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PurposeAntitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen).Experimental designSerum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses were subsequently validated in ProACT (n = 33), an independent phase II study of sipuleucel-T. Association of IgG responses with overall survival (OS) was assessed using multivariate Cox models adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase levels.ResultsIn patients from IMPACT and ProACT, levels of IgG against multiple secondary antigens, including PSA, KLK2/hK2, K-Ras, E-Ras, LGALS8/PCTA-1/galectin-8, and LGALS3/galectin-3, were elevated after treatment with sipuleucel-T (P < 0.01), but not control. IgG responses (≥ 2-fold elevation posttreatment) occurred in ≥ 25% of patients, appeared by 2 weeks after sipuleucel-T treatment, and persisted for up to 6 months. IgG responses to PSA and LGALS3 were associated with improved OS in sipuleucel-T-treated patients from IMPACT (P ≤ 0.05).ConclusionsSipuleucel-T induced humoral antigen spread in patients with mCRPC. IgG responses were associated with improved OS in IMPACT. The methods and results reported may identify pharmacodynamic biomarkers of clinical outcome after sipuleucel-T treatment, and help in clinical assessments of other cancer immunotherapies. See related commentary by Hellstrom and Hellstrom, p. 3581.

As the Covid-19 pandemic continues into its 4th year, reports of long-term morbidity and mortality are now attracting attention. Recent studies suggest that Covid-19 survivors are at increased risk of common illnesses, such as myocardial infarction, diabetes mellitus and autoimmune disorders. Mortality may also be increased. This article will review the evidence that supports some of these observations and provide an opinion about their validity and their relevance to insured cohorts., (Copyright © 2024 Journal of Insurance Medicine.)

New-onset diabetes mellitus following COVID-19 infection has been frequently reported. This article will review the evidence that supports this observation and provide an opinion about its validity and relevance to insured cohorts., (Copyright © 2024 Journal of Insurance Medicine.)

NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis) are time-honored acronyms, with widely popular acceptance. Experts now recommend discarding them in favor of MASLD for "metabolic dysfunction-associated steatotic liver disease" and MASH for "metabolic dysfunction-associated steatohepatitis." The reasons for this change are explored and an argument about why the change is confusing, is advanced. Should these acronyms become clinically popular, risk assessment manuals will require updates., (Copyright © 2024 Journal of Insurance Medicine.)

ChatGPT is about to make major inroads into clinical medicine. This article discusses the pros and cons of its use., (Copyright © 2024 Journal of Insurance Medicine.)

As the COVID-19 pandemic reaches the end of its third year, and as COVID-related mortality in North America wanes, long Covid and its disabling symptoms are attracting more attention. Some individuals report symptoms lasting more than 2 years, and a subset report continuing disability. This article will provide an update on long Covid, with a particular focus on disease prevalence, disability, symptom clustering and risk factors. It will also discuss the longer-term outlook for individuals with long Covid., (Copyright © 2023 Journal of Insurance Medicine.)

Pituitary adenomas were recently reclassified as "neuroendocrine tumors," and are now considered to be cancers. The evolution and justification for this change are described. Critical illness policies, which currently provide coverage of pituitary adenomas under the "Benign Brain Tumor" provision must now be modified to reflect this new taxonomy. This change also prompts questions about the use of the words 'benign' and 'tumor' in critical illness policies., (Copyright © 2024 Journal of Insurance Medicine.)

Objectives: Diffusion weighted brain imaging (DWI) is used in acute stroke, and also shows an acute ischaemic lesion in most transient ischamic attack (TIA) patients scanned acutely. However, it may [...]

Critical illness insurance was introduced 40 years ago. Medical directors continue to be challenged and frustrated with the complexities that critical illness claims offer. This article provides insights into the continued issues and possible solutions., (Copyright © 2023 Journal of Insurance Medicine.)

Critiques an article by P.J. McLeod and colleagues, published in an issue of "Medical Teacher," about clinical teachers' tacit knowledge of basic pedagogic principles. Identification of tacit knowledge; Erroneous association of tacit knowledge with informal learning and explicit knowledge with formal learning only; Acquisition of tacit knowledge through an informal process of experiential learning involving reflection during and after teaching.

Long COVID is now a recognized complication of acute COVID-19 infection. As the COVID-19 pandemic moves into its third year, the prevalence of Long COVID continues to increase. Many individuals report symptoms lasting longer than a year, and a subset of this group is unable to work. This article will provide an update on Long COVID, with a particular focus on distinguishing it from other clinical entities. It will review several proposed disease mechanisms and will attempt to anticipate the impact on disability insurance., (Copyright © 2022 Journal of Insurance Medicine.)

Study Design: Prospective observational study., Objective: To evaluate pelvic MRI muscle signal changes and their association with early heterotopic ossification (HO) in patients with spinal cord injuries., Setting: National Spinal Injuries Unit, Stoke Mandeville, UK., Methods: Forty patients were imaged with at least two interval magnetic resonance (MR) studies of the pelvis in the first 6 months following a spinal cord injury. Scans were reviewed and scored for heterotopic ossification, muscle signal change and extent of muscle involvement., Results: Muscle signal change was present in 28 (70%) on the initial MRI and 31 (77%) by the second study. Six patients developed MR changes of prodromal or immature heterotopic ossification (15%). No restricted diffusion was demonstrated and no patient developed mature HO. Patients developing MR changes of early HO were more likely to have grade 3 muscle changes., Conclusion: Increased T2 muscle signal is common following cord injury, is frequently progressive in the subacute period and is associated with complete injury and early MR signs of heterotopic ossification.

Disability due to mental health disorders has been increasing in many countries over the past years. The COVID-19 pandemic may worsen this trend because of 3 different, and at times overlapping, pathways. This article describes each pathway, and by drawing on the experience of previous coronavirus epidemics and recent recessions, attempts to estimate the likelihood that claims due to mental health disorders will increase., (Copyright © 2021 Journal of Insurance Medicine.)

The sudden emergence of the COVID-19 pandemic in early 2020 presented a unique challenge for medical directors of life insurance companies. Company leadership required quick answers about many issues, but two in particular: 1) the magnitude of the pandemic's impact on the insured lives portfolio and 2) the underwriting of new applicants during a pandemic. This article will describe the experiences of a global team of reinsurance medical directors during a pandemic. It may also serve to provide guidance for medical directors facing a similar challenge in the future., (Copyright © 2021 Journal of Insurance Medicine.)

A new syndrome called "Long COVID" has emerged amongst the survivors of acute COVID-19 infection. Its protracted and debilitating nature will almost certainly result in many short and long-term disability claims. Insurers need to understand the nature of Long COVID, including its definition, its prevalence, its natural history, and underlying risk factors. This article will summarize current knowledge of Long COVID and provide a perspective on its evolution and its impact., (Copyright © 2021 Journal of Insurance Medicine.)

Introduction: Ganglion impar block (GIB) is a well-recognised treatment for chronic coccydynia. Several side effects have previously been described with this procedure, including transient motor dysfunction, bowel, bladder, and sexual dysfunction, neuritis, rectal perforation, impingement of the sciatic nerve, cauda equina syndrome, and infection., Case Presentation: We describe the first report of imaging-documented conus infarction after an unguided-GIB performed in theatre using particulate steroids for a 17-year-old patient with coccydynia. Immediately post-GIB, patient developed transient neurological deficits in her lower limbs of inability to mobilise her legs that lasted for 24 h. These include back and leg pain, decreased power and movement, increased tone, brisk reflexes, reduced light touch sensation and proprioception of legs up to the T10 level. Urgent MRI spine showed intramedullary hyperintense signal within the conus and mild restricted diffusion on the distal cord and conus, suggestive of an acute conus infarction. On follow-up, the GIB did not result in symptom improvement of coccydynia and there was persistent altered sensation of her legs., Discussion: Various approaches of ganglion impar block have been described and performed in the past with different imaging techniques and injectants. A few cases of unusual neurological complications have been reported with the use of epidural steroid injections and ganglion impar block. Clinicians should be aware of the possible neurological complications following ganglion impar blocks and the risk of inadvertent intravascular injection of particulate steroids can potentially to be minimised by using imaging guidance., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© International Spinal Cord Society 2019.)

In order to establish effective conservation strategy, drivers of local and regional patterns of biodiversity need to be understood. The composition of local biodiversity is dependent on a number of factors including evolution and redistribution of lineages through dispersal and environmental heterogeneity. Brazilian canga is characterised by a ferrugineous substrate, found both in the Iron Quadrangle of Minas Gerais and in the Carajás mountains in Amazonia. Canga is one of several specialised habitat types comprising Brazilian campo rupestre, a montane vegetation found within or adjacent to several major Brazilian bioregions, including the Atlantic Forest and Amazonia, with exceptionally high levels of diversity and endemism arising from both history of dispersal and environmental variation. In order to inform biodiversity conservation for canga, and more broadly for campo rupestre, we performed floristic and phylogenetic analyses investigating affinities between 28 sites on different substrates (canga and quartzite) and geographic locations (Carajás, Pará [Amazonia]; Cadeia do Espinhaço, Minas Gerais; Chapada Diamantina, Bahia). Through analysis of 11204 occurrences of 4705 species of angiosperms, we found that Amazonian Carajás canga plant communities formed a cohesive group, distinct from species assemblages found in Eastern Brazil (Minas Gerais, Bahia), either on canga or quartzite. The phylogenetic megatree of species across all sites investigated shows associations between certain clades and Amazonian canga, with few shared species between the Amazonian Carajás and Eastern Brazil sites, while the floristic comparison shows high levels of heterogeneity between sites. The need for reserves for Amazonian Carajás canga has been recognized and addressed by the creation of a national park. However, current sampling does not provide sufficient reassurance that the canga areas now benefitting from full legal protection adequately represent the regional canga flora., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Chiari malformation is characterized by caudal descent of the cerebellar tonsils through the foramen magnum. Acquired Chiari malformations (ACM) have previously been described after a variety of pathologies including lumbar puncture, cerebrospinal fluid (CSF) drainage, lumboperitoneal shunts, and conditions causing craniocephalic disproportion., Case Presentation: We present four cases of ACM following spinal cord injury (SCI), which has not previously been described in the literature., Discussion: ACM is rare and typically associated with abnormalities in CSF pressure or space-occupying lesions. This case series describes the potential association of SCI with ACM. We discuss the imaging findings and clinical management of these patients. Early recognition and intervention may be important to prevent progressive neurology in this vulnerable patient group., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© International Spinal Cord Society 2019.)

Sonification, or the practice of generating sound from data, is a promising alternative or complement to data visualization for exploring research questions in the life sciences. Expressing or communicating data in the form of sound rather than graphs, tables, or renderings can provide a secondary information source for multitasking or remote monitoring purposes or make data accessible when visualizations cannot be used. While popular in astronomy, neuroscience, and geophysics as a technique for data exploration and communication, its potential in the biological and biotechnological sciences has not been fully explored. In this review, we introduce sonification as a concept, some examples of how sonification has been used to address areas of interest in biology, and the history of the technique. We then highlight a selection of biology-related publications that involve sonifications of DNA datasets and protein datasets, sonifications for data collection and interpretation, and sonifications aimed to improve science communication and accessibility. Through this review, we aim to show how sonification has been used both as a discovery tool and a communication tool and to inspire more life-science researchers to incorporate sonification into their own studies., (© 2024 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)