Citations

Abstract Seizure forecasting has progressed from theoretical aspiration to a rapidly advancing research domain, yet clinical translation remains limited. Over the past decades, advances in algorithm development, chronic electroencephalography (EEG), wearable sensors, and the characterization of seizure cycles have demonstrated that seizure risk is not random but fluctuates according to identifiable biological rhythms and patient‐specific patterns. Forecasting algorithms have shown promising performance across diverse retrospective datasets, including intracranial EEG, subscalp recordings, wearable physiological signals, and even self‐reported diaries. However, the clinical value of forecasting is contentious. Prospective real‐world validation and regulatory approval of patient‐facing forecasting systems remain rare. This review incorporates perspectives presented at the 5th International Congress on Mobile Health and Digital Technology in Epilepsy (2025). We examine barriers impeding clinical translation and current attempts to address them. Crucially, forecasting performance cannot be evaluated in isolation from intended use. Applications range from low‐risk uses, like scheduling diagnostic monitoring or visualization of historical trends, to higher risk interventions, including medication titration and adaptive neuromodulation. Each application entails distinct performance thresholds, ethical considerations, and regulatory requirements. Translational challenges include reliable seizure annotation, nonstationarity dynamics of biological cycles, and practical constraints for real‐time deployment. Ethical concerns center on miscalibrated reliance on low‐risk states, potential anxiety associated with high‐risk advisories, and the heterogeneity of patient preferences and risk tolerance. Regulatory pathways are likely to depend on clearly defined use cases and clinically meaningful endpoints, which may extend beyond seizure counts to include quality of life, anxiety, locus of control, and other patient‐reported outcomes. Ultimately, translation will require rigorous prospective evaluation against transparent benchmarks, sustainable scientific–commercial partnerships, and integration of probabilistic risk information into clinical workflows. With careful implementation, seizure forecasting may evolve from proof‐of‐concept research into a clinically meaningful component of epilepsy management, and we remain cautiously optimistic.

Abstract This article summarizes data for 13 investigational treatments for which at least preliminary seizure outcome data in patients with epilepsy were reported at the Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices held in Madrid, Spain, on May 3–6, 2026. The treatments reviewed include bexicaserin, a selective 5‐hydroxytryptamine (5‐HT, serotonin) type 2C (5‐HT 2C ) receptor superagonist investigated as a treatment for developmental and epileptic encephalopathies (DEEs); BMB‐101, a selective 5‐HT 2C receptor agonist investigated for the treatment of absence seizures and DEEs; elsunersen, an antisense oligonucleotide designed for the treatment of early‐onset SCN2A ‐DEE; EPX‐100 (clemizole hydrochloride), an antihistamine endowed with agonist activity at 5‐HT 2A and 5‐HT 2B receptors, repurposed as a treatment for DEEs; ES‐481, an antagonist of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors containing the transmembrane AMPA receptor regulatory protein γ8 (TARP‐γ8), under investigation for the treatment of drug‐resistant epilepsy; ETX‐101, a gene therapy in development for the treatment of SCN1A ‐positive Dravet syndrome; PrevEp‐006 (intranasal seletracetam), a synaptic vesicle glycoprotein 2A (SV2A) ligand under investigation as an acute seizure rescue therapy; radiprodil, a negative allosteric modulator that binds to the GluN2B subunit of the N ‐methyl‐ D ‐aspartate (NMDA) receptor, in development for the treatment of seizures and other symptoms associated with GRIN‐related neurodevelopmental disorder, tuberous sclerosis complex, and focal cortical dysplasia type II; RAP‐219, a selective negative allosteric modulator of TARP‐γ8, in development for drug‐resistant focal epilepsy; relutrigine, a selective disease‐state sodium channel modulator investigated as a treatment for SCN2A ‐ and SCN8A ‐DEE; Staccato Alprazolam, a breath‐actuated device that delivers alprazolam to the lungs for rapid seizure termination; vormatrigine, a functionally selective sodium channel modulator in development for the treatment of focal seizures; and zorevunersen, an antisense oligonucleotide engineered to restore endogenous Nav1.1 protein expression, investigated for the treatment of Dravet syndrome. Overall, the evidence reviewed justifies expectations for improved health outcomes for the millions of children and adults with epilepsy who do not fully benefit from existing therapies.

Abstract Over the last 34 years, the Eilat Conference on New Antiepileptic Drugs and Devices has provided an interactive forum for stakeholders to discuss investigational and recently licensed treatments for seizures and epilepsy. The Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVIII) took place in Madrid, Spain, on May 3–6, 2026. This article provides summaries of eight treatments in preclinical and early clinical development that were presented at EILAT XVIII. These include AUT00206, a positive allosteric modulator of Kv3.1 and Kv3.2 voltage‐gated potassium channels in development for the treatment of rare epilepsy syndromes as well as neurodevelopmental and neuropsychiatric disorders; ION283, an antisense oligonucleotide designed to suppress the expression of glycogen synthase 1, under investigation for the treatment of Lafora disease; MSCA‐7136, a selective allosteric RAS/mitogen‐activated protein kinase—extracellular signal regulated kinase (MEK) inhibitor being developed for the treatment of focal seizures associated with mesial temporal lobe epilepsy and seizures associated with tuberous sclerosis complex; OV329, a selective inhibitor of γ‐aminobutyric acid (GABA) aminotransferase, in development for the treatment of drug‐resistant focal seizures; PTI5803 (probenecid), an uricosuric agent and a blocker of pannexin 1 channels, repurposed as a treatment for seizures associated with focal cortical dysplasia; simufilam, a filamin A modulator under investigation for the treatment of tuberous sclerosis complex‐related epilepsy; SN‐2000, a selective allosteric phosphodiesterase 4B inhibitor, in development for the treatment of focal seizures; and sodium selenate, a promoter of the dephosphorylation of pathological hyperphosphorylated tau in the brain, under investigation as a disease‐modifying agent in mesial temporal lobe epilepsy. Treatments in more advanced clinical development are discussed in an accompanying article.

Aims Reverse shoulder arthroplasty (RSA) after prior rotator cuff repair (RCR) is commonly performed for recurrence of pain and arthritic progression; however, the influence of prior RCR timing and technique on outcomes of RSA has not been adequately explored. Our primary aim was to evaluate the relationship between the postoperative American Shoulder and Elbow Surgeons (ASES) score, whether prior RCR was performed open or arthroscopic, and the time interval between RSA and prior RCR. Secondary outcomes were forward elevation (FE) and external rotation (ER). Methods A prospectively collected single-institution shoulder arthroplasty database was queried to identify patients undergoing primary RSA after prior RCR between 2004 and 2022 for non-tumour and non-fracture indications with minimum two-year follow-up. We evaluated the relationship between the postoperative ASES score, FE, and ER stratified by prior RCR approach (open vs arthroscopic) and time between RSA and RCR. Multivariable analysis was used to adjust for potential confounders. Results We included 104 RSAs (99 patients) with a mean 8.8 years (SD 7.3) after RCR and a mean age of 68 years (SD 8.3). Prior RCR was performed arthroscopically in 40 RSAs (38%). Mean follow-up was 4.8 years (SD 2.8). On multivariable analysis, arthroscopic RCR was independently associated with a 13-point greater postoperative ASES score (p = 0.008), 14° greater forward elevation (p = 0.011), and 8° greater external rotation (p = 0.018) compared with open RCR. A ten-year increase in time between RCR and RSA was associated with a seven-point greater postoperative ASES score (p = 0.029) and 5° greater external rotation (p = 0.015). Conclusion A greater time interval between prior RCR and RSA, as well as arthroscopic techniques, is associated with improved outcomes after primary RSA in patients with prior RCR. Cite this article: Bone Joint J 2026;108-B(7):928–935.

Abstract Dermatomyositis is driven by overactivation of type I and II interferons and other proinflammatory cytokines that signal via the JAK-STAT pathway. We conducted a 12-week, open-label study of brepocitinib, an oral TYK2/JAK1 inhibitor, in five adults with severe cutaneous dermatomyositis. Treatment was associated with rapid, clinically meaningful improvement in cutaneous disease activity. Single-cell and spatial transcriptomic profiling of lesional skin showed marked suppression of interferon-responsive pathways and inflammatory cell states by week 4. Together with findings from a Phase 3 randomized trial in DM patients with skin and muscle involvement (VALOR, NCT05437263 ), these data support TYK2/JAK1 inhibition as a promising therapeutic strategy for DM.

Abstract Background Large language models (LLMs) offer promise for systematic review data extraction, but performance in complex multidisciplinary domains and utility for clinical statement generation remain insufficiently described. Objectives To evaluate Google NotebookLM for AI-assisted data extraction and RAND/UCLA consensus statement generation in a systematic review of IBD, obesity, and cardiometabolic comorbidities. Methods Studies were organized into domain-specific notebooks; structured prompts generated standardized evidence tables. Two independent reviewers validated outputs against full-text articles using a four-category error classification. Cell-level accuracy and critical accuracy (cells free of major factual errors) were the primary metrics; workflow time was compared against a published conventional extraction benchmark. Concordance between AI-generated and expert-finalized statements was assessed. Results Across 57 articles, 1,710 data cells were extracted; 151 (8.83%) were flagged, yielding 91.17% cell-level accuracy. Major factual errors occurred in only 4 cells (0.23%), for a critical accuracy of 99.77%. Most errors were minor omissions (59.6%) or incomplete extractions (30.5%); domain error rates ranged from 7.08% to 11.33%. The pipeline required 17.7 versus a projected 165.1 person-hours (89.3% reduction). PICO-structured prompting generated 70 candidate statements; 58 of 112 finalized panel statements (51.8%) were AI-derived, and 85.7% were retained in the finalized set. Conclusion Google NotebookLM demonstrates feasibility as a primary extraction and synthesis tool in a multidisciplinary systematic review, with extractive incompleteness as the principal limitation and substantial time savings over conventional approaches. Its novel application to RAND/UCLA consensus statement generation extends AI-assisted evidence synthesis to clinical consensus generation workflow.

Abstract Aims Transcatheter mitral valve replacement (TMVR) with the Tendyne Mitral Valve System is a treatment option for patients with severe symptomatic mitral regurgitation (MR) unsuitable for conventional mitral valve surgery or transcatheter edge-to-edge repair (TEER). This study sought to evaluate the safety and effectiveness of TMVR through 5-year follow-up. Methods and Results The Tendyne Expanded Clinical Study is a prospective, single-arm, multicentre study that enrolled patients between November 2014 and June 2020. The study enrolled 191 patients (mean age 74.1 ± 8.0 years, 62.8% male, 70.2% New York Heart Association Class (NYHA) class III/IV, 88.5% secondary MR), of whom 186 (97.4%) underwent TMVR with Tendyne. MR grade decreased from ≥3+ in 99.5% patients at baseline to grade ≤1+ in 95.3% at 5 years. In those patients surviving to 5 years (n = 49), durable symptomatic improvement was evidenced by 73.5% patients being in NYHA class I/II at 5 years. The Kansas City Cardiomyopathy Questionnaire overall summary score increased from 48.5 ± 22.5 points at baseline to 67.6 ± 21.5 points at 5 years. Serious adverse events that occurred through 5 years included life-threatening bleeding (11.5%), fatal bleeding (2.6%), renal insufficiency/failure (28.8%), endocarditis (7.3%), device thrombosis (5.8%), and new onset atrial fibrillation (13.1%). No structural device degeneration or device embolism occurred through 5 years. Conclusions The Tendyne TMVR was effective at achieving immediate and sustainable elimination of MR, which was associated with symptomatic improvement and absence of structural valve degeneration in a high-risk cohort over 5 years. These findings support TMVR with the Tendyne System as an alternative for patients with appropriate mitral valve anatomy and symptomatic secondary MR unsuitable for mitral surgery or TEER.

ABSTRACT Apheresis medicine is a continually evolving field with numerous studies published each year. To help apheresis practitioners stay up to date with the current literature, members of the American Society for Apheresis (ASFA) Attending Physician Subcommittee identified and summarized 10 seminal articles published in 2025, from the field of apheresis medicine. PubMed was used to identify articles published in four topics including donor apheresis, therapeutic apheresis, apheresis education, and apheresis collection for cellular therapy. These articles met at least one of the following criteria: novel findings, practice‐altering outcomes, international in scope, randomized‐controlled trial, relevant to current clinical practice, and/or provide evidence for category III or IV indications based on the ASFA 9th Special Issue of the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice‐Evidence‐Based Approach. Full length, peer‐reviewed manuscripts in English with data from human subjects were included while case reports, review articles, and meta‐analyses were excluded.