The rise of right-wing political movements supported by key players from big tech is transforming Western societies. This so-called techno-feudalism also implies challenges for bioethics. Racist agendas, intentional misinformation on health topics such as vaccinations, banned words and research topics in public institutions, and the massive funding of questionable biomedical research projects undermine health equity, patient safety, and autonomy. This new sociopolitical situation exacerbates a long-standing issue in healthcare that bioethics hitherto mostly failed to address adequately: societal power asymmetries that shape the roles and relationships of actors in healthcare and biomedical research. Although attempts have been made to reflect upon this issue, e.g. in feminist or postcolonial bioethics, there is no coherent bioethical approach that fundamentally focuses on power asymmetries as a lens of bioethical inquiry. In this article, I therefore introduce critical bioethics, an approach that takes epistemic lenses from critical theory, especially the so-called Frankfurt School. These epistemic lenses-totality and embeddedness, instrumental reason, dialectics and emancipation-allow us to uncover the societal causes for ethical issues in healthcare and biomedical research. Based on this methodological foundation, critical bioethics addresses health inequity as a result of power asymmetries by understanding individuals as fundamentally embedded in a concrete socioeconomic context. Through the lens of instrumental reason, it addresses the connection between disruptive technological innovations and economic interests in terms of commodification and solutionism. By using dialectics as a method to uncover contradictions in the way bioethics understands its principles, it provides an emancipatory perspective for normativity that separates it from affirmative forms of bioethical thinking that simply reproduce the suppressive status quo.
Islamic bioethics is a recent, albeit growing, academic discipline. Despite commendable contributions, the field remains critically limited. Most notably, its methodology of strict application of Islamic law to ethical analyses and recommendations often lacks sufficient moral analysis, intellectual engagement, or social context. The practice's emphasis on religio-legal rulings- without an investigation of their underpinning moral values- has resulted in a field of inquiry devoid of robust normative foundations and dependent upon ineffective and unsubstantiated claims. This paper calls for a revival of Islamic philosophical discourse to enrich Islamic bioethical practice. Although once popularized by Medieval Muslim philosophers like Ibn Sina (Avicenna) and Ibn Rushd (Averroes), philosophical discourse has fallen out of favor in the Muslim world, largely due to a perceived tension with religion. This work highlights the rich tradition of philosophical discourse in the Medieval Muslim world, disproving claims of an inherent conflict between philosophy and Islam. Following an Islamic philosophical framework, three goals for Islamic bioethics are established. First, theoretical rigor aimed at continually re-assessing and re-understanding concepts integral to the practice of bioethics such as personhood, dignity, futility, autonomy, and justice. Second, a shift from essentialist understandings of the Quran- and other sources of Islamic law- to more contextual examinations in the formulation of ethical opinions. Third, an active and interdisciplinary collaboration between Muslim scholars in the determination of Islamic rulings on medical matters. Only when these goals are met is the practice of Islamic bioethics capable of meeting the needs of Muslim patients and clinicians.
Albert R. Jonsen, ed., of Bioethics, Special Supplement, Hastings Center Report 23, no. 6 (1993). On 23-24 September 1992, of Bioethics, held at University of Washington, Seattle, gathered many of pioneers of new ethics of medicine to review its history and project its future. A pioneer was defined as one whose name had appeared in first edition of Bibliography of (1975) and who had continued to work in field. Some sixty persons made cut and, of these, forty-two came to Seattle. The occasion of this conference was thirtieth anniversary of publication of an article in Life magazine, They Decide Who Lives, Who Dies (9 November 1962). That article told story of a committee in Seattle whose duty it was to select patients for entry into chronic hemodialysis program recently opened in that city. Chronic dialysis had just been made possible by Dr. Belding Scribner's invention of arteriovenous shunt and cannula in 1961. It quickly became apparent that many more patients needed dialysis than could be accommodated. The solution was to ask a small group, composed mostly of nonphysicians, to review dossiers of all medically suitable candidates and sort out those who would receive lifesaving technology. Thus, committee was faced with unenviable task of determining suitability on grounds other than medical. Should it be personality? finances? social acceptability? past or expected contribution? family dependents and support? While committee was anonymous, word of its existence appeared in New York Times. Life correspondent Shana Alexander travelled to Seattle to cover what she described at Birth of Bioethics as the most fascinating story of [her] career. As professor of ethics in medicine at University of Washington, I thought that thirtieth anniversary of appearance of that article was worth commemorating. My university would claim a birthright and, more seriously, those who had worked for some years in bioethics could reflect on origins and evolution of our work. Quite shamelessly, I entitled event of Bioethics although, as any decent historian knows and as many of conference participants declared, dating time and place when any social movement begins is perilous and near impossible. Still, interesting events in Seattle were worth recalling, and features of those events that presaged full-grown bioethics movement were worth pointing out. Whether Seattle events were a birth, a conception, or merely a gleam in someone's eye, I thought it a good time for early workers in field to gather, reminisce, and perhaps, begin to make a history. has matured into a minor form of moral philosophy practiced within medicine. Today, soundly reasoned articles on a variety of ethical questions appear regularly in major medical journals. In almost every American medical school, students study, in one form or another, new medial ethics. Twelve thousand persons subscribe to Hastings Center Report. Ten special government employees of Hillary Rodham Clinton's Health Care Task Force were identifiable as bioethicists. The effect of these developments on medicine and health care has been remarkable. The first historian of bioethics movement, Professor David Rothman of Columbia University, writes in his Strangers at Bedside: The record of bioethics' influence ... makes a convincing case for a fundamental transformation in substance as well as in style of medical decision making.[1] Where did this new ethics of medicine, or bioethics, come from? What events occasioned its origins? What form has it taken? Who elaborated it? Who pays attention to it? What is its significance for modern medicine, health care, and health policy? Those who work in this new field are only now beginning to reflect on these questions. …
The dominance of ableist assumptions in precision medicine has recently been challenged, notably by Mintz, Stramondo, and Tabor (2024). Yet a similarly radical critique exists in Daoist traditions, particularly in the philosophy of Zhuangzi. While Mintz, Stramondo, and Tabor call for greater disability inclusion in genetics and genomics, they do not fully engage with how cultural and philosophical worldviews shape responses to genetic intervention. Drawing on our research on preimplantation genetic testing for monogenic disorders (PGT-M), we argue that concepts like ziran (naturalness) and wuwei (non-action) can deepen our understanding of disability inclusion, particularly in Asian contexts. The comparatively restrictive approval of PGT-M in Asia reflects cultural discomfort with disrupting what is seen as nature's course. Zhuangzi's allegories-especially those illustrating "the usefulness of the useless"-challenge dominant hierarchies of ability and provide clinicians with tools to engage more sensitively with patients who may see genetic testing as ethically troubling. This paper integrates Daoist insights to propose a globally inclusive bioethics, one that affirms non-intervention as a legitimate stance and broadens how we conceive of naturalness, disability, and autonomy. By doing so, we aim to enrich debates around precision medicine and support ethically pluralistic genomic care.
This commentary highlights three themes from the stories contained within this issue of Narrative Inquiry in Bioethics. First, we discuss differing perceptions of school nurses' roles and responsibilities. Administrators, parents, and nurses often have different understandings of nurses' roles. We explain why these differences may lead to confusion and conflict. Second, we describe the respective pressures that parents and school nurses often face. Doing so should help parents and nurses better understand one another's views. Third, we explore ways in which parents and nurses sometimes disagree over what is "best" for children. Drawing on work by John Moskop, we argue that resolving disagreement often requires identifying the factual, emotional, normative, and/or practical roots of conflict. As parents of children with medically complex needs, we consider each of these themes in that context. We conclude by affirming the contributors' claims that school nurses play a vital role in the care of children.
Background/Objectives: The world's interest in the applications of artificial intelligence (AI) is rapidly increasing. In medicine, machine learning-based devices have proliferated, especially for image analysis, heralding significant new challenges for the use of AI in healthcare. Based on this context, this research addresses the following question: What are the major bioethical issues related to the use of AI in radiological patient reports? Methods: This study examined the main bioethical concerns surrounding AI in radiological reports, based on a narrative literature review grounded in the works of prominent authors in the field of bioethics. Results: We highlight the legal frameworks regulating medical devices and data protection in the European Union and the United States of America, evaluating recent developments in the contemporary medical landscape. Conclusions: Despite progress, many issues remain unresolved and must be addressed in order to advance the regulation of AI applications in medicine.
The clinical development of implantable neural devices raises complex ethical questions about post-trial responsibilities to participants. Continued support for participants who continue to use investigational implantable neural devices requires ongoing specialist care, technical expertise, access to tertiary clinical infrastructure, and substantial financial resources to pay for the device and related procedures. However, continued access may not be possible if the trial shows no benefit, if financial barriers limit commercial viability, or if safety concerns lead to suspension or early termination. Specific ethical guidance on post-trial responsibility is urgently needed. To address this challenge within the Australian innovation context, we conducted a modified Delphi study with a multidisciplinary panel of 24 experts, including representatives from industry, bioethics, law, neurosurgery, clinical psychology/neuropsychology, clinical research, neural engineering, regulation and governance, and lived experience advocacy. The process involved two workshops and a survey, guided by established RAND/UCLA methods with context-specific modifications. Drawing on prior empirical research and regulatory review, the panel developed 11 consensus recommendations for responsible post-trial practices. All recommendations achieved high levels of agreement and were rated as highly important for addressing ethical risks in the Australian environment. These are the first jurisdiction-specific recommendations of their kind, and we anticipate they will substantially enhance ethical and practical standards for post-trial responsibility in implantable neural device research in Australia and internationally.
In a scientific and implementation consortium, we developed an adaptive AI platform that enables doctors to create accurate and comprehensive Electronic Health Records (EHRs) through advanced speech recognition and context analysis tailored to Polish medical language. This system ensures stability with consistent performance across real-world clinical settings, achieving expected values for speech and context recognition during extensive testing. Its robustness is demonstrated by handling diverse inputs-such as regional accents, complex terminology, and noisy environments-supported by error-correction mechanisms and a specialized acoustic probe. Sustainability is achieved through seamless integration with existing healthcare infrastructures, scalable design, and ongoing updates to medical dictionaries, facilitating long-term use and adaptation. Structured data from electronic health records (EHRs) supports scientific research based on Real-World Data (RWD), verified by medical specialists using evidence-based medicine (EBM). The platform covers 10 clinical situations. The applied method was illustrated using one situation-a breast X-ray examination-employing clinically approved structures and real-world validation. Approved by the Bioethics Committee, the system is currently being tested at the hospital, marking a significant step toward efficient, reliable, and sustainable healthcare documentation.
Multiple sclerosis (MS) has a complex pathophysiology, comprising inflammation, demyelination, and alterations in neurotransmitter levels. Dysregulation of neurotransmitters, an imbalance between GABAergic and glutamatergic activity, enhanced oxidative stress, and an inflammatory response have all been involved in the disease. These mechanisms play a crucial role in regulating neuronal plasticity and activity. This study explored the role of neurotransmitters and inflammatory mediators in experimental autoimmune encephalomyelitis (EAE)-induced MS, as well as the effect of a 1,3,4-oxadiazole derivative, i.e., 2-{[5-(3-iodophenyl)-1,3,4-oxadiazol-2-yl] sulfanyl} ethan-1-ol (abbreviated as OX-3), on reducing neurotransmitter-mediated inflammatory responses. Its activity was assessed using clinical scoring, behavioral testing, histopathological changes, molecular testing through RT-PCR, ELISA, and assessment of neurotransmitters through HPLC. Molecular docking and simulation studies were performed to analyze protein interactions. The study findings revealed that OX-3 significantly reduced the severity of the disease by improving clinical symptoms of MS. It also ameliorated the cognitive decline in MS through a significant impact on neurotransmitters. It improved the GABA/Glutamate balance and reduced the pro-inflammatory cytokine levels. The comet assay revealed a reduction in DNA damage, and antioxidant levels improved, decreasing oxidative stress. The study concludes that OX-3 exerts its neuroprotective effect by attenuating the neurotransmitter-mediated neurodegeneration.
The postmortem diagnosis of drowning is a challenge for forensic medicine. The objective of this review was to list the findings described in reports of postmortem computed tomography (PMCT) examinations and autopsies of drowning victims, as well as to show how PMCT facilitates the diagnosis. The PubMed, Google Scholar, the Brazilian Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Office for the Advancement of Higher Education) Journals, and the International Prospective Register of Systematic Reviews (PROSPERO) databases were searched. The 17 studies included evaluated a collective total of 726 bodies of drowning victims and 477 bodies of people who died from other causes. Different PMCT protocols were used, some encompassing whole-body scans and others including scans only from the skull to the pelvis, with different slice thicknesses, all without the use of contrast. The finding most commonly described was fluid in the paranasal sinuses, mastoid air cells, and airways, referred to as specific for drowning if frothy, containing dense sediment, or both. A cutoff of 37.77 HU for the density of fluid in the paranasal sinuses was suggested to characterize drowning in salt water. Paltauf spots were detected only at autopsy. Although PMCT has proven to be a useful tool in making this diagnosis, it is too early to predict whether it can replace conventional autopsy. Current limitations include the absence of established protocols, a shortage of forensic radiologists, and low availability of CT scanners at forensic medicine facilities. O diagnóstico post-mortem de afogamento é um desafio para a medicina legal. O objetivo desta revisão é elencar os achados descritos na tomografia computadorizada post-mortem (TCPM) e na autópsia de afogados e mostrar como a TCPM auxilia nesse diagnóstico. Foram pesquisadas as bases de dados PubMed, Google Acadêmico, Periódicos da Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior e International Prospective Register of Systematic Reviews. Os 17 estudos incluídos avaliaram um total de 726 corpos vítimas de afogamento e 477 corpos mortos por outras causas. Foram realizados diferentes protocolos de TCPM, alguns abrangendo a varredura de todo corpo e outros apenas do crânio até a pelve, com espessuras de corte divergentes, todos sem uso de contraste. Os achados mais descritos foram: líquido nos seios paranasais, nas células das mastoides e nas vias aéreas, referidos como específicos para afogamento se espumoso e/ou associado a sedimento denso; sugerido um cut-off de 37,77 UH na densidade do líquido nos seios paranasais para caracterizar afogamento em água salgada. Apenas a autópsia evidenciou manchas de Paltauf. A TCPM mostrou-se uma ferramenta nesse diagnóstico, porém é cedo prever se poderá substituir a autópsia convencional. Dentre os limites atuais destacam-se a ausência de protocolos estabelecidos, escassez de radiologistas forenses e baixa disponibilidade de tomógrafos nos institutos médicolegais.
The revival of psychedelic medicalization is often narrated as a story of scientific legitimacy and neurotherapeutic promise, yet the unusual sensitivity of psychedelics to environmental conditions has encouraged research on music, therapy, setting, and other contextual factors. Treating setting and context as the building blocks of felt atmospheres, this article examines how regulation actively shapes atmospheres of consumption for substances that alter affective and sensory perception. Debates over drug-centric versus therapy-centered models are situated within the broader issue of how law shapes contexts and settings of psychedelic consumption. Policy developments in the United States and Australia show how emerging legal pathways have variably defined personnel, setting, access, substance, and the permitted forms of "holding space" or providing support or therapy. We introduce the concept of regulatory atmospheres to describe the diffuse and sometimes invisible ways in which policy shapes the contextual conditions of psychedelic use. Although policy rarely addresses atmospheres directly, we argue that it powerfully conditions them, which the case of psychedelic drug policy makes particularly clear. Alongside emerging legal pathways, the persistent shadow cast by prohibition over underground and traditional contexts reveals how some ontologies of risk and efficacy are privileged over others.
ObjectiveReports from caregivers and other witnesses describe episodes of unexpected or paradoxical lucidity among adults diagnosed with dementia. However, until now, there has not been a representative national survey documenting its prevalence in the U.S. adult population. This study reports on (a) the prevalence of terminal or unexpected lucidity in adults diagnosed with Alzheimer's disease or other dementias, and (b) its distribution across sociodemographic characteristics and parameters of clinical cases.MethodData are from a nationally representative population-based survey of observers (N = 5940) of dementia patients, aged 40+, who experienced one or more episodes of unexpected lucidity.ResultsThe national prevalence of unexpected lucidity, according to observers, is 43.6% (weighted n = 2587). Episodes occur regardless of the age or sex of patients, parameters of the clinical case, or characteristics of observers.ConclusionFindings reveal that lucid episodes are not rare, but possibly a normative feature of the dementing process. If so, this has implications for clinical practice and ethical decision-making involving "deeply forgetful people."
The genetic variability of Plasmodium falciparum serves as an important marker of the parasite's ability to adapt and develop resistance to antimalarial treatments. This study sought to evaluate the diversity of the P. falciparum merozoite surface protein 2 (msp2) gene among patients receiving care in four health centers in the Mbouda Health District, Cameroon. Blood samples were obtained from 481 individuals who came for diagnostic testing with symptoms suggestive of malaria. Rapid diagnostic tests and thick blood smears were performed to confirm P. falciparum infection and determine parasite density, respectively. Positive samples were spotted onto Whatman filter paper for molecular testing. DNA was extracted using the Chelex-100 technique, and msp2 fragments were amplified via nested PCR. Amplicons were separated on 1.3% agarose gels and visualized under UV light. Phylogenetic analysis was performed in R, and statistical analyses were conducted using SPSS version 23. Out of the 481 samples analyzed, 137 (28.48%) tested positive for P. falciparum, with a mean parasite density of 2196.77 ± 1344.36 parasites/µL. Female participants showed a weakly significant association with malaria infection, while children aged 0-5 years, despite having an odds ratio above 1, did not show a statistically significant association. The msp2 gene was successfully amplified in 64% of positive samples, revealing 15 distinct alleles. The overall genetic diversity was 14.15%, with a mean multiplicity of infection (MOI) of 1.20. The proportions of mono-, double-, and triple-genotype infections were 81.68%, 18.18%, and 1.33%, respectively. Phylogenetic analysis identified 13 distinct clades, indicating genetic relatedness among circulating P. falciparum strains. A considerable level of genetic diversity and multiple infections was detected among P. falciparum isolates in the Mbouda Health District, suggesting high transmission intensity. Further studies incorporating additional molecular markers such as msp1 and GLURP are recommended to provide a more comprehensive picture of P. falciparum genetic variation in the region.
Settings characterized by significant systemic challenges face profound difficulties in building a resilient health workforce, a critical component for achieving Universal Health Coverage (UHC). In Libya, a period of prolonged instability has fragmented the primary health care (PHC) system, resulting in uncoordinated training and a workforce ill-equipped to deliver essential services. This study evaluates a multi-year initiative designed to establish a standardized, nationally-owned in-service training (IST) system to strengthen PHC capacity. A phased, multi-method intervention was implemented from 2021 to 2025. The programme comprised: (1) a national landscaping analysis using desk review and stakeholder interviews to diagnose systemic gaps; (2) collaborative development of a national IST Framework via a multi-stakeholder Technical Working Group; (3) co-creation of evidence-based training materials reviewed by a national scientific committee; and (4) implementation of a Train-the-Trainer (ToT) cascade model with supportive supervision. A programmatic evaluation was conducted using pre-post knowledge assessments and thematic analysis of qualitative feedback to measure outcomes. The programme achieved national endorsement of a standardized 5-pillar In-Service Training (IST) Framework. A cohort of 35 Master Trainers was established (66% female), with approximately 94% of the first cohort reporting increased facilitation confidence. This network trained 613 Primary Healthcare (PHC) workers (88% female) across 12 districts. Quantitative assessment (n = 599) revealed significant knowledge gains among trainees (p < 0.001), with mean scores increasing by 29.4% in the first cascade and 33.0% in the second. Thematic analysis of qualitative feedback identified themes of improved professional collaboration, empowerment, and accountability. This initiative successfully established the foundation for a coherent, nationally-led In-Service Training (IST) system in a challenging setting, demonstrating a replicable model for health workforce strengthening. The significant knowledge gains and development of sustainable training infrastructure underscore that systematic planning, deep local ownership, and adaptive management are critical for building health system resilience. Future efforts should focus on longitudinal evaluation including clinical audit to assess the impact on clinical practice and patient outcomes.
Self-care during medical education is challenging for both students and faculty, and results in high rates of burnout and depression. We analyzed data from participants in the Humanistic Elective in Advocacy, Reflective Transformation, and Integrative Medicine (HEART-IM) course as a lens for identifying potential areas of improvement in medical education for both learners and faculty. We surveyed student and faculty participants in the spring 2022 HEART-IM course shortly following course completion. Surveys involved open-ended questions, and we used a conventional content analysis approach to analyze the data. Survey completion rates were 59% and 42% for students and faculty, respectively. Our qualitative analyses identified four themes each from students and faculty. The student themes were self-care as professional development, healing from their medical education, connection with self, and confidence in being able to pursue personal wellness. The faculty themes were connection and community with/for students, crucial learning outside of current medical curriculum, faculty inspired by students, and renewed passion for medicine. Collectively, the eight qualitative themes suggested three meta themes: (a) the need for personal wellness and self-care, (b) cultivating community among students and faculty, and (c) healing the disconnect between one's whole self and one's academic self. Innovative curricula such as HEART-IM may provide a valuable lens for improving medical education for both learners and faculty.
The use of restraint in hospital settings is divisive, and internationally there are calls for its elimination. However, this is at odds with the experience of many hospital staff, who consider restraint, at times, a "necessary evil". In this paper, we explore the definition of restraint and potential ethical justifications for its use. We argue that the current ethical literature employs two definitions of restraint - outcome-oriented and intent-oriented - neither of which successfully captures all ethically relevant features of the practice. We propose a new conceptualization of restraint which centers on the number of individuals impacted by an act of patient restraint - a continuum between therapeutic restraint and public-safety restraint. Understood in this way, neither the principlist nor human rights frameworks that dominate the current literature are appropriate for assessing the ethical legitimacy of restraint. We suggest that, given the similarities between restraint and public health interventions, the use of public health ethics principles to consider the ethical justifiability of restraint in hospitals is a potentially productive way forward in this controversial area.
To examine how the WHO and the World Medical Association (WMA) frame bioethical principles and address implementation barriers in their pain management policies, providing insights for global health policy and ethical analysis. Qualitative content analysis of international policy documents using the Standards for Reporting Qualitative Research to ensure methodological transparency and analytical rigour. Analysis of publicly available policy documents produced by the WHO and WMA between January 2000 and December 2024. Documents addressing pain management with ethical content, current and not superseded (n=18 from 314 screened). 18 policy documents were retrieved through relevance screening and analysed with reference to ethical values and systemic constraints using MAXQDA Analytics Pro 2022. Thematic coding identified ethical principles, structural barriers and strategic policy directions shaping global pain management frameworks. Nine ethical principles underpin global pain management policies, including human rights-based access, professional duty to relieve suffering and equitable care. Seven major barriers, such as regulatory restrictions, educational deficiencies and systemic inequities, hinder implementation. Five policy directions were identified to bridge principles and practice. WHO and WMA frameworks articulate a shared normative commitment to equitable, safe and person-centred pain management but differ in emphasis between public health and clinical ethics perspectives. Addressing identified structural barriers, integrating biopsychosocial approaches, and promoting culturally sensitive ethical guidance are critical for improving global pain management policies. While international guidelines provide the ethical foundations, achieving equitable global pain care requires coordinated transformation across regulatory, educational and health system domains. The persistent gap between ethical commitments and real-world implementation underscores the urgent need for binding accountability mechanisms, stronger international coordination and systematic approaches to address structural determinants of inequity.
The phenomenon of euthanasia and/or assisted suicide (EAS) in unjust conditions has received much attention in the popular press, along with a handful of responses in academic venues. These responses typically defend the permissibility of EAS in unjust conditions by appeal to anti-discrimination or harm reduction arguments, which frame the issue in terms of exclusion from current EAS law. We first briefly examine these arguments within such a framing, and then argue that it fails to account for the deep moral concern elicited by EAS in unjust conditions. To address this moral concern more fully, we compare the policy of allowing EAS in unjust conditions to a hypothetical EAS policy which requires a guarantee of basic care-and thus avoids the EAS cases of moral concern from the start. We argue for the moral superiority of the latter policy and respond to several potential objections.
Chronic graft-versus-host disease (cGvHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Beyond its classical manifestations, cGvHD may involve additional organs, including the central nervous system (CNS), where involvement remains poorly characterized, and therapeutic options are undefined, particularly in steroid-refractory cases. We report the case of a 50-year-old woman who underwent allo-HSCT for myelodysplastic syndrome and subsequently developed classical acute followed by chronic GvHD-overlap syndrome. At 2 years and 9 months post-transplant, she presented with progressive spastic paraparesis, and brain MRI revealed multifocal hyperintense white-matter lesions. A diagnosis of possible CNS-cGvHD was established. Due to poor response and intolerance to prolonged corticosteroid therapy, ruxolitinib was initiated at 10 mg/day and subsequently increased to 20 mg/day, with concomitant tapering of prednisone and immunoglobulin supplementation. Over 12 months, the patient demonstrated both clinical and radiological improvement, including significant functional recovery and marked regression of CNS lesions. This case suggests that ruxolitinib may represent a potential therapeutic option for atypical CNS involvement in cGvHD. Although clinical improvement likely reflected combined treatments, the neurological and radiological response suggests meaningful contribution from JAK inhibition. Further studies are needed to better define the role of ruxolitinib in this rare manifestation of cGvHD.
Live biotherapeutic products are emerging as supports for host physiology and gastrointestinal health. However, despite their broad use and apparent safety, the in vivo toxicity of new probiotic strains must be rigorously evaluated before human application. Bacillus safensis NMCC-189, a spore-forming bacterium with promising probiotic potential, was assessed through a 14-day short-term repeated-dose tolerability study to confirm initial safety followed by sub-acute (28-day) oral toxicity study conducted in accordance with Organisation for Economic Co-operation and Development (OECD) test guideline 407. Male and female Balb/c mice were orally administered low (1 × 108 CFU/mL) and high doses (1 × 1010 CFU/mL) of B. safensis NMCC-189 corresponding to approximately 1 × 109 CFU/kg/day 1 × 1011 CFU/kg/day. Dose selection was based on established probiotic safety ranges and toxicological principles. Clinical signs, survival, body weight, food intake, haematology, serum biochemistry, organ weights, and histopathology were examined, alongside daily in-life monitoring, randomisation, and blinding. No morbidity, mortality, or treatment related clinical abnormalities were observed in either study phase. Body weight gain, food consumption, and behavioural patterns remained within normal physiological limits. Haematological and biochemical parameters showed no toxicologically relevant changes, and minor fluctuations remained within reference ranges. Gross and microscopic examination of major organs revealed no pathological changes. The no observed adverse effect level (NOAEL) was 1 × 1011 CFU/kg/day. These findings suggest that B. safensis is well tolerated following oral administration and support its safety as a probiotic candidate. Overall, the combined study design provided a structured framework for the preclinical toxicological assessment of live biotherapeutic products.