Citations

Background Patients with anti-leucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis (AIE) frequently present with faciobrachial dystonic seizures (FBDS), which are often under-detected due to their subtle motor features and lack of consistent EEG correlates. Conventional in-hospital monitoring and patient-reported seizure diaries are limited, particularly during nocturnal periods. In this pilot feasibility study, we evaluated the use of a wearable device (Empatica E4) to objectively monitor FBDS-related motor and autonomic activity in seven patients with anti-LGI1 AIE and four control subjects. Methods Wearable recordings included accelerometry (ACC), electrodermal activity (EDA), photoplethysmography (PPG) and skin temperature. A support vector machine-based algorithm was developed to identify disorder-related events using ACC and EDA features. Analyses were restricted to sleep periods to minimise confounding from voluntary movements. Results Pretreatment recordings from two patients (P1 and P2) showed significantly elevated motor event frequency, ACC magnitude and EDA activity compared to controls. Post-treatment recordings demonstrated marked reductions in these metrics, consistent with patient-reported clinical improvement. Other patients showed variable results depending on treatment timing and signal quality. Conclusion Our pilot study demonstrates the feasibility of using wearable technology for objective, real-world monitoring and assessment of patient status in anti-LGI1 AIE. Nocturnal monitoring offers a low-noise baseline for detecting seizure-related activity and may support earlier diagnosis, more accurate evaluation of treatment response and reduced reliance on resource-intensive inpatient evaluations. Future studies should expand monitoring to daytime periods and validate findings against conventional modalities such as video-EEG and electromyography polygraphy.

Early allograft failure (EAF) after living donor liver transplantation (LDLT) remains a clinical challenge. Existing prediction models developed for deceased donor transplantation poorly apply to LDLT due to distinct surgical and physiological factors. This study identifies clinical determinants of EAF and develops an LDLT-specific prediction model. We conducted a multicenter retrospective cohort study from 17 high-volume LDLT centers (January 2016–December 2020) with external validation at a tertiary center in Saudi Arabia (January 2015–December 2022). The primary outcome was EAF (graft loss or patient death ≤90 d). Multivariable mixed-effects logistic regression identified preoperative/intraoperative risk factors. The EAGLE-LDLT model was constructed using postoperative laboratory values. Performance was compared against established models (EAD, MEAF, A2ALL) using ROC analysis and decision curve analysis. The development cohort included 2944 adult LDLT recipients (67.7% male; median age 55 y; median MELD 14) with a 5.5% EAF rate. External validation included 1020 recipients (median MELD 21, 6.7% EAF). Independent risk factors for EAF were MELD (OR 1.06, 95% CI 1.04–1.08), donor BMI (OR 1.05, 95% CI 1.00–1.10), portal vein thrombosis (OR 1.73, 95% CI 1.13–2.63), and hepaticojejunostomy (OR 1.58, 95% CI 1.06–2.36). The EAGLE-LDLT model incorporating peak ALT (>468 U/L), peak INR (>1.9), and bilirubin (>3.5 mg/dL) and INR (>1.3) at POD7, demonstrated superior discrimination (AUC=0.81) compared with MEAF (AUC=0.77, p =0.004), EAD (AUC=0.67, p <0.001), and A2ALL (AUC=0.65, p <0.001). EAGLE-LDLT achieved balanced sensitivity (75.0%) and specificity (73.7%), effectively stratifying patients into high-risk (15% of patients; 40.4% EAF incidence) and low-risk groups. Preoperative and intraoperative clinical factors predict EAF in LDLT. The EAGLE-LDLT model accurately identifies LDLT recipients at the highest risk for EAF postoperatively.

Abstract Chimeric antigen receptor (CAR) T-cell therapy enriched for a memory-like phenotype may persist and function longer than a nonenriched product, thereby improving duration of response (DOR). We conducted a phase I study with bb21217 (NCT03274219), an anti–B-cell maturation antigen CAR T-cell therapy manufactured in the presence of the phosphoinositide 3-kinase inhibitor bb007 to enrich for T cells with a memory-like phenotype, in patients with relapsed/refractory multiple myeloma (N = 72). No new safety concerns were raised with bb21217 therapy (three cases each of grade ≥3 cytokine release syndrome and grade ≥3 neurotoxicity were observed). The objective response rate was 69.4% and the median DOR was 23.8 (95% confidence interval, 16.8–34.8) months. Analysis of the drug product established an association between early memory phenotype and robust expansion and depth of response. Examination of baseline characteristics indicated that tumor burden and prior therapies influenced DOR. The data indicate that generation of CAR T cells early in a disease course when tumor burden is lower and source material exhibits a more naïve phenotype may maximize the clinical benefit potential of the drug product.

Introduction Asthma is a multifactorial disease influenced by genetic and environmental factors, including diet. The gut microbiome contributes to airway inflammation via the gut-lung axis, partly through production of short chain fatty acids (SCFAs) from bacterial fermentation of dietary fiber. We hypothesized that dietary fiber supplementation could modulate the gut microbiome and increase SCFAs in children with asthma. Methods This is a double-blind, placebo-controlled trial of children who were randomized to consume 12 g of soluble corn fiber (SCF) as a supplement to their usual daily diet (50% the recommended daily fiber intake) or placebo for 4–6 weeks ( clinicaltrials.gov NCT03673618). Dietary surveys, asthma symptom questionnaires, fecal, blood and nasal samples were collected before and after the intervention period to quantify fiber intake, asthma control, nasal and gut microbiome, and serum short chain fatty acids (SCFAs). Results Of the 20 children enrolled, 15 completed the intervention with an average adherence rate of 83%. SCFA concentrations and gut microbiome changes varied by individual and treatment group. No significant differences in gut or nasal alpha or beta diversity were observed between groups post-intervention. However, differential abundance analysis showed a trend toward increased Bifidobacterium in the SCF group compared to placebo (ANCOM-BC p = 0.0004, FDR q = 0.073). Discussion Supplementation of 50% of recommended daily fiber intake had minimal impact on asthma symptoms, the microbiome, or SCFA levels. Future studies should consider higher fiber doses, different fiber types, or targeting individuals with low baseline fiber intake to account for observed variability in microbiome and SCFA responses. Clinical Trial Registration https://clinicaltrials.gov/study/NCT03673618 , identifier NCT03673618.

Abstract Introduction: Underlying tumor biology in metastatic castration-resistant prostate cancer (mCRPC) is highly complex and heterogeneous. To date, mCRPC state biomarker-enriched clinical trial designs incorporating either prognostic or predictive biomarkers are limited to alterations in homologous recombination repair pathway genes. In this study, we use an integrated clinico-molecular prognostic score in mCRPC that combines plasma prognostic proteins with a plasma-based copy number alteration (CNA) risk algorithm (PMID: 40036789; PMID: 36230636) to simulate a biomarker-enriched clinical trial design. Methods: A plasma cell-free DNA (cfDNA) prognostic risk algorithm from eight CNAs (gains in AR, MYC, PIK3CA, PIK3CB; deletions in NKX3-1, TMPRSS2, TP53, ZBTB16) is combined with clinical prognostic proteins (alkaline phosphatase, lactate dehydrogenase) to generate a prognostic risk-score (RS) in three independent treatment-naïve mCRPC cohorts. Using the RS classifier, we estimate the number of high-RS patients (pts) required to be screened from an unselected mCRPC population and the number needed for enrollment to achieve adequate statistical power in a randomized trial for a predefined effect size (Hazard Ratio- 0.70; 80% power). The trial design aims to enrich High-RS pts for targeting lethal mCRPC. Trade-offs are evaluated between number of pts screened and enrolled under varying RS enrichment thresholds and degrees of enrichment. Results: The range of RS distribution in 561 mCRPC pts from three pooled datasets was 0.362-11.737. The median overall survival (OS) (months; 95% Confidence Intervals) based on risk stratification for Low-RS (≤0.8) is 46.2 (38.8-55.4); “Intermediate-risk” (RS: 0.8-2.6) is 27.1(24.3-31.5); High-Risk (RS: &gt;2.6) is 14.9 (11.9-17.6). For a 2-year OS mCRPC endpoint, a biomarker-enriched trial restricted to pts with RS ≥2, which corresponds to the 65th percentile of the RS distribution, would require enrollment of 398 pts, after screening 1,101 mCRPC pts to achieve 80% power to detect a 0.7 treatment vs. control hazard ratio (HR). In contrast, a traditional non-enrichment clinical trial (no molecular classifier) would require 574 pts to achieve to achieve 80% power and still not achieve adequate power to detect strong treatment by risk interactions. As a pragmatic alternative, we evaluated a hybrid enrichment strategy enrolling 50% of pts from the general mCRPC population and 50% of pts with RS ≥1 (41st percentile). This biomarker enriched design which takes 50% pts with a RS of 1.0 (or more) in a trial with 24-month follow-up will require a sample size 525 patients for which 676 pts will be screened to achieve an 80% power to detect a 0.7 treatment vs. control hazard ratio. Conclusion: A plasma-based molecular classifier can be used to design an enrichment trial in biologically defined lethal mCRPC, incorporating 50% of pts with High-RS and yet balance the required sample size and number of pts to be screened enabling an adequately powered molecular classifier-based biomarker-enriched clinical trial. Citation Format: Manish Kohli, Liang Wang, Aik C. Tan, Muhammad Zaki Fadlullah, Anushka Shankar, Sumithra Mandrekar, Benjamin Haaland. Clinico-Genomic Risk Score-Based Biomarker Enrichment Clinical Trial Designs in Poor Prognosis Metastatic Castrate Resistant Prostate Cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B039.

Background In pediatric patients presenting after blunt trauma, the incidence of clinically significant cervical spine injury (CSI) is approximately 1%. Although multidetector CT (MDCT) is widely accepted for cervical spine clearance in adults, its utility in children remains uncertain. The purpose of this study is to evaluate the sensitivity of MDCT in identifying clinically significant CSI in pediatric patients, stratified by age groups: adolescents (12 years to 17 years) and children (0 years to 11 years). Methods We designed a national, multicenter, prospective observational study to assess the diagnostic performance of MDCT in detecting clinically significant CSI in pediatric trauma patients. Data are being collected from participating centers on imaging findings, clinical outcomes, and the presence of confirmed CSIs after blunt trauma. The analysis plan includes stratification by age group and calculation of sensitivity, specificity, and predictive values of MDCT for CSI. Results This abstract outlines the background, methodology, and analytical framework of the study. Data collection and analysis are ongoing. This study represents the largest known cohort of pediatric patients undergoing cervical spine imaging after blunt trauma and is the first prospective study of its kind focused exclusively on this population. Conclusions This study will provide critical data to inform guidelines for pediatric cervical spine clearance after blunt trauma. By evaluating the sensitivity of MDCT in detecting clinically significant CSI, the findings aim to support evidence-based imaging strategies and improve the safety and efficiency of pediatric trauma care.

Abstract Background Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect. Methods Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0–2) at 90 days. Recanalization, symptomatic intracranial hemorrhage (sICH), mortality, and the effect of M2 laterality, division occlusion and procedure time were assessed. Results About 1734 patients with M2 occlusions underwent either frontline aspiration (n = 711) or SR/combined (n = 958) thrombectomy between 2013 and 2024. PSM analysis favored aspiration for functional independence (49.9% vs 44.0%, OR 1.27 (1.03–1.57)), complete recanalization (61.2% vs 48.7%, OR 1.66 (1.34–2.05)), complete first pass effect (35.0% vs 27.6%, OR 1.42 (1.13–1.78)), and sICH (3.5% vs 6.2%, OR 0.55 (0.33–0.91)), with no difference in mortality. Frontline aspiration had significantly shorter procedural times (median 28 [IQR 15–49.5] vs 51 [IQR 35–78] minutes; p &lt; 0.001). For every minute increase in procedure time, the probability of functional independence decreased significantly (p &lt; 0.001) less with frontline aspiration (0.35%) compared to SR/combined (1.61%). Conclusion Frontline aspiration for M2 occlusions resulted in better clinical and angiographic outcomes compared to SRs. Future trials for MeVO with a focus on contact aspiration thrombectomy may succeed where recent trials have failed.

Background/Objectives: Postoperative opioid exposure after lumbar fusion remains a key clinical concern. Understanding which perioperative factors are associated with lower postoperative opioid use may help optimize recovery after minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF). This study aimed to determine if patients undergoing MIS-TLIF under spinal anesthesia (SA) showed lower postoperative opioid use compared to those undergoing MIS-TLIF under general anesthesia (GA). Methods: We retrospectively studied all adult patients (>18 years) undergoing 1- and contiguous 2-level MIS-TLIFs performed by a single surgeon. Patients undergoing the procedure under GA were compared to those undergoing the procedure under SA. Postoperative oral opioid use, up to 3 months post discharge, was collected. A 1:1 propensity score matching (PSM) protocol was implemented. Each outcome variable was initially assessed using univariate regression. Predictor variables with a p-value < 0.2 were included in the multivariate regression model. This was a retrospective, non-randomized study, and residual confounding cannot be excluded despite PSM. Results: The matched groups (n = 50 in each group) did not differ significantly depending on demographics or levels fused. Before regression, mean number of postoperative opioid prescriptions (p = 0.03), mean total operating room (OR) time in minutes (p < 0.01), and median length of stay (LOS) in days (p = 0.03) were significantly different. Multivariate regression showed that the GA group received 216.5 more total morphine milligram equivalents than the SA group (95% CI = 0.7–432.2, p = 0.049). The days of opioid use were higher in the GA group by 3.8 days (95% CI = 0.5 to 7.1, p = 0.025). On multivariate regression, LOS in hours was greater in the GA group by 14.1 h (p = 0.042). Conclusions: SA is an effective anesthetic modality for spinal surgery with the advantages of reduced postoperative opioid use, reduced OR time, and shorter LOS compared to GA.

ABSTRACT Introduction/Aims Scapular winging occurs as an abnormal protrusion of the scapula due to nerve injury, muscle weakness, bone, or joint pathology. The main muscular stabilizers of the scapula include the serratus anterior, trapezius, rhomboid major and minor, levator scapulae, and pectoralis minor. Needle electromyography (EMG) has historically been used as one of the primary diagnostic tests for evaluating this finding. However, sampling of these muscles can be technically difficult and carries risks for complications. Muscle ultrasound (MUS) can also reliably identify abnormalities in the muscles involved in scapular stabilization while offering the benefit of rapid side‐to‐side comparison and improved patient comfort. This study aims to highlight the concordance of ultrasound and EMG findings using our published MUS protocol in patients with scapular winging. Methods A retrospective analysis was performed of 13 patients who presented to an electrodiagnostic (EDX) laboratory with the referral diagnosis of “scapular winging” or “scapular dyskinesis.” All patients underwent MUS testing of scapular muscles according to a previously published protocol followed by EMG of muscles deemed relevant by the clinician. Results Seven patients were found to have a neurogenic cause of their scapular winging and in those patients, all had both EMG and MUS abnormalities. MUS was found to have a sensitivity of 87.5%, specificity of 95.7%, and individual muscle concordance with EMG of 90.6%. Discussion There is high concordance between EMG and MUS in patients with scapular winging. This combined with potential advantages of the MUS modality supports their concurrent use in patients with scapular winging.