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OBJECTIVE The objective was to evaluate the trajectories of hematoma resolution and functional improvement after middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH), model the temporal pattern of cSDH resolution, and identify factors associated with favorable outcomes. METHODS This real-world multicenter retrospective study included cSDH patients treated with MMAE at 24 centers between 2019 and 2024. Hematoma thickness was measured at baseline and at follow-up intervals (1–4 weeks, 1–3 months, 3–6 months, 6–12 months, and > 12 months after embolization). Resolution patterns were modeled using exponential decay functions. Modified Rankin Scale (mRS) scores assessed functional outcomes. Good functional outcome was defined as mRS score ≤ 2. Resolution patterns were modeled using exponential decay functions to estimate time to 50% and 80% reduction. Patients were categorized as complete resolution (≥ 99%) or by quartile of the remaining distribution (substantial [73%–98%], moderate [53%–73%], partial [27%–53%], minimal [< 27%]). The primary outcome was good functional status (mRS score ≤ 2). RESULTS The authors analyzed a total of 1781 patients with 2295 cSDHs who underwent MMAE. The mean ± SD age was 72.8 ± 12.4 years and 68.1% of patients were male. The initial mean hematoma thickness was 15.31 ± 6.53 mm, decreasing to 5.24 ± 5.91 mm at final follow-up (mean reduction 64.3% ± 42.1%). Resolution followed an exponential decay pattern, with an estimated time to 50% reduction of 1.8 months and to 80% reduction of 8.9 months. Complete resolution occurred in 1031 of 2224 patients (46.4%) with complete follow-up. The median (IQR) mRS score improved from 1 (0–3) at baseline to 0 (0–2) at > 12 months. Good functional outcomes were more common in patients with complete versus minimal resolution (68.9% vs 35.0%, p < 0.001). Achieving ≥ 73% resolution within 90 days was associated with better outcomes (good outcome in 76.9% of those with ≥ 73% resolution vs 67.3% in those without, p < 0.001). Neurological deterioration was the strongest predictor of lack of good outcome (23.7% in patients with neurological deterioration vs 82.4% without, p < 0.001). CONCLUSIONS After MMAE for cSDH, reduction in hematoma thickness follows a predictable exponential decay pattern. Greater extent (≥ 80%) and faster timing (within 90 days) of resolution are valuable prognostic indicators. Functional outcomes improve progressively through 6–12 months after the procedure. The relationship between resolution extent and functional outcomes provides quantitative benchmarks for evaluating treatment response.

Over the past three decades, the emergence of recombinant antibodies has positioned them as the fastest-growing class of therapeutic proteins and as well as crucial reagents for both diagnostics and specific research applications. The industrial production of most therapeutic antibodies currently relies on mammalian cell lines, primarily Chinese Hamster Ovary (CHO) cells, which remain the gold standard in biopharmaceutical manufacturing due to their exceptionally high production yields, robustness, regulatory acceptance, and consistent product quality. Nevertheless, new approaches using specifically adapted expression systems are emerging. These new host organisms enable the production of antibodies with posttranslational modifications that closely resemble those found in the human system, without the need for animal-derived source materials. For diagnostic and research purposes, a broad range of production systems has been developed. These include Gram-negative and Gram-positive bacteria, yeasts, filamentous fungi, insect cell lines, and transgenic plants. Additionally, smaller single domain antibodies and bispecific fragments that do not require glycosylation can be successfully produced in bacteria for therapeutic applications. Some of these molecules have already been approved by regulatory authorities in the European Union and the United States, and several more are currently in clinical trials. This review therefore focuses on the broad and evolving landscape of recombinant antibody production systems and their applicability across various fields.

ABSTRACT Background Anemia is an established marker of cardiovascular disease severity and risk which leads to elevations in resting myocardial blood flow (MBF) and impaired myocardial flow reserve (MFR) in patients without obstructive coronary artery disease (CAD). Anemia can potentially be detected opportunistically from blood pool density changes on computed tomography (CT) imaging. Objectives We evaluated relationships between chamber density measurements with hemoglobin, positron emission tomography (PET) findings, and cardiovascular events. Methods We included 33460 patients from 13 sites in the REFINE-PET who underwent PET and 24368 patients undergoing lung cancer screening chest CT. A deep learning model segmented cardiac chambers from CT images, then quantified chamber density. We evaluated the relationship between chamber density measures with resting MBF and MFR, as well as associations with death or myocardial infarction (MI). Results We included a total of 57,828 patients. A higher density in myocardium compared to left ventricle blood pool was associated with reduced MFR (adjusted odds ratio 3.02 per SD increase, 95% confidence interval[CI] 2.72 – 3.38) and an increased risk of death or MI in (adjusted hazard ratio[HR] 1.38 per SD increase, 95% CI 1.26-1.51). Having myocardial density higher than blood pool density was also associated with cardiovascular death in patients undergoing low-dose chest CT (adjusted HR 1.73, 95% CI 1.20-2.52). Conclusions In a large multimodality dataset, lower cardiac chamber density is associated with impaired MFR and independently associated with cardiovascular events. These biomarkers can be automatically extracted from CT to provide physiologic insights and potentially guide patient care. CONDENSED ABSTRACT Anemia is an important marker of cardiovascular disease severity and predictor of cardiovascular events. We utilized deep learning to measure cardiac chamber density on computed tomography imaging as a surrogate for anemia in 57,828 patients from two large multicenter studies. A higher density in myocardium compared to left ventricle blood pool was associated with reduced MFR and an increased risk of death or MI in patients undergoing positron emission tomography, and an increased risk of cardiovascular death in patients undergoing low-dose computed tomography. These biomarkers can provide additionally physiologic insights which could be used to guide patient care.

Expert consensus recommendations from 21 academic centers were established for appropriate radiography utilization at 12 potentially low-yield anatomic sites through a multidisciplinary process endorsed by six major American medical societies.

Abstract INTRODUCTION Research into cognitive dispersion – a cognitive process score measuring the intra‐individual variability (IIV) across a single testing session – suggests utility in neurodegenerative populations. Given widespread deficits observed in sporadic early‐onset Alzheimer's disease (EOAD), however, it is unclear if examining cognitive dispersion shows benefit in this condition. METHODS A total of 309 participants (188 amyloid‐positive EOAD, 43 amyloid‐negative early‐onset dementia [EOnonAD], 78 cognitively normal [CN]) completed neuropsychological testing twice over 12 months. Dispersion‐related differences among groups were assessed, as was cognitive dispersion's capacity to predict domain‐specific cognitive trajectories, and its convergence with imaging biomarkers. RESULTS EOAD participants displayed higher cognitive dispersion than EOnonAD participants, and associations with EOAD‐specific biomarkers. Additionally, cognitive dispersion was associated with 12‐month reliable change across several cognitive domains. DISCUSSION These preliminary results examine cognitive dispersion in sporadic EOAD. When used with baseline cognitive performance, cognitive dispersion measures may enrich future clinical trials in EOAD by enhancing treatment monitoring over time.

Abstract Introduction Sedation is routinely administered to facilitate comfort and tolerance of life support for critically ill adults dependent on invasive mechanical ventilation. Isoflurane, a widely used anesthetic during surgery, has properties that may also benefit ICU patients requiring continuous sedation. However, efficacy as a sedative and safety in this population is not well established. Methods We conducted two identically designed multicenter randomized trials, INSPIRE ICU1 and INSPIRE ICU2, at hospitals across the US. Ventilator-dependent adults were randomly assigned in a 1.5:1 ratio to receive either inhaled isoflurane or intravenous propofol as the first-line sedative for up to 48 ± 6 hours, targeting a sedation depth between Richmond agitation-sedation scale (RASS) -1 (drowsy) to -4 (responsive only to physical stimuli). Isoflurane was administered via an anesthetic conserving device (Sedaconda ACD-S). In both arms, opioids were permitted at the lowest dose required to achieve freedom from pain. The primary outcome was the percentage of time at target sedation level, assessed as a noninferiority outcome with pre-specified margin of 15%. Secondary outcomes included opioid exposure, wake-up time after end of treatment, time to extubation, and proportion of time with spontaneous breathing effort. Results A total of 470 combined participants were included in the two trials. In each trial, 142 patients were randomly assigned to isoflurane and 93 to propofol. In INSPIRE ICU1, percentage of time within target sedation depth was 77.1 [53.2, 89.9] % with isoflurane and 80.9 [58.2, 96.4] % with propofol (difference -1.5 [-8.9, &gt;99] %; p &lt; 0.01 for noninferiority). In INSPIRE ICU2, percentage of time within target sedation depth was 72.6 [66.4, 78.9] % with isoflurane and 74.5 [67.5, 81.5] % with propofol (difference -1.9 [-9.4, &gt;99] %; p &lt; 0.01 for noninferiority). In both trials, patients assigned to isoflurane received significantly less opioid, measured as fentanyl equivalents, during the treatment period. In INSPIRE ICU2, participants receiving isoflurane were significantly likelier to exhibit spontaneous breathing efforts, but this finding was not replicated in INSPIRE ICU1. There were no significant differences in time to wake-up or time to extubation between groups in either trial. No episodes of malignant hyperthermia or propofol infusion syndrome were reported. Adverse events were comparable in type and frequency between groups. Conclusions In two US multicenter trials, isoflurane was noninferior to propofol for maintaining target sedation depth in adults undergoing invasive ventilation, and was associated with significantly lower opioid exposure. (NCT05327296, NCT05312385) This abstract is funded by: Sedana Medical

Abstract Rationale Teaching invasive bedside procedures is a core responsibility of critical care physicians, yet few validated tools exist to evaluate teaching effectiveness in this high-stakes environment. Building on prior qualitative work identifying key traits and behaviors of effective IBP teachers, we aimed to develop and validate the Invasive Bedside Procedure Teacher Effectiveness Scale (IBP-TES) to advance assessment and faculty development in procedural education. Methods This multicenter validation study recruited internal medicine residents and PCCM fellows from two academic institutions (Oregon Health & Science University (OHSU) and Mayo Clinic) in which each learner reviewed two standardized videos of simulated ultrasound-guided central venous catheter insertions supervised by critical care physicians. Learners rated supervising teachers using the eight-item IBP-TES, derived from prior qualitative themes of effective procedural teaching. Factor analysis using generalized estimating equations accounted for repeated measures, and orthogonal rotation was applied for factor extraction. The number of factors retained was determined using the minimal proportion criterion and visual inspection of the scree plot. Cronbach’s α assessed internal consistency reliability. Analyses were performed in SAS v9.4. Results Thirty-eight learners (63% OHSU, 37% Mayo Clinic) completed 76 IBP-TES evaluations of supervising physicians. Factor analysis identified two underlying domains accounting for most of the variance: (1) Procedural Teaching Behaviors—pre-briefing, communication, feedback, environmental control, and procedural expertise (Cronbach’s α = 0.80); and (2) Interpersonal Traits—calmness, adaptability, and learner autonomy (α = 0.72). Overall reliability was strong (α = 0.80), and findings were consistent in sensitivity analyses unadjusted for repeated measures. These domains collectively reflect that effective IBP supervision integrates both structured teaching behaviors and interpersonal qualities that foster learner engagement and safety. No significant associations were observed between IBP-TES scores and learner demographics or postgraduate year. Conclusions The IBP-TES demonstrated strong internal consistency and a reproducible two-factor structure encompassing procedural teaching behaviors and interpersonal traits. This validated tool provides a structured framework for assessing procedural teaching effectiveness and guiding faculty development. Future work will evaluate its use in real-world ICU settings to further improve procedural supervision and patient safety. This abstract is funded by: None

Abstract Background Regulator of G protein signaling (RGS)2 terminates bronchoconstrictive Gaq signaling, and reductions in RGS2 expression associate with a hypercontractility phenotype. RGS2 promoter variants rs2746071 and rs2746072 are hypofunctional in gene reporter assays, and individuals with severe asthma homozygous for these two RGS2 variants experience higher asthma exacerbation rates. Whether these RGS2 promoter variants directly cause a hypercontractile human airway smooth muscle (HASM) phenotype is unknown. Methods We used the hTERT immortalized HASM cell line, derived from a human non-asthmatic donor. RGS2expression was reduced with siRNA (150nM anti-RGS2 vs. control siRNA) or through CRISPR transformation (Synthego©) to express the RGS2 promoter variants of interest, confirmed by Sanger sequencing. Gene and protein expression were quantified by qPCR and Western blotting. Intracellular Ca ++ flux and oscillation was measured with Fluo-8 (Abcam) with excitation/emission at 490/525 nm. HASM contractility to histamine treatment was measured using Traction Force Microscopy implemented in a 96-well plate format. Results Relative to cell lines with reference genotypes, HASM CRISPR transformed with the two RGS2 promoter variants exhibited a 41.8% (95% CI 28.6%--62.5%; p &lt; 0.0001) reduction in RGS2 relative expression by qPCR, and a 35% (95% CI 8.6%—85.7%; p = 0.024) reduction in protein expression by Western blot. Methacholine-triggered calcium flux was nearly 50% greater for the cell lines with the RGS2 homozygous variants vs. those with reference genotypes (p = 0.043) as was the contractile response to histamine. HASM with reference genotypes exposed to anti-RGS2 siRNA showed the same phenotype, consistent with a causal relationship between the variants and expression (decreased) and receptor function (enhanced). Similarly, HASM CRISPR-transformed with the two RGS2 promoter variants exhibited an up to 3-fold increase in contraction magnitude (represented by strain energy, reported in pJ) in response to histamine &gt;1uM (p &lt; 0.05) relative to cell lines with reference genotypes. Conclusion Two promoter single nucleotide polymorphisms substitutions are sufficient to reduce RGS2 expression and induce a hypercontractile HASM phenotype. This abstract is funded by: AAAAI Bridge Award, NHLBI R21