Citations

ABSTRACT Background and Objectives Converging evidence hints at neurodevelopmental effects in genetic frontotemporal degeneration (FTD). In cross-sectional studies, for some genes, young adult FTD variant carriers show differences in brain volumes and cognition compared to familial non-carriers. However, longitudinal trajectories may more sensitively capture FTD-related neurodevelopmental vs. neurodegenerative changes than cross-sectional approaches. This study examined longitudinal trajectories of brain volumes, executive function, and plasma biomarkers in young adult carriers compared to familial non-carriers, as measures of neurodevelopmental and neurodegenerative outcomes of FTD-causing variants. Methods This longitudinal cohort study comprised participants, aged 18-30 years, from the FTD Prevention Initiative across Europe, Canada, and the USA. Genetic groups included C9orf72 (47%), MAPT (30%), and GRN (23%). Linear mixed-effects models were computed to assess longitudinal outcomes across age between groups, controlling for sex, scanner (for brain volumes), and education (for executive function); random effects accounted for between-subject variability nested within family membership. Results Variant carriers ( n =147) and familial non-carriers ( n =113) did not differ in age (mean±SD, 25.9±3.2 years), sex (53% female), or number of visits (2.1±1.7). Young adult C9orf72 repeat expansion carriers exhibited smaller thalamic volumes than non-carriers at the reference age of 26 years ( b =-982.8mm 3 , SE=317.0, p= 0.0046, f 2 =0.32), with relatively stable trajectories across ages 18-30 (i.e., no change over time). Trajectories of rostral anterior cingulate volumes differed in C9orf72 carriers and non-carriers across age, where carriers showed relatively stable trajectories and non-carriers showed age-appropriate declines ( b =64.4mm 3 , SE=29.9, p= 0.035, f 2 =0.07). For MAPT and GRN , there were little to no differences in total brain, cortical, or subcortical volumes between groups and over time. No longitudinal differences were observed between carriers and non-carriers in executive function, or plasma NfL or GFAP for any genetic group. Discussion C9orf72 repeat expansions were linked to smaller average thalamic volumes and stable trajectories between ages 18 to 30, supporting potential neurodevelopmental origins. The modest evidence supporting an absence of difference in neurodegenerative biomarkers and executive function suggests minimal early neurodegeneration and functional preservation in young adulthood.

In 2024, the Journal of Wound Care ( JWC ) published best-practice guidance on wound debridement. This introduced the concept of integral debridement, defined as the combined use of complementary debridement methods on the same wound to optimise healing outcomes. This typically involves combining less invasive approaches, such as autolytic debridement, with more active adjunctive methods, including mechanical and/or sharp debridement. In 2026, JWC convened an expert panel to explore how this concept can be effectively implemented in non-specialist settings. The panel concluded that debridement is most effective when applied repeatedly throughout the healing process and introduced the concept of continuous integral debridement (CID), a cyclical four-step approach comprising cleanse, debride, cleanse and dress (CDCD). The panel propose that, when performed regularly, this will help disrupt microbial and non-microbial barriers to healing and maintain a clean wound environment. The panel consider that CID is compatible with established frameworks, such as TIME/TIMERS and the International Wound Infection Institute wound infection continuum, and complements antibiofilm strategies, including Wound Hygiene. This document provides practical guidance for integrating CID into routine wound care across all clinical settings, including recommendations on cleansing solutions, debridement methods and dressing selection, with the aim of supporting evidence-based practice and improving patient outcomes.

ABSTRACT High dose melphalan (HDM) with autologous stem cell transplant is an established treatment for systemic light chain amyloidosis, but its incremental benefit in the era of effective standard intensity therapy is unknown. We retrospectively analyzed 475 transplant‐eligible patients who completed standard intensity treatment with or without HDM within 12 months at six centers in Europe and the United States between 2010 and 2024 to evaluate outcomes by baseline risk factors, hematologic response, and receipt of HDM. Death was an equally competing risk after the 12‐month landmark chosen to address early non‐proportional hazards and to ensure completion of first‐line therapy. BMPC > 20% was associated with inferior outcomes (HR 1.7), and gain/amp 1q with shorter TTP (HR 2.15), whereas other high‐risk FISH abnormalities were not. In multivariable models, VGPR/CR after standard intensity therapy was associated with longer TTP (HR 0.49/0.29), while gain/amp 1q remained independently associated with shorter TTP (HR 2.18). Receipt of daratumumab and HDM were associated with longer TTP (HR 0.44/0.61). HDM benefited patients who had not achieved CR after standard intensity therapy (mTTP 21.0 vs. 5.7 months without HDM), whereas patients already in CR did not benefit. Higher BMPC at diagnosis was associated with earlier progression in patients not receiving HDM (HR 1.9 for 5%–20% and 4.09 for > 20%), a risk attenuated in the HDM cohort. Gain/amp 1q remained associated with shorter TTP regardless of HDM exposure. These findings support a selective role for HDM, primarily benefiting patients with residual disease after standard intensity therapy or higher BMPC burden at diagnosis.

Abstract Background Indocyanine green (ICG) fluorescence imaging is increasingly incorporated into robotic liver resections (RLR), yet clinical practice regarding timing, dosage, and staining techniques is divergent. Aims This international expert survey aimed to characterize current practices for ICG in RLR. Methods Experts in RLR were invited to participate based on surgical volume (experience of 50 RLR and 30 annual RLR). A 74-item questionnaire was developed following a literature search and reviewed by a steering committee. The survey addressed indications, timing, dosage, imaging technology, benefits, limitations, training, and future directions of ICG use. Responses collected between September and October 2025 were analyzed. Results Seventy experts from 19 countries completed the survey, corresponding to an 88% response rate. Centers performed a median of 180 annual liver resections, including 55 RLR. Most experts used ICG (96%) during RLR. Anatomical demarcation (91%), tumor localization (60%), and biliary anatomy assessment (60%) were the most frequent indications. 60% of experts use preoperative ICG, while intraoperative ICG is mainly administered for demarcation (67%) and biliary tract visualization (40%). Considerable heterogeneity exists in dosage, timing, and staining techniques, particularly in cirrhotic livers and for tumor localization. Only half of the experts had standard operating procedures, whereas 64% expressed the need for a higher degree of standardization. Reported benefits of ICG use included improved anatomical orientation, margin assessment, lesion detection, and support during complex resections. Perceived limitations included background fluorescence, tissue penetration and variable staining in diseased parenchyma. 80% anticipated improved outcomes with combined ICG and three-dimensional image-guidance. Conclusion ICG fluorescence is widely used in RLR and is an important cornerstone for precision-guided robotic liver surgery. Standardized clinical practice guidelines, structured training, and technological improvements in imaging and navigation systems are claimed to optimize its clinical use.

Aging and neurodegenerative disorders like Alzheimer’s Disease (AD) are associated with progressive dysfunction of the blood-brain barrier (BBB) and neurovascular unit (NVU), contributing to impaired vascular integrity and neuronal vulnerability. Apolipoprotein E (APOE) is a key regulator of neurovascular function, and the rare APOE3-R136S “Christchurch” variant ( APOE3Ch ) confers protection against AD. Mesenchymal stromal cells (MSCs) represent a promising cell-based therapy for the treatment of neurodegenerative diseases due to their paracrine effect exerted on vascular and neural cells. To investigate how APOE3Ch influences MSC-mediated neurovascular support, we used isogenic iPSC-derived MSCs (iMSCs) with homozygous APOE3Ch or APOE3 . We found that APOE3Ch iMSCs have stronger immunosuppressive effect on LPS-induced NFκB activation of THP1 cells. APOE3Ch iMSCs also enhanced endothelial barrier resistance and angiogenic capacity compared to APOE3 iMSCs when directly co-cultured with endothelial cells. In addition, conditioned medium from APOE3Ch iMSCs promoted neurite outgrowth more efficiently than that from APOE3 iMSCs. Metabolic profiling revealed differences between APOE3Ch and APOE3 iMSCs, suggesting altered metabolic resilience. Together, these findings demonstrate that iMSCs support vascular and neuronal function through paracrine mechanisms and suggest that APOE3Ch variant improves specific aspects of MSC-mediated neurovascular support. This work highlights the potential of combining MSC-based therapies with protective APOE variants to target BBB and NVU dysfunction in aging and neurodegeneration.

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

Abstract Introduction Clinical hypnosis is among the limited treatment options currently available to mitigate the symptom burden associated with parasomnias; however, there is scant literature regarding its effectiveness. We conducted a retrospective cohort study to examine the efficacy of clinical hypnosis in treating parasomnias. Methods We included all adult patients with research authorization on file who were referred for clinical hypnosis for the management of parasomnias at the Mayo Clinic Center for Sleep Medicine. Data on demographics, type and frequency of parasomnia(s), number of hypnosis sessions, concurrent medication(s), and polysomnographic variables were extracted. Information about the efficacy of treatment, including patient reports of change in intensity and frequency was extracted where available. A Clinical Global Impression-Improvement (CGI-I) score was assigned based on review of the follow up note. Results A total of 134 patients received clinical hypnosis. A majority of the sample was female (65.67%) with a median age of 41.5 years. The most common indications were non-rapid eye movement (REM) parasomnia (33), REM sleep behavior disorder (27), nightmare disorder (24), parasomnia overlap disorder (11), and sleep-related eating disorder (8). Follow up data were available on 76 patients (56.71%). Of these, a total of 47/76 (61.84%) reported subjective improvement in parasomnias following hypnosis. The median CGI-I score was 3.07±1.22; a total of 23/76 (30.26%) reported substantial improvement and 19/76 (25.0%) reported some impovement based on the CGI scores. Conclusion A majority of patients reported improvement in symptoms. Clinical hypnosis was effective for both non-REM and REM parasomnias. Given its relative safety and minimal potential adverse effects, clinical hypnosis remains an effective first-line treatment option for parasomnias. Support (if any)