[i-Leviathan: towards precision public health?] / i-Léviathan : vers une santé publique de précision ?

Hobbes' Leviathan symbolizes state sovereignty. In public health, this concept now extends to the prevention and promotion of health and the fight against non-communicable diseases (NCDs). This article explores the evolution towards an i-Leviathan, utilizing health data for more effective health surveillance. Precision public health, grounded in a personalized law approach, relies on the collection, availability, and use of these health data. This article analyzes the legal challenges of this precision, such as stigmatization, discrimination, and repression. It addresses the balance between public interests and individual freedoms, outlining state measures to monitor, control, and discipline healthy individuals.

Le Léviathan de Hobbes symbolise la souveraineté étatique. En santé publique, ce concept s'étend aujourd'hui à la prévention et la promotion de la santé et à la lutte contre les maladies non transmissibles. Cet article explore l'évolution vers un i-Léviathan, recourant à nos données de santé en vue d'une surveillance sanitaire plus efficace. Une santé publique de précision, ancrée dans une approche de droit personnalisé, dépend de la collecte, de la disponibilité et de l'utilisation de ces données de santé. Cet article analyse les enjeux juridiques de cette précision, tels que la stigmatisation, la discrimination et la répression. Il fait état de la balance entre intérêts publics et libertés individuelles, traçant les démarches étatiques de surveiller, contrôler et discipliner l'individu en bonne santé.

Pharmacogenetics in Italy: current landscape and future prospects.

Pharmacogenetics investigates sequence of genes that affect drug response, enabling personalized medication. This approach reduces drug-induced adverse reactions and improves clinical effectiveness, making it a crucial consideration for personalized medical care. Numerous guidelines, drawn by global consortia and scientific organizations, codify genotype-driven administration for over 120 active substances. As the scientific community acknowledges the benefits of genotype-tailored therapy over traditionally agnostic drug administration, the push for its implementation into Italian healthcare system is gaining momentum. This evolution is influenced by several factors, including the improved access to patient genotypes, the sequencing costs decrease, the growing of large-scale genetic studies, the rising popularity of direct-to-consumer pharmacogenetic tests, and the continuous improvement of pharmacogenetic guidelines. Since EMA (European Medicines Agency) and AIFA (Italian Medicines Agency) provide genotype information on drug leaflet without clear and explicit clinical indications for gene testing, the regulation of pharmacogenetic testing is a pressing matter in Italy. In this manuscript, we have reviewed how to overcome the obstacles in implementing pharmacogenetic testing in the clinical practice of the Italian healthcare system. Our particular emphasis has been on germline testing, given the absence of well-defined national directives in contrast to somatic pharmacogenetics.

Unveiling the Future of Oncology and Precision Medicine through Data Science.

Information generated via next-generation sequencing (NGS) technologies is often termed multi-omics data [...].

Individualising goal-directed haemodynamic therapy: future iterations will require novel trial designs.

Variants of perioperative cardiac output-guided haemodynamic therapy algorithms have been tested over the last few decades, without clear evidence of effectiveness. Newer approaches have focussed on individualisation of physiological targets and have been tested in early efficacy trials. Uncertainty about the benefits remains. Adoption of novel trial designs could overcome the limitations of smaller trials of this complex intervention and accelerate the exploration of future developments.

Navigating new horizons: Prospects of NET-targeted radiopharmaceuticals in precision medicine.

In the evolving landscape of precision medicine, NET-targeted radiopharmaceuticals are emerging as pivotal tools for the diagnosis and treatment of a range of conditions, from heart failure and neurodegenerative disorders to neuroendocrine cancers. This review evaluates the advancements offered by 18F-labeled PET tracers and 211At alpha-particle therapy, juxtaposed with current 123I-MIBG SPECT and 131I-MIBG therapies. The enhanced spatial resolution and capability for quantitative analysis render 18F-labeled PET tracers potential candidates for improved detection and management of diseases. Alpha-particle therapy with 211At may offer increased specificity and tumoricidal efficacy, pointing towards a shift in therapeutic protocols. While preliminary data is promising, these innovative approaches require thorough validation against current modalities. Ongoing clinical trials are pivotal to confirm the expected clinical benefits and to address safety concerns. This review underscores the need for rigorous research to verify the clinical utility of NET-targeted radiopharmaceuticals, which may redefine precision medicine paradigms and significantly impact patient care.

Noninvasive brain stimulation in autism: review and outlook for personalized interventions in adult patients.

Noninvasive brain stimulation (NIBS) has been increasingly investigated during the last decade as a treatment option for persons with autism spectrum disorder (ASD). Yet, previous studies did not reach a consensus on a superior treatment protocol or stimulation target. Persons with ASD often suffer from social isolation and high rates of unemployment, arising from difficulties in social interaction. ASD involves multiple neural systems involved in perception, language, and cognition, and the underlying brain networks of these functional domains have been well documented. Aiming to provide an overview of NIBS effects when targeting these neural systems in late adolescent and adult ASD, we conducted a systematic search of the literature starting at 631 non-duplicate publications, leading to six studies corresponding with inclusion and exclusion criteria. We discuss these studies regarding their treatment rationale and the accordingly chosen methodological setup. The results of these studies vary, while methodological advances may allow to explain some of the variability. Based on these insights, we discuss strategies for future clinical trials to personalize the selection of brain stimulation targets taking into account intersubject variability of brain anatomy as well as function.

A Quadruple Revolution: Deciphering Biological Complexity with Artificial Intelligence, Multiomics, Precision Medicine, and Planetary Health.

A quiet quadruple revolution has been in the making in systems science with convergence of (1) artificial intelligence, machine learning, and other digital technologies; (2) multiomics big data integration; (3) growing interest in the "variability science" of precision/personalized medicine that aims to account for patient-to-patient and between-population differences in disease susceptibilities and responses to health interventions such as drugs, nutrition, vaccines, and radiation; and (4) planetary health scholarship that both scales up and integrates biological, clinical, and ecological contexts of health and disease. Against this overarching background, this article presents and highlights some of the salient challenges and prospects of multiomics research, emphasizing the attendant pivotal role of systems medicine and systems biology. In addition, we emphasize the rapidly growing importance of planetary health research for systems medicine, particularly amid climate emergency, ecological degradation, and loss of planetary biodiversity. Looking ahead, we anticipate that the integration and utilization of multiomics big data and artificial intelligence will drive further progress in systems medicine and systems biology, heralding a promising future for both human and planetary health.

Advances in personalized radiotherapy.

Radiotherapy is a mainstay of cancer treatment. The clinical response to radiotherapy is heterogeneous, from a complete response to early progression. Recent studies have explored the importance of patient characteristics in response to radiotherapy. In this editorial, we invite contributions for a BMC Cancer collection of articles titled 'Advances in personalized radiotherapy' towards the improvement of treatment response.

Sepsis in surgical patients: Personalized medicine in the future treatment of sepsis.

Sepsis results when a severe infection overwhelms the normal regulatory mechanisms of the immune system, resulting in a dysregulated host response characterized by new-onset organ failure. A wide range of infectious challenges can induce sepsis, resulting in an even wider range of maladaptive immune responses. This makes sepsis a syndromic diagnosis without a unifying, underlying molecular mechanism. The next step toward personalized medicine for sepsis is to resolve the heterogeneity across the universe of septic patients in order to establish pathobiologically homogenous sepsis "endotypes" that have uniformly defined changes in physiology and immunology. Defining the mechanisms of immune dysfunction within these endotypes will provide a roadmap for the application of immunomodulatory therapies for sepsis. This approach can drive in a paradigm shift in sepsis treatment, moving beyond supportive care and toward active efforts to restore normal immune function.

Towards personalized medicine: a scoping review of immunotherapy in sepsis.

Despite significant progress in our understanding of the pathophysiology of sepsis and extensive clinical research, there are few proven therapies addressing the underlying immune dysregulation of this life-threatening condition. The aim of this scoping review is to describe the literature evaluating immunotherapy in adult patients with sepsis, emphasizing on methods providing a "personalized immunotherapy" approach, which was defined as the classification of patients into a distinct subgroup or subphenotype, in which a patient's immune profile is used to guide treatment. Subgroups are subsets of sepsis patients, based on any cut-off in a variable. Subphenotypes are subgroups that can be reliably discriminated from other subgroup based on data-driven assessments. Included studies were randomized controlled trials and cohort studies investigating immunomodulatory therapies in adults with sepsis. Studies were identified by searching PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov, from the first paper available until January 29th, 2024. The search resulted in 15,853 studies. Title and abstract screening resulted in 1409 studies (9%), assessed for eligibility; 771 studies were included, of which 282 (37%) were observational and 489 (63%) interventional. Treatment groups included were treatments targeting the innate immune response, the complement system, coagulation and endothelial dysfunction, non-pharmalogical treatment, pleiotropic drugs, immunonutrition, concomitant treatments, Traditional Chinese Medicine, immunostimulatory cytokines and growth factors, intravenous immunoglobulins, mesenchymal stem cells and immune-checkpoint inhibitors. A personalized approach was incorporated in 70 studies (9%). Enrichment was applied using cut-offs in temperature, laboratory, biomarker or genetic variables. Trials often showed conflicting results, possibly due to the lack of patient stratification or the potential influence of severity and timing on immunomodulatory therapy results. When a personalized approach was applied, trends of clinical benefit for several interventions emerged, which hold promise for future clinical trials using personalized immunotherapy.

Envisioning the Future of Personalized Medicine: Role and Realities of Digital Twins.

Digital twins have emerged as a groundbreaking concept in personalized medicine, offering immense potential to transform health care delivery and improve patient outcomes. It is important to highlight the impact of digital twins on personalized medicine across the understanding of patient health, risk assessment, clinical trials and drug development, and patient monitoring. By mirroring individual health profiles, digital twins offer unparalleled insights into patient-specific conditions, enabling more accurate risk assessments and tailored interventions. However, their application extends beyond clinical benefits, prompting significant ethical debates over data privacy, consent, and potential biases in health care. The rapid evolution of this technology necessitates a careful balancing act between innovation and ethical responsibility. As the field of personalized medicine continues to evolve, digital twins hold tremendous promise in transforming health care delivery and revolutionizing patient care. While challenges exist, the continued development and integration of digital twins hold the potential to revolutionize personalized medicine, ushering in an era of tailored treatments and improved patient well-being. Digital twins can assist in recognizing trends and indicators that might signal the presence of diseases or forecast the likelihood of developing specific medical conditions, along with the progression of such diseases. Nevertheless, the use of human digital twins gives rise to ethical dilemmas related to informed consent, data ownership, and the potential for discrimination based on health profiles. There is a critical need for robust guidelines and regulations to navigate these challenges, ensuring that the pursuit of advanced health care solutions does not compromise patient rights and well-being. This viewpoint aims to ignite a comprehensive dialogue on the responsible integration of digital twins in medicine, advocating for a future where technology serves as a cornerstone for personalized, ethical, and effective patient care.

CRISPR Advancements for Human Health.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has emerged as a powerful gene editing technology that is revolutionizing biomedical research and clinical medicine. The CRISPR system allows scientists to rewrite the genetic code in virtually any organism. This review provides a comprehensive overview of CRISPR and its clinical applications. We first introduce the CRISPR system and explain how it works as a gene editing tool. We then highlight current and potential clinical uses of CRISPR in areas such as genetic disorders, infectious diseases, cancer, and regenerative medicine. Challenges that need to be addressed for the successful translation of CRISPR to the clinic are also discussed. Overall, CRISPR holds great promise to advance precision medicine, but ongoing research is still required to optimize delivery, efficacy, and safety.

Digital twins for cardiac electrophysiology: state of the art and future challenges.

Cardiac arrhythmias remain a major cause of death and disability. Current antiarrhythmic therapies are effective to only a limited extent, likely in large part due to their mechanism-independent approach. Precision cardiology aims to deliver targeted therapy for an individual patient to maximize efficacy and minimize adverse effects. In-silico digital twins have emerged as a promising strategy to realize the vision of precision cardiology. While there is no uniform definition of a digital twin, it typically employs digital tools, including simulations of mechanistic computer models, based on patient-specific clinical data to understand arrhythmia mechanisms and/or make clinically relevant predictions. Digital twins have become part of routine clinical practice in the setting of interventional cardiology, where commercially available services use digital twins to non-invasively determine the severity of stenosis (computed tomography-based fractional flow reserve). Although routine clinical application has not been achieved for cardiac arrhythmia management, significant progress towards digital twins for cardiac electrophysiology has been made in recent years. At the same time, significant technical and clinical challenges remain. This article provides a short overview of the history of digital twins for cardiac electrophysiology, including recent applications for the prediction of sudden cardiac death risk and the tailoring of rhythm control in atrial fibrillation. The authors highlight the current challenges for routine clinical application and discuss how overcoming these challenges may allow digital twins to enable a significant precision medicine-based advancement in cardiac arrhythmia management.

Innovations in Medicine: Exploring ChatGPT's Impact on Rare Disorder Management.

Artificial intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use, ChatGPT holds a prominent position, using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for generating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT integration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex datasets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.