What is a natural cause of death? A survey of how coroners in England and Wales approach borderline cases

AIM: Many deaths fall in the "grey" area between those that are clearly natural and those that are unnatural. There are no guidelines to help doctors in dealing with such cases and death certification is often arbitrary and inconsistent. In an attempt to initiate debate on these difficult areas, and with the ultimate aim of achieving national consensus, the views of coroners in England and Wales were sought. METHODS: Sixteen clinical scenarios, with causes of death, were circulated to all coroners in England and Wales. For each case they were asked to provide a verdict, with explanation. The deaths fell into three groups: (1) postoperative, (2) a combination of trauma and natural disease, and (3) infectious disease. RESULTS: Sixty four questionnaires were returned. There was near consensus (> 80% concordance) in only two of the 16 cases. In five, there was no significant agreement between coroners in the verdicts returned ("natural causes" versus "misadventure/accidental"). These included all three cases in which death resulted from a combination of trauma and natural disease (a fall after a grand mal fit; falls resulting in fractures of bones affected by metastatic carcinoma and osteoporosis), bronchopneumonia after hip replacement for osteoarthritis, and new variant Creutzfeldt-Jakob disease. The comments made for each case indicate that the variation between coroners in whether or not to hold an inquest, and the verdict arrived at, reflect the lack of a definition for natural causes, together with differences in the personal attitudes of each coroner. CONCLUSIONS: There is considerable variation in the way in which coroners approach these borderline cases, many of which are common in clinical practice. This study indicates a need for discussion, working towards a national consensus on such issues. It highlights the importance of good communication between coroners and medical staff at a local level.     

Genetic causes of rare and common epilepsies: What should the epileptologist know?

In past decades, the identification of genes involved in epileptic disorders has grown exponentially. The pace of gene identification in epileptic disorders began to accelerate in the late 2000s, driven by new technologies such as molecular cytogenetics and next-generation sequencing (NGS). These technologies have also been applied to genetic diagnostics, with different configurations, such as gene panels, whole-exome sequencing and whole-genome sequencing. The clinician must be aware that any technology has its limitations and complementary techniques must still be used to establish a diagnosis for specific diseases. In addition, increasing the amount of genetic information available in a larger patient sample also increases the need for rigorous interpretation steps, when taking into account the clinical, electroclinical, and when available, functional data. Local, multidisciplinary discussions have proven valuable in difficult diagnostic situations, especially in cases where precision medicine is being considered. They also serve to improve genetic counseling in complex situations.In this article, we will briefly review the genetic basis of rare and common epilepsies, the current strategies used for molecular diagnosis, including their limitations, and some pitfalls for data interpretation, in the context of etiological diagnosis and genetic counseling.     

Subclassification of pleomorphic sarcomas: How and why should we care?

Pleomorphic sarcomas are a heterogeneous group of mesenchymal neoplasms with widely varied clinical behavior but overlapping histologic appearances. The following guidelines are helpful when approaching the diagnosis of a pleomorphic sarcoma. (1) Be aware of the relative incidence of the various sarcoma types: several pleomorphic sarcomas are relatively common (e.g., dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma), whereas others are exceptionally rare. (2) Pay attention to anatomic location: some pleomorphic sarcomas have a predilection for somatic soft tissues, especially the thigh (e.g., undifferentiated pleomorphic sarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma), whereas other pleomorphic sarcomas most often arise in the retroperitoneum (e.g., dedifferentiated liposarcoma). (3) Carefully sample the resection specimen, paying particular attention to areas with differences in gross appearances (e.g., fleshy, fibrous, mucoid, or gritty). (4) Search for histologic clues (i.e., myxoid stroma, lipoblasts, and osteoid matrix, in order to diagnose myxofibrosarcoma, pleomorphic liposarcoma, and extraskeletal osteosarcoma, respectively); these critical diagnostic features may be limited in extent. (5) Apply immunohistochemistry judiciously, after generating a differential diagnosis; always exclude metastatic sarcomatoid carcinoma and melanoma before diagnosing a pleomorphic sarcoma. This review will present an approach to the diagnosis of pleomorphic sarcomas, emphasizing differential diagnosis and the application of ancillary studies (immunohistochemistry and FISH), when relevant.     

Working with dreams in therapy: what do we know and what should we do?

Although a potentially helpful therapeutic tool, dream interpretation or dream work is only used occasionally in most forms of psychotherapy. Despite an interest from clinicians and clients alike in using dreams within therapy, many therapists feel unprepared to attend to their clients' dreams. The main goals of this article are to make clinicians aware that integrating dreams into their clinical practice is both accessible and potentially valuable and to allow them to make an informed decision as to what role they want dream work to play in therapy. The paper begins with a brief overview of some of the more common approaches to dream work. The literature on the usefulness and effectiveness of the clinical use of dreams is then reviewed. Finally, based on the integration of the clinical and empirical literature, several guidelines for conducting dream work are presented.     

Unexpected and unexplained increase in death due to neurological disorders in 2012 in England and Wales: Is cytomegalovirus implicated?

In early 2012 deaths (all-cause mortality) in England and Wales showed an unexpected and unexplained increase which continued for 18 months before abating. The highest percentage increase in deaths was noted to be for neurological degenerations (mainly dementia, Alzheimer’s, Parkinson’s). This study seeks to understand why increased deaths should focus on these conditions and if an unrecognized infectious outbreak could be implicated. Cause of death statistics for England and Wales were compared for 2012 versus 2011 as was the diagnosis for first outpatient appointment and inpatient admissions for these conditions. Deaths for dementia, Alzheimer’s and Parkinson’s showed a 15% increase with associated age specificity. The increase could not be explained by changes in the coding relating to cause of death. The increase coincided with increased GP referral (as first outpatient attendance) and inpatient admission for a range of neurological conditions. These increases were also observed on previous occasions of a similar event where deaths peaked in 2003 and 2008. A cascade of debility leading to immobility and institutionalization along with specific immune impairments appears to render those suffering from neurological degenerations sensitive to infectious outbreaks and more specifically to the particular agent behind these events. These and other studies point to outbreaks of a previously uncharacterized agent with the outbreak peaking in 2003, 2008 and 2012 (and in other years prior to these dates). Cytomegalovirus is a potential candidate and the necessary research to test this hypothesis is outlined.     

Complications and death causes of peripheral blood stem cell transplantation in the treatment of thalassemia major北大核心

BACKGROUND: Allogeneic hematopoietic stem cell transplantation is the only effective method to cure thalassemia major. However, the risk factors influencing the prognosis of transplantation remain unclear. OBJECTIVE: To analyze the distribution of common complications and cause of death after allogeneic hematopoietic stem cell transplantation in children with thalassemia major, and to explore the prognostic factors so as to provide references for improving the survival rate of patients. METHODS: This retrospective cohort study included 257 patients with β-thalassemia major who underwent allogeneic hematopoietic stem cell transplantation at Department of Hematology and Oncology, Guangzhou Women and Children Medical Center between September 2013 and September 2019. There were 172 males and 85 females, with a median age of 6 years at the time of transplantation. The basic clinical data before transplantation and complications after transplantation were compared between the surviving group and dead group using single factor. The overall survival rate was analyzed by the Kaplan-Meier method, and the overall survival rate was compared by the Log-rank test. Multivariate Cox regression was used to analyze factors affecting survival. RESULTS AND CONCLUSION: The median follow-up time was 29 months, and no cases were lost to follow-up. (1) Univariate analysis results showed that there were significant differences in the risk classification between surviving patients and dead patients (P=0.033). Patients with higher risk class had an increased risk of death after transplantation. Multivariate analysis showed that risk classification and severe pneumonia were independent risk factors for overall survival after thalassemia major hematopoietic stem cell transplantation (P < 0.05). (2) Among 20 dead patients, there were 13 patients with severe pneumonia and respiratory failure, 2 patients with grade IV intestinal graft-versus-host disease, 1 patient with intracranial hemorrhage due to thrombocytopenia, 1 patient with thrombocytopenia with acute pulmonary hemorrhage, 1 patient with sepsis with shock, and 1 patient with myasthenia gravis. (3) Totally 17 cases died within 1 year after transplantation, while the rest 3 patients died of severe pneumonia more than 1 year after transplantation. (4) The incidence of bronchiolitis obliterans was significantly higher in patients who died after transplantation than in those who survived (P < 0.000 1). (5) It is concluded that the important factors that affect survival rate in thalassemia major patients after hematopoietic stem cell transplantation are infection and severe graft-versus-host disease. The risk of death increased in patients with bronchiolitis obliterans after transplantation. © 2023, Chinese Journal of Tissue Engineering Research. All rights reserved.     

What causes seasonality of birth in schizophrenia?

An excess of winter-spring births (and/or a decrease of summer births) has consistently been observed in schizophrenia (SCZ). This observation may provide a significant clue about the causes of the disease if specific factors which cause the phenomenon can be determined. This paper reviews several studies which investigated factors correlated with this observation in SCZ, in an attempt to determine which factors more likely cause the seasonality. Among the candidates of the factors are meteorological variables (such as ambient temperature), several infections, maternal hormones, sperm quality, nutrition and external toxins. A variation of procreation might also have an effect. Among the factors, the most extensively studied are temperature and viral infections. Some of them have appeared promising, but further studies are definitely required. Several challenges, including complicated correlations of the factors and determination of the susceptible period during pregnancy, need to be overcome. Comparisons of the data from areas and cohorts with different patterns of the candidate factors may be helpful. Animal studies may also help investigate the molecular and physiological mechanisms of the phenomenon.     

Resveratrol supplementation: Where are we now and where should we go?

Pre-clinical findings have provided mounting evidence that resveratrol, a dietary polyphenol, may confer health benefits and protect against a variety of medical conditions and age-related complications. However, there is no consistent evidence of an increased protection against metabolic disorders and other ailments when comparing studies in laboratory animals and humans. A number of extraneous and potential confounding variables can affect the outcome of clinical research. To date, most of the studies that have investigated the effect of resveratrol administration on patient outcomes have been limited by their sample sizes. In this review, we will survey the latest advances regarding the timing, dosage, formulation, bioavailability, toxicity of resveratrol, and resveratrol–drug interactions in human studies. Moreover, the present report focuses on the actions of resveratrol treatment in combating diseases, such as cancer, diabetes, neurodegeneration, cardiovascular disease, and other age-related ailments.     

How should we grade CIN?

How should we grade CIN? The grading of cervical intraepithelial neoplasia (CIN) is problematic. CIN represents a morphological continuum, but biopsies displaying this lesion are classified into two (e.g. Bethesda) or three grade categories, sometimes with poor reproducibility. There are also difficulties in reliably distinguishing low‐grade CIN from its reactive simulants. Because of problems with inter‐ and intra‐observer disagreement in the grading of CIN and the diagnosis of low‐grade lesions, three expert contributions were commissioned to address the question `how should we grade CIN?'.     

Mouse models of global airway allergy: what have we learned and what should we do next?

Recent epidemiological and clinical data indicate that allergic rhinitis and asthma coexist and should be considered as one airway allergy syndrome. In spite of the importance of this new concept of global airway allergy, it has not fundamentally changed our daily diagnostic and therapeutic strategies so far because of the lack of essential clues to understand the correlation between allergic inflammation in upper and lower airways. Because of the resemblance of experimentally induced allergic airway inflammation in mice to inflamed airways of allergic patients, mouse models can enhance our insight into mechanisms underlying the global airway allergy syndrome. We here review data generated in mice that are relevant for understanding the development of airway allergy and provide new options for research on the so-called 'united airway disease'.     

Destined to die in hospital? Systematic review and meta-analysis of place of death in haematological malignancy

Background  

Haematological malignancies are a common, heterogeneous and complex group of diseases that are often associated with poor outcomes despite intensive treatment. Research surrounding end-of-life issues, and particularly place of death, is therefore of paramount importance, yet place of death has not been formally reviewed in these patients.     

How should we assess the impact of genetic changes on ageing in model species?

One of the most active branches of genetic research is the quest for the genetic determinants of ageing. The ultimate goal of much of this effort is to understand ageing in humans. In addition to work on human genetics, many researchers look to model organisms in order to find genetic variation that can affect ageing. The fly Drosophila, the worm Caenorhabditis elegans, rodents, and yeast are among the most widely studied species. However, while great care is given to the genetic aspects of this form of research, the methods used to assess the impact of the genetic changes on the organism in question do not always provide as complete a picture as possible of ageing's multi-facetted nature. In this commentary, I propose a systematic and rigorous approach, and draw attention to research that has already demonstrated the value of such an approach.