bims-curels Biomed News
on Leigh syndrome
Issue of 2026–04–26
sixteen papers selected by
Cure Mito Foundation
  1. Study on Leigh syndrome caused by SURF1 gene mutations and its mechanisms.
  2. iPSC generation from PBMCs of a MELAS patient for mitochondrial dysfunction studies.
  3. RNA Sequencing Resolves Cryptic Pathogenic Variants in Mitochondrial Disease.
  4. Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids.
  5. New Understanding and Treatment of Adult Mitochondrial Dysfunction: An Example of Personalized Precision Medicine.
  6. The value of patient-focused drug development.
  7. Benefits and adverse effects of ketogenic diet treatment in pediatric patients with inborn errors of metabolism.
  8. Large Language Models as Physician Recommenders: Limitations, Alternatives, and the Path Toward Hybrid AI Systems.
  9. Artificial Intelligence in Drug Discovery and Development: Transforming Pharmaceutical Innovation.
  10. Orphan Drugs and Diseases: A Systematic Review.
  11. Exploring patients' and caregivers' experience of therapeutic patient education in rare diseases: A qualitative study.
  12. Patient Preferences for Plain-Language Alternatives to Medical Jargon in Clinical Notes.
  13. Hospital at Home has expanded rapidly on the assumption it's what patients want-but what do they really think?
  14. Architectural and translational perspectives on clinical decision support systems for rare disease diagnosis: a scoping review.
  15. Personal Philosophies of Practice: Purposeful Guides for Patient Engagement.
  16. Emotional impact, burnout, and isolation among primary family caregivers of children with medical complexity.
  1. Front Neurol. 2026 ;17 1793054
    Study on Leigh syndrome caused by SURF1 gene mutations and its mechanisms.
    Chunmei Wang, Longlong Lin, Yuanfeng Zhang, Simei Wang, Xiaona Luo, Xuqin Chen.
      Leigh syndrome (LS) is a prevalent mitochondrial encephalomyopathy in childhood, triggered by mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). The protein encoded by the SURF1 gene localizes to the inner mitochondrial membrane and is involved in the biosynthesis of the cytochrome c oxidase (COX) complex. We enrolled 5 children harboring SURF1 gene variants whose clinical manifestations were highly consistent with LS. The clinical characteristics and potential pathogenic mechanisms of the disease were elucidated by systematic analysis of their clinical data. Among the 5 patients, 4 were female and 1 was male, with ages ranging from 13 months to 2 years and 7 months. Next-generation sequencing (NGS) results revealed 6 variant sites in the SURF1 gene among the 5 patients, of which 2 were known variants and 4 were unreported novel variants, namely c.314-317delTGCC (p.L105Qfs*7), c.588+1_588+3delGTA (splicing), c.655G>T (p.Glu219), and c.515+3G>C. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed on the peripheral blood of 4 patients, and the results demonstrated that the messenger RNA (mRNA) expression level of the SURF1 gene was significantly lower than that in their parents. Using 10 healthy children as controls, we analyzed the ratios of mitochondria-related NADH-ubiquinone oxidoreductase core subunit 1 (ND1), Cytochrome c oxidase subunit I (COX1), Cytochrome c oxidase subunit II (COX2), NADH-ubiquinone oxidoreductase chain 4 (ND4), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a nuclear reference gene. Mitochondrial DNA content was determined by measuring the ND1/GAPDH ratio using RT-qPCR, and further verified with COX1, COX2, and ND4. These ratios were all significantly decreased, indicating reduced mitochondrial DNA (mtDNA) copy number/mtDNA depletion. Iterative Threading ASSEmbly Refinement (I-TASSER)-based three-dimensional (3D) structural analysis indicated that all 6 variant sites induced alterations in the spatial structure of the SURF1 protein. The SURF1 protein is a hydrophilic protein, protein hydrophobicity and stability analyses showed that the 4 unreported novel variants could reduce the hydrophilicity, increase the hydrophobicity, and decrease the structural stability of the protein. The Saccharomyces cerevisiae Homolog of Yeast 1 (Shy1) domain serves as the key structural basis for SURF1 to exert its mitochondrial functions. We found that all 6 variant sites in the SURF1 gene were located within the Shy1 domain.
    Keywords:  Chinese children; Leigh syndrome; Shy1 domain; mitochondrial DNA depletion; splice-site variant
    DOI:  https://doi.org/10.3389/fneur.2026.1793054
  2. Stem Cell Res. 2026 Apr 16. pii: S1873-5061(26)00088-7. [Epub ahead of print]94 103992
    iPSC generation from PBMCs of a MELAS patient for mitochondrial dysfunction studies.
    Gautam Sharma, Abhay Srivastava, Cheryl Rockman-Greenberg, Sanjiv Dhingra.
      Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a multisystemic mitochondrial disorder primarily caused by a heteroplasmic point mutation at mitochondrial DNA (mtDNA) position 3243 (m.3243A > G) in the MT-TL1 gene, which encodes mitochondrial tRNA^Leu(UUR). In this study, we report the successful reprogramming of peripheral blood mononuclear cells (PBMCs) from a male patient diagnosed with MELAS into induced pluripotent stem cells (iPSCs). This patient-specific iPSC platform enables investigation into the relationship between heteroplasmy levels and disease manifestation and provides a valuable tool for screening potential therapeutic strategies aimed at mitigating mitochondrial dysfunction in MELAS.
    DOI:  https://doi.org/10.1016/j.scr.2026.103992
  3. Ann Clin Transl Neurol. 2026 Apr 25.
    RNA Sequencing Resolves Cryptic Pathogenic Variants in Mitochondrial Disease.
    Zhimei Liu, Xin Duan, Fatemeh Peymani, Jia Wang, Chengjia Bao, Chaolong Xu, Ying Zou, Zixuan Zhang, Yunxi Zhang, Tongyue Li, Martin Pavlov, Junling Wang, Minhan Song, Tianyu Song, Xiaodi Han, Mingxi Sun, Danmin Shen, Ruoyu Duan, Huafang Jiang, Manting Xu, Holger Prokisch, Fang Fang.
       OBJECTIVE: Mitochondrial diseases are the most common inherited metabolic disorders, characterized by pronounced clinical and genetic heterogeneity that complicates molecular diagnosis. Although DNA-based sequencing approaches have become standard in genetic testing, up to half of patients remain without a definitive diagnosis. We aimed to perform RNA sequencing (RNA-seq) of patient-derived skin fibroblasts to enhance the molecular diagnostic efficacy of mitochondrial disease in undiagnosed cases in China.
    METHODS: We performed RNA-seq on skin fibroblasts from 140 pediatric patients with suspected mitochondrial disease who remained genetically undiagnosed after whole exome sequencing (WES). Aberrant RNA expression and splicing were identified using the detection of RNA outliers pipeline (DROP). Based on WES findings, patients were stratified into a candidate group (n = 28), in which RNA-seq evaluated the pathogenicity of WES-identified variants of uncertain significance and an unsolved group (n = 112), in which RNA-seq was used to pinpoint candidate genes. In six cases where RNA-seq identified the aberrant RNA event but WES did not detect the causative variants, whole genome sequencing (WGS) was performed.
    RESULTS: Integrative RNA-seq, WES, and WGS analysis resulted in a genetic diagnosis in 25% of patients overall (20/28 [71%] in the candidate group; 15/112 [13%] in the unsolved group). Aberrant splicing explained most candidate-group diagnoses, including variants misclassified by in silico predictors such as SpliceAI. 14% of protein-truncating variants predicted to undergo nonsense-mediated decay (NMD) escaped degradation, highlighting the functional limits of current predictions. The variants identified in the unsolved cohort included synonymous, missense, deep intronic, near-splice-site variants, and large deletions. The most frequent among them was a recurrent synonymous East Asian founder mutation in ECHS1, accounting for seven cases. Interestingly, across 233 pathogenic variants associated with aberrant RNA phenotypes compiled from this study and prior reports, half were noncoding and half were coding variants.
    CONCLUSION: RNA-seq substantially enhances molecular diagnosis in mitochondrial disease by exposing cryptic splicing, regulatory, and NMD-escape events invisible to DNA sequencing alone. These data advocate transcriptome analysis as an essential component of comprehensive genomic diagnostics in neurometabolic disease.
    Keywords:  RNA sequencing; mitochondrial diseases; pediatric; whole‐exome sequencing; whole‐genome sequencing
    DOI:  https://doi.org/10.1002/acn3.70379
  4. Nat Commun. 2026 Apr 20. pii: 3570. [Epub ahead of print]17(1):
    Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids.
    Carmen Menacho, Satoshi Okawa, Iris Álvarez-Merz, Annika Wittich, Mikel Muñoz-Oreja, Pawel Lisowski, Mario López Martín, Tancredi Massimo Pentimalli, Shiri Zakin, Mathuravani Thevandavakkam, Caleb Jerred, Selene Lickfett, Laura Petersilie, Agnieszka Rybak-Wolf, Annette Seibt, Diran Herebian, Gizem Inak, Susanne Brodesser, Andrea Zaliani, Barbara Mlody, Justin Donnelly, Kasey Woleben, Francesc Xavier Soriano, Jose C Fernandez-Checa, Natascia Ventura, Sidney Cambridge, Ertan Mayatepek, Antonella Spinazzola, Markus Schuelke, Nikolaus Rajewsky, Andrea Rossi, Alex Peralvarez-Marin, Felix Distelmaier, Ethan Perlstein, Ian J Holt, Emma Puighermanal, Ole Pless, Christine R Rose, Antonio Del Sol, Alessandro Prigione.
      Leigh syndrome (Leigh) is an untreatable mitochondrial disorder characterized by lactic acidosis and basal ganglia and midbrain pathology, leading to psychomotor regression and early death. We previously uncovered impaired neuronal morphogenesis in Leigh cerebral organoids carrying SURF1 gene variants. Leveraging this phenotype, we here develop a deep learning algorithm tailored for cell type-specific drug repurposing screening. In parallel, we perform a survival drug screen in a yeast model of Leigh. The two approaches independently converge on azole compounds, two of which - talarozole and sertaconazole - rescue neuronal morphogenesis in Leigh neurons and lower lactate release and improve growth rate in Leigh midbrain organoids. Mechanistically, these compounds modulate the retinoic acid pathway and membrane-associate lipid metabolism. The findings highlight azoles as promising candidates for Leigh and demonstrate the potential of combining in silico screens with human brain organoids as new approach methodologies (NAMs) to advance the discovery of therapeutics addressing rare neurodevelopmental disorders.
    DOI:  https://doi.org/10.1038/s41467-026-71391-2
  5. Am J Med. 2026 Apr 17. pii: S0002-9343(26)00288-3. [Epub ahead of print]
    New Understanding and Treatment of Adult Mitochondrial Dysfunction: An Example of Personalized Precision Medicine.
    Gabriela R Esnaola, Edward J Goetzl.
      The principal cellular energy-generating pathways of mitochondria used to produce adenosine triphosphate (ATP) are oxidative phosphorylation and β-oxidation of fatty acids. Under anaerobic conditions, glycolysis in the cytoplasm is an alternative mechanism for production of ATP. Mitochondrial diseases result from one or more of the over 350 mutations in mitochondrial DNA (10%) or nuclear DNA (90%) that cause defective mitochondrial ATP production. The most common manifestations in adults with mitochondrial DNA mutations are diminished vision, myopathy, cardiomyopathy, neuropathy, encephalopathy and diabetes. Uncommonly there are stroke-like syndromes. The most common manifestations in adults with nuclear DNA mutations are neuropathy with prominent ataxia, ophthalmoplegia, dysarthria, myopathy, cardiomyopathy, liver disease, neuroendocrine and renal cell tumors, and hypoglycemia. Adults, especially the elderly, may only develop manifestations in the course of stressful illnesses that unmask these mutations. Children may require mitochondrial transfer or gene editing therapy. These mutations should be sought in leukocytes or muscle tissue in adults who do not respond to usual treatment for severe stressful illnesses as they may benefit from newly-approved medications.
    Keywords:  Oxidative phosphorylation; anaerobic glycolysis; fatty acid β-oxidation; gene editing; mitochondrial transfer; reactive oxygen species (ROS)
    DOI:  https://doi.org/10.1016/j.amjmed.2026.04.018
  6. Nat Med. 2026 Apr 24.
    The value of patient-focused drug development.
    Allison Martin, Russ Paulsen.
      
    DOI:  https://doi.org/10.1038/s41591-026-04364-z
  7. Adv Clin Exp Med. 2026 Apr 21.
    Benefits and adverse effects of ketogenic diet treatment in pediatric patients with inborn errors of metabolism.
    Dorota Wesół-Kucharska, Magdalena Alicja Kaczor, Ewa Ehmke Vel Emczyńska-Seliga.
       BACKGROUND: The ketogenic diet (KD) is an established therapeutic option for epilepsy and selected inborn errors of metabolism (IEMs), particularly glucose transporter type 1 deficiency (GLUT1D) and pyruvate dehydrogenase complex deficiency (PDCD). Increasing evidence suggests broader applications of KD in pediatric metabolic disorders; however, data on its safety and efficacy in heterogeneous IEM populations remain limited.
    OBJECTIVES: To evaluate the efficacy, clinical benefits, and adverse effects (AEs) of KD in pediatric patients with various IEMs.
    MATERIAL AND METHODS: A retrospective analysis was conducted in pediatric patients with IEMs receiving KD treatment. Patients were categorized into 3 groups: 1) other IEMs (n = 7), 2) mitochondrial diseases (MD) (n = 17), and 3) GLUT1D and PDCD (n = 20). The median age at initiation of KD was 37, 53, and 53 months, respectively, and the median duration of KD treatment was 5, 11, and 55 months in groups 1, 2, and 3.
    RESULTS: The KD was associated with clinical benefits in 84% of patients. Among children with epilepsy (n = 23), a seizure reduction of >50% was observed in 73.9% of patients, including complete seizure freedom in 4 individuals. Improvements were also noted in muscle tone (27.6%), exercise tolerance (51.2%), ataxia (83.3%), and involuntary movements (60%). Lactate levels decreased in 84.6% of patients with mitochondrial disease and in all patients with PDCD. The KD was discontinued in 12 patients due to insufficient efficacy (n = 5) or AEs (AEs; n = 7). The most common AEs included gastrointestinal (GI) symptoms, dyslipidemia, hyperuricemia, metabolic acidosis, and decreased free carnitine; most were transient. No significant association was found between median β-hydroxybutyrate (BHB) levels and clinical outcomes.
    CONCLUSIONS: The KD is an effective and generally well-tolerated therapeutic option in pediatric IEMs, with benefits extending beyond seizure control. Adverse effects are typically manageable, although GI intolerance may limit long-term use. Ketogenic diet should be considered not only for refractory epilepsy but also for selected metabolic indications.
    Keywords:  epilepsy; inborn errors of metabolism; ketogenic diet; mitochondrial diseases; pediatric metabolic disorders
    DOI:  https://doi.org/10.17219/acem/219994
  8. Jt Comm J Qual Patient Saf. 2026 Mar 28. pii: S1553-7250(26)00077-2. [Epub ahead of print]
    Large Language Models as Physician Recommenders: Limitations, Alternatives, and the Path Toward Hybrid AI Systems.
    Mohammad Mahdi Bagheri Asl, Alejandro M Spiotta.
      Digital tools are increasingly used by patients to access health information and navigate care, including choosing clinicians, but the evidence supporting "best doctor" recommendations varies widely across available methods. This manuscript compares the emerging use of consumer-facing large language models (LLMs) for this purpose with four alternative physician-selection strategies: patient networks, expert referrals, consumer rating/search platforms, and outcome-informed artificial intelligence / machine learning (AI/ML) recommender systems. Consumer rating platforms mainly reflect patient experiences rather than technical skills and often show weak or inconsistent links with objective performance measures. General-purpose LLMs may produce convincing rationales that highlight visibility and reputation, but they remain limited by hallucinations, prompt sensitivity, and uncertainty about whether their explanations truly reflect the underlying reasoning. Outcome-informed AI/ML recommender systems could, in theory, incorporate risk-adjusted clinical performance, but they face significant challenges, including unreliable physician-level measurement, incomplete data, residual confounding, and limited transparency, which can undermine trust and informed consent. We suggest that a hybrid system should be seen as a guiding concept and a testable approach rather than a final solution. Such a system could integrate proven, auditable performance measures with transparent patient-preference filters and verifiable, patient-facing explanations. We present key design principles, including clinical relevance, explainability, autonomy, equity, and governance, in line with current US Food and Drug Administration (FDA) guidance related to clinical decision support and adaptive AI life cycle management.
    DOI:  https://doi.org/10.1016/j.jcjq.2026.03.011
  9. Drug Dev Res. 2026 May;87(3): e70281
    Artificial Intelligence in Drug Discovery and Development: Transforming Pharmaceutical Innovation.
    Mohd Shoab Ali, Taha Alqahtani, Humood Al Shmrany, Garima Gupta, Khang Wen Goh, Amirhossein Sahebkar, Prashant Kesharwani.
      Drug discovery remains a lengthy, costly, and high-risk endeavor, often requiring over a decade from target identification to clinical translation. Artificial intelligence (AI) is reshaping this paradigm by enabling more efficient and accurate decision-making across the discovery and development pipeline. Advances in machine learning, deep learning, and natural language processing now support target identification, hit finding, lead optimization, and drug repurposing with unprecedented speed and precision. AI-driven insilico platforms further enhance early-stage predictability by forecasting toxicity, pharmacokinetics, and developability, thereby reducing late-stage attrition. This review critically examines the evolving role of AI in modern drug discovery and its expanding impact on pharmaceutical formulation development and personalized medicine. Collaborative models between AI developers and the pharmaceutical industries, essential for accelerating translational outcomes, are also highlighted. Finally, key challenges, including algorithmic transparency, data quality, interoperability, and regulatory acceptance, are discussed, along with future directions for harnessing AI's full potential in pharmaceutics.
    Keywords:  artificial intelligence; deep learning; drug discovery; in silico modeling; machine learning; pharmaceutical development
    DOI:  https://doi.org/10.1002/ddr.70281
  10. J Pharm Bioallied Sci. 2026 Apr-Jun;18(2):18(2): 93-95
    Orphan Drugs and Diseases: A Systematic Review.
    Heena Dixit Tiwari, Manoj Kumar Sahoo, M R Murali, Rahul Tiwari, Kamatham Manjusha, M C Prashant.
      Rare diseases, though individually infrequent, collectively affect over 300 million people worldwide. The development of orphan drugs to treat these conditions is hampered by regulatory inconsistencies, high costs, and limited clinical trial populations. To systematically review the current landscape of orphan drugs and rare diseases, focusing on definitions, therapeutic approaches, health economic evaluations, and stakeholder perspectives. A systematic review was conducted using 70 reference-screened articles, out of which 10 were selected based on relevance to rare diseases or orphan drug policy, economics, or clinical management. Study types included systematic and scoping reviews, observational studies, and health economic evaluations. Data extraction focused on definitions, healthcare roles, cost analyses, and clinical outcomes. Definitions of rare diseases varied globally, impacting drug approval processes. Economic evaluations revealed disparities in funding orphan drugs. Studies emphasized the growing role of pharmacists and stakeholders in therapeutic access. High-cost burdens, ethical considerations, and diagnostic advancements were recurring themes. Pediatric and syndromic rare conditions, like Duchenne muscular dystrophy and Turner syndrome, were notably covered. Effective rare disease care requires harmonized definitions, ethical pricing models, interdisciplinary healthcare roles, and evidence-based policies to ensure equitable access and sustainability.
    Keywords:  Healthcare policy; orphan drugs; pharmacoeconomics; rare diseases; systematic review
    DOI:  https://doi.org/10.4103/jpbs.jpbs_937_25
  11. Patient Educ Couns. 2026 Apr 17. pii: S0738-3991(26)00178-3. [Epub ahead of print]149 109645
    Exploring patients' and caregivers' experience of therapeutic patient education in rare diseases: A qualitative study.
    Robin Bouillé, Soumaya Balbolia, Audrey Barbet, Caroline Barry, Émilie Cappelle, Ariane David, Laurine Durot, Géraldine Fayet, Nicolas Guérin, Éric Hachulla, Christine Hassler, Élisabeth Lehu, Hélène Maillard, Rachel Pamart, Thomas Sannié, Laurence Schuller, Hélène Thiollet, Fréderic Gottrand, Stéphanie Ringenbach, Sophie Susen, Géraldine Wojtasik, Meryem-Maud Farhat.
       BACKGROUND: Therapeutic Patient Education (TPE), defined in the French Public Health Code, is part of the healthcare pathway, aiming to enhance autonomy, treatment adherence, and quality of life. TPE programmes are structured, person-centred processes helping patients with chronic diseases self-manage their health. For patients with rare diseases (RD) and their caregivers, specialised TPE is essential to anticipate lifelong disruptions and provide support in contexts of vulnerability and isolation.
    RESULTS: This qualitative study involved 23 one-hour semi-structured interviews with 12 RD adult patients and 11 adult caregivers in France between January and May 2023, recruited through RD networks and patient organisations. Interviews explored participation context, expectations, satisfaction, and difficulties. Data were analysed using NVivo to identify recurring themes. Participants reported improved understanding of their RD and treatments, psychological and social well-being, and autonomy through TPE. Key themes included preference for face-to-face sessions for human interaction, though remote sessions offered practical benefits. The study highlighted diagnostic odyssey, emotional impact of diagnosis, and need for psychological support. Challenges included recruitment biases, geographical barriers, and insufficient communication about TPE. Participants emphasised TPE's role in improving their acceptance and management of the disease, transforming relationships with healthcare providers and reducing isolation.
    CONCLUSION: TPE addresses medical and psychosocial needs of patients with RD and caregivers, enhancing participation and quality of life. Face-to-face sessions are preferred, but remote options improve accessibility. Given the qualitative design, heterogeneity of RD and recruitment bias, findings are not fully generalisable. Future efforts should improve communication, involve patient organisations, and integrate caregivers for holistic care.
    Keywords:  Caregivers; Interviews as Topic; Patient; Patient experience; Qualitative research; Rare diseases; Therapeutic Patient Education
    DOI:  https://doi.org/10.1016/j.pec.2026.109645
  12. J Gen Intern Med. 2026 Apr 20.
    Patient Preferences for Plain-Language Alternatives to Medical Jargon in Clinical Notes.
    Katherine A Allen, Michelle M Kelly, Michael B Pitt, Jordan Marmet, Emily Hause, Zachary Linneman, Scott Lunos, Rheanne Maravelas, Sage Marmet, Brett Norling, Alexis Quade, Aarabhi S Rajagopal, Madeline Suk, Marissa A Hendrickson.
       BACKGROUND: Patients are increasingly able to access their medical records, in part due to legislation mandating this access in the USA. Many terms used in medical documentation can be confusing or perceived as offensive, risking damage to the patient-clinician relationship; little evidence exists to guide alternative phrasing.
    OBJECTIVE: To identify adults' preferences between traditional medical phrases and plain-language alternatives in clinical notes.
    DESIGN: A cross-sectional observational survey at the 2023 Minnesota State Fair.
    PARTICIPANTS: Electronic surveys were offered to adults (≥ 18 years old) who spoke or read English and did not have formal healthcare training.
    MAIN MEASURES: We described nine clinical scenarios and offered documentation choices using medical jargon or plain-language. We collected participants' preferred documentation option and associated free-text comments.
    KEY RESULTS: In total, 276 respondents were recruited; 271 fully completed the survey. The mean age was 45 years; 56% were women, and 67% had a bachelor's degree or higher. Traditional medical phrases were highly unfavored compared to plain-language alternatives, including "failed outpatient treatment" (2%) vs. "did not improve" (70%); "refused antibiotics" (6%) vs. "preferred to skip" (43%) or "declined" (43%); "denies alcohol use" (16%) vs. "does not drink alcohol" (82%); and "chief complaint" (20%) vs. "reason for visit" (79%). "Non-compliant" and "non-adherent" were equally disfavored (2% each) vs. "has been unable to take" (56%) and "stopped taking the medicine" (39%). Eight qualitative themes were identified: (1) clear and thorough communication; (2) objective and accurate information; (3) direct and concise messaging; (4) empathetic, personal, and affirming language; (5) respect for patient autonomy and agency; (6) financial sensitivity in documentation; (7) recognition of patient dependency; and (8) maintenance of a formal, professional tone.
    CONCLUSION: Our findings highlight a strong preference for plain-language in medical documentation, along with identifying a number of preferred alternative plain-language phrasing options.
    Keywords:  communication; electronic medical records; medical jargon; patient preferences
    DOI:  https://doi.org/10.1007/s11606-026-10353-2
  13. BMJ. 2026 Apr 24. 393 s769
    Hospital at Home has expanded rapidly on the assumption it's what patients want-but what do they really think?
    Sally Howard.
      
    DOI:  https://doi.org/10.1136/bmj.s769
  14. Int J Med Inform. 2026 Apr 16. pii: S1386-5056(26)00182-6. [Epub ahead of print]215 106442
    Architectural and translational perspectives on clinical decision support systems for rare disease diagnosis: a scoping review.
    Erdener Özçetin, Sümeyye Ebrar Baş, Furkan Özpay.
       BACKGROUND: Rare diseases remain difficult to diagnose because of phenotypic heterogeneity, limited clinical familiarity, and fragmented health data infrastructures. Clinical decision support systems (CDSS) have emerged as promising tools to support earlier recognition and more consistent diagnostic reasoning. However, the literature spans diverse technological paradigms, making it difficult to understand how these systems collectively contribute to clinical decision-making and their translational implementation.
    OBJECTIVE: This scoping review aimed to map diagnostic CDSS developed for rare disease diagnosis and to examine how data infrastructures, phenotype-driven reasoning frameworks, and artificial intelligence-based approaches contribute to clinical decision support and their translation into practice.
    METHODS: A PRISMA-ScR-guided scoping review was conducted. Searches were performed primarily in PubMed (MEDLINE), with supplementary screening in Google Scholar; the final search was completed on 30 November 2025. Records were screened in two stages and eligible studies were charted according to CDSS type, data sources, analytical methods, validation strategies, explainability features, interoperability elements, and reported evidence of clinical integration. Findings were synthesized using a taxonomy-based thematic approach rather than through quantitative pooling.
    RESULTS: The reviewed literature clustered into four main technological paradigms: information-retrieval systems, phenotype- and ontology-driven reasoning tools, data-driven predictive models based on EHRs and AI methods, and interoperable infrastructures such as federated learning and knowledge graphs. In addition, a separate group of studies addressed clinical evaluation and translation readiness across these paradigms. Across these areas, the field showed substantial methodological diversity, but evidence for external validation, workflow-level integration, and real-world clinical implementation remained limited. Interoperability, explainability, and governance were recurring challenges across paradigms.
    CONCLUSIONS: Rare disease CDSS research is moving from isolated diagnostic tools toward broader, interconnected diagnostic ecosystems. Progress toward clinically actionable implementation will depend on standardized data representations, stronger cross-institutional validation, explainable outputs aligned with clinical workflows, and interoperable infrastructures supported by appropriate governance. This review provides a taxonomy and conceptual framework to support the translational development of rare disease diagnostic CDSS.
    Keywords:  Artificial intelligence; Clinical decision support systems; Diagnostic reasoning; Electronic health records; Phenotype ontology; Rare diseases
    DOI:  https://doi.org/10.1016/j.ijmedinf.2026.106442
  15. South Med J. 2026 Apr 03. 119(4): 203-206
    Personal Philosophies of Practice: Purposeful Guides for Patient Engagement.
    William Ventres.
      At a time when many physicians feel frustrated and burned out, the author invites them to create their own personal philosophies of practice, statements that clarify the purposeful meanings they choose to instill in their work beyond the exigencies of their daily endeavors. Three tasks frame the process of creating a personal philosophy of practice: thinking about what purpose individual physicians attribute to the work of medicine; considering what core concepts steer their professional activities such that they, their patients, and the health of the public at large all benefit; and documenting their own personal philosophy of practice, with an eye toward the future. The author includes three example personal philosophies of practice to help guide readers' creative efforts.
    DOI:  https://doi.org/10.14423/SMJ.0000000000001949
  16. Fam Syst Health. 2025 Dec;43(4): 724-735
    Emotional impact, burnout, and isolation among primary family caregivers of children with medical complexity.
    Ansley E Kenney, Julia B Tager, Paulina S Lim, Samantha Everhart, Sarah Johaningsmeir, Kathryn A Balistreri, Amy Morgan-Tautges, K Jane Lee, Maura A Brophey, Matthew C Scanlon, Charles B Rothschild, W Hobart Davies, Jessica L Schnell.
       INTRODUCTION: Children with medical complexity (CMC) often have substantial health care needs, are medically fragile, and experience functional limitations. Caregiving for these children can be extremely stressful. We sought to understand the emotional impacts of caregiving and burnout among caregivers of CMC to provide insight into areas where providers who work with children and their families can intervene.
    METHOD: Twenty caregivers of CMC participated in qualitative interviews. Qualitative data were analyzed using interpretive phenomenological analysis. Emergent themes were identified and categorized into superordinate themes.
    RESULTS: Caregivers of CMC described the "emotional impact of caregiving," including "hospitalizations are emotionally demanding," "child in pain is distressing," "fearing child would not come home from the hospital," "an awareness child may die," "anticipatory anxiety about future medical events," and "traumatic memories of past medical events." Caregivers conveyed themes of "caregiver burnout," indicating that "stress is constant," "a need for constant vigilance," "caregiving is emotionally and physically exhausting," "self-care is limited," "helplessness," and "difficulty self-regulating emotions." Caregivers revealed "caregiver isolation," including "others don't understand daily struggles," "child's medical situation is unique," "the limited community and emotional support," "social reactions to child's needs," and "comparing child to other children makes limitations stand out."
    DISCUSSION: Findings provide insight into the lived experience across primary caregivers of CMC. Identifying these experiences enables providers to effectively intervene, including prevention tactics, screening, and/or intervention. These healthcare providers play an important role in promoting optimal care and outcomes for these caregivers and, in turn, better outcomes for their children. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
    DOI:  https://doi.org/10.1037/fsh0001022
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