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Purpose: In people with cystic fibrosis (pwCF), elexacaftor/tezacaftor/ivacaftor (ETI) therapy is associated with an average improvement in FEV1 of 10–14%. However, a subset of individuals fails to achieve a clinically meaningful increase in spirometric indicators. In this study, we aimed to assess whether the lung clearance index (LCI2.5), a more sensitive indicator of lung involvement, improves following ETI initiation in this population. Methods: We conducted a prospective observational study in a specialized CF center in Italy. PwCF performed a spirometry and a multiple breath nitrogen washout test the day they initiated ETI therapy and after 6 and 12 months. They were grouped according to the 12-month change in FEV1 into two groups: Individuals who experienced a change in FEV1 ≥ a minimal clinically important difference (MCID) of 3% and those who did not. Mean changes in LCI2.5 were estimated using generalized estimating equations. Results: The study included 129 pwCF who initiated ETI at our center (Age Range: 12–36 years). In 20 subjects (15.5%), the FEV1 change was < MCID. These individuals had better baseline pulmonary function than those with FEV1 changes ≥ MCID (Median FEV1: 102.5 vs 87.0%), with the majority (90%) having FEV1 values ≥ 90%. Mean changes in LCI2.5 at 12-month follow-up visit were − 1.44 units (95% CI: − 2.12; − 0.75) in individuals with changes in FEV1 < MCID and − 2.64 units (95% CI: -3.05; -2.23) in those with values ≥ MCID. Conclusion: LCI2.5 is a useful measure to monitor the effectiveness of ETI in pwCF with normal spirometry and limited FEV1 change following treatment initiation. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly aggressive adult brain cancer, characterised by poor prognosis and a dismal five-year survival rate. Despite significant knowledge gains in tumour biology, meaningful advances in patient survival remain elusive. The field of neuro-oncology faces many disease obstacles, one being the paucity of faithful models to advance preclinical research and guide personalised medicine approaches. Recent technological developments have permitted the maintenance, expansion and cryopreservation of GBM explant organoid (GBO) tissue. GBOs represent a translational leap forward and are currently the state-of-the-art in 3D in vitro culture system, retaining brain cancer heterogeneity, and transiently maintaining the immune infiltrate and tumour microenvironment (TME). Here, we provide a review of existing brain cancer organoid technologies, in vivo xenograft approaches, evaluate in-detail the key advantages and limitations of this rapidly emerging technology, and consider solutions to overcome these difficulties. GBOs currently hold significant promise, with the potential to emerge as the key translational tool to synergise and enhance next-generation omics efforts and guide personalised medicine approaches for brain cancer patients into the future. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa is an inflammatory skin disease for which adalimumab is an effective treatment in just over half of cases. Few factors associated with therapeutic response, and therefore potentially predictive of response, are known to date. This real-life study retrospectively explores the existence of such factors in a Belgian cohort of 82 patients, using several response scores: the Hidradenitis Suppurativa Clinical Response (HiSCR), the International Hidradenitis Suppurativa Severity Scoring System-55 (iHS4-55), and the dynamic metascore (a combination of the Hurley score, the 2007 version of the Sartorius score, the iHS4 and the HiSCR). Among the factors associated with a good therapeutic response, we find, for example, the "Frictional furunculoid" and "Conglobata" phenotypes, in contrast to the "Scarring folliculitis" phenotype, which is associated with a poorer response to treatment. Other factors associated with a good response to treatment were observed, such as the patient's description of longer flares, or, among others, the presence of inflammatory bowel disease. Subject to our sample size, the window of opportunity for adalimumab, whereby the treatment would be more effective if administered earlier, was not found in this study. [ABSTRACT FROM AUTHOR]

Objective: To review the available literature on variant genital gender‐affirming surgery (GGAS), including the reasons for performing it, the surgeries themselves and their outcomes. Methods: A systematic review on the performance of variant GGAS was conducted (International Prospective Register of Systematic Reviews [PROSPERO] identifier: CRD42022306684) researching PubMed, Embase, Web of Science and Cochrane databases from inception up to 31 December 2023. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed, and risk of bias was assessed for each study using the five‐criteria quality assessment checklist. Results: In total 23 case series were included, of which 17 on masculinising and six on feminising surgeries. Patients mainly choose these surgical procedures out of personal desire to avoid risk of complication or because they do not have dysphoria about certain parts of their genitalia. Complications in masculinising surgeries primarily arose from the extended urethra, which could be mitigated through primary perineal urethrostomy. Both phalloplasty and metoidioplasty carried a higher risk of urethral complications when the vagina was preserved. In feminising surgeries, risk of visceral damage and requirement for lifelong self‐dilation could be avoided when vulvoplasty was performed without vaginal canal creation. All studies had a high risk of bias. Conclusion: This review highlights the importance of variant GGAS and acknowledges the preferences of transgender and gender‐diverse individuals. Patients should be informed about the risks and benefits of each step in these procedures. [ABSTRACT FROM AUTHOR]

Representative models of intestinal diseases are transforming our knowledge of the molecular mechanisms of disease, facilitating effective drug screening and avenues for personalised medicine. Despite the emergence of 3D in vitro intestinal organoid culture systems that replicate the genetic and functional characteristics of the epithelial tissue of origin, there are still challenges in reproducing the human physiological tissue environment in a format that enables functional readouts. Here, we describe the latest platforms engineered to investigate environmental tissue impacts, host-microbe interactions and enable drug discovery. This highlights the potential to revolutionise knowledge on the impact of intestinal infection and inflammation and enable personalised disease modelling and clinical translation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Digital twin technology, initially developed for engineering and manufacturing, has entered healthcare. In plastic surgery, digital twins (DTs) have the potential to enhance surgical precision, personalise treatment plans, and improve patient outcomes. This systematic review aims to explore the current use of DTs in plastic surgery and evaluate their effectiveness, challenges, and future potential. Methods: A systematic review was conducted by searching PubMed, Scopus, Web of Science, and Embase databases from their infinity to October 2024. The search included terms related to digital twins and plastic surgery. Studies were included if they focused on applying DTs in reconstructive or cosmetic plastic surgery. Data extraction focused on study characteristics, technological aspects, outcomes, and limitations. Results: After 110 studies were selected for screening, 9 studies met the inclusion criteria, covering various areas of plastic surgery, such as breast reconstruction, craniofacial surgery, and microsurgery. DTs were primarily used in preoperative planning and intraoperative guidance, with reported improvements in surgical precision, complication rates, and patient satisfaction. However, challenges such as high costs, technical complexity, and the need for advanced imaging and computational tools were frequently noted. Limited research exists on using DTs in postoperative care and real-time monitoring. Conclusions: This systematic review highlights the potential of digital twins to revolutionise plastic surgery by providing personalised and precise surgical approaches. However, barriers such as cost, complexity, and ethical concerns must be addressed. Future research should focus on validating clinical outcomes through large-scale studies and developing soft tissue modelling and real-time monitoring capabilities. [ABSTRACT FROM AUTHOR]

Simple Summary: This review focuses on the classification, risk stratification, and metabolic characteristics of acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) and their importance in the advancement of treatment. It discusses current management strategies, including standard chemotherapy regimens and targeted therapies, while highlighting the challenges of drug toxicity and resistance. It also emphasises the importance of understanding metabolic vulnerabilities in leukaemia cells for developing more effective and personalised treatments. Special attention is given to asparaginase therapy and its mechanism of action, limitations, and potential for improvement in both ALL and AML treatment. Acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) remain significant challenges in haematological oncology. This review examines the pathophysiology, classification, and risk stratification of these aggressive malignancies, emphasising their impact on treatment strategies and prognosis. We discuss current standard-of-care treatments, including chemotherapy regimens and targeted therapies, while addressing the associated adverse effects and hypersensitivity reactions. Delving into the metabolic characteristics and vulnerabilities of leukaemia cells, the review highlights the key differences between lymphoid and myeloid leukaemia and how metabolic insights can be utilised for therapeutic purposes, with special focus on asparaginase therapy and its potential for improvement in both ALL and AML treatment. The review conveys the importance of personalised medicine approaches based on individual metabolic profiles and the challenges posed by metabolic heterogeneity and plasticity in leukaemia cells. Combining molecular and metabolic profiling can enhance and refine treatment strategies for acute leukaemia, potentially improving patient outcomes and quality of life. However, integrating these into routine clinical practice requires overcoming various practical, technical, and logistical issues. [ABSTRACT FROM AUTHOR]

The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer (TNBC). Recent research indicates the aberrant expression of diverse tyrosine kinases (TKs) within this cancer, contributing significantly to tumor cell proliferation, survival, invasion, and migration. The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies, given their pivotal roles in tumor initiation, progression, and advancement. Intensive investigations have focused on various monoclonal antibodies (mAbs) and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), cellular mesenchymal-epithelial transition factor (c-MET), human epidermal growth factor receptor 2 (HER2), among others, for combating TNBC. These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents. Despite these advances, a substantial terrain of unexplored potential lies within the realm of TK targeted therapeutics, which hold promise in reshaping the therapeutic landscape. This review summarizes the various TK targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC, dissecting the outcomes and revelations stemming from diverse clinical investigations. A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies. [ABSTRACT FROM AUTHOR]

Aims: Personalised medicine in chronic complex diseases such as rheumatoid arthritis (RA) is within reach but requires international multi-stakeholder collaboration. We exemplify how national implementations of the General Data Protection Regulation (GDPR) have introduced administrative delays and created disincentives for data sharing and collaborative research. Methods: Our Danish/Swedish/Norwegian research collaboration (the 3-year NordForsk-funded "NORA" project) aims to develop a personalised medicine approach for the management of RA, built on the exploitation of unique existing data sources: longitudinal data from clinical rheumatology registries, research cohorts, nationwide health care registries, and biobank material from >20 sample collections. Data and results are shared and accessed remotely by collaborators at secure servers. New biomarker assays and patient-centric implementations of the results are to be explored, validated, and disseminated to patients and health care via the development of digital tools. Results: Following the advice of legal experts at the involved academic or public institutions and private companies, GDPR compliance resulted in >20 legal documents to govern the collaboration (consortium-, joint controller-, research collaboration-, data sharing-, and a series of unique two-way data processing-, and material transfer agreements). Lack of agreed-upon templates, policies, procedures, and a shortage of legal resources have caused considerable delays. Thus, our research consortium has spent more time ensuring GDPR compliance than on actual research activities. Conclusions: The current interpretation and implementation of the legal premises (rather than the GDPR per se) for research collaborations caused unnecessary barriers and delays. Our experiences call for Nordic trust-based code-of-conduct-like framework agreements, and for harmonisation of procedures and templates, lest the Nordic advantage in research be lost. [ABSTRACT FROM AUTHOR]

The relatively recent adoption of Endoscopic Sleeve Gastroplasty (ESG) amongst obese patients has gained approval within the surgical community due to its notable benefits, including significant weight loss, safety, feasibility, repeatability, and potential reversibility. However, despite its promising clinical outcomes and reduced invasiveness, there is still a lack of standardised procedures for performing ESG. Multiple suture patterns and stitching methods have been proposed over time, yet rational tools to quantify and compare their effects on gastric tissues are absent. To address this gap, this study proposed a computational approach. The research involved a case study analyzing three distinct suture patterns (C-shaped, U-shaped and Z-shaped) using a patient-specific computational stomach model generated from magnetic resonance imaging. Simulations mimicked food intake by placing wire features in the intragastric cavity to replicate sutures, followed by applying a linearly increasing internal pressure up to 15 mmHg. The outcomes facilitated comparisons between suture configurations based on pressure–volume behaviours and the distribution of maximum stress on biological tissues, revealing the U-shaped as the more effective in terms of volume reduction, even if with reduced elongation strains and increased tissues stresses, whereas the Z-shaped is responsible of the greatest stomach shortness after ESG. In summary, computational biomechanics methods serve as potent tools in clinical and surgical settings, offering insights into aspects that are challenging to explore in vivo, such as tissue elongation and stress. These methods allow for mechanical comparisons between different configurations, although they might not encompass crucial clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer (TNBC). Recent research indicates the aberrant expression of diverse tyrosine kinases (TKs) within this cancer, contributing significantly to tumor cell proliferation, survival, invasion, and migration. The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies, given their pivotal roles in tumor initiation, progression, and advancement. Intensive investigations have focused on various monoclonal antibodies (mAbs) and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), cellular mesenchymal-epithelial transition factor (c-MET), human epidermal growth factor receptor 2 (HER2), among others, for combating TNBC. These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents. Despite these advances, a substantial terrain of unexplored potential lies within the realm of TK targeted therapeutics, which hold promise in reshaping the therapeutic landscape. This review summarizes the various TK targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC, dissecting the outcomes and revelations stemming from diverse clinical investigations. A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.

The healthcare landscape has undergone a profound transformation due to digitalisation in recent decades, shifting from manual practices to automated processes. Digital biomarkers have become increasingly important in healthcare across multiple domains for regular monitoring of health parameters, aiding in early disease detection and prevention. The present narrative review aims to explore the utility and advantages of digital biomarkers in healthcare. Notably, the literature emphasises portable biomarkers capable of actively recording user data. These advanced biomarkers efficiently identify physiological, biochemical and psychological parameters, offering predictive capabilities for health conditions and treatment outcomes. In this dynamic healthcare landscape, digital science has brought transformative changes. Investments in digital health show promising outcomes for disease management and patient care. Overall, the integration of digital biomarkers into healthcare represents a significant leap forward in improving healthcare delivery, diagnosis and treatment. It leverages technology to enhance the precision and efficiency of healthcare, ultimately benefiting both healthcare professionals and patients. While the scope of digital biomarkers continues to expand and is expected to grow in the future, addressing potential challenges is essential for sustained innovation in this field.

Genetic factors influence medication response (pharmacogenetics), affecting the pharmacodynamics and pharmacokinetics of many medicaments used in clinical care. The ability of medications to cross the blood–brain barrier (BBB) represents a critical putative factor in the effectiveness and tolerability of various medications relevant to central nervous system disorders (CNS), cancer, and broader medical conditions at a pharmacokinetic (dosing) level. Pharmacogenetics has the potential to personalise medicine to a greater extent than has been possible, with the potential to help reduce heuristic delays to effective tolerable pharmacotherapy. Here, we critically examine and summarise the evidence, particularly for ABCB1 polymorphisms associated with drug transportation and other clinical relevance. These transporters appear to have a role in BBB pharmacogenetics and may indicate new avenues of research that extend beyond the current paradigm of CYP450 polymorphisms. We identify some of the most promising variants for clinical translation while spotlighting the complexities of the involved systems and limitations of the current empirical literature.

INTRODUCTION. National pharmacy compounding is a priority for providing the population with medicinal products, particularly the medicinal products lacking in the Russian Federation. Investigating opportunities to improve the operation of compounding pharmacies in the Russian Federation remains essential, especially in the context of the developing personalised approach to treatment, growing practice of orphan drug development, and import substitution needs.AIM. This study aimed to identify the factors driving the development of compounding pharmacies under the current conditions.MATERIALS AND METHODS. The study focused on the Russian regulatory framework for pharmacy compounding, as well as the range of dosage forms and administration routes of the medicinal products that had been produced and packaged by the compounding pharmacies in Irkutsk in 2021–2023.RESULTS. This study showed a demand for compounded medicinal products among both healthcare providers and patients. These medicinal products covered a traditional range of compounded medicines, including custom formulae, medicines for paediatrics and geriatrics, stock preparations, and pharmacy-packaged items. In 2021–2023, the mean annual production of Irkutsk pharmacy organisations amounted to ~500,000 units of compounded medicinal products, with a variety of doses and dosage forms. The medicinal products were compounded using ~100 different active substances and over 20 approved medicinal products. This study examined the evolution of Russian pharmacy compounding legislation. The key aspects included the establishment of a pharmaceutical quality system for compounded medicinal products, the extension of shelf life for specific dosage forms, and the authorisation to use medicinal products approved in the Eurasian Economic Union in compounding. The study showed that the main factors driving the operation of compounding pharmacies were the ongoing regulatory framework transformation and the transition from standardised treatment to personalised medicine. The main impediments for compounding pharmacies included the lack of state support, the ban on compounding medicinal products produced by pharmaceutical companies, the shortage of skilled staff, the inadequate supply of equipment (first of all, production machinery), the poor availability of active substances and excipients in small packages, and the challenges associated with regulatory control and oversight over the quality of compounded medicinal products.CONCLUSIONS. Further stimulation of the active development of compounding pharmacies requires further investigation into their operation in other regions, which will help to develop legal arrangements for the federal and regional state support of compounding pharmacies, procure up-to-date materials and equipment, and train the staff for compounding pharmacies.

Traditional wound dressings, despite their widespread use, face limitations, such as poor infection control and insufficient healing promotion. To address these challenges, bioactive materials have emerged as a promising solution in wound care. This comprehensive review explores the latest developments in wound healing technologies, starting with an overview of the importance of effective wound management, emphasising the need for advanced bioactive wound dressings. The review further explores various bioactive materials, defining their characteristics. It covers a wide range of natural and synthetic biopolymers used to develop bioactive wound dressings. Next, the paper discusses the incorporation of bioactive agents into wound dressings, including antimicrobial and anti‐inflammatory agents, alongside regenerative components like growth factors, platelet‐rich plasma, platelet‐rich fibrin and stem cells. The review also covers fabrication techniques for bioactive wound dressings, highlighting techniques like electrospinning, which facilitated the production of nanofibre‐based dressings with controlled porosity, the sol–gel method for developing bioactive glass‐based dressings, and 3D bioprinting for customised, patient‐specific dressings. The review concludes by addressing the challenges and future perspectives in bioactive wound dressing development. It includes regulatory considerations, clinical efficacy, patient care protocol integration and wound healing progress monitoring. Furthermore, the review considers emerging trends such as smart materials, sensors and personalised medicine approaches, offering insights into the future direction of bioactive wound dressing research. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is any cancer that starts in the colon or the rectum and presents a significant health concern. It is the third most diagnosed and the second deadliest cancer, with an estimated 153,020 new cases and 52,550 deaths in 2023. The severity of colon cancer may be attributed to its ability to avoid the host immune system and growth suppressors, its asymptomatic nature in the early stages, its association with a continually ageing population and unfavourable diet and obesity. The composition of the gut microbiome plays an important role in the development of CRC and presents as an important target in early detection and in predicting treatment outcomes in CRC. This study aims to identify microbiome‐specific derived clusters in CRC patients and conduct subsequent survival analysis using the specific microbiome features within clusters. Methods: Consensus clustering and feature selection, involving a Kruskal–Wallis test, a random forest and least absolute shrinkage and selection operator (LASSO) were applied resulting in the identification of differently expressed microbiomes between clusters. Lastly, survival analysis was performed on the selected features using Kaplan‐Meier curves and Cox regression. K‐means clustering, as selected using consensus clustering interpretation, presented three distinct clusters with clear differences in alpha and beta diversity and baseline clinical variables. Results: A total 1311 of the 1406 microbes were selected using the Kruskal Wallis and passed to the random forest and LASSO, which narrowed the dataset to 140 features. Following the survival analysis, eight microbiome species, namely N4likevirus, Ambidensovirus, Synechococcus, Thermithiobacillus, Hydrocarboniphaga, Rhodovibrio, Gloeobacter and Candidatus Nitrosotenuis, were selected as significant in clustering and survival. Conclusion: This study reveals the heterogeneity of the CRC microbiome and its effect on disease prognosis and necessitates further exploration of the biological mechanisms of these selected microbiomes as well further investigation of whether the approach depicted here is applicable to other cancer types. [ABSTRACT FROM AUTHOR]

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Pharmacogenetics is the study of genetic variants in genes which may impact on the outcome of drug treatment, either through safety considerations (occurrence of adverse drug reactions or therapeutic failure) or altered drug pharmacokinetics. This paper provides a brief history of pharmacogenetics research in the Aotearoa/New Zealand context, and a commentary on our current state. Factors that have limited translation of pharmacogenetic knowledge into ou r healthcare system are considered, and possible solutions to these are proposed. Pharmacogenetic knowledge has long been invoked as a way to improve the safety and success of drug prescribing, but (with some notable exceptions) it has largely failed to achieve this promise. Several barriers to clinical implementation need to be overcome to ensure that pharmacogenetics becomes a key component of precision health for all people in Aotearoa/New Zealand. [ABSTRACT FROM AUTHOR]

Pharmacogenomic (PGx) testing can help personalise psychiatric prescribing and improve on the currently adopted trial-and-error prescribing approach. However, widespread implementation is yet to occur. Understanding factors influencing implementation is pertinent to the psychiatric PGx field. Normalisation Process Theory (NPT) seeks to understand the work involved during intervention implementation and is used by this review (PROSPERO: CRD42023399926) to explore factors influencing PGx implementation in psychiatry. Four databases were systematically searched for relevant records and assessed for eligibility following PRISMA guidance. The QuADS tool was applied during quality assessment of included records. Using an abductive approach to codebook thematic analysis, barrier and facilitator themes were developed using NPT as a theoretical framework. Twenty-nine records were included in the data synthesis. Key barrier themes included a PGx knowledge gap, a lack of consensus in policy and guidance, and uncertainty towards the use of PGx. Facilitator themes included an interest in PGx use as a new and improved approach to prescribing, a desire for a multidisciplinary approach to PGx implementation, and the importance of fostering a climate for PGx implementation. Using NPT, this novel review systematically summarises the literature in the psychiatric PGx implementation field. The findings highlight a need to develop national policies on using PGx, and an education and training workforce plan for mental health professionals. By understanding factors influencing implementation, the findings help to address the psychiatric PGx implementation gap. This helps move clinical practice closer towards a personalised psychotropic prescribing approach and associated improvements in patient outcomes. Future policy and research should focus on the appraisal of PGx implementation in psychiatry and the role of pharmacists in PGx service design, implementation, and delivery. [ABSTRACT FROM AUTHOR]

The healthcare landscape has undergone a profound transformation due to digitalisation in recent decades, shifting from manual practices to automated processes. Digital biomarkers have become increasingly important in healthcare across multiple domains for regular monitoring of health parameters, aiding in early disease detection and prevention. The present narrative review aims to explore the utility and advantages of digital biomarkers in healthcare. Notably, the literature emphasises portable biomarkers capable of actively recording user data. These advanced biomarkers efficiently identify physiological, biochemical and psychological parameters, offering predictive capabilities for health conditions and treatment outcomes. In this dynamic healthcare landscape, digital science has brought transformative changes. Investments in digital health show promising outcomes for disease management and patient care. Overall, the integration of digital biomarkers into healthcare represents a significant leap forward in improving healthcare delivery, diagnosis and treatment. It leverages technology to enhance the precision and efficiency of healthcare, ultimately benefiting both healthcare professionals and patients. While the scope of digital biomarkers continues to expand and is expected to grow in the future, addressing potential challenges is essential for sustained innovation in this field. [ABSTRACT FROM AUTHOR]

Precision in dosing is crucial for optimizing therapeutic outcomes and preventing overdosing, especially in preterm infants. Traditional manual adjustments to adapt the dose often lead to inaccuracies, contamination risks, and reduced precision. To overcome these challenges, semi-solid extrusion 3D printing was used to create personalised gel-based caffeine dosage forms. The hydrogels, made from agar and hydroxypropyl methylcellulose, demonstrated excellent rheological properties, ensuring uniform extrusion and accurate shape retention during and after printing. This gel formulation allowed for precise adjustments of caffeine volume and content tailored to a neonate weighing 1.36 kg, achieving a recovery of 103.46%, well within acceptable limits. Additionally, three production batches confirmed the process's reproducibility with minimal variability. Forced degradation studies showed that both pure caffeine and caffeine in the gel matrix exhibited similar stability profiles, confirming the drug's chemical integrity. The printed gel dosage forms also displayed immediate-release characteristics, with over 80% of caffeine released within 45 min, highlighting their suitability for rapid therapeutic action. These findings emphasise the potential of SSE 3DP and gel-based formulations to produce personalised drug delivery systems with high precision, reproducibility, and reliability. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a promising intervention for treatment-resistant psychiatric disorders. However, conventional TMS typically utilises a one-size-fits-all approach when determining stimulation targets. Recent retrospective brain circuit-based analyses using lesion network mapping have suggested that a left dorsal lateral prefrontal cortex target has a higher efficacy for alleviating depression symptoms, a dorsomedial prefrontal cortex target is more effective for anxiety symptoms, and a rostromedial prefrontal cortex target is effective for schizophrenia-associated psychiatric symptoms. Nonetheless, symptom-specific brain circuit targeting has not been tested prospectively. We conducted a narrative review of selected literature to investigate individualised targeting for TMS and discuss potential future directions to elucidate the efficacy of this approach. [ABSTRACT FROM AUTHOR]

Background: The aging paradox highlights the coexistence of increased life expectancy with a persistent desire to maintain a youthful appearance, driven by biological, psychological, and social factors. Advances in healthcare have extended human lifespans, yet societal pressure to appear youthful remains strong. Understanding the genetic, epigenetic, and environmental contributors to skin aging is crucial for optimising aesthetic procedures. Methods: This literature review synthesises research on the aging paradox, genetic influences on skin aging, and the effectiveness of non-surgical aesthetic interventions. The review involved a comprehensive search across databases including PubMed, Google Scholar, Web of Science, and Scopus using keywords like "aging paradox", "genetic imprint", "non-surgical aesthetics", "epigenetics", and "anti-aging treatments". Studies were selected based on relevance, credibility, recency, and diversity of perspectives. Results: The review identified 64 studies relevant to the aging paradox and non-surgical interventions. These studies underscore the significant roles of genetic variations and epigenetic mechanisms, such as DNA methylation and microRNA regulation, in determining aging trajectories and treatment responses. The proposed "PERSONAL" (Personalised Epigenetic Regime for Skin Optimisation, Nurturing Aesthetic Longevity) paradigm advocates for a comprehensive, personalised approach, integrating genetic and epigenetic profiling to tailor treatments to individual needs. Conclusions: By leveraging the complex interplay of genetic, epigenetic, and environmental factors, practitioners can enhance the precision and efficacy of non-surgical aesthetic interventions, improving patient satisfaction and promoting long-term skin health. Continuous monitoring and iterative adjustments within this paradigm are essential for achieving optimal outcomes. Level of evidence: Level 4, therapeutic study [ABSTRACT FROM AUTHOR]

Simple Summary: This research is the first comprehensive study in New Zealand to categorise and examine the characteristics of breast cancer based on HER2 status. We explored three HER2 categories: HER2-zero, HER2-low, and HER2-positive, in women diagnosed with invasive breast cancer. Utilising Te Rēhita Mate Ūtaetae (Breast Cancer Foundation NZ National Register), our study analysed data spanning 21 years, revealing that most women underwent HER2 testing. Significantly, many cases previously not recognised as having significant HER2 levels were in fact HER2-low, qualifying them for newer, targeted drug therapies. These findings are particularly crucial as they suggest that newer therapies could benefit a larger segment of patients, notably those with advanced breast cancer; approximately 60% of these women might now benefit from these innovative HER2-targeted treatments. The study underscores the urgent need for standardised HER2 testing to personalise and optimise treatment, enhancing outcomes for patients with invasive breast cancer. Objectives: To perform the first national analysis of demographic and clinicopathological features associated with the HER2 positive, HER2-low, and HER2-zero invasive breast cancers in New Zealand. The study will reveal the proportion of women who may benefit from new HER2-targeted antibody drug conjugate (ADC) therapies. Methods: Utilising data from Te Rēhita Mate Ūtaetae (Breast Cancer Foundation NZ National Register), the study analysed data from women diagnosed with invasive breast cancer over a 21-year period. The HER2 status of tumours was classified into three categories—HER2-zero, HER2-low, HER2-positive. Results: From 2009–2021, 94% of women underwent HER2 testing, with 14% diagnosed with HER2-positive breast cancer. For advanced-stage disease, 38% of those formerly classified as HER2-negative were reclassified as HER2-low. Including HER2-positive breast cancers, this indicates that 60% of women with advanced breast cancer may potentially benefit from the new HER2-directed ADCs (approximately 120 women per year). Conclusions: The findings suggest a significant proportion of women with invasive breast cancer in New Zealand could benefit from new HER2-targeted treatments. There is a need to standardise HER2 testing to enhance personalised treatment and improve outcomes. [ABSTRACT FROM AUTHOR]

Personalised medicine, facilitated by advancements like 3D printing, may offer promise in oncology. This scoping review aims to explore the applicability of 3D printing for personalised pharmaceutical dosage forms in paediatric cancer care, focusing on treatment outcomes and patient experiences. Following the Joanna Briggs Institute (JBI) methodology, a comprehensive search strategy was implemented to identify the relevant literature across databases including PubMed, Embase, and Web of Science. Three independent reviewers conducted study selection and data extraction, focusing on studies involving paediatric patients under 18 years old and pharmaceutical dosage forms manufactured using 3D printing technology. From 2752 records screened, only six studies met the inclusion criteria, none of which specifically targeted paediatric cancer patients. These studies examined aspects of acceptability, including swallowability, taste, and feasibility of 3D-printed formulations for children. While the studies demonstrated the potential benefits of 3D printing in paediatric medication, particularly in personalised dosing, there is a notable lack of evidence addressing its acceptability in paediatric cancer patients. Further interdisciplinary collaborative research is needed in this area to fully assess preferences and acceptability among children with cancer and their parents or caregivers. [ABSTRACT FROM AUTHOR]

Genetic factors influence medication response (pharmacogenetics), affecting the pharmacodynamics and pharmacokinetics of many medicaments used in clinical care. The ability of medications to cross the blood–brain barrier (BBB) represents a critical putative factor in the effectiveness and tolerability of various medications relevant to central nervous system disorders (CNS), cancer, and broader medical conditions at a pharmacokinetic (dosing) level. Pharmacogenetics has the potential to personalise medicine to a greater extent than has been possible, with the potential to help reduce heuristic delays to effective tolerable pharmacotherapy. Here, we critically examine and summarise the evidence, particularly for ABCB1 polymorphisms associated with drug transportation and other clinical relevance. These transporters appear to have a role in BBB pharmacogenetics and may indicate new avenues of research that extend beyond the current paradigm of CYP450 polymorphisms. We identify some of the most promising variants for clinical translation while spotlighting the complexities of the involved systems and limitations of the current empirical literature. [ABSTRACT FROM AUTHOR]

Telemedicine in heart failure (HF) management may positively impact health outcomes, but varied effects in studies hinder guidance in HF guidelines. Evidence on the effectiveness of telemedicine in HF subpopulations is limited. We conducted a scoping review to evaluate and synthesise evidence on the effectiveness of telemedicine across HF subpopulations that could guide telemedicine strategies in routine practice. Meta-analyses concerning randomised controlled trials (RCTs) with subgroup analyses on telemedicine effectives were identified in PubMed. We identified 15 RCTs, encompassing 21 different subgroups based on characteristics of HF patients. Findings varied across studies and no definite evidence was found about which patients benefit most from telemedicine. Subgroup definitions were inconsistent, not always a priori defined and subgroups contained few patients. Some studies found heterogeneous effects of telemedicine on mortality and hospitalisation across subgroups defined by: New York Heart Association (NYHA) classification, previous HF decompensation, implantable device, concurrent depression, time since hospital discharge and duration of HF. Patients represented in the RCTs were mostly male, aged 65–75 years, with HF with reduced ejection fraction and NYHA class II/III. Traditional RCTs have not been able to provide clinicians with guidance; continuous real-world evidence generation could enhance monitoring and identify who benefits from telemedicine. [ABSTRACT FROM AUTHOR]

Abstract The KidGen Collaborative's Policy Implementation Workshop 2023 celebrated the 10th anniversary of Australia's first kidney genetics clinic in Brisbane. This event marked the establishment of a national network now comprising 19 kidney genetics clinics across Australia, all dedicated to providing equitable access to genomic testing for families affected by genetic kidney diseases. The workshop reflected on past progress and outlined future objectives for kidney genetics in Australia, recognising the collaborative efforts of clinical teams, researchers, and patients. Key insights from the workshop are documented in the proceedings.

Abstract Genetic heterogeneity in ovarian cancer indicates the need for personalised treatment approaches. Currently, very few G-protein coupled receptors (GPCRs) have been investigated for active targeting with nanomedicines such as antibody-conjugated drugs and drug-loaded nanoparticles, highlighting a neglected potential to develop personalised treatment. To address the genetic heterogeneity of ovarian cancer, a future personalised approach could include the identification of unique GPCRs expressed in cancer biopsies, matched with personalised GPCR-targeted nanomedicines, for the delivery of lethal drugs to tumour tissue before, during and after surgery. Here we report on the systematic analysis of public ribonucleic acid-sequencing (RNA-seq) gene expression data, which led to prioritisation of 13 GPCRs as candidates with frequent overexpression in ovarian cancer tissues. Subsequently, primary ovarian cancer cells derived from ascites and ovarian cancer cell lines were used to confirm frequent gene expression for the selected GPCRs. However, the expression levels showed high variability within our selection of samples, therefore, supporting and emphasising the need for the future development of case-to-case personalised targeting approaches.

Abstract Introduction n-of-1 trials are undertaken to optimise the evaluation of health technologies in individual patients. They involve a single patient receiving treatments, both interventional and control, consecutively over set periods of time, the order of which is decided at random. Although n-of-1 trials are undertaken in medical research it could be argued they have the utility to be undertaken more frequently. We undertook the National Institute for Health Research (NIHR) commissioned DIAMOND (Development of generalisable methodology for n-of-1 trials delivery for very low volume treatments) project to develop key points to assist clinicians and researchers in designing and conducting n-of-1 trials. Methods The key points were developed by undertaking a stakeholder workshop, followed by a discussion within the study team and then a stakeholder dissemination and feedback event. The stakeholder workshop sought to gain the perspectives of a variety of stakeholders (including clinicians, researchers and patient representatives) on the design and use of n-of-1 trials. A discussion between the study team was held to reflect on the workshop and draft the key points. Lastly, the stakeholders from the workshop were invited to a dissemination and feedback session where the proposed key points were presented and their feedback gained. Results A set of 22 key points were developed based on the insights from the workshop and subsequent discussions. They provide guidance on when an n-of-1 trial might be a viable or appropriate study design and discuss key decisions involved in the design of n-of-1 trials, including determining an appropriate number of treatment periods and cycles, the choice of comparator, recommended approaches to randomisation and blinding, the use of washout periods and approaches to analysis. Conclusions The key points developed in the project will support clinical researchers to understand key considerations when designing n-of-1 trials. It is hoped they will support the wider implementation of the study design.

INTRODUCTION. Small interfering RNAs (siRNAs) are among the most promising types of therapeutic nucleic acids aiming at the inhibition of pathogenetically relevant gene expression through the RNA interference mechanism. However, the limited bioavailability and immunogenicity of siRNAs and imperfect delivery systems hinder the clinical potential and applicability of siRNA medicinal products.AIM. This study aimed to summarise recent advances in the development of siRNA medicinal products and the corresponding delivery systems, review clinical trial results, and outline future development prospects for these medicinal products.DISCUSSION. This article covers the molecular mechanisms underlying RNA interference, the considerations for siRNA development, and the techniques for effective siRNA delivery. The article dwells upon various systems for nucleic acid delivery to targeted cells. The most promising delivery systems are non-viral systems, including liposomes, exosomes, nanoparticles, polymers, cell-penetrating peptides, and GalNAc ligands. Their main advantages include their ease of complexation with nucleic acids, modification and functionalization potential, favourable safety profile, ability to cross biological barriers, and tropism to target tissues. The article summarises the information that has accumulated over the past few years in clinical trials of siRNA medicinal products for a range of conditions, including metabolic disorders, infections, and cancers, as well as hereditary, ophthalmic, renal, and hepatic diseases. Special attention is paid to siRNA medicinal products undergoing clinical trials (over 10 products) and approved for clinical use (6 products, including MIR 19, the first authorised Russian siRNA medicinal product).CONCLUSION. Ultimately, siRNA medicinal products are a promising tool for personalised medicine, exhibiting therapeutic potential for a wide range of pathological conditions. Further studies of siRNA medicinal products should aim at improving siRNA production technology to increase their bioavailability and half-life period. In addition, these studies should aim at enhancing delivery systems for these products to mitigate toxicity risks and maximise efficacy.

INTRODUCTION. Pharmacogenetic (PGx) testing plays a significant role in predicting the risk of adverse drug reactions (ADRs) associated with valproic acid (VPA) products, which are among the most prescribed medicinal products in neurology and psychiatry. However, the sensitivity and specificity of PGx screening panels may be insufficient as individual valproate metabolism varies across ethnically/racially diverse patient populations.AIM. The study aimed to identify implementation areas for a personalised approach to the development of PGx panels for assessing the safety and risk of valproate therapy in various ethnic and racial groups residing in the Russian Federation.DISCUSSION. The authors reviewed the results of population studies concerning the frequency of non-functional and low-function alleles of genes encoding isoenzymes that play key roles in VPA P-oxidation in the liver. This review focused on studies published in eLIBRARY.RU, PubMed, Scopus, and Google Scholar in 2012–2022. The inclusion criteria were full-text original articles, systematic reviews, meta-analyses, Cochrane reviews, and clinical cases in Russian or English. The analysis revealed that the need for personalised assessment of the risk and safety of VPA may depend on the frequency of risk alleles for slowing down VPA P-oxidation in the liver across racial and ethnic groups worldwide, and particularly in Russia. The authors identified new areas to implement the personalised approach to the development of PGx panels for assessing the safety and risk of valproate therapy with consideration of the rates of hepatic VPA P-oxidation in patients of different ethnic and racial backgrounds. However, the review of population-based associative genetic research from around the world demonstrated the current lack of clarity in the prospects of translating international findings directly into Russian clinical practice through the development of PGx panels due to Russia’s ethnic/racial diversity and vast territory.CONCLUSIONS. To increase the sensitivity and specificity of Russian PGx panels, bridging studies are required to extrapolate the associations established between the most common risk alleles and VPA P-oxidation disorders in other ethnic groups to a specific population of a specific Russian region.

Abstract Background Artificial intelligence (AI) has become a pivotal tool in advancing contemporary personalised medicine, with the goal of tailoring treatments to individual patient conditions. This has heightened the demand for access to diverse data from clinical practice and daily life for research, posing challenges due to the sensitive nature of medical information, including genetics and health conditions. Regulations like the Health Insurance Portability and Accountability Act (HIPAA) in the U.S. and the General Data Protection Regulation (GDPR) in Europe aim to strike a balance between data security, privacy, and the imperative for access. Results We present the Gemelli Generator - Real World Data (GEN-RWD) Sandbox, a modular multi-agent platform designed for distributed analytics in healthcare. Its primary objective is to empower external researchers to leverage hospital data while upholding privacy and ownership, obviating the need for direct data sharing. Docker compatibility adds an extra layer of flexibility, and scalability is assured through modular design, facilitating combinations of Proxy and Processor modules with various graphical interfaces. Security and reliability are reinforced through components like Identity and Access Management (IAM) agent, and a Blockchain-based notarisation module. Certification processes verify the identities of information senders and receivers. Conclusions The GEN-RWD Sandbox architecture achieves a good level of usability while ensuring a blend of flexibility, scalability, and security. Featuring a user-friendly graphical interface catering to diverse technical expertise, its external accessibility enables personnel outside the hospital to use the platform. Overall, the GEN-RWD Sandbox emerges as a comprehensive solution for healthcare distributed analytics, maintaining a delicate equilibrium between accessibility, scalability, and security.

Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as “precision medicine”. With respect to bronchiectasis, many comorbidities and underlying causes have been identified. Inflammatory endotypes have also been widely studied and reported. Additionally, several genes have been shown to affect disease progression. However, the lack of a clear classification has also hampered our understanding of the disease’s natural course. The aim of this review is, thus, to summarize the current knowledge on biomarkers and actionable targets of this complex pathologic condition and to point out unmet needs, which are required in the design of effective diagnostic and therapeutic trials.

The KidGen Collaborative's Policy Implementation Workshop 2023 celebrated the 10th anniversary of Australia's first kidney genetics clinic in Brisbane. This event marked the establishment of a national network now comprising 19 kidney genetics clinics across Australia, all dedicated to providing equitable access to genomic testing for families affected by genetic kidney diseases. The workshop reflected on past progress and outlined future objectives for kidney genetics in Australia, recognising the collaborative efforts of clinical teams, researchers, and patients. Key insights from the workshop are documented in the proceedings. [ABSTRACT FROM AUTHOR]

Radiomics is a promising tool for the development of quantitative biomarkers to support clinical decision-making. It has been shown to improve the prediction of response to treatment and outcome in different settings, particularly in the field of radiation oncology by optimising the dose delivery solutions and reducing the rate of radiation-induced side effects, leading to a fully personalised approach. Despite the promising results offered by radiomics at each of these stages, standardised methodologies, reproducibility and interpretability of results are still lacking, limiting the potential clinical impact of these tools. In this review, we briefly describe the principles of radiomics and the most relevant applications of radiomics at each stage of cancer management in the framework of radiation oncology. Furthermore, the integration of radiomics into clinical decision support systems is analysed, defining the challenges and offering possible solutions for translating radiomics into a clinically applicable tool. [ABSTRACT FROM AUTHOR]