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).
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 endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of pain and inflammation. The specific roles of currently identified endocannabinoids that act as ligands at endogenous cannabinoid receptors within the central nervous system (primarily but not exclusively CB1 receptors) and in the periphery (primarily but not exclusively CB2 receptors) are only partially elucidated, but they do exert an influence on nociception. Exogenous plant-based cannabinoids (phytocannabinoids) and chemically related compounds, like the terpenes, commonly found in many foods, have been found to exert significant analgesic effects in various chronic pain conditions. Currently, the use of Δ9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking), as well as regulatory or legal constraints. However, other phytocannabinoids in combination, especially cannabidiol and β-caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles. This review will provide the reader with the foundational basic and clinical science linking the endocannabinoid system and the phytocannabinoids with their potentially therapeutic role in the management of chronic pain.
Objective: To assess the association between normal CA125 levels at diagnosis of epithelial ovarian carcinoma (EOC) with prognostic factors and with outcome.
Methods: The study group consisted of histologically confirmed EOC patients with normal pretreatment CA125 levels, and the controls consisted of EOC patients with elevated (≥35 U/mL) pretreatment CA125 levels, diagnosed and treated between 1995 and 2012. Study and control group patients fulfilled the following criteria: 1) their pretreatment CA125 levels were assessed; 2) they had full standard primary treatment, i.e. cytoreductive surgery and cisplatin-based chemotherapy; and 3) they were followed every 2–4 months during the first two years and every 4–6 months thereafter.
Results: Of 114 EOC patients who fulfilled the inclusion criteria, 22 (19.3%) had normal pretreatment CA125 levels. The control group consisted of the remaining 92 patients with ≥35 U/mL serum CA125 levels pretreatment. The proportion of patients with early-stage and low-grade disease, with optimal cytoreduction, and with platin-sensitive tumors was significantly higher in the study group than in the control group. The progression-free survival (PFS) and overall survival (OS) were significantly higher in the study group than in the control group on univariate analysis but not on multivariate analysis.
Conclusion: It seems that a normal CA125 level at diagnosis in EOC may also be of prognostic significance for the individual patient.
While the essence of nursing has long been whole person (body, mind, and spirit) and whole system-focused, in reality the contemporary practice of nursing in many settings around the globe has become increasingly fragmented and de-stabilized. Nursing shortages in many parts of the world are significant, and hierarchies and bureaucracies often remove nurses from the point of care, be that the bedside, home, or clinic, replacing them with less skilled workers and filling their time with documentation and other administrative tasks. Integrative nursing is a framework for providing whole person/whole system care that is relationship-based and person-centered and focuses on improving the health and wellbeing of caregivers as well as those they serve. It is aligned with what is being called the “triple aim” in the United States—an effort focused on improving the patient experience (quality and satisfaction), improving the health of populations, and reducing the cost of care. The principles of integrative nursing offer clear and specific guidance that can shape and impact patient care in all clinical settings.
This review examines ways to decrease preventable effects of hospitalization on older adults in acute care medical (non-geriatric) units, with a focus on the Israeli experience at the Rambam Health Care Campus, a large tertiary care hospital in northern Israel. Hospitalization of older adults is often followed by an irreversible decline in functional status affecting their quality of life and well-being after discharge. Functional decline is often related to avoidable effects of in-hospital procedures not caused by the patient’s acute disease. In this article we review the literature relating to the recognized effects of hospitalization on older adults, pre-hospitalization risk factors, and intervention models for hospitalized older adults. In addition, this article describes an Israeli comprehensive research study, the Hospitalization Process Effects on Functional Outcomes and Recovery (HoPE-FOR), and outlines the design of a combined intervention model being implemented at the Rambam Health Care Campus. The majority of the reviewed studies identified preadmission personal risk factors and psychosocial risk factors. In-hospital restricted mobility, under-nutrition care, the over-use of continence devices, polypharmacy, and environmental factors were also identified as avoidable processes. Israeli research supported the findings that preadmission risk factors together with in-hospital processes account for functional decline. Different models of care have been developed to maintain functional status. Much can be achieved by interdisciplinary teams oriented to the needs of hospitalized elderly in making an impact on hospital processes and continuity of care. It is the responsibility of health care policy-makers, managers, clinicians, and researchers to pursue effective interventions to reduce preventable hospitalization-associated disability.
Medicine is developing through biomedical technology and innovations. The goal of any innovation in medicine is to improve patient care. Exponential growth in technology has led to the unprecedented growth of medical technology over the last 50 years. Clinician-scientists need to understand the complexity of the innovation process, from concept to product release, when working to bring new clinical solutions to the bedside. Hence, an overview of the innovation process is provided herein. The process involves an invention designed to solve an unmet need, followed by prototype design and optimization, animal studies, pilot and pivotal studies, and regulatory approval. The post-marketing strategy relative to funding, along with analysis of cost benefit, is a critical component for the adoption of new technologies. Examples of the road to innovation are provided, based on the experience with development of the transcatheter aortic valve. Finally, ideas are presented to contribute to the further development of this worldwide trend in innovation.
Urological malignancies are a major source of morbidity and mortality in men over 40. Screening for those malignancies has a potential benefit of reducing both. However, even after more than two decades of screening for prostate cancer, the implications of most resulting information are still a matter of debate. Controversy extends over several aspects of prostate cancer screening programs, including age of onset, defining populations at risk, most appropriate intervals, as well as the optimal methods to be used for screening. The medical community is still divided regarding the effectiveness of prostate cancer-related death prevention and its benefits-to-harms ratio, reflecting an inconsistency regarding screening recommendations. Similarly, benefits of screening for urothelial and kidney tumors are yet lacking high- level evidence, although recent evidence supports screening of populations at risk. Clearly, the current era of evolving molecular and genetic biomarkers harbors the potential to change screening practice. In this paper, we review current guidelines as well as giving an update on new developments which might influence screening strategies in common urological malignancies.
An ideological case study based on medical profession norms during the Third Reich will be used to exemplify the importance of diversity in the manifestations of professional ethics. The German professional medical community banned their Jewish colleagues from treating German citizens. This included legally mandated employment discrimination and outright censure which led to a professional ethic devoid of diverse voices. While the escalation to the T-4 program and medicalized genocide was influenced by many causes, the intentional, ethnocentric-based exclusion of voices was an important contributing element to the chronicled degradation of societal mores. For illustration, six core Jewish values—life, peace, justice, mercy, scholarship, and sincerity of intention—will be detailed for their potential to inspire health-care professionals to defend and protect minorities and for readers to think critically about the role of medical professionalism in Third Reich society. The Jewish teachings highlight the inherent professional obligations physicians have toward their patients in contrast to the Third Reich’s corruption of patient-centered professionalism. More fundamentally, juxtaposing Jewish and Nazi teachings exposes the loss of perspective when a profession’s identity spurns diversity. To ensure respect for persons in all vulnerable minorities, the first step is addressing professional inclusion of minority voices.
BACKGROUND: The energy crisis hypothesis, which is a widely accepted model for the pathogenesis of myofascial pain, has been corroborated by experimental observations. However, the nature of the insult leading to the energy crisis remains elusive. A commonly cited model for this insult is the Cinderella hypothesis, suggesting that hierarchical recruitment of motor units leads to a disproportional load on small units, thus driving them towards an energy crisis. New findings cast doubt on this model, showing that in postural muscles motor units are recruited in rotation, rather than in a hierarchical order, precluding the formation of the so-called Cinderella units.
OBJECTIVE: To explore the influence of common myofascial predisposing factors such as muscle load and muscle strength on the relaxation time of postural muscle motor units, assuming they are recruited in rotation.
METHODS: A stochastic model of a postural skeletal muscle was developed which integrates the energy crisis model and motor unit rotation patterns observed in postural muscles. Postulating that adequate relaxation time is essential for the energetic replenishment of motor units, we explored the influence of different parameters on the relaxation time of individual motor units under varying conditions of muscle loads and muscle strengths.
RESULTS: The motor unit relaxation/contraction time ratio decreases with elevated muscle loads and with decreased total muscle strength.
Conclusions: In a model of a postural muscle, in which motor units are recruited in rotation, common predisposing factors of myofascial pain, such as increased muscle load and decreased muscle force, lead to shortened motor unit relaxation periods.
