Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained vir-al response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, pro-longed, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4+CD25+Foxp3+ regulatory T cells (Treg cells). We and others have recently identified fi-brinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to pre-dict disease progression in HCV patients and be a logical target for the development of novel therapeu-tic approaches for the treatment of patients with HCV infection.
Moses Maimonides, the illustrious medieval rabbi and philosopher, dedicated the last decade of his life primarily to medicine. His strong interest in medicine was an integral component of his religious-philosophical teachings and world view. In this paper various sources from his rabbinic writings are presented that explain Maimonides’ motivation regarding and deep appreciation for medicine: (A) The physician fulfills the basic biblical obligation to return lost objects to their owner, for with his knowledge and experience the physician can restore good health to his sick fellow human being; (B) medicine provides a unique opportunity to practice imitatio dei, as it reflects the religious duty to maintain a healthy life-style; (C) as an important natural science, medicine offers tools to recognize, love and fear God. These three aspects address man’s relationship and obligation towards his fellow man, himself and God. Biographical insights supported by additional sources from Maimonides’ writings are discussed.
In this brief review, written from the perspective of a physician-leader who has fostered the development of comprehensive quality improvement efforts at two academic medical centers, I review the need for improvement, some conceptual barriers that must be overcome, the goals of a comprehensive quality improvement (QI) effort, some of the results we have obtained, and some observations on how to develop a culture of continuous improvement in an academic medical center. The mandate for quality improvement is clear; current healthcare is wasteful and error-prone, leading to excessive morbidity and mortality and unsustainably high costs. Successful quality improvement requires the abandonment of two paradigms: the craft model of medical practice and the notion that many forms of harm to patients are not preventable. I will describe how dramatic improvement has been achieved in reducing, by up to 10-fold, rates of central line infections, ventilator-associated pneumonias, peritonitis in peritoneal dialysis patients, and mortality due to cardiac arrest in hospital. I will describe as well how these methods can improve access to out-patient clinics dramatically and enhance the reliability and safety of hand-offs between covering physicians. To develop and maintain systematic quality improvement in all phases of medical care we must articulate a culture in which: everyone working at the medical center makes improvements every day; front-line staff, who know best how the work is done, are empowered to improve the processes of care; and multidisciplinary teams create the protocols that reduce variation that is due to physician preference, leaving only the variation required by the individual needs of patients. I will review as well the crucial elements of education of trainees and faculty members needed to guide and sustain a culture of quality. Finally, I will add some observations on how oversight boards and medical center leaders can help create systematic quality improvement in their medical centers.
Pharmacogenomics is the study of an individual’s interaction with a specific drug based upon the genetic make-up of the individual. Pharmacogenomic testing can be a powerful tool in testing a drug’s potential efficacy and toxicity on an individual patient. For this tool to be used correctly, certain criteria have to be met. First and foremost is the strength of association between the genetic variation and the drug’s interaction. The predictiveness of pharmacogenomics for the individual patient must be factored in as well. If these criteria are not met, requiring pharmacogenomic testing is at best a waste of money and in some cases can endanger the patient’s life. Stent thrombosis is a serious and many times fatal outcome in a small minority of patients who have received drug-eluting stents. Here, we discuss a case in which the FDA issued a “boxed warning” about the use of the anti-clotting medication, clopidogrel, used to prevent stent thrombosis, the pharmacogenomic data available at the time the warning was issued, and the medical community’s response to the FDA’s warning. This article also discusses developments in the field of anti-clotting therapy since the FDA’s warning.
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.
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.
The hematopoietic stem cell (HSC) is a unique cell positioned highest in the hematopoietic hierarchical system. The HSC has the ability to stay in quiescence, to self-renew, or to differentiate and generate all lineages of blood cells. The path to be actualized is influenced by signals that derive from the cell’s microenvironment, which activate molecular pathways inside the cell. Signaling pathways are commonly organized through inducible protein–protein interactions, mediated by adaptor proteins that link activated receptors to cytoplasmic effectors. This review will focus on the signaling molecules and how they work in concert to determine the HSC’s fate.
In August of 2014, Manduca P et al. published “An open letter for the people in Gaza” in The Lancet. This letter was the response of those authors to their perspective of what was happening in Gaza during the summer-long conflict between Israel and Gaza. Israel was finally responding to years of bombardment from Gaza into civilian areas in the south of Israel. Two of the authors of the letters were known anti-Semites, and held connections with David Duke, a former Ku Klux Klan Grand Wizard in Louisiana and advocate of Nazism. Both these authors expressed sympathy and support for Duke’s rabidly anti-Jewish positions. In their letter they accused Israel’s medical community of complicity in committing terrible atrocities and even implied that chemical warfare was being used by Israel.
The “curative potential” in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve “narrative competence” in discerning and acting in accord with their preferences and best interests. The “narrative medicine” model of shared “close reading of literature and reflective writing” among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM), broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah’s death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including—especially—beneficence, non-maleficence, and autonomy.
Professionalism is a core competency of physicians. Clinical knowledge and skills (and their maintenance and improvement), good communication skills, and sound understanding of ethics constitutes the foundation of professionalism. Rising from this foundation are behaviors and attributes of professionalism: accountability, altruism, excellence, and humanism, the capstone of which is professionalism. Patients, medical societies, and accrediting organizations expect physicians to be professional. Furthermore, professionalism is associated with better clinical outcomes. Hence, medical learners and practicing physicians should be taught and assessed for professionalism. A number of methods can be used to teach professionalism (e.g. didactic lectures, web-based modules, role modeling, reflection, interactive methods, etc.). Because of the nature of professionalism, no single tool for assessing it among medical learners and practicing physicians exists. Instead, multiple assessment tools must be used (e.g. multi-source feedback using 360-degree reviews, patient feedback, critical incident reports, etc.). Data should be gathered continuously throughout an individual’s career. For the individual learner or practicing physician, data generated by these tools can be used to create a “professionalism portfolio,” the totality of which represents a picture of the individual’s professionalism. This portfolio in turn can be used for formative and summative feedback. Data from professionalism assessments can also be used for developing professionalism curricula and generating research hypotheses. Health care leaders should support teaching and assessing professionalism at all levels of learning and practice and promote learning environments and institutional cultures that are consistent with professionalism precepts.
