The emerging issue of cardiac dysfunction induced by antineoplastic angiogenesis inhibitors

Left ventricular dysfunction from anticancer drugs has emerged as a relevant problem in the clinical and scientific communities. Anthracycline toxicity has always been the most relevant, but with the increasing use of biological targeted therapies in treatment protocols, with an increasing number of cancer survivors, new toxicities have been increasing in more recent years. Cardiomyopathy after ErbB2 inhibitors has been intensively studied. Another important class of biological anticancer drugs are vascular endothelial growth factor (VEGF) inhibitors. VEGF signalling is crucial for vascular growth, but it also has a major impact on myocardial function. Also, it is important to note that such angiogenesis inhibitors are multitargeted in most cases, and can produce a broad spectrum of cardiovascular side effects. Here we review the mechanisms and pathophysiology of the most significant cardiotoxic effects of antiangiogenic drugs, and particular attention is drawn to LV dysfunction, discussing the assessment and management on the basis of the most recent cardio‐oncological findings and heart failure guidelines.     

抗肿瘤治疗引发的心功能不全

常规肿瘤治疗包含了化疗、放疗和手术治疗等方式。在抗肿瘤治疗的同时，心血管毒副反应，如心肌缺血、心功能不全等日益受到重视。不同的治疗方法有着不同的机理和多种毒副反应，及时有效的监测早期心血管损害和评估心脏收缩、舒张功能，对患者的长期预后和生存显得至关重要。抗肿瘤治疗仍在不断进步中，层出不穷的治疗方式和未知的毒副反应将成为心脏病学家和肿瘤学家需要联合面对的难题。     

Patient adherence to oral anticancer drugs: an emerging issue in modern oncology

The steady increase in the use of oral anticancer drugs in modern oncology has created a paradigm shift, challenging traditional attitudes towards cancer care and requiring new concepts of organization of oncology services. Important issues are the prolonged treatment period, management of toxicity, treatment adherence, reimbursement conditions and patient and family education. Although most patients generally prefer oral therapy over intravenous treatment for reasons of convenience, the daily use of oral anticancer drugs can be a challenging commitment for many patients. Reports on adherence and persistence among patients with cancer show that adherence ranges from 16% to 100%, depending on the type of therapy and the measurement/definition of adherence. Apart from demographic, disease and therapy related factors, the determinants that mostly influence (non-)adherence are the satisfaction with care activities performed at the initiation of the drug treatment, and the perceived necessity of treatment. Therefore, patient education addressing these issues is considered the cornerstone of successful oral anticancer treatment. Studies examining the role of different health care providers in the pharmacotherapeutic care of patients with cancer, treated with oral anti-cancer drugs, support the need for a multidisciplinary approach to achieve a maximum benefit for the individual patient and consequently for the whole health system. Limiting adverse events and developing appropriate supportive care are only some aspects that need to be considered in this.     

Cardiac resynchronization therapy: the issue of non-response

Cardiac resynchronization therapy reduces mortality and morbidity in heart failure patients with wide QRS and severe impairment of left ventricular systolic function, who are symptomatic despite optimal medical therapy. However, a high percentage of patients fail to show clinical or echocardiographic response to this treatment. Beyond current selection criteria, other elements, such as QRS duration and morphology, concomitant medical therapy, degree of right ventricle dysfunction, myocardial viability, presence of left ventricular dyssynchrony, and associated renal dysfunction, play a crucial role in modulating the response to cardiac resynchronization. Consequently, they should be part of the standard pre-implant evaluation, as they could be used to identify patients who are very unlikely to be responders.     

Water conservation: an emerging but vital issue in hemodialysis therapy

Water conservation refers to reducing the usage of water and recycling of wastewater for different purposes such as irrigation, laundry and sanitation. As water scarcity increases worldwide, dialysis facilities should be focused on salvaging water. However, most of them still ignorantly discard to the sewer huge volumes of this reusable resource. This article reviews the current water conservation techniques in hemodialysis and the potential benefits drawn when using this technology.     

Care of the elderly in Ghana: An emerging issue

Data are presented on the social and economic conditions influencing the care of the elderly in Ghana. The data consist of research findings, personal observations, and field studies of University of Ghana social work students as well as information from case studies of HelpAge Ghana's Adopt a Granny Program. Changes in the traditional family pattern indicate that the nuclear family, including grandchildren, is taking on a crucial role in the care of the elderly.     

Cardiac resynchronization therapy in pediatrics: Emerging technologies for emerging indications

Optional statement Cardiac resynchronization therapy (CRT) has become the standard of care for the treatment of heart failure in adults with decreased ventricular function and conduction delay who remain symptomatic despite optimal medical therapy. Indications for CRT in adults include medically refractory heart failure with a QRS duration of ≧ 120 msec and a left ventricular end-diastolic dimension of ≧ 55 mm with ejection fraction ≦ 35%. No such consensus guidelines exist in pediatrics; however, recent preliminary data indicate that CRT is effective therapy for symptomatic heart failure in children in both the acute postoperative setting as well as in the ambulatory setting. CRT is a viable therapeutic option in children with decreased ventricular function and ventricular conduction delay. It is preferable to high-dose inotropic therapy and should be given serious consideration for the treatment of refractory heart failure prior to proceeding with heart transplantation.     

Cardiac dysfunction during acute lung injury induced by oleic acid in dogs

Circulatory abnormalities are common during the adult respiratory distress syndrome and contribute importantly to the high mortality seen with this illness, but what causes them is not well characterized. Oleic acid-induced acute lung injury is an experimental model of the human syndrome in which hemodynamic changes are also common. To characterize a possible link between lung injury and cardiac dysfunction in this model, we evaluated cardiac function in mongrel dogs after oleic acid administration. Stroke volume index decreased, the radionuclide ventriculographically determined ejection fraction decreased, and end-diastolic volume increased after oleic acid. These results suggested a decrease in myocardial contractility, a conclusion confirmed when other experiments demonstrated a consistent rightward displacement of the end-systolic pressure-diameter relationship after oleic acid. Histologic examination of the myocardium showed little evidence of vascular injury, and myocardial tissue wet-to-dry weight ratios were normal. Thus, although the pulmonary effects of oleic acid are due to microvascular injury, similar mechanisms are not responsible for the depression in myocardial contractility.     

Cardiac resynchronization: a novel therapy for heart failure

Despite advances in medical therapy for patients with congestive heart failure, morbidity and mortality remain high. Conduction abnormalities, such as left bundle branch block, right bundle branch block, and nonspecific conduction delay, are observed commonly in patients with dilated cardiomyopathy. In patients with heart failure, the presence of intraventricular conduction delay is associated with more severe mitral regurgitation and worsened left ventricular systolic and diastolic function, and is an independent risk factor for increased mortality. Conventional dual-chamber (right atrial and right ventricular) pacing with a short atrioventricular delay was initially introduced as therapy for patients with advanced congestive heart failure to improve diastolic dysfunction and reduce mitral regurgitation. The acute beneficial hemodynamic effects observed in early, uncontrolled studies were not confirmed in subsequent randomized, controlled studies with longer follow-up. Cardiac resynchronization with novel biventricular (left and right ventricular) pacing systems has resulted in hemodynamic and functional benefits in patients with congestive heart failure and an underlying intraventricular conduction delay. Improvements in cardiac index, systolic blood pressure, and functional class have been reported with biventricular pacing, both acutely and at more than 1 year of follow-up. These encouraging preliminary results with biventricular pacing in patients with congestive heart failure will be validated in two prospective, randomized, controlled trials, Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION). These studies are designed to evaluate the long-term efficacy of biventricular pacing in improving exercise capacity and in reducing morbidity and mortality in patients with advanced, symptomatic congestive heart failure. (c)2001 by CHF, Inc.     

MicroRNAs in hematological malignancies: a novel approach to targeted therapy

MicroRNAs (miRNAs) are about 19-24 nucleotide small single-stranded noncoding RNAs that are involved in crucial cell processes such as proliferation, apoptosis, and differentiation. Several studies reported show the involvement of miRNA in cancer. It has been suggested that miRNA profiling has the potential to classify a variety of tumors and possibly predict outcome. MicroRNA can act as an oncogene as well as tumor suppressor gene and this dual function of miRNA can be utilized as a therapeutic tool. The oncogenic character of miRNA can be silenced through various RNA interference-type strategies. The involvement of miRNA in the tumorogenesis processes makes them an important therapeutic tool and a novel biomarker. In this review, we have highlighted the role of miRNA in hematological malignancies and its utility in targeted therapy.     

Photoangioplasty: An emerging clinical cardiovascular role for photodynamic therapy

Photodynamic therapy (PDT) has been studied and applied to various disease processes. The potential of PDT for selective destruction of target tissues is especially appealing in cardiovascular disease, in which other existing interventional tools are somewhat nonselective and carry substantial risk of damage to the normal arterial wall. Enthusiasm for photoangioplasty (PDT of vascular de novo atherosclerotic and, potentially, restenotic lesions) is fueled by more effective second-generation photosensitizers and technological advances in endovascular light delivery. This excitement revolves around at least 4 significant attributes of light-activated therapy: the putative selectivity and safety of photoangioplasty, the potential for atraumatic and effective debulking of atheromatous plaque through a biological mechanism, the postulated capability to reduce or inhibit restenosis, and the potential to treat long segments of abnormal vessel by simply using fibers with longer light-emitting regions. The available nonclinical data, coupled with the observations of a new phase I trial in human peripheral atherosclerosis, suggest a promising future for photoangioplasty in the treatment of primary atherosclerosis and prevention of restenosis.     

Microvascular dysfunction: An emerging pathway in the pathogenesis of obesity-related insulin resistance

The prevalence of type 2 diabetes mellitus (T2DM) and its major risk factor, obesity, has reached epidemic proportions in Western society. How obesity leads to insulin resistance and subsequent T2DM is incompletely understood. It has been established that insulin can redirect blood flow in skeletal muscle from non-nutritive to nutritive capillary networks, without increasing total blood flow. This results in a net increase of the overall number of perfused nutritive capillary networks and thereby increases insulin-mediated glucose uptake by skeletal muscle. This process, referred to as functional (nutritive) capillary recruitment, has been shown to be endothelium-dependent and to require activation of the phosphatidylinositol-kinase (PI3K) pathway in the endothelial cell. Several studies have demonstrated that these processes are impaired in states of microvascular dysfunction. In obesity, changes in several adipokines are likely candidates to influence insulin signaling pathways in endothelial cells, thereby causing microvascular dysfunction. Microvascular dysfunction, in turn, impairs the timely access of glucose and insulin to their target tissues, and may therefore be an additional cause of insulin resistance. Thus, microvascular dysfunction may be a key feature in the development of obesity-related insulin resistance. In the present review, we will discuss the evidence for this emerging role for the microcirculation as a possible link between obesity and insulin resistance.     

新型冠状病毒导致多器官功能衰竭的机制探讨

2019年末新型冠状病毒(2019-nCoV)很快在全球范围内传播,成为2020年的国际公共卫生事件。目前临床病例数据提示2019-nCoV引起多器官功能衰竭(MODS)是导致患者死亡的重要原因,但是其具体机制仍不清楚。本文结合目前临床数据及前期研究结果,初步探讨2019-nCoV导致MODS的机制。     

Cardiac mechanical dysfunction induced by ischemia-reperfusion in perfused heart isolated from stroke-prone spontaneously hypertensive rats

We investigated the difference in mechanical function after ischemia and reperfusion between Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) or stroke-prone SHR (SHRSP) using the isolated working heart model, in order to examine postischemic mechanical dysfunction in the severely hypertrophied heart. Systolic blood pressure of SHRSP was higher than that of SHR and WKY, and the left ventricular wall in SHRSP was thicker than in WKY. Mechanical dysfunction of the heart during reperfusion following ischemia (11 min) in SHRSP was severer than that in SHR and WKY, and recovery of the cardiac energy charge potential (ECP) level in SHRSP was lower than that in SHR and WKY. Twenty-five, 12 and 11 min-ischemia in WKY, SHR and SHRSP, respectively, caused a similar level of cardiac mechanical damage. Also, the ECP levels were almost equivalent among them at the end of 20 min reperfusion following each time of ischemia. Under each ischemic condition, a Ca2+-channel blocker, diltiazem, and an adenosine potentiator, dilazep, produced a beneficial effect on the post-ischemic dysfunction in SHR and WKY. However, neither cardioprotective drug led to recovery of the mechanical dysfunction of the heart during reperfusion following ischemia in SHRSP. Thus, the severely hypertrophied heart such as that in SHRSP was more susceptible to cardiac reperfusion dysfunction, than the moderately hypertrophied heart such as that in SHR. These results suggest that the cardioprotective effects of drugs may be deteriorated in severe hypertrophied hearts.     

Heparin: An emerging, counterintuitive therapy for inflammatory bowel disease

Conclusion Heparin’s promise has begun to be confirmed as a useful therapy in IBD. The counterintuitive nature of the therapy may reveal under-appreciated elements of the pathophysiology of UC and Crohn’s disease as central to the pathophysiology of these diseases. The possible therapeutic benefit of heparin likely extends beyond its action as an anticoagulant, and includes anti-inflammatory mechanisms as well as promotion of endothelial and mucosal healing. The full potential of heparin remains to be defined with further ongoing and planned studies.