Organ transplantation has progressed tremendously with improvements in surgical methods, organ preservation, and pharmaco-immunologic therapies and has become a critical pathway in the management of severe organ failure worldwide. The major sources of organs are deceased donors after brain death; however, a substantial number of organs come from live donations, and a significant number can also be obtained from non-heart-beating donors. Yet, despite progress in medical, pharmacologic, and surgical techniques, the shortage of organs is a worldwide problem that needs to be addressed internationally at the highest possible levels. This particular field involves medical ethics, religion, and society behavior and beliefs. Some of the critical ethical issues that require aggressive interference are organ trafficking, payments for organs, and the delicate balance in live donations between the benefit to the recipient and the possible harm to the donor and others. A major issue in organ transplantation is the definition of death and particularly brain death. Another major critical factor is the internal tendency of a specific society to donate organs. In the review below, we will discuss the various challenges that face organ donation worldwide, and particularly in Israel, and some proposed mechanisms to overcome this difficulty.
Hereditary, environmental, and stochastic factors determine a child’s growth in his unique environ-ment, but their relative contribution to the phenotypic outcome and the extent of stochastic pro-gramming that is required to alter human phenotypes is not known because few data are available. This is an attempt to use evolutionary life-history theory in understanding child growth in a broad evolutionary perspective, using the data and theory of evolutionary predictive adaptive growth-related strategies. Transitions from one life-history phase to the next have inherent adaptive plasticity in their timing. Humans evolved to withstand energy crises by decreasing their body size, and evolutionary short-term adaptations to energy crises utilize a plasticity that modifies the timing of transition from infancy into childhood, culminating in short stature in times of energy crisis. Transition to juvenility is part of a strategy of conversion from a period of total dependence on the family and tribe for provision and security to self-supply, and a degree of adaptive plasticity is provided and determines body composition. Transition to adolescence entails plasticity in adapting to energy resources, other environmental cues, and the social needs of the maturing adolescent to determine life-span and the period of fecundity and fertility. Fundamental questions are raised by a life-history approach to the unique growth pattern of each child in his given genetic background and current environment.
Epidemiologic studies now strongly support the hypothesis, proposed over 2 decades ago , that developmental programming of the kidney impacts an individual’s risk for hypertension and renal disease in later life. Low birth weight is the strongest current clinical surrogate marker for an adverse intrauterine environment, and based on animal and human studies, is associated with a low nephron number. Other clinical correlates of low nephron number include female gender, short adult stature, small kidney size and prematurity. Low nephron number in Caucasian and Australian Aboriginal subjects has been shown to be associated with higher blood pressures, and conversely, hypertension is less prevalent in individuals with higher nephron numbers. In addition to nephron number, other programmed factors associated with the increased risk of hypertension include salt-sensitivity, altered expression of renal sodium transporters, altered vascular reactivity and sympathetic nervous system overactivity. Glomerular volume is universally found to vary inversely with nephron number, suggesting a degree of compensatory hypertrophy and hyperfunction in the setting of a low nephron number. This adaptation may become overwhelmed in the setting of superimposed renal insults e.g. diabetes mellitus, or rapid catch-up growth, leading to the vicious cycle of ongoing hyperfiltration, proteinuria, nephron loss and progressive renal functional decline. Many millions of babies are born with low birth weight every year, hypertension and renal disease prevalences are increasing around the globe. At present, little can be done clinically to augment nephron number; therefore adequate pre-natal care and careful post-natal nutrition are crucial to optimize an individual’s nephron number during development, and potentially to stem the tide of the growing cardiovascular and renal disease epidemics world-wide.
As more reports emerge of improved mortality and morbidity rates in infants born at the edge of viability, there may be need to reassess protocols and recommendations that encourage only comfort care for infants who are born at less than 24 weeks’ gestation. Analysis of those studies that report extremely poor survival of these infants reveals that, all too often, the results are measures of a self-fulfilling prophesy that reflects a predetermined non-aggressive global policy of no resuscitation and minimal investment in intensive care. Furthermore, little distinction is made between high- and low-risk infants of the same gestational age despite repeated studies that indicate that one can identify - subpopulations that have as much as a 20-50% increased chance of surviving with little if any long-term neurodevelopmental impairment. Thus, the need to reassess current policies is discussed.
The past few decades have seen many advances in the treatment of a variety of cancers. Unfortunately, for ovarian cancer, which is the most lethal type of gynecologic malignancy, no new therapeutic approach has been successfully introduced since the 1990s. Ovarian cancer is usually detected in later stages, when remission rates are high and tumors are resistant to chemotherapy. Little is known about the primary lesion in ovarian cancer. Recently, it has been shown that the origin of ovarian cancer can be cells from adjacent tissue or cells from other primary tumors, which make their way to the ovaries due to the unique nature of their microenvironment during ovulation. The tumor in ovarian cancer is heterogeneous and hierarchically organized. In this review, we discuss the role of ovarian cancer stem cells in the process of tumor formation and recurrence. We propose the need to shift the paradigm away from the classification of ovarian cancer as a single disease with a single cellular origin. Understanding the complexity of the disease will facilitate devising new methods for fighting this cancer and improving the life of many women inflicted with the disease.
Crohn's disease (CD) is a heterogeneous disorder that can involve any segment of the gastrointestinal tract.The pathogenesis of CD is unknown but is thought to involve an uncontrolled immune response triggered by an environmental factor in a genetically susceptible host.The heterogeneity of disease pathogenesis and clinical course, combined with the variable response to treatment and its associated side effects creates an environment of complex therapeutic decisions.
Despite this complexity, significant progress has been made which allows physicians to start and predict disease behavior and natural course, response to therapy and factors associated with significant side effects.
In this manuscript the data pertaining to these variables including clinical, endoscopic and the various biological and genetic markers are reviewed and the possibility of tailoring personal treatment is discussed.
Mitral valve regurgitation (MR) is the most prevalent valvular heart disease in the community, its prevalence increasing along with population aging and heart failure. While surgery remains the gold standard treatment in low-risk patients with degenerative MR, in high-risk patients and in those with functional MR, transcatheter procedures are emerging as an alternative therapeutic option. MitraClip is the device with the largest clinical experience to-date, as it offers sustained clinical benefit in selected patients. Further to MitraClip implantation, several additional approaches are developing, to better match with the extreme variability of mitral valve disease. Not only repair is evolving, initial steps towards percutaneous mitral valve implantation have already been undertaken and initial clinical experience has just started.
Four decades of innovations in the field of interventional cardiology are presented as an example for the great growth of high technology in medicine, sidebyside with the development of general technology and science. The field of percutaneous coronary intervention (PCI) was enabled by the development of X-ray systems,allowing us to view the pathology,and was critically dependent on courageous and imaginative physicians and scientists who developed percutaneous transluminal coronary angioplasty (PTCA), stents, and transarterial aortic valve replacement (TAVR). Today, outstanding research continues to progress, with stem cell research and IPC technologiespresenting new challenges and yet taller mountains to climb. The rapid development we have witnessed was due to tight collaborations between clinical and academic institutions and industry. The combination of all these elements, with a proper mechanism to handle conflict of interest,is an essential linkage for any progress in this field. We will continue to see exponential growth of innovations and must be prepared with appropriate bodies to encourage such developments and to provide early-stage funding and support for novel ideas.
Cardiovascular disease is the most prevalent disease mainly in the Western society and becoming the leading cause of death worldwide. Standard methods by which health care providers screen for cardiovascular disease have only minimally reduced the burden of disease while exponentially increasing costs. As such, more specific and individualized methods for functionally assessing cardiovascular threats are needed to identify properly those at greatest risk, and appropriately treat these patients so as to avoid a fate such as heart attack, stroke, or death. Currently, endothelial function testing—in both the coronary and peripheral circulation—is well-established as being associated with the disease process and future cardiovascular events. Improving such testing can lead to a reduction in the risk of future events. Combining this functional assessment of vascular fitness with other, more personalized, testing methods should serve to identify those at the greatest risk of cardiovascular disease earlier and subsequently reduce the affliction of such diseases worldwide.
The Cox maze III and Cox maze IV procedures are surgical solutions for the treatment of symptomatic stand-alone atrial fibrillation. Despite their proven efficacy, these procedures have not gained widespread acceptance because of the invasiveness, complexity, and technical difficulty. Endocardial pulmonary vein isolation is the cornerstone of percutaneous catheter ablation for atrial fibrillation. It is currently accepted as an invasive therapy, if rhythm control has failed using antiarrhythmic drugs or electrical cardioversions. Pulmonary vein isolation is reported to be effective in 60%–85% of patients with paroxysmal atrial fibrillation and in 30%–50% of patients with persistent atrial fibrillation. A second or third ablation is often necessary to achieve these results, and complications may occur in up to 6% of patients.
Surgical treatment of atrial fibrillation has seen important improvements in the last decade. New technologies have simplified creation of transmural lesions on the beating heart through a less-invasive, thoracoscopic procedure. This allows for pulmonary vein isolation, isolation of the posterior wall, and left atrial appendage exclusion—usually combined with ganglionic plexi evaluation and destruction. Nonethe¬less, it is still uncertain whether these procedures are effective in restoring permanent sinus rhythm since transmurality of a lesion set cannot be guaranteed with current ablation catheters on the beating heart.
In an attempt to limit the shortcomings of an endo- or an epicardial technique, a hybrid approach has recently been introduced. This approach is based on a close collaboration between the surgeon and the electrophysiologist, employing a patient-tailored procedure which is adapted to the origin of the patient’s atrial fibrillation and takes into consideration triggers and substrate. Using a mono- or bilateral energy source, a thoracoscopic epicardial approach is combined with a percutaneous endocardial ablation in a single-step or in a sequential-step procedure.
This article provides our experience and an overview of the current knowledge in the hybrid treatment of stand-alone atrial fibrillation.
