bims-curels 2026-05-17 papers

bims-curels

Biomed News

on Leigh syndrome

Issue of 2026–05–17
twenty-two papers selected by
Cure Mito Foundation

Therapeutic Impact of Mitochondrial Transplants for Cardiovascular Diseases.
Progressive White Matter Changes in Mitochondrial Disease: A Quantitative MRI Study.
Mitochondria and Qi: Merging Eastern and Western Medicine.
170 Years of Mitochondrial Research and the Emergence of Mitochondrial Medicine.
Mitochondrial morphology in human fibroblasts and induced pluripotent stem cells in Leigh syndrome: A comparative analysis.
Predicting recurrence risk of leigh syndrome using prenatal mtDNA heteroplasmy assessment.
Neurodegenerative Diseases in Children: A Comprehensive Review.
Mitochondrial transfer technologies with molecular insights into clinical applications.
Gene Therapy for Leber Hereditary Optic Neuropathy (LHON): A Systematic Review and Meta-Analysis.
What Would We Do with All That Data? A Patient Perspective.
Serious illness communication as a patient safety competency.
Single-molecule mitochondrial DNA imaging reveals heteroplasmy dynamics shaped by developmental bottlenecks and selection in vivo.
Patient experience informing outcomes and research in rare disease: Citrin deficiency as a case study.
Sponsor Initiated Requests to Delay Pediatric Postmarketing Studies.
Developing prognostic models that predict onset and progression rates in genetic neurodegenerative diseases: perspectives of healthcare professionals in genetic counselling.
Genetic counseling assistant-led education supports efficiency in rare disease care.
Patient engagement for quality improvement and knowledge translation in paediatric orthopaedic care - a patient partner led initiative.
Communicating empathy sympathy and compassion in healthcare consultations: a systematic review of applied linguistic research.
To refer or not to refer? Exploring the cognitive process of genetic counselors' decision to refer a patient to another professional.
Role of Artificial Intelligence in Health Research: Opportunities, Challenges, and Implications for Medical Education.
Advancing Deep Variant Phenotyping of Mitochondrial Enzyme Complexes For Precision Medicine in Allogeneic Hematopoietic Stem-Cell Transplantation.
Development, Implementation, and Preliminary Results of a Novel Social Network for Rare Disease Communities: Mixed Methods Study.

Int J Mol Sci. 2026 Apr 30. pii: 4018. [Epub ahead of print]27(9):

Therapeutic Impact of Mitochondrial Transplants for Cardiovascular Diseases.

Konstantina Antoniadou, Ioannis Shiammoutis, Christina Piperi.

  Mitochondria are vital organelles for human cells with fundamental roles in major metabolic processes such as calcium homeostasis, ATP production, apoptosis and signal transduction. Defective morphology and activity of these organelles have been tightly associated with the pathological onset of severe human disorders, including cardiovascular diseases. Targeting mitochondrial dysfunction has been an area of extensive research encompassing several approaches ranging from pharmacological agents to mitochondrial replacement techniques. Among them, mitochondrial transplantation has been a rapidly evolving approach, especially in the field of cardiovascular dysfunction for the restoration of injured or damaged myocardial cells. Various methods including tunneling nanotubes, nanoblade and "mitopunch" ensure the effective mitochondrial transfer from the donor to the recipient cell, with the internalization of the organelles, via endocytosis, enabling functional restoration. Results of preclinical and clinical trials involving mitochondrial transfer support the application of this technique in improving the function of the myocardium after damage caused by ischemia reperfusion injury. Herein, we discuss the beneficial role of mitochondrial transplantation in cardiovascular diseases and the current technical challenges of mitochondrial isolation, preservation, and targeted delivery, as well as their role in advancing precision medicine, offering a patient tailored therapeutic approach.

Keywords:  CVD; ischemia/reperfusion injury; mitochondrial replacement therapy; mitochondrial transplantation; mtDNA

DOI:  https://doi.org/10.3390/ijms27094018
JIMD Rep. 2026 May;67 e70093

Progressive White Matter Changes in Mitochondrial Disease: A Quantitative MRI Study.

Nora Mickelsson, Jussi Hirvonen, Mika H Martikainen.

  Primary mitochondrial diseases frequently affect the central nervous system, yet the extent, distribution and progression of white matter hyperintensities (WMHs) remain insufficiently characterised, particularly in terms of quantitative volumetrics and longitudinal progression. Although WMHs are typically attributed to cerebral small-vessel disease, mitochondrial disorders may cause white matter injury through distinct vascular and metabolic mechanisms. We conducted a retrospective single-centre study at Turku University Hospital including 36 patients with mitochondrial disease, each with at least one brain MRI (73 images). Longitudinal data were available for 15 patients. Three-dimensional T1-weighted and FLAIR images (1.5/3 T) were analysed with the FDA-cleared cNeuro tool to obtain intracranial volume-normalised WMH and lesion volumes and an automated global Fazekas score. At baseline (median age 49 years), WMHs were present in all supratentorial regions. Over time, WMH volumes increased significantly in periventricular, deep and juxtacortical regions, while lesion progression was predominantly periventricular. Fazekas scores remained generally low and stable. In follow-up imaging, women and patients carrying the m.3243A>G variant showed a greater burden of WMHs and lesions, compared with men and those with other mitochondrial diagnoses. WMH load did not differ according to history of stroke-like episodes. Mitochondrial disease is associated with early and progressive WMH accumulation, particularly in individuals with the m.3243A>G variant, and the pattern exceeds what would be expected from conventional vascular risk factors alone. These findings support a disease-specific mechanism of white matter vulnerability and highlight the importance of quantitative MRI for monitoring progression in mitochondrial disease.

Keywords:  disease progression; longitudinal imaging; mitochondrial disease; quantitative MRI; small‐vessel pathology; white matter hyperintensities

DOI:  https://doi.org/10.1002/jmd2.70093
Pharmacol Res. 2026 May 11. pii: S1043-6618(26)00158-1. [Epub ahead of print] 108243

Mitochondria and Qi: Merging Eastern and Western Medicine.

Wanqing Xie, Deborah G Murdock, Douglas C Wallace.

  Since the discovery of mitochondrial DNA (mtDNA) diseases almost 40 years ago, large numbers of diseases have been linked to mutations in both mtDNA and nuclear DNA (nDNA) genes that perturb the mitochondrial energy-generating system, oxidative phosphorylation (OXPHOS). Mitochondrial dysfunction is being implicated not only in rare primary mitochondrial diseases but also a wide range of common diseases, yet the availability of effective mitochondrial therapies remains limited. One potential source of mitochondrial therapeutic approaches is Traditional Chinese Medicine (TCM). TCM emphasizes the health-preservation philosophy and practical experience centered around the concept of "Qi", or vital force, and has generated Qi-oriented therapies over the past several thousand years. We propose that various properties and functions attributed to Qi may be explained by modulation of mitochondrial bioenergetics, the interplay between OXPHOS and fatty acid oxidation versus glycolysis and the pentose phosphate pathway (PPP), and the mitochondrial regulation of the immune system through mitochondrial reactive oxygen species (mROS). Hence, TCM therapeutics may provide approaches for treating the increasing spectrum of mitochondria associated diseases.

Keywords:  Mitochondria; Qi; TCM; energy; mtDNA; therapy

DOI:  https://doi.org/10.1016/j.phrs.2026.108243
J Clin Pharmacol. 2026 May;66(5): e70209

170 Years of Mitochondrial Research and the Emergence of Mitochondrial Medicine.

Volkmar Weissig.

  One hundred and sixty-eight years lie between the first description of mitochondria as "pale roundish granules" and their eventual recognition as the "chief executive organelle" of the cell. Booming mitochondrial research during the last three decades has revealed that being the "powerhouse of the cell" is just one of many fundamental roles mitochondria play for cellular life. Mitochondria are at the crossroads of complex metabolic pathways; they regulate cellular signaling and innate immunity, and they determine whether a cell should divide, differentiate, or die. Human disorders caused by malfunctioning mitochondria have been described starting at the beginning of the 1960s, nowadays, it seems widely accepted that there are hardly any human diseases anymore that are not associated with dysfunctioning mitochondria. Even the process of aging seems to be controlled by this powerful organelle. This review is written for Pharmacologists, Physicians, and Healthcare Providers who are not familiar with mitochondrial biology and with the tremendous insights gained during the last three decades into the vital roles this cell organelle plays for life and death. It is aimed at raising awareness of still underappreciated mitochondrial diseases, which represent the largest group of inborn errors of metabolism.

Keywords:  aging; apoptosis; cellular signaling; drug development; energy metabolism; immunity; mitochondria; mitochondrial diseases

DOI:  https://doi.org/10.1002/jcph.70209
Physiol Rep. 2026 May;14(9): e70911

Mitochondrial morphology in human fibroblasts and induced pluripotent stem cells in Leigh syndrome: A comparative analysis.

Fibi Meshrkey, Ajibola B Bakare, Raj R Rao, Shilpa Iyer.

  Mitochondria are dynamic organelles that regulate several vital cellular functions in both health and disease. Accurately quantifying different mitochondrial shapes using simple, affordable techniques remains challenging. We have previously developed a Mitochondrial Cellular Phenotype (MitoCellPhe) tool to quantify 24 different mitochondrial shapes, enabling sensitive analysis and quantification of mitochondrial phenotype in health, under stress, and in diseased conditions. This approach permits us to study the morphological changes, if any, associated with perturbations in the mitochondrial genome and function that contribute to mitochondrial diseases like Leigh Syndrome (LS), a fatal pediatric neurodegenerative and muscular disorder represented with different clinical phenotypes in infancy. Using images generated from normal and diseased fibroblasts and human induced pluripotent stem cells (hiPSCs) (undifferentiated), we have identified and characterized differences in morphologies between a healthy and diseased state in both undifferentiated hiPSCs and differentiated fibroblasts. These results will help us better understand the pathophysiology of devastating mitochondrial diseases like LS, especially in its early developmental stages.

Keywords:  mitochondria; morphology; networks; stem cells; structure

DOI:  https://doi.org/10.14814/phy2.70911
Mitochondrion. 2026 May 13. pii: S1567-7249(26)00055-3. [Epub ahead of print] 102165

Predicting recurrence risk of leigh syndrome using prenatal mtDNA heteroplasmy assessment.

Maria Shishimorova, Hong Ma, Amy Koski, Crystal Van Dyken, Nuria Marti Gutierrez, Daniel Frana, Ying Li, Daniel Eyberg, Sergei Tevkin, Tomonari Hayama, Eunju Kang, Paula Amato, Kevin Havlin, Christopher Goodier, Roger Newman, Sally Shields, Shoukhrat Mitalipov.

  Predicting recurrence risk for mitochondrial DNA (mtDNA) disorders is challenging because heteroplasmy levels can shift during development. We examined whether prenatal heteroplasmy measurements predict postnatal outcomes for the pathogenic m.13513G > A variant associated with Leigh syndrome. In a longitudinal family-based study involving three naturally conceived pregnancies, mtDNA heteroplasmy was assessed by chorionic villus sampling at 10-12 weeks of gestation and, when available, amniocentesis at 16 weeks, with follow-up in neonatal and postnatal tissues. Prenatal heteroplasmy levels below ∼30% were associated with unaffected outcomes, whereas an affected sibling exhibited near-homoplasmic variant loads in critical organs. These findings suggest prenatal heteroplasmy assessment may inform recurrence risk for the mtDNA m.13513G > A disorder.

Keywords:  Chorionic villus sampling; Heteroplasmy; Leigh syndrome; Mitochondrial DNA; Prenatal diagnosis

DOI:  https://doi.org/10.1016/j.mito.2026.102165
Int J Mol Sci. 2026 May 03. pii: 4096. [Epub ahead of print]27(9):

Neurodegenerative Diseases in Children: A Comprehensive Review.

Constantin Ailioaie, Laura Marinela Ailioaie, Cristinel Ionel Stan, Anca Sava, Dragos Andrei Chiran.

  Neurodegenerative diseases (NDDs) in children represent a heterogeneous group of rare but collectively significant disorders characterized by progressive neurological decline, developmental regression, and substantial morbidity and mortality. Unlike adult-onset neurodegeneration, pediatric conditions are predominantly genetic and frequently arise from defects in fundamental cellular pathways, including lysosomal degradation, mitochondrial oxidative phosphorylation, peroxisomal lipid metabolism, and myelin maintenance. This comprehensive review synthesizes current knowledge regarding the epidemiology, molecular classification, pathophysiology, and emerging therapeutic strategies of major pediatric neurodegenerative disorders. Epidemiological data indicate a "rare-but-many" landscape, where individually uncommon diseases collectively impose a measurable population burden. Mechanistically, disease progression reflects converging processes such as toxic substrate accumulation, impaired autophagy-lysosome flux, mitochondrial bioenergetic failure, oxidative stress, neuroinflammation, and glial dysfunction. Representative groups discussed include lysosomal storage disorders, leukodystrophies, mitochondrial encephalopathies, peroxisomal disorders, and other monogenic neurodegenerative syndromes. Advances in next-generation sequencing, metabolic profiling, and neuroimaging have substantially improved diagnostic accuracy and enabled earlier detection, including through newborn screening programs. Therapeutic paradigms are shifting from primarily supportive care toward mechanism-based interventions, including enzyme replacement therapy, hematopoietic stem cell transplantation, substrate reduction strategies, and gene therapy approaches. Early molecular diagnosis is increasingly recognized as critical for optimizing outcomes, particularly in disorders amenable to presymptomatic intervention. Continued integration of genomic medicine, standardized epidemiologic surveillance, and translational research will be essential to refine disease classification, improve prognostication, and expand access to targeted therapies. Collectively, pediatric neurodegenerative diseases exemplify the intersection of developmental neurobiology and inherited metabolic dysfunction, underscoring the need for multidisciplinary, precision-based clinical strategies.

Keywords:  developmental regression; gene therapy; leukodystrophies; lysosomal storage disorders; mitochondrial diseases; neuroinflammation; oxidative stress; pediatric neurodegeneration; peroxisomal disorders; precision medicine

DOI:  https://doi.org/10.3390/ijms27094096
Stem Cells. 2026 May 07. pii: sxag026. [Epub ahead of print]

Mitochondrial transfer technologies with molecular insights into clinical applications.

Vahan Martirosian, Berney Peng, Michael A Teitell.

  Mitochondria are essential cell signaling, survival, and bioenergetic organelles that uniquely harbor a maternally inherited, multicopy genome called mitochondrial DNA (mtDNA). The occurrence or accumulation of mtDNA mutations underlies a spectrum of inherited and acquired mitochondrial syndromes and diseases and is increasingly recognized as a source of metabolic plasticity, clonal fitness, and therapy tolerance in cancer. Recent studies have revealed mitochondrial transfer as a potential mode of intercellular communication that could compensate for mtDNA mutation-associated mitochondrial dysfunction. Transfer of mitochondria can restore homeostasis in stressed recipient cells by rebuilding respiratory capacity, rebalancing redox state, and reshaping cell fate. Reported mechanisms of transfer include tunneling nanotubes, extracellular vesicles, cell fusion, and others, such as macropinocytosis. Here, we review and evaluate emerging technologies developed for mitochondrial transfer studies and define the impact of transfer on cell physiology and pathology. We discuss translational opportunities for mitochondrial transfer-based interventions, as well as how mitochondrial exchange may represent a new framework for understanding tumor heterogeneity, adaptation, and aggressiveness.

Keywords:  Mitochondria; Mitochondrial transfer; mtDNA; techniques; transplantation

DOI:  https://doi.org/10.1093/stmcls/sxag026
Neuroophthalmology. 2026 ;50(3): 215-221

Gene Therapy for Leber Hereditary Optic Neuropathy (LHON): A Systematic Review and Meta-Analysis.

Lama Nasser Alghamdi, Ali Saleh Alsudais, Salma Hamdan Almarwani, Rose Abdullah Alraddadi, Abdulrahman Hamid Alsamadani, Abdulrahman Ahmed Alnamlah, Saif Kamal Aljehani, Yousof Fahad Allarakia, Amer M Alghamdi, Daniah Alshowaeir.

   Background: LHON is a rare mitochondrial disease causing bilateral vision loss, most commonly due to the m.11778G>A mutation. rAAV2/2-ND4 gene therapy is a potential disease-modifying treatment.
Methods: Systematic review and meta-analysis of three RCTs (RESCUE, REVERSE, REFLECT) including 175 patients.
Results: Gene therapy significantly improved best-corrected visual acuity but did not significantly increase responder rates. Adverse events were mostly mild ocular inflammation, with no treatment-related mortality.
Conclusions: rAAV2/2-ND4 is a moderately effective and safe treatment for LHON, though long-term outcomes and predictors of response remain unclear.

Keywords:  Leber hereditary optic neuropathy; gene therapy; intravitreal injection; mitochondrial DNA; rAAV2/2-ND4; retinal disease

DOI:  https://doi.org/10.1080/01658107.2026.2624440
Ophthalmol Glaucoma. 2026 May 11. pii: S2589-4196(26)00069-4. [Epub ahead of print]

What Would We Do with All That Data? A Patient Perspective.

L H Engrav, H A Golden, A Lin.

DOI: https://doi.org/10.1016/j.ogla.2026.05.003
Acad Med. 2026 May 09. pii: wvag148. [Epub ahead of print]

Serious illness communication as a patient safety competency.

Ganesh Asaithambi.



Keywords:  communication; death; medical education; patient safety

DOI:  https://doi.org/10.1093/acamed/wvag148
Dev Cell. 2026 May 13. pii: S1534-5807(26)00123-1. [Epub ahead of print]61(5): 1146-1161.e8

Single-molecule mitochondrial DNA imaging reveals heteroplasmy dynamics shaped by developmental bottlenecks and selection in vivo.

Rajini Chandrasegaram, Sara Gottardo, Abhilesh Dhawanjewar, Antony M Hynes-Allen, Beitong Gao, Suvagata Roy Chowdhury, Luis-Carlos Tábara, Michele Frison, Stavroula Petridi, Patrick F Chinnery, Julien Prudent, Hansong Ma, Jelle van den Ameele.

  Mitochondrial DNA (mtDNA) exists in many copies per cell, with cell-to-cell variability in mutation load, which is known as heteroplasmy. Developmental and age-related expansion of heteroplasmic mtDNA mutations contributes to the pathogenesis of mitochondrial and neurodegenerative diseases. Here, we describe an approach for in situ sequence-specific detection of single mtDNA molecules (mtDNA-single-molecule fluorescent in situ hybridization [smFISH]). We apply this method to visualize and measure mtDNA and heteroplasmy levels in situ at single-cell resolution in whole-mount Drosophila tissue and cultured human cells. In Drosophila, we identify a somatic mtDNA bottleneck during neurogenesis. This amplifies heteroplasmy variability between neurons, as predicted by a mathematical bottleneck model, predisposing individual neurons to a high mutation load. However, both during neurogenesis and oogenesis, mtDNA segregation is accompanied by purifying selection, promoting wild-type (WT) over pathogenic mtDNA. mtDNA-smFISH thus elucidates how developmental cell-fate transitions, accompanied by changes in cell morphology, behavior, and metabolism, can shape the transmission and selection of deleterious mtDNA variants.

Keywords:  Drosophila; bottleneck; heteroplasmy; mitochondria; mitochondrial DNA; mitochondrial disease; neurogenesis; oogenesis; purifying selection; single-molecule fluorescent in situ hybridization

DOI:  https://doi.org/10.1016/j.devcel.2026.03.011
Mol Genet Metab. 2026 May 05. pii: S1096-7192(26)00424-5. [Epub ahead of print]148(3): 110141

Patient experience informing outcomes and research in rare disease: Citrin deficiency as a case study.

Yurika Asami, Li Eon Kuek, Su Kit Chew, Barbara Yu.

  The rapid expansion of therapies for rare diseases, including urea cycle disorders (UCDs), has intensified the need for endpoints that reflect meaningful benefit to patients. In rare inborn metabolic disorders, conventional clinical assessments and fragmented natural history data may not fully capture the daily disease burden. Citrin deficiency (CD) exemplifies this challenge: despite heterogeneous, age-dependent phenotypes, a "silent" or "adaptive" period is often described as largely asymptomatic based on clinical and biochemical measures. We present a patient-organization-led, patient-centered qualitative survey as a complementary approach to uncover "hidden" disease burden in a rare metabolic and urea cycle disorder. In an in-depth survey of seven adult CD patients, findings identified gaps between clinical descriptions and patient-reported disease burden. Fatigue and symptoms triggered by high carbohydrate intake emerged as key impacts on quality of life (QoL) among all surveyed patients. Other symptoms included under-recognized gastrointestinal (GI) issues, poor appetite, and psychological impacts. These findings contrasted with existing literature and questioned the concept of an asymptomatic adaptive phase. Although limited by the cohort size (n = 7), the current study illustrates how this approach can identify patient-important domains that standard clinical frameworks may under-capture. We propose that these domains should inform the development of fit-for-purpose patient-reported outcome measures (PROMs) and be integrated with relevant biochemical or molecular markers as endpoints for therapeutic studies and inform better research priorities and clinical management. More broadly, patient-organization-led qualitative surveying offers a scalable strategy to align translational efforts with outcomes that matter to patients across rare diseases.

Keywords:  Citrin deficiency; Patient lived experience; Patient reported outcome measures; Patient-centered data; Rare disease patient organizations; Urea cycle disorders

DOI:  https://doi.org/10.1016/j.ymgme.2026.110141
Pharmaceut Med. 2026 May 10.

Sponsor Initiated Requests to Delay Pediatric Postmarketing Studies.

Susan M Abdel-Rahman, Yutao Gong, Caleb Choi, Niquiche Guity, Gilbert J Burckart, Lynne Yao.

BACKGROUND AND OBJECTIVES: Lagging pediatric safety and effectiveness data increase the risks to children associated with off-label drug use. The objective of this study was to delineate the frequency of, and reasons behind, delays in the completion of mandated pediatric postmarketing requirement (PMR) studies.
METHODS: Publicly accessible and internal US Food and Drug Administration (FDA) data were aggregated to characterize pediatric PMRs issued from 2012 to 2024, including relevant dates, durations, and deferral extension (DE) requests. Sponsor size, and clinical trial enrollment status were also examined.
RESULTS: There were 1160 pediatric PMRs identified, 459 of which were associated with 1176 DE requests. Despite a significant decline in the annual number of PMRs issued (slope [95% confidence interval]: - 3.64 [- 6.50, - 0.79] year-1, p = 0.02), an increase in the annual number of DE requests (5.24 [2.16, 8.31] year-1, p < 0.01) was observed. Declines in negotiated timelines for PMR completion and durations of time granted per request were also seen. Issues related to clinical trial conduct predominated DE rationale in every year and accounted for 48% of all requests. One in 10 delayed trials failed to initiate enrollment before the PMR due date and 1 in 5 cited problems with clinical trial conduct before enrollment began. Smaller companies (< 500 employees) exhibited higher DE request rates, lower PMR success rates, and accounted for an increasing proportion of PMRs over the review period (from 17% in 2012 to 72% in 2024).
CONCLUSIONS: Year-on-year increases in DE requests reinforce ongoing challenges to timely and successful pediatric trial completion. Difficulties with clinical trial conduct appear to be the primary driver for these delays although the underlying root causes have yet to be elucidated. Regulators, sponsors, and stakeholder partners should work cooperatively to remediate delayed pediatric drug development timelines and reduce the duration of off-label drug use in children.

DOI: https://doi.org/10.1007/s40290-026-00610-4
Orphanet J Rare Dis. 2026 May 13.

Developing prognostic models that predict onset and progression rates in genetic neurodegenerative diseases: perspectives of healthcare professionals in genetic counselling.

Max J Rensink, L L E Bolt, A Tibben, M Oosterloo, B P C van de Warrenburg, M H N Schermer.

   BACKGROUND: Research on the development of prognostic biomarker-based models for genetic neurodegenerative diseases lacking disease-modifying treatments is advancing rapidly. Currently, prognostic models are being developed to predict individual disease onset and progression rates for Huntington's disease, spinocerebellar ataxia type 1, and spinocerebellar ataxia type 3. These models have potential applications in research, such as evaluating onset-delaying treatments and their timing, and in clinical practice, where they may offer personal utility to mutation carriers. However, the perspectives of healthcare professionals in genetic counselling have not yet been adequately explored.
METHODS: In this qualitative interview study, we interviewed 18 Dutch healthcare professionals in genetic counselling, representing the majority of the Dutch counselling practice for these conditions, to explore their views on using onset and progression predictions in clinical practice.
RESULTS: Healthcare professionals highlighted potential benefits, such as reducing uncertainty and supporting informed life and family planning, which are among the pivotal reasons for mutation carriers to opt for predictive genetic testing. They also noted possible drawbacks, including psychological distress for mutation carriers, discussed challenges in defining clinical disease onset, and some questioned the degree of personal utility of these predictions. Finally, healthcare professionals emphasised several key conditions for implementing such prognostic models, including sufficient predictive accuracy, a narrower and more precise age range, and the need for additional counselling.
CONCLUSION: This study provides insights in the perspectives, views, and concerns of the majority of healthcare professionals in the Dutch counselling practice regarding the use of onset and progression predictions. Healthcare professionals identified several potential benefits and drawbacks of onset and progression predictions and discussed the conditions necessary for their implementation. During model development and before clinical implementation, clarity is needed on how disease onset is defined in the model and what constitutes sufficient model performance. Furthermore, aligning the model with its intended goals, such as providing personal utility, and assessing the feasibility of achieving meaningful predictions are crucial steps.

Keywords:  Age of onset; Disease progression; Hereditary neurodegenerative disease; Medical ethics; Predictive genetic testing; Prognostic model

DOI:  https://doi.org/10.1186/s13023-026-04396-1
J Genet Couns. 2026 Jun;35(3): e70220

Genetic counseling assistant-led education supports efficiency in rare disease care.

Laura Duncan, Jessa Bidwell, Kayla Troe, Corinne Berg, Emily Toering, Gabrielle Eversole, Alyssa Knudson, Kaitlin Sikkink Brown, Carolyn R Rohrer Vitek, Yan Li, Filippo Pinto E Vairo, Jennifer Kemppainen.

  Genetic counseling assistants (GCAs) support genetic counselors (GCs) and genetics clinic workflows, but their potential roles in pretest genetic counseling for rare diseases have not been explored. A pilot within the Mayo Clinic Center for Individualized Medicine's Genetic Testing and Counseling Clinic (GTAC), which offers predefined tests for patients with rare disease, explored the impact of GCA pretest education on appointment time and patient questions. After training, GCAs met GTAC patients prior to the GC to provide scripted information on genetics concepts, the visit purpose, and the test including result types and disclosure plans. Data from the pilot and a control group were collected and analyzed using descriptive statistics and two-sided t-tests. Patient cohort characteristics did not differ between the two models. When a GCA provided pretest education, the GC spent an average of 11.2 minutes less with the patient during their session compared to visits completed solely by the GC (p < 0.0001). Total appointment time was not impacted by GCA education. Questions asked to GCAs were often not within GCA scope to answer (72.7%), and some patients asked repetitive questions to both the GC and GCA (63.2%). Reduction in GC time per patient could lead to increased accessibility by allowing additional patients to be seen in a day. Similar models may support GCA professional development while allowing GCs to remove repetitive education from their genetic counseling sessions, leading to less burnout and/or increased job satisfaction. Impact on administrative workflows, access, revenue, patient satisfaction and outcomes and GC/GCA satisfaction and benefits can continue to be explored when trialing models incorporating GCAs in pretest education roles.

Keywords:  appointment time; genetic counseling assistant; genetic counselor; genetic testing; genetics services; intervention study; practice models; pretest; rare disease

DOI:  https://doi.org/10.1002/jgc4.70220
J Patient Rep Outcomes. 2026 May 14.

Patient engagement for quality improvement and knowledge translation in paediatric orthopaedic care - a patient partner led initiative.

Marisa Wong, Philippa Crerar, Anthony Philip Cooper, Harpreet Chhina.

   BACKGROUND: In healthcare, a shift towards patient-centric models has gained traction, emphasizing patient empowerment. This is exemplified by initiatives such as the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR), which aims to foster a more sustainable and equitable healthcare system, as well as the increased support provided by the Patient-Centered Outcomes Research Institute (PCORI), which supports research that provides useful and reliable healthcare information to users. Despite progress in various healthcare domains, patient-engagement initiatives remain underexplored in paediatric orthopaedic care, highlighting a gap in tailored engagement strategies for this population.
METHODS: This project took place within the department of orthopaedics at a provincial tertiary care children's hospital. Utilizing patient-partner led focus groups as a collaborative approach, we implemented engagement strategies guided by SPOR principles and informed by patient and caregiver feedback. Small focus groups facilitated meaningful discussions and allowed participants to contribute valuable insights into research, treatment, and knowledge translation (KT).
RESULTS: The focus groups identified action items to enhance patient engagement and research collaboration. Initiatives included the development of patient and family directories, patient resources, patient partnerships, patient spotlights on Instagram, and clinic gathering rooms. Co-creating KT materials ensured relevance and accessibility, fostering cooperation between patients, caregivers, and healthcare professionals.
CONCLUSIONS: This initiative marks a shift towards patient-centric paediatric orthopaedic care, emphasizing inclusivity, support, and collaboration. Patient-partners played a pivotal role in the success of the project, ensuring patient perspectives were central to the planning and execution of initiatives.

Keywords:  Focus groups; Knowledge translation; Patient collaboration; Patient-centric; Patient-led; Patient-oriented research

DOI:  https://doi.org/10.1186/s41687-026-01062-9
BMC Health Serv Res. 2026 May 12.

Communicating empathy sympathy and compassion in healthcare consultations: a systematic review of applied linguistic research.

Binh Ta, Rachael Drewery, Virginia Calabria, Charlotte Albury.

   BACKGROUND: Communicating with empathy is an essential skill for healthcare professionals (HCPs). However, current communication training curricula fail to show how empathy communication is done, hindering the effectiveness of this training. This systematic review synthesizes applied linguistic research that shows how empathy is communicated, and what functions empathy communication serves.
METHOD: We included research that analysed naturalistic recorded interactions between HCPs and patients in all healthcare settings. We systematically searched five databases for studies published in English up to August 2024. We analysed results and discussion sections of included studies using aggregative thematic synthesis.
RESULTS: We identified 1112 studies through systematic searches and included 43 studies in our review. We found eight categories of empathy communication: 1) naming emotions or characterising experiences, 2) sharing similar emotions or experiences, 3) compassionate witnessing and minimal response, 4) claiming or displaying understanding of patients' experiences and emotions, 5) displaying empathy multimodally, 6) response cries, 7) claiming of similar emotions or experiences, and 8) others. Regarding functions of empathy communication, we found four groups: 1) facilitating advice-giving or problem-solving, 2) assisting patients to work with emotions, 3) facilitating patient-centred care, 4) facilitating history-taking activities.
CONCLUSION: The reviewed studies provide evidence that empathy communication can be seamlessly incorporated into healthcare consultations. Empathy enhances patient engagement, aids emotional expression, supports problem-solving and helps in situations where patients' and HCPs' views diverge, making it an essential component of healthcare.

Keywords:  Compassion; Conversation analysis; Empathy; Healthcare interactions; Real-life interactions; Sympathy; Systematic review

DOI:  https://doi.org/10.1186/s12913-026-14609-9
J Genet Couns. 2026 Jun;35(3): e70223

To refer or not to refer? Exploring the cognitive process of genetic counselors' decision to refer a patient to another professional.

R Beth Dugan, Kestutis Micke, Andrea Shugar, Samantha Glowacki, Beverly M Yashar.

  Genetic Counselors (GCs) hold the dual responsibility to engage in patient-centered psychosocial counseling and to recognize when a patient's needs require referral to another healthcare professional (HCP). While previous work has shown that GCs use a variety of patient factors to determine when they could benefit from additional supportive services, we sought to better understand how GCs determine whether to refer a patient to another HCP or engage in more complex psychosocial counseling. Utilizing a multimethods approach, we used two sets of surveys to learn about our participants but ultimately prioritized the qualitative data from in-depth semistructured interviews with 15 participants (N = 15). Initial data collection and analysis relied on constructivist interpretive frameworks of grounded theory, which supported learning directly from participants while maintaining our ability to delve into issues raised by the participants. An iterative process of coding, reviewing, memoing, and testing resulted in the development of several conceptual models of possible theories. Through continued review of the data and guided by an interpretivism paradigm, we elected to honor the breadth of information shared by participants, abandoning our initial goal of defining a single theory to instead define three core conceptual categories related to GCs' consideration of providing psychosocial counseling or referring: (1) For GCs, it's personal! GC beliefs in themselves, their personal identities, and their conceptualization of the role of a "GC" influence their engagement in psychosocial assessment and support; (2) Training matters, but experience is key; and (3) Referrals occur when GCs are aware of and trust that another HCP/resource will be a good fit for a patient's need and that a patient can actually access it. These findings suggest that GC confidence in managing patient care evolves with experience and highlight the value of ongoing skill development for all practitioners.

Keywords:  genetic counseling; psychosocial; referral

DOI:  https://doi.org/10.1002/jgc4.70223
Cureus. 2026 Apr;18(4): e106579

Role of Artificial Intelligence in Health Research: Opportunities, Challenges, and Implications for Medical Education.

Raywat Deonandan.

  Artificial intelligence (AI) is fundamentally reshaping the landscape of health research, with applications spanning drug discovery, clinical diagnosis, patient monitoring, and medical education. This paper examines the transformative potential of AI technologies, including machine learning, deep learning, and natural language processing, across these domains, while critically evaluating the ethical, legal, and infrastructural challenges their adoption entails. Particular attention is paid to issues of algorithmic bias, data privacy, clinical accountability, and the growing imperative to integrate AI literacy into medical training. Particularly relevant to the Canadian context, this paper contends that realizing AI's promise in health research demands simultaneous progress on three fronts: technical innovation, a contextually grounded ethical framework, and a healthcare workforce equipped to navigate an AI-augmented practice environment.

Keywords:  algorithmic bias; artificial intelligence; clinical diagnosis; drug discovery; health research; machine learning; medical education

DOI:  https://doi.org/10.7759/cureus.106579
Transpl Rep. 2025 Feb;pii: 100171. [Epub ahead of print]10(1):

Advancing Deep Variant Phenotyping of Mitochondrial Enzyme Complexes For Precision Medicine in Allogeneic Hematopoietic Stem-Cell Transplantation.

Jing Dong, Michael T Zimmermann, Neshatul Haque, Shahram Arsang-Jang, Wael Saber, Xiaowu Gai, Raul Urrutia.

Allogeneic hematopoietic stem-cell transplantation (allo-HCT), an early developed methodology for precision medicine, remains the only curative therapy for myelodysplastic syndromes (MDS). However, allo-HCT carries significant risks of morbidity and mortality due to relapse and transplant-related complications. Recurrent mutations in mitochondrial DNA (mtDNA) have been identified as significant prognostic indicators for MDS outcomes following allo-HCT. However, the biological mechanisms of mtDNA mutations remain unclear. Thus, here we performed deep variant phenotyping by integrating computational biophysics and structural genomics approaches to reveal the molecular mechanisms underlying mtDNA variant dysfunction. This emerging genomics discipline employs structural models, molecular mechanic calculations, and accelerated molecular dynamic simulations to analyze gene products, focusing on their structures and motions that determine their function. We applied this methodology on the variants in the mitochondria-encoded complex I genes that are associated with MDS pathobiology and prognosis after allo-HCT. Our results demonstrate that this approach significantly outperforms conventional analytical methods, providing enhanced and more accurate information to support the potential pathogenicity of these variants and better infer their dysfunctional mechanisms. We conclude that the adoption and further expansion of computational structural genomics approaches, as applied to the mitochondrial genome, have the potential to significantly increase our understanding of molecular mechanisms underlying the disease. Our study lays a foundation for translating mitochondrial biology into clinical applications, which will advance the integration of precision medicine with allo-HCT.

DOI: https://doi.org/10.1016/j.tpr.2025.100171
JMIR Hum Factors. 2026 May 15. 13 e80230

Development, Implementation, and Preliminary Results of a Novel Social Network for Rare Disease Communities: Mixed Methods Study.

Lara Fendrich, Henriette Högl, Ralf Schmidt, David Bascom, Armin Berger, Max Lübbering, Gundula Ernst, Justus Schumacher, Sabrina Hölzer, Lorenz Grigull.

   Background: Rare diseases affect approximately 20 million Europeans, presenting unique challenges such as delayed diagnoses, limited therapies, and significant personal and financial burden. While resilience-supporting factors such as peer support are available and artificial intelligence-based diagnostic tools are being developed further, there is a lack of a dedicated online social network connecting patients, caregivers, relatives, and experts. This study presents the development and preliminary findings of Unrare.me, a novel social network designed to provide a secure space for experts and individuals affected by rare and chronic diseases (diagnosed and undiagnosed).
Objective: This study aimed to design, develop, and evaluate a social networking platform tailored to the needs of different stakeholders of the rare disease community, facilitating interaction, knowledge exchange, and emotional support while prioritizing data security.
Methods: This multidisciplinary, multicenter initiative brought together patient groups, health care professionals, psychologists, and web design experts. A literature review assessed existing networking approaches in the rare disease community. Structured interviews and user journey mapping defined user needs and essential app features. Iterative prototyping and stakeholder discussions informed the final design, which was developed into a functional app launched in December 2023 on major platforms. A survey conducted four months post-launch evaluated user feedback. Data security was prioritized throughout development.
Results: A total of 270 users (approximately 1 in 7 users at the time) participated in the evaluation. Most of them (n=221, 81.9%) registered to connect with others in similar situations, whereas 56.7% (n=153) sought expert input and 44.4% (n=120) looked for disease-related information. The app received positive ratings for usability (mean 6.12, SD 1.03; out of 7), accessibility (mean 5.59, SD 1.22), and design (mean 5.84, SD 1.12), as well as overall impression (mean grade of 2.24, SD 0.90 on a scale from 1-6, with 1 being the best score). Data security was highly rated (mean 5.58, SD 1.15). The app's ontology was suitable for 77% (n=208) of the participants, enabling them to find their diagnosis, and 60.7% (n=164) of users found at least one match. Matching preferences centered on shared diagnosis (mean 82.5, SD 25.1 on a visual analog scale from 0 to 100), symptoms (mean 74.2, SD 25.8), and everyday experiences (mean 69.6, SD 29.5). Overall, users welcomed the opportunity to network with each other securely and highlighted areas for further improvement, such as enhanced matching features and group chat options.
Conclusions: Unrare.me has generated significant interest and engagement within the German rare disease community, serving as a valuable tool for peer support, knowledge sharing, and expert identification. Current challenges include optimizing user acquisition and refining matching algorithms. Planned features include group chats, expert interaction, and gamification elements. Unrare.me illustrates the potential of tailored digital solutions to address unmet needs in the rare disease community.

Keywords:  AI; app; artificial intelligence; mutual support; rare disease; social network

DOI:  https://doi.org/10.2196/80230