In many research studies, tumor biopsies are an unavoidable requirement for achieving key scientific aims. Yet some commentators view mandatory research biopsies as coercive and suggest they should be optional, or at least optional until further data are obtained regarding their scientific usefulness. Further complicating the ethical picture is the fact that some research biopsies offer a potential for clinical benefit to trial participants. We interviewed and surveyed a convenience sample of participants in phase I clinical trials at a single (...) institution. Our primary aim was to describe phase I participants’ understanding of whether a research biopsy offered them the prospect of medical benefit. We also endeavored to describe participants’ views about biopsies—specifically, the benefits of biopsies, if any, and whether biopsies were acceptable, risky, or discouraged trial participation. Finally, we collected data on demographics and attitudes to see if any strong correlations with misunderstanding, acceptability, or riskiness existed. Overall, the respondents tended to view research biopsies as acceptable, though they did not succeed in identifying the lack of benefit of a research biopsy. These findings call for renewed efforts in consent conversations and documents to carefully describe the benefits, or lack thereof, of research biopsies. (shrink)

The Emergency Medical Treatment and Active Labor Act in 1986 was intended to bring an end to incidents of “patient dumping.” However, due to the conflation of various federal legislative provisions, hospitals faced with the prospect of long‐term unreimbursed care of an immigrant patient, whether legally present in the United States or not, are in some cases having such patients transported to another country. These transfers are often being effectuated without patient consent. After an overview of the flaws in the (...) legal system that have effectively encouraged such patient transfers, this essay uses a clinical case to demonstrate how physicians can collaborate with an interdisciplinary team and with family members to ensure that the best interests of immigrant patients are met. Finally, the essay calls on physicians to advocate for the development of hospital policies and practices that will protect patients from international patient dumping. (shrink)

Background: Post-mortem needle biopsies have been used in resource-poor settings to determine cause of death and there is interest in using them in Bangladesh. However, we did not know how families and communities would perceive this procedure or how they would decide whether or not to consent to a post-mortem needle biopsy. The goal of this study was to better understand family and community concerns and decision-making about post-mortem needle biopsies in this low-income, predominantly Muslim country in order to (...) design an informed consent process. Methods: We conducted 16 group discussions with family members of persons who died during an outbreak of Nipah virus illness during 2004-2008 and 11 key informant interviews with their community and religious leaders. Qualitative researchers first described the post-mortem needle biopsy procedure and asked participants whether they would have agreed to this procedure during the outbreak. Researchers probed participants about the circumstances under which the procedure would be acceptable, if any, their concerns about the procedure, and how they would decide whether or not to consent to the procedure. Results: Overall, most participants agreed that post-mortem needle biopsies would be acceptable in some situations, particularly if they benefitted society. This procedure was deemed more acceptable than full autopsy because it would not require major delays in burial or remove organs, and did not require cutting or stitching of the body. It could be performed before the ritual bathing of the body in either the community or hospital setting. However, before consent would be granted for such a procedure, the research team must gain the trust of the family and community which could be difficult. Although consent may only be provided by the guardians of the body, decisions about consent for the procedure would involve extended family and community and religious leaders. Conclusions: The possible acceptability of this procedure during outbreaks represents an important opportunity to better characterize cause of death in Bangladesh which could lead to improved public health interventions to prevent these deaths. Obstacles for research teams will include engaging all major stakeholders in decision-making and quickly building a trusting relationship with the family and community, which will be difficult given the short window of time prior to the ritual bathing of the body. (shrink)

Cancer is the second leading cause of death in developed countries, making it a global public health problem. In this scenario, early detection is the key to successful treatment. Tissue biopsy, the current gold standard for cancer diagnosis, offers reliable results, but it is feasible only when the mass becomes detectable. On the other hand liquid biopsy, a promising experimental system, not yet implemented within clinical practice, allows early detection as its functioning relies on the analysis of body (...) fluids. Yet, its results are less reliable if compared to those of tissue biopsy as, for instance, false positives and false negatives might occur. Despite technical features, the tradeoff between a reliable diagnosis available at a later time and a potentially less reliable diagnosis available at an early stage poses significant ethical challenges in the clinical scenario which involve, among other aspects, informed consent, communication, and patient-physician encounter. (shrink)

Cancer is the second leading cause of death in developed countries, making it a global public health problem. In this scenario, early detection is the key to successful treatment. Tissue biopsy, the current gold standard for cancer diagnosis, offers reliable results, but it is feasible only when the mass becomes detectable. On the other hand liquid biopsy, a promising experimental system, not yet implemented within clinical practice, allows early detection as its functioning relies on the analysis of body (...) fluids. Yet, its results are less reliable if compared to those of tissue biopsy as, for instance, false positives and false negatives might occur. Despite technical features, the tradeoff between a reliable diagnosis available at a later time and a potentially less reliable diagnosis available at an early stage poses significant ethical challenges in the clinical scenario which involve, among other aspects, informed consent, communication, and patient-physician encounter. (shrink)

Mainstream breast cancer social movements such as that of Susan G. Komen have called on all women to race or fight for the cure for breast cancer. They suggest that the fight can be won by buying and wearing pink ribbons, taking part in races and walks, donating money, and participating in research. For some patients with breast cancer, research participation may involve non-diagnostic tumor biopsies. While this clinical research is performed in the hope of gaining new knowledge through the (...) removal and study of breast cancer tissue, these procedures have been heavily criticized because they offer little potential benefit to the patient providing the tissue (Helft and Daugherty 2006; Kimmelman et al. 2012;... (shrink)

Conducting marine mammal research can raise several important ethical issues. For example, the continuation of whaling for commercial purposes despite the international moratorium provides opportunities for scientists to obtain data and tissue samples. In 2021 we analysed 35 peer-reviewed papers reporting research based on collaborations with Icelandic whalers. Results highlighted little consideration or understanding of the legal and ethical issues associated with the deliberate killing of whales amongst those researchers, funding bodies, universities and journals involved. Ethical statements were rarely provided. (...) Those that were written were incomplete. Whilst research using whaling data may seem acceptable to some, it often becomes hard to justify when subject to scrutiny by the media and the public. Thus, there is a particular danger of reputational harm for early career researchers who may become unwittingly involved in such activities. Here we also consider the broader variety of ethical issues raised by non-lethal research (both historical and recent) on marine mammals including tagging and biopsy. We discuss instances where study animals were harmed or even killed and where the public mistook tags for harpoons. Without clear guidelines, reviewers and journal editors are put in an impossible position when considering whether to reject papers on ethical grounds. We propose that for such studies, universities, funders, journals, and permit issuers must require ethical assessments and that journals more effectively implement their existing policies on publishing ethical statements. The professional marine mammal societies need to work together to produce modern ethical guidance. Such guidance should require transparency in the provenance of data and samples while including advice on law, welfare issues, involvement of local scientists, and offshoring. Furthermore, it should require appraisal of and justification for the absolute necessity of invasive procedures. As is already the case in biomedical disciplines, ethical statements should be required in marine mammal science. (shrink)

Renal biopsy is a potentially hazardous procedure, generally performed for therapeutic reasons. An open renal biopsy was performed when there appeared to be no accepted clinical indication and its results published in a specialty journal, whose editors declined publication of subsequent correspondence, questioning the ethical propriety of such a procedure. The implications for clinical practice, authors, editors and readers are discussed.

Many people believe that if we could produce meat without animal suffering—say, in ‘humane’ or ‘happy’ farms, or by growing it in a lab from biopsied cells—there would be no moral problem with doing so. This chapter argues otherwise. There is something morally ‘off’ with eating the flesh of sentient beings however it is produced. It is ‘off’ because anyone who truly understands the intimate relationship that an animal’s body stands in to all the value and disvalue in their lives (...) would not want to eat flesh. The chapter concludes by arguing that, as a society, we should not switch over to ‘happy’ or lab-grown meat. Instead, it is imperative that we pursue a public reckoning on our treatment of animals in factory farms, not only for the sake of animals, but for the sake of humanity itself. (shrink)

Screening for prostate cancer with the prostate-specific antigen blood test is controversial, as evidence to date has not demonstrated such screening does more good than harm. While the potential benefit of PSA screening on reducing prostate cancer mortality has not been documented in randomized trials, many risks of PSA screening have been well documented. These risks include a substantially higher risk of a prostate cancer diagnosis over a screenee’s lifetime, false-positive and false-negative test results, possible complications from biopsies done in (...) response to suspicious test results, and substantial risks of side effects from subsequent prostate cancer treatments. Nevertheless, PSA screening is widespread in the United States, and many physicians in a national survey reported supporting routine PSA screening as well as getting PSA tests themselves, despite the lack of evidence. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:It's Not Always Just a RashAdam BossertI looked at the emergency department track board and saw a patient waiting for a provider who was "roomed" in a hallway stretcher with a chief complaint of a rash. I briefly considered his ultimate disposition, "He's probably fine. He can't be that sick if he was triaged as safe for the hallway." I was tired and close to the end of an (...) overnight shift and thought he would be a quick turnaround, likely discharged, since rashes are typically benign. I walked over to his stretcher after a quick chart biopsy that highlighted his mildly increased heart [End Page 24] rate on arrival as well as his history of polysubstance use and homelessness."Hey doc, I don't feel so good.""I'm sorry to hear that. What's specifically bothering you?""I am itching all over with these bumps. My skin is red, and I also think I'm withdrawing since I have body aches and chills."The interview continued.I discovered his last heroin use was approximately eight hours prior to arrival. I thought he was an ideal candidate for buprenorphine since he was actively withdrawing. I was recently licensed to prescribe this medication and excited to use my license for the first time. He declined the suggestion, however, preferring methadone instead. Buprenorphine can precipitate withdrawal if not given long enough after opioid use or if an incorrect dose is given; thus, many patients are hesitant to take it. He also stated he was predominantly here for his rash and did not want rehabilitation placement. I ordered our initiation methadone dose as well as a screening COVID-19 test and a urine drug screen test, which are both needed for rehabilitation placement in case he changed his mind.His rash was highly suspicious for scabies. He was covered with red bumps that spared only his face, some in linear distributions, and was actively scratching his arms and legs during the interview. I prefer oral ivermectin over topical permethrin for the homeless population simply for ease of administration, lower cost, and increased compliance. He received ivermectin for his scabies and knew he could return to the emergency department for a repeat dose if he was unable to fill a prescription.What happened next is, in my experience, an all-too-common scenario.The patient told me that the methadone is "doing nothing." I explained he could no longer take buprenorphine since he already received methadone, which only made him more frustrated. Unfortunately, I am restricted with the amount of methadone I can give in the emergency department, largely due to the drug's long half-life, and thus I was unable to give him more, let alone attempt titrating to his tolerance.Opioid withdrawal is not a life-threatening diagnosis; these patients are not typically admitted to the hospital. The management consists of initiating either methadone or buprenorphine, symptomatic treatment and then outpatient referral or rehabilitation placement. I explained the options to him, and he requested to be discharged since he was deferring rehabilitation. He was discharged. I was able to treat his rash but his chronic illness, opioid use disorder, was not controlled.I discharge a patient in opioid withdrawal or who has opioid use disorder almost every day, and I think most emergency medicine physicians would echo that statement. The disposition is not wrong from the perspective of the individual physician, but it feels like the system has failed these patients when I think of the frequency that they return and their baffling risk of overdose. The latter can be reduced by giving patients Narcan, the drug to reverse opioid overdose, upon discharge but this is just placing a bandage over the problem and not all emergency departments can fund this risk-reduction tool.I saw my patient's COVID-19 result return as I wrapped up my shift. It was positive. And, of course, he was in our department's hallway the whole time, only intermittently using his mask. I suddenly realized that while yes, he was withdrawing, he also may have had a symptomatic COVID-19 infection! I quickly reopened his chart, only to... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Feminist Studies 41, no. 3. © 2015 by Feminist Studies, Inc. 571 Moving through Cancer: An Interview with Carol Collins Artist Carol Collins spoke with Feminist Studies editorial collective member Stephanie Gilmore about her experience of cancer, treatment, and recovery and how it gave rise to an art series that examines what nature means in the midst of unnatural treatments. SG: Carol, thank you for the opportunity to speak (...) with you about your artwork. Having just lost my sister to cancer, your work reminds me of much pain and loss, but also of love and the desire to survive. Before we discuss the work itself, I would like to hear about your journey through cancer, treatment, and recovery. CC: The breast cancer patient’s journey is complex and perilous. When I was healthy, I was ignorant about the magnitude of suffering many cancer patients undergo. And, although I am a private person, I’m now publicly sharing my cancer experience in order to be a voice for those who have suffered through similar treatments—and worse—and those who sadly are no longer with us to tell their story. Being bald and nauseated are not the most awful possible side effects of the treatments, although they are the most well known. Some women survive the cancer but can die from the treatments, or others suffer through the treatments and die anyway. Often, it seems many believe patients can overcome their 572 Carol Collins adversity solely with positive thinking and persistence. However, not discussing the array of physical and psychological damage that even those with good prognoses incur propagates ignorance about this malady. I hope that my artwork and story will promote a deeper understanding of a breast cancer patient’s plight and will encourage more support for research for individualized therapies and prevention. My cancer journey began when I received a breast cancer diagnosis in January 2014. Life just before that point was good; the future was bright. Tendon pain, caused by my flat feet and a lot of exercising, was my only known ailment. But one day a routine mammogram revealed three tumors in my right breast. The radiology oncologist said the masses were highly likely to be cancerous, so he immediately did painful core biopsies at the sites of my three tumors. The next day, it became clear that we needed to act quickly. The biopsy results revealed I had a very aggressive invasive breast cancer with estrogen, progesterone, and HER2 receptors. Breast cancer in premenopausal women grows quickly due to the high level of hormones present. The oncologists and surgeons said I would, at a minimum, need a mastectomy and possibly lymph node resection, and they warned that I would likely need chemotherapy, which would destroy my eggs and ovaries. After learning of my limited options, I approved the removal of one breast and my sterilization. I knew I needed to think rationally and face the giant raven before me head on. However, I did not realize the magnitude and multitude of physical and psychological pains, illnesses, and losses that were soon to come. The first year of cancer treatments inflicted much physical pain. I received three extremely painful injections into my right breast with a radiolabeled colloid just prior to the mastectomy. The pain came from the injected dye, not from the needle. The modified radical mastectomy was more excruciatingly painful than I anticipated, even with painkillers and overnight hospitalization. Breast reconstruction was an option that added more pain and discomfort from weekly fillings of the installed “expander” and additional surgeries. Extreme pain after the mastectomy prevented me from lying down for months. Foolishly, I did not get an injection port installed in my chest. Instead, I endured numerous deep (and often unsuccessful) needle pricks into the seemingly few veins of my left arm (which still had its lymph nodes) that were appropriate for infusions over the period of a year. Shooting pains across my chest and arm were the norm. Carol Collins 573 In addition to the surgically induced physical pain, the chemotherapy quickly caused a myriad of undesirable physical side effects. It is scary to realize that the medical community does not often fully understand... (shrink)

During a prostate exam, Mr. Watson, age 65, learns that his prostate appears to be abnormal. The family physician conducting the exam, Dr. Kleinman, informs Mr. Watson that he may have prostate cancer. Mr. Watson agrees to a variety of tests, including blood tests, bone scans, ultrasound scanning, and a biopsy. After learning about this possible diagnosis and these tests, Mr. Watson surfs the Web for information about prostate cancer and gathers data from many different sources, including the National (...) Cancer Society, the National Institutes of Health, Johns Hopkins University, the Mayo Clinic, and medicine sites. He also searches for information from medical journals using MEDLINE, visits several chat rooms on prostate cancer, and joins some e-mail lists. He arrives in Dr. Kleinman's office for a follow-up appointment with a stack of material and many questions. Dr. Kleinman is surprised, irritated, and offended. He recommends that Mr. Watson have a prostatectomy followed by radiation, but Mr. Watson does not want this operation. He would rather receive a form of radiation therapy recently approved by the FDA that he learned about through his own research. Dr. Kleinman admits that he does not know much about this new treatment, but he says that he would read up on it and consult an oncologist. (shrink)

Purpose The search for cause of death is important to improve knowledge and provide answers for the relatives of the deceased. Medical autopsy following unexplained death in hospital is one way to identify cause of death but is difficult to carry out routinely. Post mortem sampling (PMS) of tissues via thin biopsy needle or ‘mini incisions’ in the skin may be a useful alternative. A study was undertaken to assess how this approach is perceived by intensive care doctors and (...) also to evaluate how this practice is considered in ethical terms in France. Methods A study of PMS practices immediately after death in 10 intensive care departments was performed. The medical director of each centre was interviewed by telephone and asked to describe practices in their unit and to outline the questions raised by this practice. Results PMS is routinely performed in 70% of the units which responded, without systematically obtaining formal consent and without precise rules for communicating results. Approaches to PMS differed between centres, but all physicians felt that PMS is useful for the scientific information it gives and also for the information it provides for relatives. All physicians regret the lack of standards to structure PMS practices. Conclusion Information from post mortem examinations is important for society to inform about causes of death, for doctors to improve practices and for decision-makers responsible for organising care. Debate persists regarding the balance between individual rights and community interests. It is suggested that an approach for identifying cause of death could easily be integrated into the relationship between carers and relatives, provided full transparency is maintained. (shrink)

Moral principles or the rules of conduct are based in the society. If the purpose of ethics in research is to take into consideration the needs and the rights of the experimental subject, his social milieu must then largely determine the ethical considerations of a projected study. The inability to comprehend such rights may often be due to ignorance, disease and his societal values. Blood letting, biopsy and post-mortem examinations may so conflict with local beliefs that so called 'consent' (...) to these is much more than a surrender of the rights of the individual. It is difficult to conform with the highest principles of ethics in research in any uniform society. It is more so when the many variables are further complicated by cultural demands and social taboos. The best custodians of ethical standards must relate intimately with the norms of the local population. (shrink)

Background:: Over the past few years, research ethics committees have increasingly demanded explicit consent before archival tissue samples can be used in research projects. Current UK guidance in this area requires an assessment of whether it is “practical” to obtain explicit consent. Ethics committees have little experience or evidence to help them to judge what is “practical” in this context.Methods:: We attempted to obtain general consent for research use of surplus tissue from renal transplant biopsies from the entire patient population (...) of the renal transplant unit in Leicester. The nature of this patient population would be expected to facilitate this task.Results:: A total of 495 letters were sent. Attempts were made to contact non-responders when they attended the outpatient clinic. One year after the initiation of the project, the opinions of 26% of the patients had still not been ascertained.Conclusions:: The results confirm that the vast majority of patients are happy for “surplus” biopsy material to be used for research; the situation does not parallel the use of autopsy tissue. A requirement to obtain explicit consent for the study of archival tissue is likely, however, to block or at least seriously delay research, which is contrary to the public interest and specifically may harm the interests of the patients concerned. In the UK, the problem of tissue being used against the wishes of the donor has now been largely replaced by the problem of prohibition of tissue use against the wishes of the donor. (shrink)

The Knowledge Based System for Diagnosing Breast Cancer is used to assist medical students to improve their education on diagnosis and counseling the process of analyzing the biopsy image of the microscope, determining the type of tumor and the treatment method for each case and identifying the disease related questions. According to the Ministry of Health in its annual report in Gaza, between 2009 and 2014 there are 7069 cases of breast cancer, and in 2014 there are 1502 cases (...) of breast cancer . We are now in the age of visual information where 65% of the populations are visual learners; the Knowledge Based System is the easiest way to ensure students remember the information in the long term, using visual and textual information. The Knowledge Based System has an easy-to-use interface to help students diagnose the disease and enhance their information about the disease; the system can be used on smart phones. This Knowledge Based System can be divided into three main parts: The first part is specific questions for the patient, to help student to know questions type. The second part is the process of analyzing the biopsy sample image, to see if the biopsy image is intact or infected. The last part is the video shows ways to treat breast cancer in the form of animation. (shrink)

BackgroundThe psychological burden possibly deriving from not immediately undergoing radical treatment for prostate cancer could be a potential disadvantage of active surveillance, especially in the eve of some relevant clinical exams [i.e., re-biopsy, prostate-specific antigen test, and medical examination]. Even if it is known from the literature that the majority of PCa men in AS do not report heightened anxiety, there is a minority of patients who show clinically significant levels of anxiety after diagnosis. The present study aimed to (...) investigate if demographic, clinical, and psychological variables at the entrance in AS were associated with the risk of developing clinically significant PCa-related anxiety 2 months before the first re-biopsy and to offer psychological support to improve quality of life.Materials and MethodsA total of 236 patients participated in the PCa Research International: AS protocol and in PRIAS-QoL study. Demographic/clinical features, health-related QoL domains, coping with cancer, PCa-related anxiety [Memorial Anxiety Scale for PCa ], personality traits, and decision-making-related factors were assessed at T0. MAX-PC was also administered at T1. PCa-related anxiety at T1 was considered to be of clinical significance if the MAX-PC score was ≥1.5. Multivariable logistic regression coupled to bootstrap was used to detect factors associated with high levels of anxiety.ResultsThe median age was 64.4 years. Fifty-six patients reported MAX-PC total score above the cutoff. Three factors were associated with a high level of PCa anxiety at T1: anxious preoccupation [odds ratio = 4.36], extraversion, and prostate-related symptoms. Physical well-being was associated with a low PCa anxiety subscale ; neuroticism and functional well-being were associated with PSA anxiety. Neuroticism and helplessness/hopelessness were associated with fear of progression.ConclusionOnly a partial portion of the sample experienced significant levels of anxiety after 10 months. Psychological assessment should be routinely conducted to detect risk factors for increased anxiety, offering tailored psychological interventions aimed at promoting interpersonal awareness and emotional well-being. (shrink)

Bradford C Bemiss, Chad A WittDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO, USA: Chronic rejection is a major cause of death after the first year following lung transplantation. Bronchiolitis obliterans is the most common pathologic finding on biopsy, characterized by fibrous granulation tissue, which obliterates the lumen of the bronchiole. Clinically, in the absence of tissue for pathology, BO syndrome refers to a progressive irreversible drop in the (...) forced expiratory volume in 1 second. Recently, a broader definition of chronic rejection, termed "chronic lung allograft dysfunction", has been used to encompass a more inclusive definition of posttransplant dysfunction. Recently, the lung transplant community has come to realize that chronic rejection may be the final common result after repetitive epithelial insults. Acute rejection, infection, and alloreactivity to mismatched HLA antigens are a few of these insults that damage the surface of the bronchioles. Recent evidence of autoimmunity to the normally hidden structural proteins collagen V and K-α1 tubulin have been correlated with a BO phenotype as well, perhaps correlating the epithelial damage with a mechanism for developing BO lesions. Many immunomodulatory medications and treatments have been studied for effectiveness for the treatment of chronic lung allograft dysfunction. New drugs, which more precisely target the immune system, are being developed and tested. Further study is required, but recent advances have improved our understanding of the pathogenesis and potential intervention for this common and deadly complication of lung transplantation.Keywords: lung transplant, bronchiolitis obliterans syndrome, rejection. (shrink)

We present the case of a six-year-old child with a fatal brainstem tumour, who was left in a ‘locked-in state’ post-decompressive biopsy. A discussion of the ethical dilemma this situation presents, together with the deliberations of the ethics service when consulted about the optimal course of action, follow. The issues raised highlight an important conflict between the parental view of what is in the child's best interests and what may appear, prima facie, to clinical staff, to be in that (...) child's best interests. We discuss how creative ethical thinking may facilitate resolution of seemingly insoluble situations. (shrink)

Prostate cancer (PCa) is one of the the most common cancers in men. A blood test called prostate-specific antigen (PSA) has a potential to pick up this cancer very early and is used for screening of this disease. However, screening for prostate cancer is a matter of debate. Level 1 evidence from randomised controlled trials suggests a reduction in cancer-specific mortality from PCa screening. However, there could be an associated impact on quality of life due to a high proportion of (...) overdiagnosis and overtreatment as part of the screening. The US Preventive Services Task Force (USPSTF) in 2012 recommended that PSA-based PCa screening should not to be offered at any age. However, considering the current evidence, USPSTF recently revised its recommendation to offer the PSA test to men aged 55–69 years with shared decision-making, in line with earlier guidelines from the American Cancer Society and the American Urological Association. A shared decision making is necessary since the PSA test could potentially harm an individual. However, the literature suggests that clinicians often neglect a discussion on this issue before ordering the test. This narrative discusses the main controversies regarding PCa screening including the PSA threshold for biopsy, the concept of overdiagnosis and overtreatment, the practical difficulties of active surveillance, the current level 1 evidence on the mortality benefit of screening, and the associated pitfalls. It offers a detailed discussion on the ethics involved in the PSA test and highlights the barriers to shared decision-making and possible solutions. (shrink)

This paper reports on recent regulations and guidelines in the Federal Republic of Germany bearing on perinatal medical ethics, embryo research and trophoblast biopsy. Some of the regulations are defensive responses to new moral opportunities. In contrast, this paper calls for a more aggressive moral cost-benefit assessment of high technology medicine, which would include large-scale research on embryos prior to the fiftieth day post-menstruation. Keywords: abortion, embryo research, moral triage, prenatal diagnosis, withholding treatment CiteULike Connotea Del.icio.us What's this?

Should offenders with psychopathy or those exhibiting extreme forms of antisocial behav- iour be considered criminally responsible? The current debate seems to have reached a stalemate. Several scholars have argued that neuropsychologi- cal data on individuals with psychopathy might be relevant for determining their criminal responsibil- ity. However, relying on such data has not produced a consensus among legal scholars and philosophers on whether individuals with psychopathy should be excused from responsibility. We offer a diagnosis about why this debate has (...) reached a standoff. We argue that part of the problem is that psychopathy, being a syndrome-based category, is too heterogeneous and thus offers low prospects for being integrated with neuropsychological data that might support significant conclusions about the criminal responsibility of individuals with psychopathy. Moreover, the construct of psychopathy was not originally devised to discriminate criminally accountable from unac- countable antisocial individuals. To overcome these difficulties and advance the debate, we extend a currently less discussed theoretical framework for bridging biopsychology and the law that focuses on neuropsychological constructs, domains, and processes that directly measure capacities of offenders that are relevant for criminal responsibility, without necessarily relying on mediating syndrome-based constructs. The novelty of our contribution is that the biopsy- chological bases of exculpation can be further devel- oped and used for determining more fine-grained cat- egorisations of antisocial personality types. We show how this framework provides guidelines for inter- disciplinary research that can significantly advance our understanding of the preconditions for criminal responsibility and help the legal practice of ascribing or withholding it. (shrink)

On September 27, 2016 people across the world looked down at their buzzing phones to see the AP Alert: “Baby born with DNA from 3 people, first from new technique.” It was an announcement met with confusion by many, but one that polarized the scientific community almost instantly. Some celebrated the birth as an advancement that could help women with a family history of mitochondrial diseases prevent the transmission of the disease to future generations; others held it unethical, citing medical (...) tourism and consequences for the future of the therapy. The child in question was actually born a few months earlier on April 6, 2016, but the research was published a few months later in the October edition of Fertility and Sterility. The mother carries DNA that could have given the baby Leigh Syndrome, a severe neurological disorder characterized by psychomotor regression that typically results in death between ages two and three.[1] Also known as subacute necrotizing encephalomyelopathy, Leigh Syndrome is caused by genetic mutations in mitochondrial DNA, which causes defective oxidative phosphorylation. Because people with this condition cannot re-form ATP, “demyleniation, gliosis, necrosis, spongiosis, or capillary proliferation”[2] can occur, thereby producing bilateral lesions across the central nervous system. The 36-year-old mother previously had four miscarriages and successfully birthed two children, both of whom survived less than six years due to the syndrome. For religious reasons, the mother opted for Spindle Nuclear Transfer instead of Pronuclear Transfer,[3] which many religious organizations oppose because it entails the destruction of fertilized eggs.[4] In Pronuclear Transfer, both the parent and donor egg are fertilized. The parent’s nuclear material is then removed from the egg containing mutated mitochondria and inserted into the fertilized donor egg—from which the original nuclear material has been removed and destroyed. Spindle Nuclear Transfer, on the other hand, removes the mother’s nuclear material from the egg with unhealthy mitochondria, then implants it into a donor’s egg. The newly created egg is then fertilized with the father’s sperm. This Spindle Nuclear Transfer was performed in Mexico by a team of doctors led by Dr. John Zhang, the founder of the New Hope Fertility Center in New York City. In their report, the doctors outline that five oocytes were successfully reconstituted, four of which developed into blastocysts. Only one was euploid: containing 46 XY chromosomes. Researchers then biopsied that blastocyst and found that the transmission rate of maternal mtDNA was, “5.10 ± 1.11% and the heteroplasmy level for 8993T>G was 5.73%.”[5] This indicates that at the blastocyst stage, around five percent of the mitochondria are from the original maternal egg with the mutation for Leigh Syndrome. After birth, they biopsied different tissues and found that they had an average of less than 1.60 ± 0.92% of transmitted mtDNA from the original maternal egg. The baby is reportedly doing well and the team of doctors concluded that “[h]uman oocytes reconstituted by SNT are capable of producing a healthy live birth. SNT may provide a novel treatment option in minimizing pathogenic mtDNA transmission from mothers to their babies."[6] Even when considered theoretically, Spindle Nuclear Transfer is controversial. Many doctors believe that the risks at this stage of research are too great. Dr. Trevor Stammers, a bioethicist at St. Mary’s University in London, points out: “We do not yet have a clear picture of the interaction between nuclear DNA and mitochondria.”[7] Others hold that faulty mitochondrial DNA can still be transferred during the procedure. Still more argue this technology could create problems because of germline modification.[8] Dr. Paul Knoepfler, a cell biologist at the UC Davis School of Medicine, explains: “Since this is uncharted territory and the children born from this technology would have heritable genetic changes, there are also significant unknown risks to future generations.”[9] However, proponents counter these arguments. They say the benefits outweigh the risks, as “mitochondrial replacement techniques [like Spindle Nuclear Transfer] would eliminate maternal transmission of mitochondrial disease… allowing a woman with a family history of mitochondrial diseases to ensure her children would not be affected.”[10] Additionally, experts say that no symptoms will occur if less than 20% of the transferred mitochondrial DNA is faulty.[11] And while opponents see potential germline modification as a problem, advocates answer that this could stop a family history of mitochondrial disease, which they deem a more serious concern. In this case specifically, however, there are more issues at hand. While the team of doctors did eliminate the possibility of germline modification by selecting a male embryo, there are other ethical concerns. Some argue that this case could be described as “medical tourism.” While New Hope Medical Clinic does maintain a branch in Mexico, Dr. Zhang stated that Mexico has “no rules.”[12] It is a country with underdeveloped regulations, making it difficult to confirm that doctors adhere to widely-held medical and ethical standards. Furthermore, while it is highly unlikely that the child will develop Leigh’s Syndrome, Dr. Dietrich Egli of the New York Stem Cell Foundation says the 5% mitochondrial transfer rate indicates that the technique “was not carried out well.”[13] He points to studies of embryos where the rate of mtDNA transfer was almost ten times lower. Spindle Nuclear Transfer is currently legal in the UK,[14] and many are hoping to see it legalized in the US, although Congress currently prohibits the FDA from considering applications that would entail trials in people.[15] While Dr. Zhang’s work is arguably revolutionary, many wonder if the manner in which this study was performed—in Mexico and with a high mitochondrial transfer rate—will impact the technology’s future in the US. Last week, Dr. Zhang presented the report to scientists gathered in Salt Lake City, saying that while science isn’t a race, it is “in a sense, a race for the family to find a cure, to find hope.”[16] Only time will tell if this study set back other families racing and hoping for a cure. References 1. "Leigh Syndrome." Genetics Home Reference, US National Library of Medicine, 25 Oct. 2016. Accessed 26 Oct. 2016. 2. McKusick, Victor A., and Ada Hamosh. "LEIGH SYNDROME; LS." Online Mendelian Inheritance in Man, Johns Hopkins University, 20 Jan. 2016. Accessed 30 Oct. 2016. 3. Zhang, J, H Liu, S Luo, A Chavez-Badiola, and Z Liu. "First live birth using human oocytes reconstituted by spindle nuclear transfer for mitochondrial DNA mutation causing Leigh syndrome." Fertility and Sterility, vol. 106, no. 3, 2016, pp. e375-76. Accessed 30 Oct. 2016. 4. Sample, Ian. "‘Three-parent’ babies explained: what are the concerns and are they justified?" The Guardian, 2 Feb. 2015. Accessed 30 Oct. 2016. 5. Zhang, et al. 6. Ibid. 7. Knapton, Sarah. "Three-parent babies: the arguments for and against." The Telegraph, 3 Feb. 2015. 8. Ibid. 9. Ibid. 10. "Mitochondrial Replacement Therapy FAQs." New York Stem Cell Foundation Research Institute, New York Stem Cell Foundation. Accessed 30 Oct. 2016. 11. Reardon, Sara. "‘Three-parent baby’ claim raises hopes — and ethical concerns." Nature, 28 Sept. 2016. Accessed 30 Oct. 2016. 12. Hamzelou, Jessica. "Exclusive: World’s first baby born with new “3 parent” technique." New Scientist, 27 Sept. 2016. Accessed 30 Oct. 2016. 13. Reardon, Sara. "‘Three-parent baby’ claim raises hopes — and ethical concerns." Nature, 28 Sept. 2016. Accessed 30 Oct. 2016. 14. "3-Person IVF: A Resource Page." Center for Genetics and Society, 24 Oct. 2016. Accessed 30 Oct. 2016. 15. Ritter, Malcolm. "Baby born with DNA from 3 people, first from new technique." Associated Press, 27 Sept. 2016. Accessed 30 Oct. 2016. 16. Chen, Daphne. "Controversy swirls around first three-parent baby." Deseret News, 19 Oct. 2016. Accessed 30 Oct. 2016. Works consulted Swetlitz, Ike. "FDA urged to approve ‘three-parent embryos,’ a new frontier in reproduction." STAT, 3 Feb. 2016. Accessed 30 Oct. 2016. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Life in LimboM. ChiuWhen my son was 7 years old, he began complaining of headaches. They were frequent, but never seemed severe. “I have a headache!” was always followed by “Can I watch TV?” I didn’t believe the pain was real until it woke him up in the middle of the night. I knew then that something must be wrong. I approached our pediatrician, who said it sounded like (...) migraines, but we should order an MRI to rule anything out. The appointment was scheduled several months in advance, and I always had the urge to cancel it. I was pretty sure my son just wanted to watch TV. The pediatrician told me I might as well do the MRI. He told me that if we skipped it and something was wrong, I would never be able to live with the regret. We kept the Monday morning appointment, and went to the MRI expecting reassurance that nothing was wrong. Instead, we got a phone call later that day. They needed to see us on immediately, but wouldn’t tell me why. Of course, I knew something was wrong. “Is it a tumor?” I asked. “This isn’t something we can discuss on the phone” was the answer I got. An appointment was scheduled for Wednesday. Two days might be “immediately” to medical professionals, but to a parent who just heard that her child had an abnormal MRI, it was an eternity. I planned my son’s funeral in those two days.Our meeting with the Neurologist began with reviewing the MRI. “See this spot here? It shouldn’t be there”. A tumor. 1 ½ × 1 ½ × 2 ½ cm tumor, in the right thalamus. Small, they said. Looks like a Low Grade Glioma they said. The kind of tumor you want to have, if you have to have a brain tumor. A biopsy was scheduled for two weeks later. The [End Page E2] biopsy confirmed it was a Juvenile Pilocytic Astrocytoma (JPA). The neurosurgeon was confident she could remove all of the tumor. We were at one of the best Children’s Hospitals in the world. We were in good hands.A few days before the surgery, a friend who is a medical doctor suggested we get a second opinion. “It couldn’t hurt, it could help”, my husband said. Fortunately, he just sold a start–up company, and was planning to take a few months off from work before starting his next venture. He had time to research, talk to friends in the medical field and make phone calls.Our second opinion from another leading hospital reviewed the MRI’s with us. The neurosurgeon asked, “Did they say tumor? One?” Yes, they did. “See this here?” he said, pointing to a second spot on the MRI. He said it was possibly a second tumor, or more likely, an extension of the first. It was in inoperable location. Surgery wasn’t an option. Chemo would be our best choice. Why would we cut into our son’s brain to remove part of the tumor when he would need to do chemo anyway? Why not try chemo first?I would like to say that we do not fault our original neuro–oncology team for missing this second abnormality. It is hard to notice an ant in the room when there is an elephant staring at you. People make mistakes, and tumors don’t always look the same. That’s what second opinions are for. That is why doctors should encourage patients to get second opinions.We scheduled the surgery for port implantation, and got busy educating ourselves about chemo regimes. It was going to be a long journey. 18 months of transfusions with a pretty low success rate and a high rate of secondary complications. Unsure if we were doing the right thing, we got a third opinion. I am so grateful that my husband was between jobs and had time to devote to finding the best possible treatment for our son. We were financially stable and had great insurance. What do people do when they don’t have this luxury?By now, several months had passed since our first MRI. Our... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Consenting for Novel and Dangerous Surgical Procedures with Minimal Supporting EvidenceMichelle J. ClarkeFrank1 was a 19–year–old man referred to me after a workup for back pain led to the discovery of a large, aggressive tumor in his sacrum. The tumor wrapped around the nerves controlling bowel, bladder, and leg function. We performed a needle biopsy and learned that the tumor was an angiosarcoma, an extremely aggressive and usually (...) deadly form of cancer. However, the tumor was unique in that it theoretically could be cured if removed in one piece. But, to do so would necessitate sacrificing the nerves, leaving the patient irreversibly incontinent, lacking sexual function, and confined to a wheelchair.Once we knew the diagnosis, Frank came to the office with his family to discuss treatment options. He appeared terrified and was almost silent through the appointment, deferring most questions to his parents. Due to the speed of tumor growth, we discussed palliative therapy, conventional treatment, and the one–piece or “en bloc” surgery, which was new and unproven for his disease. Based on the remarkable tumor growth we noted during the work–up, with palliative treatment the patient would likely survive for less than six months. Conventional treatment, in which surgery is done to remove part of the tumor while sparing the nerves to bowel and bladder function, was known to have a high rate of recurrence and death. Further, this tumor didn’t respond well to radiation and chemotherapy, so chance of survival was limited, although his life might have been extended for a short period. Thus our conversation turned to the novel “en bloc” procedure.The en bloc procedure offered a hope of long–term survival unlike the other options. However, this came with an enormous cost. The surgery itself would be planned to occur over three days with five separate surgical teams and a very real chance of major complications or death. Nerves to bowel and bladder would be cut, irreversibly leaving the patient without sexual function, and completely incontinent with a urinary catheter and colostomy. Walking was expected to be disrupted or potentially impossible due to the nerve resection. We went to great lengths over the course of many visits to describe the impact of the surgery on the patient’s function, and the impact on his quality of life. To make matters more challenging, as this procedure was so new and the tumor so rare, research did not yet exist to quantify his likelihood of long–term survival.Personally I was very uncomfortable with the situation. From a medical standpoint, the surgery offered was the best distillation of research and professional experience. En bloc surgery offered the best—if not the only—chance for survival in [End Page 5] this young man. Additionally, having treated many spine–injured patients I was aware that many patients with similar deficits led happy and productive lives following an emotional and physical adjustment period. However the surgery was also extreme. I worried that we would not be able to accomplish the goal of a one–piece resection and would accidentally spill some of the tumor, creating all of the deficits but no survival benefit. Frankly, I thought there was a 25% chance that would happen, which was explained to the family preoperatively. Were we overreaching our abilities and making a dying patient’s life worse by proceeding?Second, I was uneasy about the social situation. The patient’s family was very supportive, traveling with him to all appointments and assisting with his care. The patient himself usually deferred all scheduling to his mother, which wasn’t entirely unusual for such a young man. However it was difficult to grasp how much the patient understood of his disease or supported the plan. We attempted to delve more deeply into his thoughts, including without his parents present, but got only short answers, which revealed little. While the family appeared to have accepted the diagnosis and wanted to get to the business of treatment, the patient seemed to me to still carry the shock of his recent cancer diagnosis. Pushed by the rapid tumor growth, we were limited in how long we could wait for... (shrink)

Anna J Dare,1 Anthony RJ Phillips,1–3 Michael Chu,1 Anthony JR Hickey,2 Adam SJR Bartlett1–31Department of Surgery, 2Maurice Wilkins Centre for Biodiscovery, University of Auckland, Auckland, New Zealand; 3New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New ZealandBackground: Hepatic steatosis is increasingly encountered among organ donors. Currently, there is no consensus guideline as to the type or degree of donor steatosis considered acceptable for liver transplantation, and little is known about local practices in this area. The aim of this survey (...) was to evaluate current clinical practices amongst liver transplant surgeons in Australia and New Zealand in the evaluation and use of steatotic donor livers in LT.Methods: An anonymous online twelve-question survey was emailed to all practicing LT surgeons in ANZ in January 2010.Results: The response rate was 83%. Estimated prevalence of steatosis in donor livers was between 40% and 60%. In determining suitability for LT, 90% of respondents reported rejecting organs with "severe" steatosis based on visual and palpation grounds alone. A total of 68% sought further histological assessment if the donor liver looked bad and there were risk factors for steatosis. The majority of respondents performed only one biopsy of the liver, using hematoxylin and eosin staining for fat assessment. There was wide variation in the upper limit of steatosis considered to be acceptable for LT. A total of 21% of respondents still considered microvesicular steatosis a risk factor for primary graft nonfunction.Conclusion: This survey highlights the significant variation in the appraisal and use of steatotic grafts by LT surgeons in ANZ. Accurate evaluation and judicious use of mild and moderately steatotic grafts is required if we are to utilize the available donor pool best.Keywords: liver transplantation, steatosis, fatty liver, organ donors. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Michael’s Story or the Paradox of NormalcyMichael KreuzerI was born in Montreal in 1974. My parents were both “older.” My mother was almost 45; my father was in his 50’s. I have a sister who is six years older than me. What I know about my mother’s prenatal care is that it was quite basic.I was premature. My mother’s due date was in mid–August, however I showed up about (...) three weeks earlier. I know that initially upon my birth I was declared male. However, upon closer examination, a few “abnormalities” of my genitals were found. I urinated through a small hole at the base of my penis; adjacent to this hole was another opening, barely big enough for a Q–tip. My scrotum was empty; my gonads had not descended.The doctors who examined me decided that they could not assign a gender without further testing. They told my mother I would need to remain in the hospital until such testing was completed. Apparently not being able to determine sex/gender is a life–threatening condition that requires hospitalization.It was determined that I had a uterus and it was presumed that my undescended gonads were ovaries (not verified by biopsy). There was a small vaginal opening behind my small urethral opening. Structures such as the labia were not developed. I found out later my vagina had fistulated into both my urethra and my perineum. Karyotyping was performed resulting in 46,XX with a diagnosis of female pseudo–hermaphroditism. My parents were informed that in spite of my external genitalia I was female and I would never develop as a male. I would require “corrective surgeries” which should be performed as soon as possible so I would not have any issues with my gender identity. They were even told that I would be able to become pregnant if I had the surgeries. In fact, I never ovulated and I have a small unicornuate uterus.My father refused all surgeries on my behalf most likely because he was a full–blooded Navajo who had suffered from abuse in an Indian boarding school during his childhood in New Mexico. His family was traditional, and because they didn’t adapt to prevailing Christian values, he and several of his siblings were removed from their parents. My dad was the oldest of 12 children and by the time his youngest siblings were born, the practice to take children away from their families had been changed.I think my father was deeply traumatized by his childhood and did not associate much with his family, nor did he want to visit the reservation. He spoke the language but never encouraged us to learn it. He did teach us some of the traditions. He told me about the nadleh, which is the other gender besides male and female in the Navajo tradition. There are two kinds of nadleh, which are almost like male–to–female and female–to–male transsexuals. Mostly I educated myself later and learned about the Navajo belief system in which the creation story is an important part. In the Navajo tradition, the creation story tells of First Man and First Woman; the first children born to them are the Hermaphrodite Twins. [End Page E7]My father was a US Army Master Sergeant, which was an unusual career for a man of his origins; he was a veteran of the Second World War. After he left the army he took his family to Montreal where he had a job in security. I think he preferred to live outside the U.S. He used to say that in Germany, where he had managed to stay for a long time while serving in the Army, he was just another American soldier. In spite of his career, he had a deep mistrust for “white people.” I remember he used to say that he was in the Army because this was his country long before the white people came and he loved it. He did not love the people who governed it. All this very much played into the decision not to listen to the doctors’ recommendations about surgery. My... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:When OPRR Comes Calling:Enforcing Federal Research RegulationsCharles R. Mccarthy (bio)In an update following this article, Ruth Macklin responds to the revelation that the controversial Hall-Stillman embryo-splitting experiment at George Washington University was conducted—contrary to federal regulations—without prior institutional review board (IRB) review. This revelation altered Dr. Macklin's view of the ethical status of the research. Undoubtedly such revelations also raise general questions for administrators and researchers in many institutions, (...) including, for example: How do allegations of noncompliance with federal regulations arise? When should allegations of infractions of the regulations be reported? Who has an obligation to report? To whom should reports be made? What sort of inquiry should take place? Who should conduct the inquiry? If a determination is made that infractions have occurred, what sanctions are appropriate? And, what publicity is given to the allegations, before, during, and after an evaluation?Some of these questions can be answered in a straightforward manner, while the answers to others depend on the circumstances of the case. This article provides some general answers to these questions.1BackgroundThe Department of Health and Human Services (DHHS) is the largest supporter of biomedical and behavioral research in the world. Somewhere between 25 and 33 percent of its medical research budget is devoted to the support of research involving human subjects. In accordance with the Public Health Service Act, DHHS has issued Regulations for the Protection of Human Subjects (45 CFR 46). The DHHS Secretary has delegated responsibility for promulgating and administering the regulations to the Office for Protection from Research Risks (OPRR), which is located within the National Institutes of Health.When an institution receives an award from a DHHS agency to carry out research involving human subjects, it is required to negotiate, or to have on file, an "assurance of compliance" document that provides detailed information [End Page 51] specifying how the institution plans to comply with the regulations for the protection of human subjects. Most major research institutions in the country have on file a "multiple project assurance" (MPA) document, which extends DHHS regulations to all human subjects research conducted or sponsored by that institution, irrespective of the source of funding. The regulations and the assurance of compliance require any research project involving human subjects to be reviewed and approved by an institutional review board (IRB) prior to initiation of the research. In addition, the project must be re-reviewed by the IRB at appropriate intervals—in no case, less than once a year. Institutional compliance with these and other requirements of the regulations has improved during the last 30 years and appears to be at a high level. However, from time to time, allegations of noncompliance arise, as they did in the George Washington University embryo-splitting experiment, and set in motion the review process described below.How do Allegations of Noncompliance Arise?Allegations or indications of noncompliance with federal regulations for the protection of human subjects may come from a variety of sources. Most commonly, the institution's IRB discovers that research involving humans is going forward without the required prior IRB review and approval, or that approved research is being conducted in a way that is contrary to the stipulations of the IRB. The Hall-Stillman case came to the attention of George Washington University's IRB because the research protocol was submitted to the IRB after the research had been carried out. In this case, there could be no doubt that an infraction had occurred.Information about possible noncompliance also frequently derives from a funding agency's Initial Review Group (IRG) (commonly called a Study Section) when it has reason to suspect noncompliance in a project it is reviewing for possible funding. An actual case that occurred some years ago involved a research application that proposed to perform brain biopsies on normal volunteers. The IRG that reviewed the application lost little time in questioning whether an IRB had approved the protocol. In this case, it was not enough for the IRG to recommend disapproval of the proposal for funding; it also was obliged to report the possible infraction to OPRR.Whistleblowers, including research subjects, nurses, students, members of the... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Ice Cream for BreakfastMichelle MethvenIn June of 2011, on a warm sunny day in Toronto, Canada, my partner and I brought our daughter Stella into the local hospital emergency room for what we believed would be a routine check–up. She had been exhibiting worsening clumsiness and limping for the previous two weeks and we thought it would be easier just to get her seen and have whatever it was (...) dealt with rather than wait two months to see a specialist. My partner and I believed it was likely a severe ear infection, or maybe Lyme disease from a recent camping trip. We each called our workplaces and said we would be an hour or so late. Nothing could have prepared us for the news 22 hours after arriving at the hospital, that Stella had a cancerous mass in her brain. After a biopsy three days later to confirm the diagnosis, Stella was diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG), and given less than a year to live.Parents most often describe DIPG as “a monster.” The tumour saturates the pons and shuts down nerve pathways one at a time. In no particular order, and in no particular time, sufferers (most often young children) lose the ability to walk, sit up, hold up their head, speak and see. The pons is also responsible for breathing, swallowing and regulating the heartbeat, so death can come in many forms at any given time. Though it destroys the brain’s ability to command, the person continues to think and understand as the main part of the brain is untouched. Different from most cancers, chemotherapy and radiation have almost no effect on DIPG; even trials with the most toxic chemotherapies do not slow its progress.My partner and I were shaken to the core at this diagnosis. Looking at our energetic, redheaded [End Page 31] mop–topped little imp, it was impossible to fathom that she had just been given a fatal diagnosis. Yet we knew the doctors at the hospital were among the best and most sought–after in the world, so denial was never a part of our mantra.A week after Stella was diagnosed, we met with a neuro–oncologist to discuss our plans. The only treatment that is slightly effective for DIPG is focal radiation, which can stall the tumor’s growth, granting what is known as a “honeymoon period” of no new symptoms. The honeymoon lasts approximately six months, but there are no guarantees. Twenty percent of children get no honeymoon whatsoever after radiation, and others get only weeks. The doctor we met with confirmed radiation would not be curative, but would “buy time”. He explained that radiation involved six weeks of treatment, seven days a week. Following the six weeks of treatment, there would be a period of anywhere from one to six months in which Stella would likely be asymptomatic. However, at some point, the symptoms generally return and when they do, children deteriorate relatively quickly. Sometimes it takes a month or two, but on occasion there is as little as two weeks between progression and death.As Stella’s parents, we were not convinced that the prescribed radiation was something we wanted to subject Stella to. Because she was only two, and a very spirited and energetic child, it would have been virtually impossible to have her lie quietly on the table in hospital each day for six weeks while radiation was put behind her ear. The neuro–oncologists’ solution was that Stella be sedated for each daily radiation treatment, which would make her groggy for a big part of the day and necessitate needles and IV. As parents, we were presented with an impossible gamble. Do we risk taking away six weeks of her still somewhat symptom–free life for a possible extra three to six months later? And the timing was difficult as well. It was late June. If we chose to radiate it would mean spending the entire summer shuttling her between hospital and home with no weeks at the cottage, and much less time to attend neighbourhood BBQ’s, parties, trips to the park, the library, science centre and zoo... (shrink)

A woman with breast cancer takes a genetic test that predicts how active the tumors are and whether the benefits of chemotherapy outweigh the risks of side effects.A newlywed couple sends saliva samples to a start-up company to test for carrier genes for over one hundred inherited diseases, many of which are incurable or lethal.A heart transplant patient takes a blood test that detects patterns in gene expression to check for signs of rejection, making an invasive biopsy unnecessary.Each of (...) the tests described above either exists or is under development. Now, ten years after the release of a working draft of the human genome, major changes have made their way into medical practice, the marketplace, research, and .. (shrink)

Efforts to improve the means to diagnose and treat human genetic diseases have a long history in biomedical research and medicine. Now, preimplantation genetic diagnosis provides a new way to prevent the transmission of certain types of human genetic diseases to the next generation. It is an alternative to elective termination of pregnancies.PGD is used to test for genetic diseases that are due to defective single genes or abnormal chromosomes within days of fertilization and prior to the establishment of pregnancy. (...) The procedure essentially begins with the biopsy of one or more cells of a cleavage stage or blastocyst stage preimplantation human embryo that has been produced by in vitro fertilization. In certain cases, PGD can be done on polar bodies—discarded by-products of egg formation containing excess chromosomes—of unfertilized eggs. Then, the cell, or a polar body, is placed into a tube for single gene analysis ), or for chromosome analysis by spreading the nucleus of the cell on a microscope slide ). (shrink)

Efforts to improve the means to diagnose and treat human genetic diseases have a long history in biomedical research and medicine. Now, preimplantation genetic diagnosis provides a new way to prevent the transmission of certain types of human genetic diseases to the next generation. It is an alternative to elective termination of pregnancies.PGD is used to test for genetic diseases that are due to defective single genes or abnormal chromosomes within days of fertilization and prior to the establishment of pregnancy. (...) The procedure essentially begins with the biopsy of one or more cells of a cleavage stage or blastocyst stage preimplantation human embryo that has been produced by in vitro fertilization. In certain cases, PGD can be done on polar bodies—discarded by-products of egg formation containing excess chromosomes—of unfertilized eggs. Then, the cell, or a polar body, is placed into a tube for single gene analysis ), or for chromosome analysis by spreading the nucleus of the cell on a microscope slide ). (shrink)

What are we to make of Henrietta Lacks? After dying at a young age more than half a century ago, she has now become immortal twice—once biologically, and once culturally.She was first immortalized when cells from her cervical biopsy were cultured and became the first immortal cell line. The idea that this made Lacks herself immortal illustrates the dangerous temptations of genetic reductionism and literary license. Such literary license is illustrated by the title of Rebecca Skloot’s remarkable 2011 bestselling (...) book about Lacks and her cells. Skloot wrote a treatise that is at once a detective novel, an analysis of the conundrums of research ethics, a call for health system reform, and an exploration of racism in... (shrink)

The use of preimplantation genetic diagnosis (PGD) has expanded both in number and scope over the past 2 decades. Initially carried out to avoid the birth of children with severe genetic disease, PGD is now used for a variety of medical and non-medical purposes. While some human studies have concluded that PGD is safe, animal studies and a recent human study suggest that the embryo biopsy procedure may result in neurological problems for the offspring. Given that the long-term safety (...) of PGD has not been clearly established in humans, this study sought to determine how PGD safety is presented to prospective patients by means of a detailed website analysis. The websites of 262 US fertility centres performing PGD were analysed and comments about safety and risk were catalogued. Results of the analysis demonstrated that 78.2% of centre websites did not mention safety or risk of PGD at all. Of the 21.8% of centres that did contain safety or risk information about PGD, 28.1% included statements highlighting the potential risks, 38.6% presented information touting the procedure as safe and 33.3% included statements highlighting potential risks and the overall safety of the procedure. Thus, 86.6% of PGD-performing centres state that PGD is safe and/or fail to disclose any risks on their websites despite the fact that the impact of the procedure on the long-term health of offspring is unproven. This lack of disclosure suggests that informed consent is inadequate; this study examines numerous factors that are likely to inhibit comprehensive discussions of safety. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Gaining a Heart But Missing MyselfLeilani R. GrahamI gathered it in my hands as it fell from my hair-brush, too saturated to hold anymore. It felt as if I were inside a movie and waiting for someone to yell “Cut!” but no call came. It continued to fall, feather-like onto the ground, individual strands glinting in the light of the bathroom window. My hair, nearly all of it, was (...) gone.Between the time of my heart transplant and the moment my hair began to fall out, I arguably had suffered enough. Transplant brought four open-heart surgeries, ten days on ECMO, an intra-aortic balloon pump, delirium, necrotizing pneumonia, and so much muscular atrophy that I had to re-learn how to walk. CPR, broken ribs, and the scar of a tricuspid clip from a botched biopsy: it was not the miracle I was hoping for.The internal trauma had certainly taken its toll. I no longer knew how I really felt, thanks to copious pain meds that altered my mind and body. Each limb was foreign as I re-acclimated to how one grabs hold of a cup, signs their name, touches their legs. Externally, I was a mess: covered in deep purple bruises across my torso from the diabetes treatments, dead skin pooling in unwashed pores, my ankles swollen and indiscernible from my legs. But lacking a good mirror (or the desire to find one), I still felt like “myself” during my forty-five day hospital stay. I could feel my cheekbones protruding from thinning skin, saw through unfocused eyes from the tempestuous blood sugars, and my hair sat in a rat’s nest atop my head; but I was still me.Arriving home, I felt like a newborn being brought into the real world for the first time. I needed help with everything—showers, sitting up, putting on shoes, even going to the bathroom. At age twenty-four, I felt I had regressed to the point of no return as I relied on others to do the simplest tasks. In addition, I was quarantined inside for three months, due to the risk of obtaining a fungal infection from the outside. Caged, and alone in my body, I a trapped and wounded tiger: angry, hurting, and scared. [End Page 109]When I had been prepared for transplant—and I use “prepared” loosely because the information packet I was handed was insulting at best—I knew to expect the scars. I had no issue with that, having been cut open at my throat and chest for previous surgeries. I knew to expect a 12-inch line from neck to navel: the most evident sign I would now carry that I was disabled.What I did not expect were the bullet holes— the sealed entrances of thick chest tubes that now dotted my lower torso. I did not anticipate the bruises on my arms and groin from arterial pokes. I felt violated as if I had walked into some kind of abduction and was rolled out, beaten, bruised, and, worst, touched.But it wasn’t the physical trauma that hurt the most. It was that no one seemed surprised.Immediately after transplant, the team’s focus is purely on survival. Survive the 30 days post-surgery. Survive the year. Metrics, uncomfortably tied to transplant center success statistics, funding, and clout have little to do with the patients themselves. What did I care to only survive a year? I wanted years. I wanted decades. It felt I wanted more than anyone was willing to pay attention to.The conversation was narrowed to high-risk issues: infection, rejection, or other life-threatening conditions. While this makes sense on a clinical level, what constitutes a major event for a clinician may not be of the same emotional value to the patient. In my case, I was less occupied by how the steroids were working and more obsessed with their side effects, such as how much weight I was rapidly gaining. I walked into the clinic one day with the beginnings of stretch marks and a week later had claw-like ripples down my sides. My mood swings were explosive... (shrink)

In 1951 Henrietta Lacks felt a lump in her cervix, entered Johns Hopkins Hospital, and was examined in a colored-only exam room by a physician who biopsied the lump. Called back to Hopkins for treatment of diagnosed carcinoma of the cervix, Henrietta signed a one-line “Operation Permit,” and under general anesthesia received her first round of radium treatment. Before sewing a tube of radium into her cervix, the surgeon on duty took samples of tumor and healthy tissue, and as with (...) many other samples taken from charity patients at Hopkins, handed the samples to researchers trying to develop an immortal human cell line (an important research tool, an immortal cell line is a population of cells from a multicellular .. (shrink)

IntroductionRheumatologists are the primary healthcare professionals responsible for patients with rheumatic diseases and should acquire medical ethical competencies, such as the informed consent process. The objective clinical structured examination is a valuable tool for assessing clinical competencies. We report the performance of 90 rheumatologist trainees participating in a station designed to evaluate the ICP during the 2018 and 2019 national accreditations.MethodsThe station was validated and represented a medical encounter in which the rheumatologist informed a patient with systemic lupus erythematosus with (...) clinically active nephritis about renal biopsy. A trained patient–actor and an evaluator were instructed to assess ICP skills in obtaining formal informed consent, delivering bad news and overall communication with patients. The evaluator used a tailored checklist and form.ResultsCandidate performance varied with ICP content and was superior for potential benefit information but significantly reduced for potential complications and biopsy description. Only 17.8% of the candidates mentioned the legal perspective of ICP. Death was omitted by the majority of the candidates ; after the patient–actor challenged candidates, only 57.1% of them gave a clear and positive answer. Evaluators frequently rated candidate communications skills as superior, but ≥1 negative aspect was identified in 69% of the candidates.ConclusionsEthical competencies are mandatory for professional rheumatologists. It seems necessary to include an ethics competency framework in the curriculum throughout the rheumatology residency. (shrink)

The UK Human Fertilisation and Embryology Authority was right to permit tissue typing preimplantation genetic diagnosisOn July 21 2004, the Human Fertilisation and Embryology Authority , Britain’s regulatory agency for reproductive technologies, revised its policy on preimplantation genetic diagnosis for tissue typing.1,2 The authority of the HFEA to enact such a policy was affirmed by the UK’s highest court, the House of Lords, on April 28 2005.3 Preimplantation genetic diagnosis combines in vitro fertilisation with genetic testing. In PGD, embryos generally (...) undergo biopsy prior to the eight cell stage, followed by genetic testing for a particular trait. Tissue typing PGD is done to identify an embryo that is tissue matched for a child suffering from a severe disease requiring bone marrow or cord blood stem cell transplantation and for whom no living donor exists. This procedure was first performed in 2000.4 Precise matching of tissue types is critical to successful tissue transplant, and the donors of such tissues are often referred to as “saviour siblings”.Where a tissue matched individual already exists, extracting bone marrow from that individual or collecting cord blood already in storage, rather than creating a match, presents the most immediate treatment alternative. Bone marrow donation from adults or other medically competent individuals is not generally ethically contested, and bone marrow donation from medically incompetent individuals is also permissible under certain conditions.5 Where no living tissue donor exists, however, intentionally creating a donor through tissue typing PGD is among a short list of possible treatment options.The July HFEA policy change makes PGD licensable in cases where tissue typing is the only purpose of testing. Previously, PGD was licensable in the UK only for disease testing, and tissue typing PGD was permissible only when …. (shrink)

High-resolution neuroimaging modalities are used often in studies involving healthy volunteers. Subsequently, a significant increase in the incidental discovery of asymptomatic intracranial abnormalities raised the important ethical issues of when follow-up and treatment may be necessary. We examined the literature to establish a practical set of criteria for approaching incidental findings. Our objective is to develop an algorithm for when follow-up may be important and to provide recommendations that would increase the likelihood of follow-up. A systematic literature search was performed (...) using the PubMed and MEDLINE databases to identify articles describing brain tumors and intracranial aneurysms. The treatment algorithm we present suggests that incidental intracranial masses suspicious for glioma should be biopsied or resected, while other masses are to be followed with serial imaging based on the expected growth pattern. Lack of follow-up can result in adverse outcomes that can be mitigated by using technology to facilitate communication and improve follow-up care. The importance of training physicians to be good communicators is also stressed. New technology including automated telephone systems, texting and email will improve access to patients and hopefully encourage compliance and follow-up. (shrink)

Detection of genetic aberrations in prenatal samples, obtained through amniocentesis or chorion villus biopsy, is increasingly performed using chromosomal microarray, a technique that can uncover both aneuploidies and copy number variants throughout the genome. Despite the obvious benefits of CMA, the decision on implementing the technology is complicated by ethical issues concerning variant interpretation and reporting. In Belgium, uniform guidelines were composed and a shared database for prenatal CMA findings was established. This Belgian approach sparks discussion: it is evidence-based, (...) prevents inconsistencies and avoids parental anxiety, but can be considered paternalistic. Here, we reflect on the cultural and moral bases of the Belgian reporting system of prenatally detected variants. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Bringing Cancer Care to Those who Don't Have ItLawrence N. ShulmanI have been treating cancer patients in the Harvard Medical School hospitals since 1977, and in those 35 years we have made tremendous progress. Though work still needs to be done, and far too many patients still die of cancer, many are cured. In particular, children and young adults have a high rate of cure from such diseases as (...) Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and childhood sarcoma. Patients with breast cancer in the US have a greater than 80% chance for long-term survival. The death rate from cervical cancer in the US is very low. These results have been achieved by making diagnoses earlier, in many cases surgical excision, and often systemic therapies such as chemotherapy, hormonal therapy, radiation therapy, and more recently by using so-called "targeted" therapies—those directed at particular molecular characteristics of the cancer cells.Princess Dina Mired has said that the opportunity to survive cancer should not be an accident of geography. In cases where we already have effective and inexpensive tools to cure cancer, these treatments should be considered a basic human right, a life-saving medical service.I met Patty, a young woman living in the U.S. during November of her senior year in high school, after she discovered a small lump above her left collar bone. Though she felt entirely well, she called her primary care doctor who saw her the next day, felt the enlarged lymph node, and referred her to a surgeon, who did a biopsy later that week. Her primary care doctor also called me, and we scheduled a visit when the pathology results were available. The following week the pathologist notified Patty's pediatrician that the biopsy showed Hodgkin's lymphoma. When I met Patty, she was a bright and focused young woman, waiting to hear about her college applications and enjoying her senior year. Her cancer diagnosis was completely out of context with her life as she planned it, but with the support of her family and boyfriend, she seemed prepared to take things one step at a time. A PET CT scan demonstrated a modest mass in the mediastinum (chest), but no other disease. She was in an early stage of the disease with an excellent prognosis. We recommended and administered six months of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine—four chemotherapy agents that are off-patent, and relatively inexpensive. She lost her hair, not a trivial issue for her, but otherwise felt reasonably well during the treatment. She was determined to graduate with her classmates, and was able continue to attend school and keep up with her work. In June, seven months into her cancer diagnosis and treatment, she graduated with honors, and was on track to enroll in college in September.Like other 18-year-old women with Hodgkin's lymphoma, Patty had an over 80% chance for cure with the potential for a long and productive life ahead of her because we could perform a biopsy, make a diagnosis, and safely and effectively treat her with four inexpensive, off-patent, chemotherapy drugs. She had nearly the same likelihood of living a long and fruitful life as her classmates, and had the same chances for childbearing. In my line of work, with the knowledge we now possess, to allow someone like Patty to die without a chance of curative care is simply unacceptable. Treatment of curable cancers should be considered on par with the right to clean water, adequate nutrition, treatment for infectious disease, and access to maternal and child healthcare services.But in many places in the world, people with cancers we could easily eradicate in Boston have no access to cancer services, and do die unnecessarily. The local healthcare infrastructure has no [End Page E10] capacity to evaluate a patient, perform or process a biopsy, make a diagnosis, or treat the patient with potentially curative surgery, chemotherapy and radiation. I have rounded on the wards of hospitals in developing countries, stopping to talk with numerous patients like Patty: young women, some of whom might have had Hodgkin's lymphoma, but no... (shrink)

In this paper I will discuss three areas in which advances in human reproductive technology could occur, their uses and abuses, and their effects on society. First is the potential to drastically increase the success rate and availability of in vitro fertilization and embryo freezing. Second is the ability to perform biopsies on embryos prior to the onset of pregnancy. Finally, I will consider the adding or altering of genes in embryos, commonly referred to as genetic engineering.As new reproductive technologies (...) pass from experimental models into the potential for medical utilization, I believe that it will be important for lawmakers everywhere to avoid the impulse to outlaw procedures that a society believes to be unnatural at a first glance. Rather, I would hope that they can respond thoughtfully with legislation that serves two purposes — to protect the rights of couples to overcome infertility or to reduce the risk of genetic disease in their children-to-be, and more importantly, to protect children-to-be from the abuses that could result from some of the practices that I will discuss. (shrink)