The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders. The current review focuses on emerging data linking coagulation and some psychiatric disorders.
Genetic aberrations have become a dominant factor in the stratification of myeloid malignancies. Cytogenetic and a few mutation studies are the backbone of risk assessment models of myeloid malignancies which are a major consideration in clinical decisions, especially patient assignment for allogeneic stem cell transplantation. Progress in our understanding of the genetic basis of the pathogenesis of myeloid malignancies and the growing capabilities of mass sequencing may add new roles for the clinical usage of genetic data. A few recently identified mutations recognized to be associated with specific diseases or clinical scenarios may soon become part of the diagnostic criteria of such conditions. Mutational study may also advance our capabilities for a more efficient patient selection process, assigning the most effective therapy at the best timing for each patient. The clinical utility of genetic data is anticipated to advance further with the adoption of deep sequencing and next-generation sequence techniques. We herein suggest some future potential applications of sequential genetic data to identify pending deteriorations at time points which are the best for aggressive interventions such as allogeneic stem cell transplantation. Genetics is moving from being mostly a prognostic factor to become a multitasking decision support tool for hematologists. Physicians must pay attention to advances in molecular hematology as it will soon be accessible and influential for most of our patients.
Harnessing the immune system to recognize and destroy tumor cells has been the central goal of anti-cancer immunotherapy. In recent years, there has been an increased interest in optimizing this technology in order to make it a clinically feasible treatment. One of the main treatment modalities within cancer immunotherapy has been adoptive T cell therapy (ACT). Using this approach, tumor-specific cytotoxic T cells are infused into cancer patients with the goal of recognizing, targeting, and destroying tumor cells. In the current review, we revisit some of the major successes of ACT, the major hurdles that have been overcome to optimize ACT, the remaining challenges, and future approaches to make ACT widely available.
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.
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.
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.
This paper is provided for the convenience of our readers and represents a full edited transcription of the Rambam Grand Rounds Lecture by Dr. Richard Horton, Editor-in-Chief of The Lancet. The lecture was given on October 2, 2014. The Editorial Board wishes to express its gratitude to Dr. Horton for giving permission to present his Rambam Grand Rounds lecture in Rambam Maimonides Medical Journal, in both the original video format and in this printed form.
In both primary care and consultative practices, patients presenting with fibromyalgia (FM) often have other medically unexplained somatic symptoms and are ultimately diagnosed as having central sensitization (CS). Central sensitization encompasses many disorders where the central nervous system amplifies sensory input across many organ systems and results in myriad symptoms. A pragmatic approach to evaluate FM and related symptoms, including a focused review of medical records, interviewing techniques, and observations, is offered here, giving valuable tools for identifying and addressing the most relevant symptoms. At the time of the clinical evaluation, early consideration of CS may improve the efficiency of the visit, reduce excessive testing, and help in discerning between typical and atypical cases so as to avoid an inaccurate diagnosis. Discussion of pain and neurophysiology and sensitization often proves helpful.
The Jewish principle concerning a decision with regard to a dangerous treatment is as following: A patient who is estimated to die within 12 months because of a fatal illness is permitted to undergo a treatment that on the one hand may extend his life beyond 12 months, but on the other hand may hasten his death. There are, however, several limitations to this ruling related to the chances of success with the proposed treatment, the nature of the treatment, whether it is intended to be curative or merely to postpone the danger and death, whether the treatment is absolutely necessary, and others. One is not obligated to undergo a dangerous treatment, but one is permitted to do so. The permissibility to forfeit a short life expectancy in order to achieve more prolonged life applies only with the patient’s consent. That consent is valid and is not considered a form of attempted suicide. Neither is a refusal to submit to treatment considered an act of suicide; the patient has the right to refuse a dangerous procedure. In all situations where a permissive ruling is granted for a patient to endanger his short life expectancy, the ruling should be arrived at after careful reflection and with the approval of the rabbinic authorities acting on the recommendation of the most expert physicians.
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.
