Citations

Study Design: Case presentation. Objective: The interlaminar endoscopic lateral recess decompression (IE-LRD) represents a novel surgical alternative to consider in carefully selected cases, particularly when patients do not respond to conservative treatment. Background: Lumbar spinal stenosis (LSS) constitutes one of the most prevalent spinal conditions in the elderly population around the world. A myriad of causes have been elucidated, and although infrequent, vertebral compression fractures (VCF) may also cause LSS. Conservative treatment might be the first option; however, patients often require surgery. Methods: A 76-year-old woman with a medical history of dementia consulted for radicular pain in her left leg during the past 6 months, without any favorable response to conservative treatment. Neurological examination revealed a positive straight leg raising test on the left. A spine MRI revealed a VCF in L5, linked with spondylolisthesis (grade I) at L5–S1. An IE-LRD was planned, as the patient did not consent to a classical open surgery. The incision was placed over the inferior medial edge of the left L4 lamina. Following sequential dilatators, the working channel was located on the inferomedial edge of the left L4 lamina. Lateral fluoroscopy (LF) guided the entire procedure. During the procedure, laminotomy was extended cranially and caudally to ensure sufficient vertebral decompression. Results: After surgery, the patient was mobilized in the first 6 hours and discharged in the next 24 hours. Her lower back pain score improved significantly to 2–3, while her leg VAS pain improved to 0–1. After a follow-up for 18 months, the patient did not manifest complications or recurrences, and no additional treatment was carried out. Conclusion: (1) IE-LRD might be a useful and safe surgical procedure for the surgical management of LSS caused by VCF. (2) Consider this surgical alternative for elderly patients without a previous response to conservative medical treatment.

Abstract Background Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for the management of pediatric central nervous system (CNS) tumors. However, implementation remains concentrated to a relatively limited number of specialized centers with established clinical research infrastructure and sequencing expertise. Many pediatric neuro-oncology programs face substantial barriers to developing similar capabilities, limiting broader participation in and contribution to liquid biopsy research. Methods We describe the development of a pediatric CNS ctDNA program at a quaternary children's hospital with limited research infrastructure and genomic testing capabilities. Key elements include protocol development, Institutional Review Board approval, patient identification and enrollment, longitudinal blood and cerebrospinal fluid (CSF) collection workflows, specimen processing and storage procedures, and partnerships for molecular sequencing and analysis. Results Fifty-seven patients were enrolled over four years, resulting in collection of 417 longitudinal blood and cerebrospinal fluid samples. Standardized workflows for enrollment, specimen collection, processing, storage, and clinical annotation were successfully implemented. Strategic funding facilitated stability of a sample biorepository. Successful implementation required coordination among a multidisciplinary team spanning clinical care, research operations, laboratory sciences, and institutional administration. Conclusions Development of a pediatric CNS tumor liquid biopsy program is feasible at institutions without extensive pre-existing liquid biopsy infrastructure. Structural, operational and cultural barriers can be overcome by establishing standardized collection workflows, multidisciplinary collaboration, and external partnerships. Our experience provides a practical framework for other centers seeking to participate in pediatric CNS tumor liquid biopsy research.

To compare the 1-year risk of biliary/pancreatic adverse events among patients with obesity and type 2 diabetes treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus dipeptidyl peptidase-4 inhibitors (DPP-4i), and to directly compare tirzepatide with semaglutide. Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Global Collaborative Network. Adults with obesity and type 2 diabetes without prior biliary or pancreatic disease were included. Two prespecified comparisons were performed: GLP-1RA (semaglutide or tirzepatide) versus DPP-4i, and tirzepatide versus semaglutide. The primary outcome was incident cholelithiasis at 1 year. Secondary outcomes included cholecystitis, cholangitis, acute pancreatitis, and cholecystectomy. Hazard ratios (HRs) were estimated using Cox proportional hazards models. Results: After matching, 281,283 patients were included in each GLP-1RA and DPP-4i cohort, and 242,876 patients in each tirzepatide and semaglutide cohort. Compared with DPP-4i, GLP-1RA therapy was associated with lower risks of cholelithiasis (1.02% vs. 1.16%; HR 0.92, 95%CI 0.87–0.96), cholecystitis (HR 0.88, 95%CI 0.79–0.98), cholangitis (HR 0.46, 95%CI 0.36–0.58), acute pancreatitis (HR 0.68, 95%CI 0.61–0.76), and cholecystectomy (HR 0.51, 95%CI 0.38–0.69). In the head-to-head comparison, semaglutide was associated with higher risks of cholelithiasis (HR 1.11, 95%CI 1.05–1.18) and cholecystitis (HR 1.22, 95%CI 1.10–1.37) compared with tirzepatide, while risks of pancreatitis, cholangitis, and cholecystectomy did not differ significantly. Conclusions: In this large real-world study, GLP-1RA therapy was associated with lower risks of biliary and pancreatic events compared with DPP-4i. Tirzepatide demonstrated a modestly more favorable biliary safety profile than semaglutide, supporting the overall hepatobiliary safety of contemporary GLP-1-based therapies.

T cell exhaustion is often viewed as a terminal state marked by irreversible loss of function during chronic infection and cancer. However, the rapid recovery of antitumor activity in clinical responders after PD-1 blockade suggests that some exhausted T cells retain hidden functional potential. To explain this paradox, we present a theoretical framework that separates latent effector capacity from active effector function. Latent effector capacity represents a history-dependent state reflecting preserved epigenetic accessibility and regulatory readiness, distinct from ongoing gene expression. In this model, PD-1 signaling acts as a reversible mask that suppresses effector function without eliminating the underlying effector capacity. The framework explains preserved chromatin accessibility, rapid reinvigoration after checkpoint blockade, and variable therapeutic responses. By incorporating nonlinear maintenance and erosion of latent effector capacity, the model predicts a bistable system with a point of no return beyond which exhaustion becomes irreversible. These principles may guide development of mechanistically informed biomarkers and artificial intelligence models predicting response to PD-1 therapy.

Purpose The purpose of this study was to identify risk factors and evaluate clinical outcomes associated with incidental left common iliac vein compression on CT imaging. Methods This is a retrospective study that reviewed venous-phase abdomen and pelvis CT scans to identify patients with incidental extrinsic compression of the left common iliac vein due to an overlying right common iliac artery. A total of 726 patients were included (364 females, 362 males; mean patient age: 61.9 ± 15.9 years). Board-certified radiologists reviewed all CT scans. Significant left iliac vein compression was defined as >50% luminal narrowing. Results Significant iliac vein compression was identified in 114 (15.7%) patients and was more common in females (19.5%) versus males (11.9%) ( p < 0.01). Patients with iliac vein compression >50% had significantly lower BMI than those without compression (24.8 ± 6.2 vs 28.7 ± 7.2 kg/m 2 , p < 0.01). Patients with incidental left iliac vein compression had a higher rate of prior left lower extremity DVT ( p = 0.02). Conclusion Incidental left common iliac vein compression was present in approximately 16% of patients and was more frequent among females. Compression was associated with lower BMI and more than twice the rate of ipsilateral DVT, despite no prior diagnosis of MTS. These findings suggest that incidental iliac vein compression could have more clinical significance than previously recognized.

ABSTRACT Lipotoxic endoplasmic reticulum (ER) stress is a fundamental feature of metabolic dysfunction- associated steatohepatitis (MASH). ER stress activates adaptive signaling processes that aim to restore ER homeostasis. Yet, depending on the duration, magnitude, and cellular context, sustained ER stress becomes maladaptive and leads to cell death. The regulatory pathways that determine adaptive versus maladaptive ER stress outcomes remain incompletely understood. Here we integrated transcriptomic and chromatin-accessibility analyses in complementary models of proteotoxic and lipotoxic ER stress to identify previously unrecognized regulators of the ER stress response. These analyses identified the dual DNA- and RNA-binding protein AT-rich interaction domain 5A (ARID5A) as an ER stress-responsive gene. ARID5A protein was abundantly expressed in hepatocytes, and ARID5A mRNA and protein were upregulated in palmitate-induced lipotoxic ER stress across multiple hepatocyte models. Using complementary genetic and pharmacological approaches, we demonstrated that ARID5A induction was independent of IRE1α and ATF6α signaling and was attenuated by inhibition of the PERK pathway. To determine the functional relevance of ARID5A in MASH, we employed hepatocyte-directed AAV9-mediated ARID5A overexpression in mice fed a MASH-inducing diet. ARID5A overexpression attenuated steatohepatitis, inflammation, and fibrosis. Together, these findings identify ARID5A as a previously unrecognized PERK-dependent effector of the hepatocyte ER stress response and demonstrate that increasing hepatocyte ARID5A is protective in experimental MASH. This work provides a foundation for defining the mechanisms by which ARID5A regulates hepatocyte stress responses and MASH severity.

ABSTRACT Background There is a spectrum of clinical presentations after facial nerve injury, from complete facial paralysis (CFP) to facial synkinesis (FS). Objective To measure and compare how laypersons perceive faces with CFP versus FS. Methods Lay observers were presented with standardized videos of 24 individuals' faces: 8 with CFP, 8 with FS, and 8 nonparalyzed Controls performing common facial expressions. Observers were given a questionnaire and asked to rate the faces on varying subjective measurements of facial perception. Results Five hundred and fifty‐seven observers completed the survey. Observers viewed Control faces most favorably with higher perceived attractiveness and quality of life than CFP ( p < 0.01; p < 0.01) and FS ( p = 0.02; p < 0.01) faces. FS faces were rated more favorably than CFP faces ( p < 0.01). Conclusions There are measurable differences in how casual observers perceive faces with different subtypes of facial paralysis. Compared to nonparalyzed faces, both FS and CFP were viewed more negatively; however, CFP was perceived more negatively compared to FS. Level of Evidence N/A.

Abstract Comprehensive genomic profiling has expanded the ability to identify potentially actionable molecular alterations across cancers, but identification of an actionable finding does not ensure that a patient will receive a genomically matched therapy. Studies of precision-oncology programs and molecular tumor boards consistently demonstrate substantial attrition between treatment recommendation and treatment initiation. The reasons extend beyond molecular interpretation and include the timing of genomic profiling, clinical deterioration, geographic availability of biomarker-selected trials, insurance and financial barriers, and disparities in access to specialty cancer care. Importantly, these barriers arise after a potentially useful molecular finding has already been identified, creating a distinction between molecular actionability and practical treatment access. This commentary argues that the next implementation challenge for precision oncology is to make clinically meaningful genomic findings realistically actionable. Comprehensive genomic profiling should occur early enough to inform treatment planning; molecular tumor board recommendations should be linked to realistic treatment and trial opportunities; financial and insurance barriers should be anticipated when recommendations are made; and equity should be evaluated beyond access to testing to include receipt of genomically informed treatment. As genomic profiling becomes increasingly integrated into routine cancer care, precision oncology should be judged not only by its ability to identify therapeutic opportunities but also by whether patients can reach those opportunities while they remain clinically relevant.

Abstract Background GLP-1 receptor agonists reduce major adverse cardiovascular events among patients with diabetes, overweight, and obesity. Whether these benefits extend to patients undergoing aortic valve replacement (AVR) for severe aortic stenosis (AS) remains unknown. Thus, we investigated the association between GLP-1 receptor agonist treatment and cardiovascular outcomes after AVR. Methods Nationwide population-based cohort study including consecutive patients with severe AS undergoing TAVI or SAVR in Western Denmark between January, 2016 and April, 2022. Patients were followed until death, emigration, crossover, or end of follow up on May 12, 2026. Propensity score-matching was performed to balance confounding. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, or aortic valve reoperation. Secondary outcomes included all-cause mortality, heart failure hospitalization, aortic valve reoperation, with analyses accounting for the competing risk of death. Results Among 5259 eligible patients undergoing AVR, 292 propensity score-matched patients were included in the final analyses. During a mean follow up of 4.8±2.4 years, GLP-1 receptor agonist treatment was associated with a lower risk of the primary composite outcome compared with controls (HR 0.69, 95%CI 0.50-0.96, p=0.029). GLP-1 receptor agonist treatment was also associated with lower risk of all-cause mortality (HR 0.66, 95%CI 0.46-0.95, p=0.025). In competing risk analyses accounting for death, lower risks were observed for heart failure hospitalization (HR 0.67, 95%CI 0.48-0.93, p=0.018), and aortic valve reoperation (HR 0.69, 95%CI 0.49-0.98, p=0.037). Conclusion Treatment with GLP-1 receptor agonists was associated with lower risk of cardiovascular outcomes including mortality following AVR among patients with severe AS.