Studying complex biological systems in a holistic rather than a “one gene or one protein” at a time approach requires the concerted effort of scientists from a wide variety of disciplines. The Institute for Systems Biology (ISB) has seamlessly integrated these disparate fields to create a cross-disciplinary platform and culture in which “biology drives technology drives computation.” To achieve this platform/culture, it has been necessary for cross-disciplinary ISB scientists to learn one another’s languages and work together effectively in teams. The focus of this “systems” approach on disease has led to a discipline denoted systems medicine. The advent of technological breakthroughs in the fields of genomics, proteomics, and, indeed, the other “omics” is catalyzing striking advances in systems medicine that have and are transforming diagnostic and therapeutic strategies. Systems medicine has united genomics and genetics through family genomics to more readily identify disease genes. It has made blood a window into health and disease. It is leading to the stratification of diseases (division into discrete subtypes) for proper impedance match against drugs and the stratification of patients into subgroups that respond to environmental challenges in a similar manner (e.g. response to drugs, response to toxins, etc.). The convergence of patient-activated social networks, big data and their analytics, and systems medicine has led to a P4 medicine that is predictive, preventive, personalized, and participatory. Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease. For example, in 10 years each patient will be surrounded by a virtual cloud of billions of data points, and we will have the tools to reduce this enormous data dimensionality into simple hypotheses about how to optimize wellness and avoid disease for each individual. P4 medicine will be able to detect and treat perturbations in healthy individuals long before disease symptoms appear, thus optimizing the wellness of individuals and avoiding disease. P4 medicine will 1) improve health care, 2) reduce the cost of health care, and 3) stimulate innovation and new company creation. Health care is not the only subject that can benefit from such integrative, cross-disciplinary, and systems-driven platforms and cultures. Many other challenges plaguing our planet, such as energy, environment, nutrition, and agriculture can be transformed by using such an integrated and systems-driven approach.
Non-Hodgkin lymphoma (NHL) is one of the most common hematologic malignancies worldwide. The incidence of NHL has been rising for several decades; however, in the last 20 years, it reached a plateau. NHL incidence among males is significantly higher than in females. In addition to gender itself, gravidity has a protective role against NHL occurrence. Gender also matters in terms of NHL clinical characteristics. For example, female predominance was found in three extra-nodal sites (the breast, thyroid, and the respiratory system) occasionally involved in NHL. The diagnosis of NHL during pregnancy is associated with a unique clinical behavior. It is usually diagnosed in the second or third trimester and in advanced stage. Furthermore, the histological subtype is highly aggressive, and reproductive organ involvement is common. The reduced rate of NHL among females may be explained by direct effects of estrogens on lymphoma cell proliferation or by its effect on anti-tumor immune response. Gender has an important role in responsiveness to standard B cell NHL treatment. Among older adults, women benefited more from the addition of the anti-CD20 antibody rituximab to standard chemotherapy regimens. This phenomenon can be explained by the difference in clearance rate of rituximab that was found to be significantly lower among older females than older males. In mantle cell lymphoma, women receiving lenalidomide have higher rates of response. An understanding of the mechanisms responsible for gender-associated NHL differences will ultimately improve the clinical approach, allowing for a more accurate assessment of prognosis and patient-tailored treatment.
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.
CD4+CD25+Foxp3+ regulatory T cells (Treg) are critical to the maintenance of immune tolerance. Treg are known to utilize a number of molecular pathways to control immune responses and maintain immune homeostasis. Fibrinogen-like protein 2 (FGL2) has been identified by a number of investigators as an important immunosuppressive effector of Treg, which exerts its immunoregulatory activity by binding to inhibitory FcγRIIB receptors expressed on antigen-presenting cells including dendritic cells, endothelial cells, and B cells. More recently, it has been suggested that FGL2 accounts for the immunosuppressive activity of a highly suppressive subset of Treg that express T cell immunoreceptor with Ig and ITIM domains (TIGIT). Here we discuss the important role of Treg and FGL2 in preventing alloimmune and autoimmune disease. The FGL2–FcγRIIB pathway is also known to be utilized by viruses and tumor cells to evade immune surveillance. Moving forward, therapies based on modulation of the FGL2–FcγRIIB pathway hold promise for the treatment of a wide variety of conditions ranging from autoimmunity to cancer.
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.
In the early seventeenth century, the Jews formally established two separate communities in Amsterdam, the Portuguese Sephardi and the High German Ashkenazi congregations. Until the end of the eighteenth century, medical care for the Amsterdam indigent Jews had been controlled and regulated by the powerful Parnasim, the de facto rulers, of each community. The primary communal organizations that were exclu¬sively responsible for medical care for the poor were the Bikur Holim societies. This approach for the care of the indigent Jewish sick became ineffective in the nineteenth century and was replaced by a hospital-based system. This essay describes how seriously ill indigent Jews in nineteenth-century Amsterdam received hospital care, tracing the establishment and development of the first Ashkenazi and Sephardi hospitals in the city. Although each community established their own hospital, they used different approaches to accomplish this goal.
Alfred Nobel was one of the most successful chemists, inventors, entrepreneurs, and businessmen of the late nineteenth century. In a decision later in life, he rewrote his will to leave virtually all his fortune to establish prizes for persons of any nationality who made the most compelling achievement for the benefit of mankind in the fields of chemistry, physics, physiology or medicine, literature, and peace among nations. The prizes were first awarded in 1901, five years after his death. In considering his choice of prizes, it may be pertinent that he used the principles of chemistry and physics in his inventions and he had a lifelong devotion to science, he suffered and died from severe coronary and cerebral atherosclerosis, and he was a bibliophile, an author, and mingled with the literati of Paris. His interest in harmony among nations may have derived from the effects of the applications of his inventions in warfare (“merchant of death”) and his friendship with a leader in the movement to bring peace to nations of Europe. After some controversy, including Nobel’s citizenship, the mechanisms to choose the laureates and make four of the awards were developed by a foundation established in Stockholm; the choice of the laureate for promoting harmony among nations was assigned to the Norwegian Storting, another controversy. The Nobel Prizes after 115 years remain the most prestigious of awards. This review describes the man, his foundation, and the prizes with a special commentary on the Nobel Prize in Physiology or Medicine.
Introduction: Many patients and their families are hesitant to consult a palliative care (PC) team. In 2014, approximately 6,000,000 people in the United States could benefit from PC, and this number is expected to increase over the next 25 years.
Objectives: The purpose of this review is to shed light on the significance of PC and provide a holistic view outlining both the benefits and existing barriers.
Methods: A literature search was conducted using MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, and Web of Science to identify articles published in journals from 1948 to 2019. A narrative approach was used to search the grey literature.
Discussion: Traditionally, the philosophy behind PC was based on alleviating suffering associated with terminal illnesses; PC was recommended only after other treatment options had been exhausted. However, the tenets of PC are applicable to anyone with a life-threatening illness as it is beneficial in conjunction with traditional treatments. It is now recognized that PC services are valuable when initiated alongside disease-modifying therapy early in the disease course. Studies have shown that PC decreased total symptom burden, reduced hospitalizations, and enabled patients to remain safely at home.
Conclusion: As the population ages and chronic illnesses become more widespread, there continues to be a growing need for PC programs. The importance of PC should not be overlooked despite existing barriers such as the lack of professional training and the cost of implementation. Education and open discussion play essential roles in the successful early integration of PC.
By their very nature both man-made and natural disasters are unpredictable, and so we recommend that all health-care institutions be prepared. In this paper, the authors describe and make a number of recommendations, regarding the importance of crisis and turnaround management using as a model the New Orleans public health system and Tulane University Medical School post-Hurricane Katrina. Leadership skills, articulation of vision, nimble decision making, and teamwork are all crucial elements of a successful recovery from disaster. The leadership team demonstrated courage, integrity, entrepreneurship, and vision. As a result, it led to a different approach to public health and the introduction of new and innovative medi¬cal education and research programs.
Determining appropriate care for patients who cannot speak for themselves is one of the most challenging issues in contemporary healthcare and medical decision-making. While there has been much discussion relating to patients who left some sort of instructions, such as an advance directive, or have someone to speak on their behalf, less has been written on caring for patients who have nobody at all available to speak for them. It is thus crucial to develop clear and rigorous guidelines to properly care for these patients. The Jewish tradition offers an important perspective on caring for unrepresented patients and determining approaches to guide care providers. This article develops an understanding of fundamental Jewish principles that can provide clear guidance in navigating this challenge. It applies those values to a specific set of suggested behaviors, one of which adds a novel ritualized component to what has been recommended by bioethicists in the past.
