Citations

ABSTRACT Introduction Changes in peripheral eosinophils follow endoscopic sinus surgery (ESS) in chronic rhinosinusitis with nasal polyps (CRSwNP), with and without aspirin sensitivity. Cytometry by time‐of‐flight (CyTOF) identifies more immune cell subsets than conventional assays or clinical testing. We hypothesized that ESS‐associated changes in peripheral immune cell subsets differ between aspirin‐tolerant (AT)‐CRSwNP and aspirin‐exacerbated respiratory disease (AERD) as measured by CyTOF. Methods Pre‐ and post‐ESS peripheral blood from patients with CRSwNP ( n = 13) or with AERD ( n = 15) was analyzed for immune cell populations using a 37‐marker CyTOF panel. CITRUS analysis identified cell clusters most predictive of patient group or sample timepoint. Results In the combined cohort of 28 patients, circulating CD4 + naïve T cells and CD194 + neutrophils increased after ESS, while eosinophils decreased. When stratified by disease, CD4 + naïve T cells increased in both AERD and CRSwNP post‐ESS; however, eosinophils decreased after ESS only in CRSwNP. Neutrophil subsets showed a mixed response in both patient groups after ESS. Dendritic cells increased in CRSwNP but not in AERD after ESS. Individual timepoint analyses showed more CD141 + monocyte‐derived DCs (moDCs) in CRSwNP than in AERD pre‐ and post‐ESS. Pre‐ESS, both CD185 + and CD194 + neutrophils were higher in AERD compared to CRSwNP. Conclusion CD141 + moDCs were more prevalent in CRSwNP versus AERD, both before and after ESS. Naïve CD4 + T cells increased, and neutrophil subsets changed in all groups after ESS, but eosinophils decreased only in CRSwNP. Our study points to possible systemic immune effects of ESS and candidate immune signatures in CRSwNP and AERD.

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.

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 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.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCAs) and angina with nonobstructive coronary arteries (ANOCAs) present diagnostic and therapeutic challenges. We assessed the frequency of coronary microvascular disease (CMD) and its subtypes in MINOCA compared with ANOCA and evaluated long-term cardiovascular outcomes. METHODS: Patients with nonobstructive coronary arteries undergoing invasive coronary function testing from 2012 to 2022 were prospectively enrolled and retrospectively classified as MINOCA or ANOCA (reference group). Myocardial infarction due to atherothrombosis, myocarditis, and Takotsubo syndrome were excluded. Invasive provocation testing was performed. CMD was classified as endothelium-independent (coronary flow reserve <2.5 with adenosine) and endothelium-dependent (<50% increase in coronary blood flow with acetylcholine). Major adverse cardiovascular events (cardiac death, nonfatal myocardial infarction, heart failure hospitalization, urgent revascularization, stroke) were recorded over 8 years. RESULTS: Of 622 patients, 73 (12%) had MINOCA (69% female, median age 56 years) and 549 (88%) ANOCA (72% female, median age 53 years). CMD was common in both groups (71% versus 64%; P =0.271), while endothelium-independent CMD was more frequent in MINOCA (41% versus 21%; P <0.001). Over a median follow-up of 4.5 years, major adverse cardiovascular events occurred more often in MINOCA (40% versus 11%; adjusted hazard ratio, 2.4; P =0.001). CMD predicted higher major adverse cardiovascular events in both MINOCA (hazard ratio, 3.6 [95% CI, 1.1–12.0]; P =0.038) and ANOCA (hazard ratio, 7.9 [95% CI, 2.9–21.8]; P <0.001). CONCLUSIONS: CMD is common in both MINOCA and ANOCA. The higher prevalence of endothelium-independent CMD in MINOCA suggests a potential mechanistic role in infarction. Patients with MINOCA have a worse prognosis than ANOCA, particularly when CMD is present.

Abstract Immune cell function is tightly coupled to cellular metabolism, with glycolysis, oxidative phosphorylation, and amino acid and lipid metabolism governing activation, differentiation, survival, and effector responses. In rheumatoid arthritis (RA), an autoimmune disease characterized by destructive joint inflammation, metabolic checkpoints have emerged as critical regulators of immune-cell behavior and drivers of tissue pathology. RA CD4+ T cells undergo profound metabolic reprogramming: glycolysis is suppressed, and glucose is redirected into the pentose phosphate pathway, resulting in NADPH accumulation, reduced ROS levels, and a highly reductive intracellular environment. Concurrent defects in mitochondrial DNA repair and electron transport chain function compromise mitochondrial fitness, leading to NAD+ depletion, altered tricarboxylic acid cycle activity, and metabolic exhaustion. The resulting accumulation of citrate and acetyl-CoA promotes lipogenesis and protein acetylation, driving membrane remodeling, tissue invasiveness, and proinflammatory effector functions. Depletion of oxaloacetate and aspartate limits NAD+ regeneration, inducing endoplasmic reticulum expansion and enhanced tumor necrosis factor production. Defective lysosomal coordination of AMPK and mTORC1 signaling uncouples energy sensing from anabolic programs, enabling cellular activation and proliferation despite metabolic insufficiency. Macrophage fate and function are similarly shaped by metabolic state. In synovial macrophages, GLUD1-dependent glutamine oxidation sustains mitochondrial respiration and ATP production, enabling survival under nutrient-deprived conditions while promoting antigen presentation. Conversely, metabolic stress in MerTK+ macrophages activates the NAD+ hydrolase SARM1, triggering NAD+ depletion, mitochondrial collapse, and PANoptotic cell death. Together, these findings identify NAD+ availability, mitochondrial fitness, and organelle-based signaling as central metabolic gatekeepers linking bioenergetic stress to immune-cell dysfunction and chronic inflammation in RA.