死亡,因此它们被广泛研究。然而,其他疗法(如激素疗法、酪氨酸激酶抑制剂、抗血管内皮生长因子药物等)也会影响心血管系统,导致缺血、高血压或血管血栓栓塞。尽管在过去几十年中进行了大量研究,但仍然没有关于最适当的方法的指导方针,既不能检测和预防严重的心脏毒性,这种毒性最终会导致心力衰竭和死亡,也不能在检测到心脏毒性后对患者进行进一步管理。缺血生物标志物(肌钙蛋白 T 和 I)和负荷过重生物标志物(BNP 和 NT-proBNP)与定期超声心动图检查(评估总体纵向应变)是医生用于评估这类患者心脏疾病的两种最重要的方法。鉴于目前还没有国际公认的针对不同人群的筛查和监测指南,心脏肿瘤团队在这些患者的管理中起着至关重要的作用,通过他们的合作可以制定出个性化的治疗方案。在对不同的变量(治疗效果、恶性肿瘤状态和患者的原有疾病)进行仔细评估后,决定减少用药剂量或用药速度、更换药物或中断治疗并启动心脏保护治疗联合疗法。因此,绝对有必要制定个性化的治疗指南,并开展多项临床研究,以证明其对长期生存的影响。
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引用次数: 0
Biomimetic Scaffolds in Skeletal Muscle Regeneration. 骨骼肌再生中的仿生支架。
Pub Date : 2019-03-31 DOI: 10.15190/d.2019.3
Greta D Mulbauer, Howard W T Matthew

Skeletal muscle tissue has inherent capacity for regeneration in response to minor injuries. However, in the case of severe trauma, tumor ablations, or in congenital muscle defects, these myopathies can cause irreversible loss of muscle mass and function, a condition referred to as volumetric muscle loss (VML). The natural muscle repair mechanisms are overwhelmed, prompting the search for new muscle regenerative strategies, such as using biomaterials that can provide regenerative signals to either transplanted or host muscle cells. Recent studies involve the use of suitable biomaterials which may be utilized as a template to guide tissue reorganization and ultimately provide optimum micro-environmental conditions to cells. These strategies range from approaches that utilize biomaterials alone to those that combine materials with exogenous growth factors, and ex vivo cultured cells. A number of scaffold materials have been used in the development of grafts to treat VML. In this brief review, we outline the natural skeletal regeneration process, available treatments used in the clinic for muscle injury and promising tissue bioengineering and regenerative approaches for muscle loss treatment.

骨骼肌组织在轻微损伤后具有固有的再生能力。然而,在严重创伤、肿瘤消融或先天性肌肉缺陷的情况下,这些肌病会导致肌肉质量和功能的不可逆转的损失,这种情况被称为体积性肌肉损失(VML)。自然肌肉修复机制被淹没,促使人们寻找新的肌肉再生策略,例如使用可以向移植或宿主肌肉细胞提供再生信号的生物材料。最近的研究涉及使用合适的生物材料作为模板来指导组织重组,并最终为细胞提供最佳的微环境条件。这些策略的范围从单独利用生物材料的方法到将材料与外源性生长因子和体外培养细胞相结合的方法。许多支架材料已被用于移植治疗VML的发展。在这篇简短的综述中,我们概述了自然骨骼再生的过程,临床上用于肌肉损伤的可用治疗方法,以及有前途的组织生物工程和再生方法用于肌肉损失治疗。
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引用次数: 17
Discoveries Interview: Chad Walkaden cancer survivor on how to live a healthier and longer life while diagnosed with cancer. 发现采访:查德·沃克登癌症幸存者如何在被诊断患有癌症的情况下生活得更健康、更长寿。
Pub Date : 2019-03-20 DOI: 10.15190/d.2019.1
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引用次数: 0
The Curious Case of ZEB1. ZEB1的奇特案例。
Pub Date : 2018-12-31 DOI: 10.15190/d.2018.7
Mecca Madany, Tom Thomas, Lincoln A Edwards

The Zinc Finger E-box binding homeobox (ZEB1/TCF8 or DeltaEF1) is at the forefront of transcription factors involved in controlling epithelial-to-mesenchymal transitions (EMT). Essentially, EMT allows for the reorganization of epithelial cells to become migratory cells with a mesenchymal phenotype.  In addition to ZEB1 being involved in embryonic development, ZEB1 has also been linked to processes involving micro-RNAs, long non-coding RNAs and stem cells. In recent years there has been an accumulation of evidence with regard to ZEB1 in various cancers. Although increased ZEB1 expression has largely been associated with EMT, cancer invasion, and tumorigenicity, there have been some episodic reports that have gone against the traditional reporting of the role of ZEB1. Indicating that the function of ZEB1 and the mechanisms by which ZEB1 facilitates its activities is more complex than was once appreciated. This complexity is further exacerbated by the notion that ZEB1 can act not only as a transcriptional repressor but a transcriptional activator as well. This review seeks to shed light on the complexity of ZEB1 with respect to cancer.

锌指E-box结合同源盒(ZEB1/TCF8或DeltaEF1)是参与控制上皮-间质转化(EMT)的转录因子的前沿。本质上,EMT允许上皮细胞重组成为具有间充质表型的迁移细胞。除了ZEB1参与胚胎发育外,ZEB1还与涉及微rna、长链非编码rna和干细胞的过程有关。近年来,关于ZEB1在各种癌症中的作用的证据越来越多。尽管ZEB1表达的增加在很大程度上与EMT、癌症侵袭和致瘤性相关,但也有一些零星的报道与ZEB1的传统作用报道相反。这表明ZEB1的功能及其促进其活动的机制比以前认为的要复杂得多。ZEB1不仅可以作为转录抑制因子,还可以作为转录激活因子,这进一步加剧了这种复杂性。本综述旨在阐明ZEB1在癌症方面的复杂性。
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引用次数: 8
HER2 Oncogene Amplification and Immunohistochemical Profiling in Gastric Adenocarcinoma. 胃腺癌中HER2癌基因扩增及免疫组化分析。
Pub Date : 2018-12-31 DOI: 10.15190/d.2018.6
Nisha Raj, Divya Verma, Ashok Kumar, Praveer Rai, Ram Nawal Rao

Background and Objectives: Gastric adenocarcinoma is one of the most common malignant tumors and a major cause of cancer death worldwide, especially in developing countries. Her2/neu gene amplification and protein overexpression in breast cancer is a golden criterion for the targeted therapy with trastuzumab. However, the role of Her2 as a prognostic factor in gastric cancer is still controversial. The purpose of this study was to evaluate the frequency of Her2 oncogene overexpression and concordance between the results for Her2 protein expression and gene amplification. Materials and Methods: A total of 65 retroprospective cases with gastric adenocarcinoma, including biopsy and resected specimens obtained between July 2015 to December 2017, were analyzed. Her2/neu expression was determined by Immuno-histochemistry (IHC). Equivocal and some selected cases were submitted for FISH to detect Her2/neu gene amplification. Results: In the present study, out of 65 patients of gastric adenocarcinoma, there were 50 males and 15 females, with mean age of 54.52 years. The majority of tumors were located within the antropyloric region. We found 27 (41.4%) positivity, scored as IHC 3+ and IHC 2+, and 38 (58.3%) negativity, scored as IHC 1+ and IHC 0. We also evidentiated a significant difference between Her2/neu expression with age (p=0.010) and depth of invasion (p=0.020).Her2/neu gene was amplified only in 13 cases, 4 cases were of Her2/neu (3+) positive, 11 cases (39.3%) Her2/neu (2+) with IHC staining. The concordance rate between the results of IHC and FISH in all 18 cases was 83.3%. Conclusion: IHC detection can be carried out to guide the treatment when FISH detection cannot be performed. Overexpression of Her 2/neu in gastric adenocarcinoma could potentially be used in selecting the patients who can get benefit from the anti-Her2/neu targeted therapy.

背景与目的:胃腺癌是世界上最常见的恶性肿瘤之一,也是癌症死亡的主要原因之一,特别是在发展中国家。乳腺癌中Her2/neu基因扩增和蛋白过表达是曲妥珠单抗靶向治疗的黄金标准。然而,Her2作为胃癌预后因素的作用仍存在争议。本研究的目的是评估Her2癌基因过表达的频率以及Her2蛋白表达和基因扩增结果之间的一致性。材料与方法:回顾性分析2015年7月至2017年12月共65例胃腺癌,包括活检和切除标本。免疫组化(IHC)检测Her2/neu表达。模棱两可和部分选定的病例提交FISH检测Her2/neu基因扩增。结果:本组65例胃腺癌患者中,男性50例,女性15例,平均年龄54.52岁。大多数肿瘤位于幽门区。阳性27例(41.4%),分为IHC 3+和IHC 2+;阴性38例(58.3%),分为IHC 1+和IHC 0。我们还证实了Her2/neu的表达随年龄(p=0.010)和浸润深度(p=0.020)有显著差异。Her2/neu基因扩增仅13例,Her2/neu(3+)阳性4例,IHC染色Her2/neu(2+) 11例(39.3%)。18例患者免疫组化结果与FISH结果的符合率为83.3%。结论:在FISH无法检测的情况下,可采用免疫组化检测指导治疗。在胃腺癌中,Her2/neu的过表达可能用于选择能够从抗her2 /neu靶向治疗中获益的患者。
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引用次数: 3
Platelet-rich plasma as a site-targeted approach in wound healing: a molecular perspective. 富血小板血浆在伤口愈合中的定位方法:分子视角。
Pub Date : 2018-12-31 DOI: 10.15190/d.2018.8
Teodora Veronica Grigore, Christian Cozma

Wound healing remained an equation with multiple variables that experts in the medical field are trying to solve. The need to find an adjuvant that can quicken the healing process is increasing with every day, as longer wound healing times raise the risk of infections. Platelet-rich plasma is a promising tool promoting faster healing in a variety of wounds (thermal wounds, burn wounds, surgeries, etc.), as a series of studies present encouraging results in patients that received platelet-rich plasma treatment. The aim of this paper is to review and comment on the useful benefits and limitations of using platelet-rich plasma as an adjuvant strategy in wound healing, emphasizing on skin related wounds.

伤口愈合仍然是一个包含多个变量的方程,医学领域的专家们正试图解决这个问题。由于较长的伤口愈合时间增加了感染的风险,因此每天都需要寻找一种可以加速愈合过程的佐剂。富血小板血浆是一种很有前景的工具,可以促进各种伤口(热伤口、烧伤伤口、手术等)的更快愈合,因为一系列研究在接受富血小板血浆治疗的患者中显示出令人鼓舞的结果。本文的目的是回顾和评论使用富血小板血浆作为伤口愈合辅助策略的有用益处和局限性,重点是皮肤相关伤口。
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引用次数: 6
期刊
Discoveries (Craiova, Romania)
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