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.
Robotic cardiac operations evolved from minimally invasive operations and offer similar theoretical benefits, including less pain, shorter length of stay, improved cosmesis, and quicker return to preoperative level of functional activity. The additional benefits offered by robotic surgical systems include improved dexterity and degrees of freedom, tremor-free movements, ambidexterity, and the avoidance of the fulcrum effect that is intrinsic when using long-shaft endoscopic instruments. Also, optics and operative visualization are vastly improved compared with direct vision and traditional videoscopes. Robotic systems have been utilized successfully to perform complex mitral valve repairs, coronary revascularization, atrial fibrillation ablation, intracardiac tumor resections, atrial septal defect closures, and left ventricular lead implantation. The history and evolution of these procedures, as well as the present status and future directions of robotic cardiac surgery, are presented in this review.
Extracellular vesicles (EVs), comprised of exosomes, microparticles, apoptotic bodies, and other microvesicles, are shed from a variety of cells upon cell activation or apoptosis. EVs promote clot formation, mediate pro-inflammatory processes, transfer proteins and miRNA to cells, and induce cell signaling that regulates cell differentiation, proliferation, migration, invasion, and apoptosis. This paper will review the contribution of EVs in hematological disorders, including hemoglobinopathies (sicklecell disease, thalassemia), paroxysmal nocturnal hemoglobinuria, and hematological malignancies (lymphomas, myelomas, and acute and chronic leukemias).
The coagulation system constitutes an important facet of the unique vascular microenvironment in which primary and metastatic brain tumors evolve and progress. While brain tumor cells express tissue factor (TF) and other effectors of the coagulation system (coagulome), their propensity to induce local and peripheral thrombosis is highly diverse, most dramatic in the case of glioblastoma multiforme (GBM), and less obvious in pediatric tumors. While the immediate medical needs often frame the discussion on current clinical challenges, the coagulation pathway may contribute to brain tumor progression through subtle, context-dependent, and non-coagulant effects such as induction of inflammation, angiogenesis, or by responding to iatrogenic insults (e.g. surgery). In this regard, the emerging molecular diversity of brain tumor suptypes (e.g. in glioma and medulloblastoma) highlights the link between oncogenic pathways and the tumor repertoire of coagulation system regulators (coagulome). This relationship may influence the mechanisms of spontaneous and therapeutically provoked tumor cell interactions with the coagulation system as a whole. Indeed, oncogenes (EGFR, MET) and tumor suppressors (PTEN, TP53) may alter the expression, activity, and vesicular release of tissue factor (TF), and cause other changes. Conversely, the coagulant microenvironment may also influence the molecular evolution of brain tumor cells through selective and instructive cues. We suggest that effective targeting of the coagulation system in brain tumors should be explored through molecular stratification, stage-specific analysis, and more personalized approaches including thromboprophylaxis and adjuvant treatment aimed at improvement of patient survival.
Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved and expanded worldwide. New indications beside acute leukemia and aplastic anemia have been constantly explored and now include congenital disorders of the hematopoietic system, metabolic disorders, and autoimmune disease. The use of matched unrelated donors, umbilical cord blood units, and partially matched related donors has dramatically extended the availability of allogeneic transplantation. Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients. However, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress. Intense research aiming to improve adoptive immunotherapy and increase graft-versus-leukemia response while decreasing graft-versus-host response might bring the next breakthrough in allogeneic transplantation. Strategies of graft manipulation, tumor-associated antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy have already proved clinically efficient. In the following years, allogeneic transplantation is likely to become more complex, more individualized, and more efficient.
The recognition that the development of cancer is associated with acquired immunodeficiency, mostly against cancer cells themselves, and understanding pathways inducing this immunosuppression, has led to a tremendous development of new immunological approaches, both vaccines and drugs, which overcome this inhibition. Both “passive” (e.g. strategies relying on the administration of specific T cells) and “active” vaccines (e.g. peptide-directed or whole-cell vaccines) have become attractive immunological approaches, inducing cell death by targeting tumor associated antigens. Whereas peptide-targeted vaccines are usually directed against a single antigen, whole-cell vaccines (e.g. dendritic cell vaccines) are aimed to induce robust responsiveness by targeting several tumor-related antigens simultaneously. The combination of vaccines with new immuno-stimulating agents which target “immunosuppressive checkpoints” (anti-CTLA-4, PD-1, etc.) is likely to improve and maintain immune response induced by vaccination.
Background: The positive effects of ozone therapy have been described in many gastrointestinal disorders. The mechanisms of this positive effect of ozone therapy are poorly understood. The purpose of the present study was to investigate whether the use of ozone may potentiate the gut intestinal mucosal homeostasis in a rat model.
Methods: Adult rats weighing 250–280 g were randomly assigned to one of three experimental groups of 8 rats each: 1) Control rats were given 2 ml of water by gavage and intraperitoneally (IP) for 5 days; 2) O3-PO rats were treated with 2 ml of ozone/oxygen mixture by gavage and 2 ml of water IP for 5 days; 3) O3-IP rats were treated with 2 ml of water by gavage and 2 ml of ozone/oxygen mixture IP for 5 days. Rats were sacrificed on day 6. Bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, and cell proliferation and apoptosis were evaluated following sacrifice.
Results: The group of O3-IP rats demonstrated a greater jejunal and ileal villus height and crypt depth, a greater enterocyte proliferation index in jejunum, and lower enterocyte apoptosis in ileum compared to control animals. Oral administration of the ozone/oxygen mixture resulted in a less significant effect on cell turnover.
Conclusions: Treatment with an ozone/oxygen mixture stimulates intestinal cell turnover in a rat. Intraperitoneal administration of ozone resulted in a more significant intestinal trophic effect than oral administration.
Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code was transcribed to RNA and translated to proteins, but how proteins were degraded had remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis was largely non-lysosomal, but the mechanisms involved have remained obscure. The discovery of the ubiquitin-proteasome system resolved the enigma. We now recognize that degradation of intracellular proteins is involved in regulation of a broad array of cellular processes, such as cell cycle and division, regulation of transcription factors, and assurance of the cellular quality control. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of human disease, such as malignancies and neurodegenerative disorders, which led subsequently to an increasing effort to develop mechanism-based drugs.
This paper presents the full debate held on October 1, 2014, which focused on the following resolution: “Publications which promote political agendas have no place in scientific and medical journals, and academics should refrain from publishing in such journals.”
The debate moderator was Professor Shimon Glick. Taking the pro stance was Professor A. Mark Clarfield; the con stance was held by Professor Rael D. Strous. Following the first part of the debate, Dr Richard Horton, Editor-in-Chief of The Lancet, gave his thoughts on the topic. This was followed by the opportunity for rebuttal by Professors Clarfield and Strous. The debate was summarized and closed by Professor Glick.
This paper provides a slightly edited text of the debate, for ease of reading.
