Citations

Abstract Patients with atypical variants of Alzheimer's disease (AD) often present at a younger age with predominantly non‐amnestic impairments and a more aggressive disease course. Historically, individuals with atypical presentations have not been included in large‐scale clinical trials, which typically focus on late‐onset, sporadic amnestic‐predominant AD. Consequently, treatment options and research efforts specific to atypical AD remain limited. The emergence of amyloid‐targeting therapies that slow disease progression underscores these challenges, as evidence supporting their efficacy in early‐onset amnestic and non‐amnestic AD variants is scarce. This perspective article argues that atypical AD represents an excellent disease model for clinical trials and proposes strategies to address critical gaps in clinical trial design for this population. Key considerations include optimizing participant selection approaches, establishing syndrome‐specific or surrogate biological and clinical endpoints, and fostering advocacy to enhance early and accurate diagnosis, equitable representation, and outcomes for these populations.

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.

Abstract Background Ventilated patients in the intensive care unit are often complex and require multiple care team members including bedside nurses, respiratory therapists, advanced practice providers, and physicians. A Quality Improvement initiative was created to address any barriers in communication. Spontaneous breathing trials (SBT) are often used as a surrogate for multidisciplinary communication. Both Respiratory therapist (RT) and provider led spontaneous breathing trial protocols are often performed but not necessarily documented or communicated appropriately. Our primary aim was to increase spontaneous breathing trial documentation from a baseline of 12% to 80% with a counterbalance of not increasing the 24-hour reintubation rate. Methods Using the DMAIC framework, we defined the gap in quality by getting baseline patient data for 3 months including SBT completion rate, SBT documentation rate, time to first SBT, total time on ventilator, 24-hour reintubation rate, and total ICU days. All care team members including providers, RTs, and nurses completed a 10-questions Likert 5-scale survey regarding their views of multidisciplinary communication and SBT completion. We identified the lack of documentation of SBTs and implemented a standardized respiratory therapy shift summary note which included SBT details and major ventilator changes. We then collected the same data over 3 months after implementation. Results Post intervention analysis revealed documentation of daily spontaneous breathing trials improved from 12% to 79%. Pre and post intervention means for patient focused outcomes were statistically unchanged for time to first SBT 26 hours vs 32 hours (p = 0.16), Total ventilator time 5.6 vs 5.4 (p = 0.83), total ICU days 1.9 days vs 2.7 days (p = 0.11), and reintubation rate 14% vs 15%.Survey results showed that there was a statistically significant improvement in overall satisfaction regarding multidisciplinary communication, satisfaction regarding ventilator management discussion on rounds, and if documentation amount was appropriate. Also, there was a significant improvement in the percentage of care team members that were aware of daily SBTs occurring. Conclusion The implementation of RT shift summary greatly improved staff member satisfaction, multidisciplinary discussion during rounds, and awareness of SBT occurrence among providers, RTs, and nurses. While patient centered outcomes were statistically unchanged over this very brief period of observation, having better staff satisfaction and communication may eventually lead to improved outcomes over time and can lead to further analysis to avoid mishaps that can arise from miscommunication. This abstract is funded by: None

Abstract Background Spinal cord ischemia (SCI) is an uncommon but devastating complication of Veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Peripheral femoral cannulation, while rapidly deployable, may compromise spinal cord perfusion. We report a case of thoracolumbar spinal cord ischemia presenting as paraplegia with cauda equina enhancement in a patient on femoral VA-ECMO. Case Presentation A 57-year-old man with nonischemic cardiomyopathy (EF 30%), atrial fibrillation on apixaban, and ICD (2023) suffered a witnessed out-of-hospital cardiac arrest requiring 45 minutes of CPR before return of spontaneous circulation. Peripheral femoral-femoral VA-ECMO was initiated, complicated by left femoral artery injury requiring repair. He was supported with the right axillary Impella 5.5 and listed UNOS Status 1 for heart transplantation. On ECMO day 5, the patient developed acute bilateral lower extremity weakness with preserved sensation and allodynia of the soles. Neurologic exam demonstrated flaccid paralysis below the quadriceps, consistent with a T12 motor level (ASIA C). Given his prolonged low-flow state and ECMO configuration, spinal cord ischemia was suspected. Hemodynamic augmentation and conversion of ECMO drainage from femoral to left subclavian were performed, along with corticosteroids. Following orthotopic heart transplantation on 8/8/2025, MRI of the thoracic and lumbar spine showed thickening, clumping, and enhancement of the cauda equina nerve roots without cord infarction. CSF analysis was negative for infection or inflammation, supporting an ischemic etiology. Despite rehabilitation and neuropathic pain management with pregabalin, lower extremity weakness persisted. He was discharged to inpatient rehabilitation with residual paraplegia. Discussion SCI is a rare neurological complication of femoral VA-ECMO, likely resulting from compromised spinal perfusion due to retrograde aortic flow, vascular injury, or systemic hypoperfusion during cardiac arrest. Post-ischemic cauda equina enhancement may reflect reperfusion-related breakdown of the blood-nerve barrier. Conclusion This case underscores the need for early recognition of spinal cord ischemia in ECMO-supported patients with new-onset paraplegia. Maintaining adequate mean arterial pressure, minimizing femoral arterial compromise, and early reevaluation of cannulation strategy may mitigate irreversible neurologic injury. This abstract is funded by: None

FRACTURE MRI demonstrated strong agreement with conventional radiography and CT in evaluating key bone tumor characteristics, including lesion type, location, and matrix content.

Abstract Background Frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominant atrophy is an emerging area of interest. Recent findings by the International Working Group (IWG) have identified this subtype as having a distinct clinical profile within the FTD spectrum (Ulugut et al., 2024, A&D). However, its genetic and pathological underpinnings remain unexplored in large, multicultural cohorts. Methods Retrospective analyses encompassing clinical, genetic, pathological, and neuroimaging data from 23 IWG sites across 13 countries in Asia, Middle East, Europe, North and South America were conducted. The study included 444 patients with FTD exhibiting predominant RATL atrophy. Results Genetic screening was performed on 51% ( n = 225) of the cohort for at least the major frontotemporal lobar degeneration (FTLD) mutations including microtubule‐associated protein tau ( MAPT ), progranulin ( GRN ), and chromosome 9 open reading frame 72 ( C9orf72 ), or dementia panels encompassing extended sets of genes. Of these, 81% were sporadic, showing negative results for the screened genes and a modified Goldman Score of ≥ 3, indicating a negative family history for dementia. The MAPT mutation was the most common genetic variant, identified in 7% of the screened cases (Figure 1). Pathological confirmation was available for 63 patients. Among the sporadic cases, transactive response DNA‐binding protein 43 type C (TDP‐C) pathology was most prevalent (60%, n = 32), while tau‐MAPT pathology was most common in the genetic cases (38%, n = 16). Fifteen cases did not fit neatly into genetic or sporadic categories, displaying heterogeneous pathologies (Figure 2). At the initial visit, compared to genetic cases, patients with TDP‐C pathology were older, and more frequently exhibited semantic deficits, with less frequent attention difficulties and executive dysfunction. No differences were observed in sex distribution, symptom duration or disease severity between genetic and sporadic TDP‐C cases. However, left handedness was more common in TDP‐C cases (14%) compared to genetic cases (5%). Conclusion While FTD with RATL atrophy primarily appears sporadic, a significant proportion of cases exhibit genetic variants. These sporadic and genetic subtypes display distinct neuropathological features and clinical manifestations. Given the implications for therapeutic strategies, precise clinical and molecular subtyping is critical for enhancing patient management and ensuring appropriate enrollment in clinical trials.

Summary Esophageal high-resolution manometry (HRM) is the gold standard for evaluating esophageal motility disorders but can be limited by patient intolerance. With increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for obesity and type 2 diabetes, delayed gastric emptying raises concerns for HRM feasibility and safety. This study assessed HRM tolerability in patients on GLP-1RAs. We conducted a retrospective case–control study of adult patients who underwent HRM at our tertiary care center between January 2014 and November 2024. Patients actively taking GLP-1RAs during HRM were identified as cases, while an equal number of consecutive eligible patients not on GLP-1RAs served as controls. Patients with established gastrointestinal dysmotility, prior foregut surgery, esophageal mechanical obstruction, large hiatal hernias, malignancy, or recent opioid use were excluded. From a prospective database of 7194 HRM attempts, 83 cases and 83 matched controls were identified. Among 166 patients, 15 (9.0%) had incomplete HRM due to intolerance, with similar rates between GLP-1RA users and controls (10.84% vs. 7.2%, P = 0.59). Predictors of incomplete HRM included younger age (44.9 ± 17.4 vs. 60.4 ± 13.7 years, P < 0.01), globus (P = 0.02), dyspepsia (P = 0.02), and depression (P = 0.04). No aspiration or adverse events occurred in either group. Duration of HRM before abortion was similar between cases and controls. GLP-1RA use was not associated with increased risk of HRM abortion or adverse events, suggesting these medications do not significantly impact HRM feasibility or safety.

ABSTRACT Weight recurrence is a late complication after Roux-en-Y gastric bypass. The transoral outlet reduction (TORe) emerged as an endoscopic alternative to revisional surgery for weight recurrence due to a dilated and incompetent gastrojejunal anastomosis. The procedure has been documented as safe and effective in clinical trials and other high-quality medical literature. Several cases of squamous metaplasia of the gastric pouch after repeated TORe procedures using argon plasma coagulation have been reported. We present a case of a late-onset adenocarcinoma of the gastrojejunal anastomosis after a TORe procedure performed using argon plasma coagulation and suturing.