The current review addresses contemporary technological answers toadvances in cardiac surgery performed on octogenarian patients, namely off-pump coronary artery bypass grafting (CABG), proximal anastomosis device, routine use of intraoperative epiaortic ultrasound, proximal anastomosis without clamping, transcatheter aortic valve implantation (TAVI), and brain protection during cardiac surgery.
Gaucher disease (GD) is an inherited lysosomal disorder, originating from deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Normally, GCase hydrolyzes glucocerebroside (GC) to glucose and ceramide; however, impaired activity of this enzyme leads to the accumulation of GC in macrophages, termed "Gaucher cells". GD is associated with hepatosplenomegaly, cytopenias, skeletal complications and in some forms involves the central nervous system.
Coagulation abnormalities are common among GD patients due to impaired production and chronic consumption of coagulation factors. Bleeding phenomena are variable (as are other symptoms of GD) and include mucosal and surgical hemorrhages.
Four main etiological factors account for the hemostatic defect in GD: thrombocytopenia, abnormal platelet function, reduced production of coagulation factors, and activation of fibrinolysis. Thrombocytopenia relates not only to hypersplenism and decreased megakaryopoiesis by the infiltrated bone marrow but also to immune thrombocytopenia. Autoimmunity, especially the induction of platelet antibody production, might cause persistent thrombocytopenia.
Enzyme replacement therapy reverses only part of the impaired coagulation system in Gaucher disease. Other therapeutic and supportive measures should be considered to prevent and/or treat bleeding in GD. Gaucher patients should be evaluated routinely for coagulation abnormalities especially prior to surgery and dental and obstetric procedures.
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.
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.
Objective: This pilot study was designed to describe changes in spiritual well-being (SWB), spiritual coping, and quality of life (QOL) in patients with brain cancer or other neurodegenerative diseases participating in a chaplain-led spiritual life review interview and development of a spiritual legacy document (SLD).
Methods: Eligible participants were enrolled and completed baseline questionnaires. They were interviewed by a board-certified chaplain about spiritual influences, beliefs, practices, values, and spiritual struggles. An SLD was prepared for each participant, and one month follow-up questionnaires were completed. Two cases are summarized, and spiritual development themes are illustrated within a spiritual development framework.
Results: A total of 27 patients completed baseline questionnaires and the interview; 24 completed the SLD, and 15 completed the follow-up questionnaire. Increases in SWB, religious coping, and QOL were detected. The majority maintained the highest (best) scores of negative religious coping, demonstrating minimal spiritual struggle.
Conclusions: Despite the challenges of brain cancers and other neurodegenerative diseases, participants demonstrated improvements in SWB, positive religious coping, and QOL. Patient comments indicate that benefit is related to the opportunity to reflect on and integrate spiritual experiences and to preserve them for others. Research with a larger, more diverse sample is needed, as well as clinical applications for those too vulnerable to participate in longitudinal follow-up.
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.
This brief introduction is followed by a published version of my Nobel Laureate lecture, re-published herein with the kind permission of the Nobel Foundation. Much has happened since my original research, for which that prize was awarded. Hence, I am pleased to offer a few thoughts about the future of my research and its possible impact on humankind.
Although the original work on nuclear transfer and reprogramming was done over half a century ago, advances continue to be made. In particular the Takahashi and Yamanaka induced pluripotent stem cells (iPS) procedure has opened up the field of cell replacement to a great extent. Now, more recently, further advances make this whole field come closer to actual usefulness for humans. Recently, in the UK, the government approved the use of mitochondrial replacement therapy to avoid the problems associated with genetically defective mitochondria in certain women. Although the House of Commons (members of Parliament) and the House of Lords had to debate and discuss whether to allow this kind of human therapy, I was very pleased to find that both bodies approved this procedure. This means that a patient can choose to make use of the procedure; it does not in any way force an individual to have a procedure that they are not comfortable with. In my view, this is a great advance in respect to giving patients a choice about the treatment they receive. I am told that the UK is the first country in the world to approve mitochondrial replacement therapy.
Now that the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPr) technology is being widely used and works well, one can foresee that there will be those who wish to use this technology to make genetic changes to humans. For example, if a human has a gene that makes it susceptible to infection or any other disorder, the removal of that gene might give such a person immunity from that disease. If this gene deletion is done within the germ line, the genetic change will be inherited. However, one can imagine that various people will strongly object and say that this technology should not be allowed. I would very much hope that various regulatory bodies, governments, etc. will allow the choice to remain with the individual. I can see no argument for such bodies to make a law that removes any choice whatsoever by an individual.
The number needed to treat (NNT) is a simple measure of a treatment’s impact, increasingly reported in randomized trials and observational studies. It has been found to be incorrectly calculated in several studies involving varying follow-up times. We discuss the NNT in these contexts and illustrate the concept using several published studies. The computation of the NNT is founded on the cumulative incidence of the outcome. Instead, several published studies use simple proportions that do not account for varying follow-up times, or use incidence rates per person-time. We show how these approaches can lead to erroneous values of the NNT and misleading interpretations. For example, a trial of 3,845 very elderly hypertensives randomized to a diuretic or placebo reported a NNT of 94 treated for 2 years to prevent one stroke, though the correct approach results in a NNT of 63. We also note that meta-analyses involve trials of differing lengths, but often report a single NNT. For example a meta-analysis of 22 trials of the anticholinergic tiotropium in chronic obstructive pulmonary disease reported a NNT of 16 patients “over one year,” even if the trials varied in duration from 3 to 48 months, with the more specifically computed NNTs varying widely from 72, 15, and 250 for the 3-month, 12-month, and 48-month trials, respectively. Finally, we describe the value of the NNT in assessing benefit–risk, such as low-dose aspirin use in secondary prevention, where prevention of mortality was assessed against the risk of gastrointestinal bleeding. As the “number needed to treat” becomes increasingly used in the comparative effectiveness and safety of therapies, its accurate estimation and interpretation become crucial to avoid distorting clinical, economic, and public health decisions.
Feelings of guilt have tormented Holocaust survivors, ranging from immediately after the liberation to later in life, for shorter or longer periods, and persisting for some throughout their entire post-war lives. Descriptions of the guilt experienced by survivors of the Nazi camps occupy an impressive amount of literature: “Why me?” was the question, when a younger and more able family member perished; “Why me?” when more productive members of the community perished; “Why me?” when a million and a half children were deprived of their lives. Many found the answer by retelling their stories, witnesses of what happened. This type of guilt is much different from the recently described phenomenon of survivor syndrome, namely the secondary guilt felt by Nazi-persecuted Jewish writers. Despite successes in all aspects of their life, these writers developed a self-incriminating guilt due to their perceived inadequacy of communicating, particularly in light of the resurging anti-Semitism worldwide. This paper deals with the survival and suicides of Nazi-persecuted Jewish writers and offers a possible explanation for their late self-destructive acts.
