bims-curels 2026-06-21 papers

bims-curels

Biomed News

on Leigh syndrome

Issue of 2026–06–21
thirteen papers selected by
Cure Mito Foundation

Enrichment of Rare Mitochondrial DNA Variants Among Individuals With Kidney Disease Reveals Undiagnosed Mitochondrial Disease.
From Pharmacodynamic Biomarker to Evaluating Treatment Response: Biomarkers in Primary Mitochondrial Diseases.
Clinical Spectrum, Heteroplasmy-Phenotype Correlation, and Prognosis of the MT-ND3 m.10191 T > C Mutation.
Editorial: Beyond energy production: exploring mitochondrial dynamics and disease.
Common Principles Underlie Mitochondrial DNA Heteroplasmy Dynamics in the Germline and Soma.
Enhancing the adoption of patient engagement in critical care research: Insights from a qualitative study.
Case Study on the Use of Real-World Evidence in a Feasibility Assessment of a Randomized Controlled Trial Design to Support the Fulfillment of Pediatric Requirements with the FDA and EMA.
Facilitators and barriers to engaging patient partners in knowledge syntheses: A stage-based approach.
Minimizing nocebo side effects in health care: The unrecognized role of patient involvement.
The effect of source expertise on the persuasiveness and sharing of health information on social media: A systematic review.
Involving patient partners as appraisers of shared decision making: an explanatory sequential mixed-methods study.
Meaningful Engagement of Patients in Research.
Secure healthcare data management using federated learning, blockchain, and explainable artificial intelligence: a systematic review.

Kidney Int Rep. 2026 Jul;11(7): 106578

Enrichment of Rare Mitochondrial DNA Variants Among Individuals With Kidney Disease Reveals Undiagnosed Mitochondrial Disease.

Daniel R Schecter, Rory J Tinker, Patrick O'Connell, Jiuhong Pang, Simon SzeKing Lee, Meltem Ece Kars, Aysegul Guvenek, Michael Preuss, Yuval Itan, Eva Morava, Tamas Kozicz, Michio Hirano, Ali Naini, Jaya Ganesh.

   Introduction: Pathogenic mitochondrial DNA (mtDNA) variants cause multisystem disease, yet their contribution to kidney disease remains incompletely characterized, partly because of exclusion of the mitochondrial genome from genetic studies.
Methods: We evaluated mtDNA variation in 27,747 participants from the Mount Sinai Million Health Discoveries Program (MSM), an ancestrally diverse biobank with whole-exome sequencing and linked electronic health records (EHR). mtDNA variants were identified using MitoVerse and classified with MITOMAP. Kidney disease was defined using renal PheCodes for glomerular disease (GU_580) and renal failure (GU_582). Previous mitochondrial diagnoses were ascertained from EHR to identify undiagnosed individuals. Associations were adjusted for age, self-reported gender, and ancestry, with genotype-phenotype review.
Results: Among 3935 individuals with kidney disease, 45 carried clinically associated mtDNA variants, 42 of whom had no previous clinical mitochondrial diagnosis. mtDNA variants were enriched among individuals with kidney disease and associated with increased odds of renal involvement (odds ratio [OR] = 1.72). Associations were strongest for chronic kidney disease (CKD; GU_582.2; OR = 1.55) and renal failure (GU_582; OR = 1.53). Among undiagnosed carriers, genotype-phenotype review identified concordant manifestations in 14%, including mitochondrial CKD with hyperuricemia. Variant-level analysis identified enrichment of m.1630A>G in MT-TV (OR = 5.56), with additional variants showing trends. Both renal- and nonrenal-associated pathogenic mtDNA variants were observed.
Conclusion: Pathogenic mtDNA variants are overrepresented among individuals with kidney disease, often without a known mitochondrial diagnosis. These findings support a contributory role for mtDNA in renal disease and highlight the value of mtDNA analysis into kidney disease research and clinical evaluation, particularly for identifying unrecognized mitochondrial disease with renal involvement.

Keywords:  mitochondrial DNA; mitochondrial disease; population biobank; precision medicine; variant-level association

DOI:  https://doi.org/10.1016/j.ekir.2026.106578
Clin Transl Sci. 2026 Jun;19(6): e70634

From Pharmacodynamic Biomarker to Evaluating Treatment Response: Biomarkers in Primary Mitochondrial Diseases.

Sydney Stern, Karryn Crisamore, John Patton, Robert Schuck, Michael Pacanowski.

Primary mitochondrial diseases (PMDs) result from genetic variants in nuclear DNA and mitochondrial DNA which commonly lead to aberrant oxidative phosphorylation. The clinical complexity, often attributed to the underlying genetics, includes several distinct syndromes (e.g., Barth syndrome; Pearson syndrome; Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes), some with overlapping symptoms. PMDs are highly heterogenous and affect multiple organs and tissues, prominently those with high energy demand such as muscle and neurologic tissues. Disease-modifying therapies for PMDs approved by the United States Food and Drug Administration are few and disease-specific, and treatment remains largely supportive in nature. The lack of robust biomarkers contributes to challenges associated with quantifying treatment responses in drug development. Recognizing this area of critical need, we sought to understand the landscape of molecular biomarkers that may inform treatment response, support clinical trials, and may be useful for regulatory decision-making. In this review, we assess the extent of evidence and challenges for each biomarker. We propose considerations for future biomarker development to measure treatment response and facilitate early drug development in PMDs by guiding dose selection and trial enrichment.

DOI: https://doi.org/10.1111/cts.70634
CNS Neurosci Ther. 2026 Jun;32(6): e70997

Clinical Spectrum, Heteroplasmy-Phenotype Correlation, and Prognosis of the MT-ND3 m.10191 T > C Mutation.

Zimeng He, Huafang Jiang, Tongyue Li, Yang Liu, Ying Zou, Chaolong Xu, Zhimei Liu, Danmin Shen, Ruoyu Duan, Minhan Song, Yunxi Zhang, Zixuan Zhang, Mingxi Sun, Rui Shen, Hong Xue, Fang Fang.

   AIM: To systematically characterize the phenotypic spectrum, neuroimaging features, heteroplasmy-phenotype correlation, and prognosis of the m.10191 T > C mutation.
METHODS: We collected and analyzed data from 52 patients (14 newly recruited; 38 from literature). Phenotypes were pre-classified as Leigh syndrome (LS), Leigh-like syndrome (LLS), MELAS/LS overlap syndrome, and MELAS-like syndrome. Neuroimaging data were subjected to statistical analysis to explore inter-lesional associations and lesion-symptom correlations. Heteroplasmy level underwent k-means clustering and latent class analysis (LCA) to define data-driven subgroups and model genotype-phenotype correlations. Prognostic factors were evaluated through Bayesian logistic regression, and survival analysis was conducted.
RESULTS: The cohort exhibited phenotypic heterogeneity, dominated by LS (46.2%). Key features included epilepsy, developmental delay, and dystonia. Globus pallidus involvement frequently co-occurred with midbrain and pontine lesions. Heteroplasmy level differed significantly across phenotypes. LCA identified three classes corresponding to clinical phenotypes. High heteroplasmy level, medullary involvement, and severe hyperlactatemia were associated with disease progression. Survival analysis indicated a 5 year survival rate of 80.0%, with high heteroplasmy level, hypotonia, and cerebellar lesions predicting poorer survival.
INTERPRETATION: The m.10191 T > C mutation is linked to a continuous clinical spectrum correlated with heteroplasmy level. Specific clinical and neuroimaging features serve as valuable biomarkers for phenotypic classification and prognostic assessment.

Keywords:   MT‐ND3 ; complex I deficiency; leigh syndrome; m.10191 T > C; mitochondrial encephalomyopathy with lactate acidosis and stroke‐like episodes (MELAS)

DOI:  https://doi.org/10.1002/cns.70997
Front Cell Dev Biol. 2026 ;14 1872916

Editorial: Beyond energy production: exploring mitochondrial dynamics and disease.

Nahid A Khan, Ruben Torregrosa-Muñumer.



Keywords:  cell fate regulation; metabolic signaling; mitochondria; mitochondrial disease; mitochondrial dynamics; mitochondrial quality control; mitochondrial therapy; redox metabolism

DOI:  https://doi.org/10.3389/fcell.2026.1872916
Annu Rev Genomics Hum Genet. 2026 Jun 15.

Common Principles Underlie Mitochondrial DNA Heteroplasmy Dynamics in the Germline and Soma.

Cameron Ryall, Patrick F Chinnery, Jelle van den Ameele.

Heteroplasmy is the mixture of mutant and wild-type mitochondrial DNA (mtDNA) within each of our cells. Heteroplasmy levels in cells, tissues, and organisms change over time, thus contributing to mitochondrial disease, aging, and evolution. Germline and pedigree studies first revealed heteroplasmy shifts between generations and have long offered a window into the dynamics of mtDNA inheritance through single oocytes. Single-cell technologies are now uncovering similar mechanisms that operate in somatic tissues throughout life. Stochastic processes (relaxed replication and vegetative segregation, enhanced through genetic bottlenecks) generate cell-to-cell variation, while selection mechanisms such as intercellular competition, mitophagy, and preferential replication allow or drive directional shifts. Single-cell sequencing, mtDNA imaging, and genetic screening, combined with mtDNA-editing technology and heteroplasmic model systems, have transformed our ability to dissect these processes, revealing heteroplasmy dynamics at molecular resolution. These approaches are uncovering quantifiable principles governing heteroplasmy across cell types and life stages, transforming our understanding from descriptive observations to predictive mechanistic models and novel therapeutic avenues.

DOI: https://doi.org/10.1146/annurev-genom-120324-032239
Aust Crit Care. 2026 Jun 19. pii: S1036-7314(26)00100-1. [Epub ahead of print]39(4): 101630

Enhancing the adoption of patient engagement in critical care research: Insights from a qualitative study.

Elizabeth Kusi-Appiah, Saleema Allana, Oleksa Rewa, Carmel Montgomery, Elizabeth Papathanassoglou.

   BACKGROUND: In the rapidly evolving healthcare delivery, patient engagement in clinical research is emerging as a prerequisite for developing patient-centred care models, implementing value-based care, and creating metrics to enhance learning healthcare systems. In a high-acuity setting like critical care, this practice represents a paradigm shift from medical paternalism and the traditional disease-centred approach. It acknowledges the experiences and expertise of patients and families in the research cycle and clinical practice. However, patient engagement is a relatively new practice in critical care research with limited evidence.
OBJECTIVES: Our aim was to share insights and strategies from our qualitative study on women's experiences of critical care to advance the science of patient engagement adoption in critical care research.
METHODS: We collaborated with five patient partners, including two former intensive care unit patients and three informal caregivers, to design and conduct a qualitative study exploring the psychological distress experienced by women in critical care. Our engagement approach was guided by the Canadian Institute of Health Research principles: mutual respect, inclusivity, a supportive environment, and coproduction. Patient partners' input was facilitated through scheduled consultations, email correspondence, and flexible participation options. A designated research coordinator managed the process, ensuring meeting materials were shared in advance and notes were documented. We utilised the Saskatchewan Centre for Patient-Oriented Research level of engagement tool to tailor activities across project stages. Patient partners played important, self-determined roles such as assisting in proposal refinement, ensuring the cultural and linguistic relevance of research materials, coproducing data collection material, and developing engagement tools (such as terms of reference). They also copresented our engagement strategy at a conference. A trauma-informed approach was used to prevent retraumatisation. Patient partners received compensation and were offered opportunities for study dissemination.
FINDINGS: Patient partners possess valuable resources and insights that can enrich the research process. Emerging themes include the importance of defining expectations, relationship building, engagement as a cyclical process, and working with a diversity of perspectives.
CONCLUSION: Through ongoing revision, our patient engagement strategies and lessons learned would be invaluable for researchers seeking to adopt patient engagement in critical care research.
REGISTRATION: This project was not registered.

Keywords:  Critical care; Lessons learned; Patient engagement; Strategies for engagement; Women

DOI:  https://doi.org/10.1016/j.aucc.2026.101630
Ther Innov Regul Sci. 2026 Jun 19.

Case Study on the Use of Real-World Evidence in a Feasibility Assessment of a Randomized Controlled Trial Design to Support the Fulfillment of Pediatric Requirements with the FDA and EMA.

Neal E Storm, Christine Kubik, Ghislaine Priem, Min Kim, Tzu-Chieh Lin, Jeff Lange, Chelsea O'Connell, Anthony Glennane, Brian D Bradbury, Mark J Taisey.

   INTRODUCTION: Regulatory agencies may require industry sponsors of new drugs or biologics to conduct clinical trials that assess the benefits versus the risks of these new medicines in pediatric patients as a means of facilitating their development and availability for children when there is a medical need. Amgen Inc. (henceforth "the company") agreed to conduct a randomized, controlled trial (RCT) in pediatric subjects with Glucocorticoid-induced Osteoporosis (GiOP) under a Paediatric Investigation Plan (PIP) and Pediatric Study Plan (PSP) with the European Medicines Agency (EMA) and the United States (US) Food and Drug Administration (FDA), respectively, as one of the pediatric studies that were a condition of registration for Prolia (denosumab). Enrollment of pediatric subjects with GiOP into the agreed clinical study was exceedingly low despite the implementation of multiple mitigation measures. As a result, the company explored the use of real-world epidemiological analyses of the disease in children with GiOP for further insight into the clinical feasibility challenges with the RCT design.
MATERIALS AND METHODS: We initiated a phase 3 randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of denosumab in pediatric subjects with GiOP (Study 20140444). Following difficulties in recruiting we re-assessed the enrollment potential and overall clinical trial feasibility of Study 20140444 using real-world epidemiological analyses evaluating the size of the pediatric GiOP population using real-world data (RWD) from 3 different databases: (1) the US MarketScan, (2) the United Kingdom (UK) Clinical Practice Research Datalink (CPRD), and (3) the IQVIA Disease Analyzer (Germany).
RESULTS: The results from the RWD show that very few pediatric patients met the clinical diagnosis of GiOP, irrespective of the database used. In sum, approximately 1 eligible subject per 1,000,000 people per year was estimated to be available for Study 20140444.
CONCLUSIONS AND RECOMMENDATIONS: The results suggest a lack of feasibility of conducting an adequate and well-controlled randomized trial in a population of pediatric patients with GiOP. The results also called into question the feasibility of other types of clinical trial designs, including potential single-arm or hybrid study designs, to fulfill the regulatory requirements. Recommendations include considering the use of RWD-based epidemiological analyses prior to agreeing with health authorities to conduct postmarketing required pediatric studies or studies in other rare diseases. This approach to clinical trial feasibility using RWD helps ensure research goals are balanced with the needs of the individual patient, further ensuring the ethical conduct of clinical trials. CLINICAL TRIAL REGISTRATION (STUDY 20140444): ClinicalTrials.gov / NCT03164928 / URL: https://clinicaltrials.gov/search? term=NCT03164928 . EudraCT / 2016-003083-39 / URL: https://www.clinicaltrialsregister.eu/ctr-search/search? query=2016-003083-39 .

Keywords:  Denosumab; Glucocorticoid-induced osteoporosis; Pediatric; Prolia; Real-world evidence; Regulatory decision-making

DOI:  https://doi.org/10.1007/s43441-026-00977-1
Res Synth Methods. 2026 Jun 15. 1-21

Facilitators and barriers to engaging patient partners in knowledge syntheses: A stage-based approach.

Anna Maria Chudyk, Sasha M Kullman, Jenna Villarba, Caroline Monnin, Janet Gunderson, Jenna Kedy, Tracy Slaney, Andrea C Tricco.

  Knowledge synthesis involves bringing together findings from individual research studies to answer a specific question or explore a particular topic, often at a global level. People with lived or living experience of health conditions or of accessing healthcare services (PWLE), such as patients and their families or friends, can provide valuable perspectives throughout this process. PWLE involvement can help shape the design and conduct of a knowledge synthesis to better reflect real-world concerns through a process called patient engagement. Patient engagement is the meaningful and active involvement of PWLE throughout the research process. While previous research shows that PWLE can contribute meaningfully when appropriate supports are in place, there is limited practical guidance on how to enact patient engagement in knowledge syntheses. This tutorial paper aims to guide researchers and PWLE who would like to engage in knowledge syntheses together. Building on existing research, our team (comprised of PWLE, researchers, and an academic librarian) shares lessons we have learned from working together throughout the stages of a knowledge synthesis. We present considerations for successful patient engagement when research teams are: (1) planning to engage, (2) recruiting PWLE, (3) establishing roles and rapport, (4) supporting capacity development, (5) conducting the knowledge synthesis, and (6) mobilizing findings. We also identify 12 common barriers to patient engagement and offer strategies to address them, alongside recommendations for integrating PWLE across every stage of the knowledge synthesis process.

Keywords:  knowledge synthesis; lived experience in health research; participatory research; patient and public involvement; patient engagement

DOI:  https://doi.org/10.1017/rsm.2026.10099
Patient Educ Couns. 2026 Jun 11. pii: S0738-3991(26)00276-4. [Epub ahead of print]150 109743

Minimizing nocebo side effects in health care: The unrecognized role of patient involvement.

Emily K Spotts, Matthew T Tull, Kate Faasse, Andrew L Geers.

   OBJECTIVE: Nocebo side effects occur when patient expectations worsen negative psychological and physiological responses to medical treatments. This phenomenon can significantly impact patient experiences and outcomes across a broad range of health conditions and treatment types. Interventions are necessary to help patients avoid and minimize nocebo side effects, and in this paper, we explore a new direction for such interventions.
DISCUSSION: Current nocebo reduction interventions, such as positive side effect framing, primarily rely on healthcare providers intervening before or during a particular side effect disclosure event. Although valuable, these approaches are limited in disrupting nocebo effects that arise outside the medical context, including those influenced by news reports, social media, or discussions with friends and family. To address this gap, we advocate for the development of nocebo reduction interventions that leverage intrapersonal processes, such as anxiety reduction practices and the deliberate avoidance of unregulated and excessive side effect information from non-reputable sources. We propose that patients can use clear and actionable cognitive, emotional, and behavioral regulation strategies for preventing and diminishing their own nocebo effects. Empowering patients with effective self-regulation tools for nocebo minimization would enable them to take an active role in managing their own nocebo responses. We describe different types of intrapersonal strategies that patients could employ, as well as benefits, challenges, and future research directions for exploring this approach.
CONCLUSIONS: Intrapersonal nocebo reduction strategies offer a novel and complementary approach to traditional healthcare communication methods for nocebo minimization. Intrapersonal strategies have the potential to empower patients and improve healthcare outcomes.

Keywords:  Nocebo effect; Patient-centered medicine; Self-regulation

DOI:  https://doi.org/10.1016/j.pec.2026.109743
Psychon Bull Rev. 2026 Jun 15. pii: 175. [Epub ahead of print]33(5):

The effect of source expertise on the persuasiveness and sharing of health information on social media: A systematic review.

Benjamin P Simmonds, Keith J Ransom, Emily Mullins, Rachel G Stephens.

  People increasingly rely on social media for health information, despite substantial variability in information quality. We conducted a systematic review and meta-analysis examining whether people are sensitive to source expertise when evaluating and sharing online health claims, and if this depends on whether the source is an individual expert (e.g., a physician) or an expert group (e.g., a health organisation). Three searches across four databases identified 25 individual studies published across 22 papers. From these studies, we found that people were only marginally more persuaded by health experts than nonexperts, and that this effect was not moderated by expert type (individual vs. group). However, we found tentative evidence that experts are more persuasive when accompanied by congruent credibility cues, but that expertise can backfire when these cues are incongruent. Evidence regarding people's sensitivity to source expertise when sharing was mixed, reflecting heterogeneity in study designs. This review highlights several limitations in the current literature, indicating the need for further research that accounts for how both experts and nonexperts are perceived in online health contexts. We discuss implications and propose several avenues for future research and potential interventions.

Keywords:  Expertise; Health information; Judgement and decision-making; Social media

DOI:  https://doi.org/10.3758/s13423-026-02943-2
Res Involv Engagem. 2026 Jun 13. pii: 90. [Epub ahead of print]12(1):

Involving patient partners as appraisers of shared decision making: an explanatory sequential mixed-methods study.

Bettina Mølri Knudsen, Mette Byg Josefsen, Mona Muusmann Petersen, Poul Risom, Henriette Witte Nielsen, Frede Donskov, Stine Rauff Søndergaard, Karina Dahl Steffensen, Dawn Stacey, Lea Lund.

   BACKGROUND: Patient and public involvement (PPI) is increasingly recognised as a valuable component of health research, yet patients are rarely included in data analysis within shared decision making (SDM) studies. We aimed to assess the feasibility and value of involving patient partner appraisers of SDM using the OPTION5 instrument. Specific objectives were to examine interrater reliability between patient partners and researchers, and to explore patient partners' perspectives on observed differences in interrater reliability.
METHODS: An explanatory sequential mixed-methods design was used. Four patient partners and three researchers used the validated Danish version of OPTION5 to independently score 102 audio-recorded oncology consultations from two randomised trials evaluating patient decision aids delivered before versus during consultations. Each consultation was scored by one trained patient partner and two researchers. Scores were converted to a 0-100 scale. Agreement was assessed using two-way mixed-effects, absolute-agreement intraclass correlation coefficients (ICC) for single and average measures. Item-level analyses included unadjusted and Bonferroni-adjusted p-values. Three patient partners participated in a semi-structured focus group interview to discuss differences in interrater reliability and to reflect on their assessments based on lived experience. Interview data were analysed using a primarily deductive thematic approach informed by hermeneutic-phenomenological principles.
RESULTS: The four patient partners appraised 25-27 consultations each. Total OPTION5 scores were median 60.0 for patient partners and 52.5 for researchers. Overall single-rater agreement was moderate (ICC = 0.60, 95% CI 0.46-0.71), and good when averaging raters (ICC = 0.75, 95% CI 0.63-0.83). Item-level differences were small. Although item 2 showed a nominal difference before correction for multiple testing, no item-level differences remained statistically significant after Bonferroni correction. Qualitative analysis revealed three overarching themes: emotion-driven scoring (atmosphere, tone, empathy and recognition), navigating the OPTION5 instrument (growing confidence and calibration over time), and evolving roles as co-researchers.
CONCLUSIONS: Involving patient partners as appraisers of SDM using OPTION5 was feasible, and their appraisal ratings showed moderate reliability with researcher ratings. Findings suggest that, while using the same structured OPTION5 scoring framework, patient partners may draw on broader relational cues when interpreting observable SDM behaviours in clinical consultations.
TRIAL REGISTRATION: Ethical approval was obtained from the Research Ethics Committee at the University of Southern Denmark (approval ID 23/555) for the involvement of patient partners as co-researchers.

Keywords:  OPTION5 ; Oncology consultations; PPI; Patient partner; Patient voice; SDM; Shared decision making

DOI:  https://doi.org/10.1186/s40900-026-00922-4
Am J Kidney Dis. 2026 Jun 19. pii: S0272-6386(26)00973-X. [Epub ahead of print]

Meaningful Engagement of Patients in Research.

Precious McCowan, Taya Joseph, Cassandra B Picataggio, Lindsay Bailey, Sahib Chandi, Amanpreet Singh, Shivani Surati, Laura M Dember, Jennifer E Flythe.

Engaging patients as research partners is increasingly recognized as essential to producing relevant, credible, and impactful research. Evidence suggests that meaningful patient engagement aligns research with patient needs and priorities, improves feasibility and acceptability of interventions, enhances recruitment and retention of participants, and promotes uptake of study findings. However, there are persistent challenges, including tokenistic involvement, poorly defined roles, limited scope of influence, and insufficient engagement across all research phases. Published frameworks and evidence-based best practices highlight mutual respect, equity, trust, empowerment, and shared ownership as central to ensuring that patient contributions are substantive and integrated in all research phases. Strategies such as capacity-building through training, co-developing communication plans, demonstrating flexibility, providing fair compensation, and assessing the quality of the engagement support meaningful engagement. In this perspective, we share the insights of patients and researchers working together on an ongoing multicenter, pragmatic clinical trial, review key principles of patient engagement in research, provide examples of engagement from our trial, and offer practical guidance for supporting meaningful partnership between patients and researchers.

DOI: https://doi.org/10.1053/j.ajkd.2026.01.020
Front Digit Health. 2026 ;8 1871960

Secure healthcare data management using federated learning, blockchain, and explainable artificial intelligence: a systematic review.

Tanisha Bhardwaj, K Sumangali.

  Due to the rapid digitization of healthcare systems, there has been a huge collection of sensitive personal data of patients. Thus, secure, privacy-preserving, and efficient data management systems are required. Current distributed healthcare systems increasingly use centralized data processing frameworks that are prone to privacy violations, data fragmentation, and malicious attacks. Despite advances in federated learning, blockchain, explainable AI, and incremental optimization, current survey literature studies each technology separately without considering how the four technologies can be harnessed to create synergies. A systematic review of 26 peer-reviewed studies published from 2018 to 2026 indicates that an integrated architecture incorporating federated learning, blockchain, explainable AI, and incremental optimization can be designed. This review identifies ten critical issues that need to be addressed when researching the four technologies. These issues include communication costs, scalability issues, interoperability concerns, limited clinical explainability, and high computational costs when applied in real-time situations. In comparison to privacy, scalability, interpretability, and efficiency, a hybrid approach can help improve data security, boost the interpretability of the models, facilitate data sharing, and prevent data-sharing risks. Overall quality assessment based on the CASP qualitative checklist analysis of all 26 studies indicated an average score of 7.0 out of 10, implying that the quality of the methods used in the studies was acceptable.

Keywords:  GDPR compliance; blockchain technology; differential privacy; explainable artificial intelligence; federated learning; healthcare data security; incremental learning; internet of medical things (IoMT)

DOI:  https://doi.org/10.3389/fdgth.2026.1871960