纤溶酶原激活物抑制剂-1启动子基因多态性与静脉血栓栓塞症的相关性研究

目的：探讨中国汉族人群纤溶酶原激活物抑制剂PAI-1启动子4G/5G基因多态性与静脉血栓栓塞症（VTE）发病的相关性。方法：采用病例-对照研究,收集南京鼓楼医院2016年1月～2018年3月VTE患者160例及正常人群160例,应用聚合酶链反应测定PAI-1启动子区域的4G/5G的多态性。结果：PAI-1基因4G/5G三种基因型4G/4G型、4G/5G型、5G/5G型在VTE组的分布频率为42.50%、35.00%、22.50%,对照组分布频率为17.50%、43.12%、39.38%,VTE组与对照组4G/4G基因型分布差异具有统计学意义（P<0.05）;通过非条件Logistic回归模型校正后,PAI-1 4G/4G基因型（OR=3.398,95% CI=2.025～5.702,P=0.000）、吸烟（OR=1.447,95% CI=1.022～2.049,P=0.037）是VTE的独立危险因素。结论：VTE组PAI-1 4G/4G基因型频率较正常人群高,证实了4G/4G基因型与静脉血栓栓塞发病有相关性,且为独立危险因素。     

临床药师参与1例新生儿股动脉血栓栓塞病例的临床实践

目的 通过临床药师参与1例新生儿股动脉血栓栓塞病例的临床治疗实践,加强对新生儿血栓栓塞症的认识,制定合理的抗栓治疗方案。方法 临床药师查阅相关文献指南,参与制定和优化患儿抗栓治疗方案,评估药物风险/收益比,并提供药学监护。结果 在临床药师和临床医生共同制定的抗栓治疗方案下,患儿血栓栓塞症得到良好的治疗效果,用药过程中未发生不良反应。结论 临床药师参与罕见病的临床治疗,保障了患儿用药的安全性、有效性。     

依度沙班预防骨科大手术后静脉血栓栓塞的meta分析

目的 比较依度沙班与低分子肝素预防骨科大手术后静脉血栓栓塞（venous thromboembolism,VTE）的有效性和安全性。方法 检索Cochrane Library、PubMed、EMBASE、中国知网、万方和维普科技期刊等数据库。收集依度沙班与低分子肝素预防骨科大手术后VTE随机对照试验。应用RevMan 5.3.5软件进行分析。结果 最终纳入5项研究,涉及2 585例患者。依度沙班组总VTE发生率[RR=0.47,95% CI（0.38,0.56）,P<0.000 01]、无症状性深静脉血栓发生率[RR=0.47,95% CI（0.31,0.71）,P=0.000 4]均低于低分子肝素组。依度沙班组总出血事件发生率高于低分子肝素组[RR=1.22,95% CI（1.01,1.49）,P=0.04]。亚组分析发现依度沙班不同剂量组总VTE发生率均低于低分子肝素组,15 mg组、30 mg组与低分子肝素组总出血事件发生率差异均无统计学意义。结论 依度沙班预防骨科大手术后VTE优于低分子肝素,但增加了总出血事件发生率。15,30 mg依度沙班可能为较安全剂量。     

Cardiovascular safety of oncologic agents: A double-edged sword even in the era of targeted therapies – part 1

Introduction: Patients with cancer are subject to the cardiotoxic effects of cancer therapy and as more patients survive cancer due to improved treatment they are exposed to various forms of cardiovascular (CV) disease as they age, and vice-versa. Such an interplay of age with both malignancy and CV disease may contribute to increased morbidity and mortality.

Areas covered: This two-part review considers the effects of cancer drug treatment on the CV system. In Part I, the various types of CV and cardiometabolic toxicity of anti-cancer drugs and the possible mechanisms involved are discussed. Also, among the specific oncologic agents, the CV effects of the classical agents and of the large molecule immunological agents (monoclonal antibodies, including immune checkpoint inhibitors) are detailed.

Expert opinion: Oncologic agents produce a variety of CV adverse effects, including cardiomyopathy and heart failure, peri-myocarditis, coronary artery disease, peripheral vascular disease, hypertension (HTN), cardiac arrhythmias, valvular heart disease, and pulmonary HTN. Both the oncologist and the cardiologist need to be aware of such adverse effects and of the specific agents that produce them. They need to join forces to prevent, anticipate, recognize, and manage such complications.     

Cardiovascular safety of oncologic agents: a double-edged sword even in the era of targeted therapies – Part 2

Introduction: Patients with cancer are subject to the cardiotoxic effects of cancer therapy. Improved cancer treatments lead to more cancer-survivors, who though are exposed to various forms of cardiovascular (CV) disease (CVD) as they age. Aging patients are at increased risk of developing both malignancy and CVD or they may have survived some form of CVD as a result of effective CV treatments. Furthermore, patients with CVD may develop cancer and require treatment (and vice versa), all contributing to increased morbidity and mortality. The prevalence of both malignancy and CVD will increase due to the trend toward a longer lifespan.

Areas covered: In part 2 of this review, the discussion of the CV effects of specific oncology drugs is completed with inclusion of additional immunological agents, current hormonal and other agents. Early detection and monitoring of cardiotoxicity, use of biomarkers and other imaging and diagnostic methods and prevention and treatment options are also discussed.

Expert opinion: As outlined in part 1 of this review, oncologists need to be aware of the CV adverse-effects of their treatments and make careful and expectant clinical decisions, especially in patients with preexisting CVD or CV risk factors. Similarly, cardiologists should consider a detailed previous history of treatment for malignant disease, including prior chemotherapy exposure, dose(s) received, and/or combined modality therapy with chest radiotherapy. Both specialists should collaborate in order to minimize the impact of these two ubiquitous diseases (cancer and CVD) and mitigate the adverse effects of treatment modalities.     

Identifying mutation‐driven changes in gene functionality that lead to venous thromboembolism

Venous thromboembolism (VTE) is a common hematological disorder. VTE affects millions of people around the world each year and can be fatal. Earlier studies have revealed the possible VTE genetic risk factors in Europeans. The 2018 Critical Assessment of Genome Interpretation (CAGI) challenge had asked participants to distinguish between 66 VTE and 37 non‐VTE African American (AA) individuals based on their exome sequencing data. We used variants from AA VTE association studies and VTE genes from DisGeNET database to evaluate VTE risk via four different approaches; two of these methods were most successful at the task. Our best performing method represented each exome as a vector of predicted functional effect scores of variants within the known genes. These exome vectors were then clustered with k‐means. This approach achieved 70.8% precision and 69.7% recall in identifying VTE patients. Our second‐best ranked method had collapsed the variant effect scores into gene‐level function changes, using the same vector clustering approach for patient/control identification. These results show predictability of VTE risk in AA population and highlight the importance of variant‐driven gene functional changes in judging disease status. Of course, more in‐depth understanding of AA VTE pathogenicity is still needed for more precise predictions.     

The impact of antipsychotics as a risk factor for thromboembolism

Patients with schizophrenia are predisposed toward developing cardiovascular disease. Although neuroleptics affect the cardiovascular system, it is also important to consider the consequences of the disease itself such as lower physical activity due to living on disability pension, inadequate nutrition, and/or nicotine addiction, being more common among patients with schizophrenia versus the general population. All these factors combined lead to an increased risk of death caused by cardiovascular conditions in schizophrenic patients. Individuals receiving typical antipsychotic drugs have been reported to have elevated concentrations of antiphospholipid antibodies, including anticoagulants and anticardiolipin antibodies. The presence of both antibodies is associated with an increased risk for thromboembolism. It is also likely that mental illness is accompanied by increased procoagulant activity. Patients with acute psychosis have been shown to have a statistically significant increase in the concentrations of D-dimer, P-selectin, and in the expression of platelet glycoprotein IIb/IIIa receptors. Learning about causes and mechanisms of venous thromboembolism could help to reduce or neutralize the adverse effects of antipsychotic treatment and facilitate the identification of appropriate markers necessary to monitor changes and provide preventive care against hazardous and potentially fatal complications such as deep venous thrombosis and pulmonary embolism. Before atypical neuroleptic treatment is administered to hospitalized patients, all possible risk factors for thromboembolism should be considered to allow the application of lower risk drugs. Also, other preventive measures should be taken into account, including hydration, compression stockings, regular exercise of lower extremities, and low-molecular-weight heparin injections.     

What Impact Does Venous Thromboembolism and Bleeding Have on Cancer Patients’ Quality of Life?

Background

Venous thromboembolism (VTE) is common in cancer patients and its treatment is associated with a high risk of recurrent VTE (rVTE) and bleeding.

平阳霉素和泼尼松龙及鱼肝油酸钠联合注射治疗颌面部静脉畸形60例报道

目的：评价平阳霉素和泼尼松龙及鱼肝油酸钠联合注射治疗颌面部静脉畸形的疗效。方法：采用平阳霉素和泼尼松龙及鱼肝油酸钠联合病变内注射治疗60例颌面部静脉畸形患者。1周注射1次，3-5次为1个疗程，治疗结束后对疗效进行评价。结果：60例患者平均疗程3周，治疗完成后随访0．5～2a，治愈和显效率达94％，有效率为100％。结论：平阳霉素和泼尼松龙及鱼肝油酸钠联合注射治疗颌面部静脉畸形安全、廉价、高效、简便，疗程适中。     

Diagnosis and management of venous malformations: An overview

Venous malformations pose some of the most difficult challenges in the practice of medicine today. Clinical manifestations of these lesions are extremely protean. Because of the rarity of these lesions, most clinicians have limited experience in their diagnosis and management, which augments the enormity of the problem and can lead to misdiagnoses, inadequate treatment, high complication rates, and poor patient outcomes. Vascular malformations are best treated in medical centers where patients with these maladies are seen regularly and the team approach is used. The occasional embolizer will never gain enough experience to treat these problematic lesions adequately. More importantly, when complications do occur, the morbidity of that complication is worsened because of this lack of experience and the absence of an experienced team of physicians. All too frequently, the patient ultimately pays for a physician＇ s initial enthusiasm, inexperience, folly, and lack of necessary clinician backup. A cavalier approach to the management of venous malformations will always lead to significant complications and dismal patient outcomes. These patients should be referred to centers that regularly treat vascular malformations, appropriately manage complications in a timely manner, and routinely deal with the dilemmas they present. Only in this fashion can significant experience be gained, improved judgment in managing these lesions develop, and definitive appropriate statements in the treatment of vascular anomalies evolve.