Citations

BACKGROUND: The activation and polarization of T cells play a crucial role in atherosclerosis and dictate athero-inflammation. The epigenetic enzyme EZH2 (enhancer of zeste homolog 2) mediates the H3K27me3 (trimethylation of histone H3 lysine 27) and is pivotal in controlling T cell responses. METHODS: To detail the role of T cell EZH2 in atherosclerosis, we used human carotid endarterectomy specimens to reveal plaque expression and geography of EZH2. Atherosclerosis-prone Apoe (apolipoprotein E)–deficient mice with CD (cluster of differentiation) 4 + or CD8 + T cell–specific Ezh2 deletion (Ezh2 cd4 -knockout [KO], Ezh2 cd8 -KO) were analyzed to unravel the role of T cell Ezh2 in atherosclerosis and T cell–associated immune status. RESULTS: EZH2 expression is elevated in advanced human atherosclerotic plaques and primarily expressed in the T cell nucleus, suggesting the importance of canonical EZH2 function in atherosclerosis. Ezh2 cd4 -KO, but not Ezh2 cd8 -KO, mice showed reduced atherosclerosis with fewer advanced plaques, which contained less collagen and macrophages, indicating that Ezh2 in CD4 + T cells drives atherosclerosis. In-depth analysis of CD4 + T cells of Ezh2 cd4 -KO mice revealed that absence of Ezh2 results in a type 2 immune response with increased Il-4 (interleukin 4) gene and protein expression in the aorta and lymphoid organs. In vitro, Ezh2 -deficient T cells polarized macrophages toward an anti-inflammatory phenotype. Single-cell RNA-sequencing of splenic T cells revealed that Ezh2 deficiency reduced naive, Ccl5 + (C-C motif chemokine ligand 5) and regulatory T cell populations and increased the frequencies of memory T cells and invariant natural killer T (iNKT) cells. Flow cytometric analysis identified a shift toward Th2 (type 2 T helper) effector CD4 + T cells in Ezh2 cd4 -KO mice and confirmed a profound increase in splenic iNKT cells with increased expression of Plzf (promyelocytic leukemia zinc finger), which is the characteristic marker of the iNKT2 subset. Likewise, Zbtb16 ([zinc finger and BTB domain containing 16], the Plzf-encoding gene) transcripts were elevated in the aorta of Ezh2 cd4 -KO mice, suggesting an accumulation of iNKT2 cells in the plaque. H3K27me3–chromatin immunoprecipitation followed by quantitative polymerase chain reaction showed that T cell–Ezh2 regulates the transcription of the Il-4 and Zbtb16 genes. CONCLUSIONS: Our study uncovers the importance of T cell EZH2 in human and mouse atherosclerosis. Inhibition of Ezh2 in CD4 + T cells drives type 2 immune responses, resulting in an accumulation of iNKT2 and Th2 cells, memory T cells and anti-inflammatory macrophages that limit the progression of atherosclerosis.

Background Brain arteriovenous malformations (AVMs) are abnormal connections between feeding arteries and draining veins, associated with significant risks of haemorrhage, seizures and other neurological deficits. Preoperative embolization is commonly used as an adjunct to microsurgical resection, with the aim of reducing intraoperative complications and improving outcomes. However, the efficacy and safety of this approach remain controversial. Methods This study is a subanalysis of the Multicenter International Study for Treatment of Brain AVMs consortium. We retrospectively analysed 486 patients with brain AVMs treated with microsurgical resection between January 2010 and December 2023. Patients were divided into two groups: those who underwent microsurgery alone (n=245) and those who received preoperative embolization, followed by microsurgery (n=241). Propensity score matching was employed, resulting in 288 matched patients (144 in each group). The primary outcomes were rates of complete AVM obliteration and functional outcomes (measured by the modified Rankin Scale (mRS)). Secondary outcomes included complication rates, mortality, hospital length of stay and postsurgical rupture. Results After matching, the complete obliteration rate was 97% with no significant difference between the microsurgery-only group and the preoperative embolization group (p=0.12). The proportion of patients with an mRS score of 0–2 at the last follow-up was similar in both groups (83% vs 84%; p=0.67). The median hospital stay was significantly longer for the embolisation group (9 days vs 7 days; p=0.017). Complication rates (24% vs 22%; p=0.57) and mortality rates (4.9% vs 2.1%; p=0.20) were comparable between the two groups. No significant differences were observed in postsurgical rupture, recurrence or retreatment rates. Conclusions In this large multicentre study, preoperative embolization did not significantly improve AVM obliteration rates, functional outcomes or reduce complications compared with microsurgery alone.

Abstract Background Incorporating image guidance into ion beam therapy is critical for minimizing beam range uncertainties and realizing the modality's potential. One promising avenue for image guidance is to capture transmission ion radiographs (iRads) before and/or during treatment. iRad image quality is typically maximized using a single‐event imaging system, which involves tracking individual ions, albeit the approach is generally not suited to clinical beam settings. An alternative faster and clinically compatible method is integrated mode imaging, where individual pencil beam data is acquired, rather than single ion data. To evaluate the usefulness of transmission ion imaging for image guidance, it is crucial to evaluate the image quality of integrated mode iRad systems. Purpose We report extensive image quality metrics of integrated mode carbon ion radiographs (cRads) and compare them with proton radiographs (pRads). Methods iRads were obtained at the Marburg Ion Beam Therapy Center using a plastic volumetric scintillator equipped with CCD cameras. The detector captures orthogonal views of the 3D energy deposition in the scintillator from individual pencil beams. Four phantoms were scanned using a field of view and a beam spacing of 1 mm. First, 9 tissue‐substitute inserts were used to evaluate water equivalent thickness (WET) accuracy. Radiographs of those inserts were reconstructed for beam spacings ranging from 1 to 7 mm to evaluate the impact of spacing on quantitative accuracy. For spatial resolution, custom 3D printed line pair (lp) modules ranging from 0.5 to 10 lp/cm were scanned. To evaluate low contrast detectability, a custom 3D printed low contrast module consisting of 20 holes with depths ranging from 1 to 8 mm and diameters from 1 to 10 mm was scanned. iRads of an anthropomorphic head phantom were also obtained. Results Spatial resolution and low contrast detection are systematically improved for cRads compared to pRads. Image resolution was 3.7 lp/cm for cRads and 1.7 lp/cm for pRads in the center of the field of view. Spatial resolution was found to vary with the object's location in the field of view. While pRads could mostly resolve low contrast holes of 10 mm in diameter, cRads could resolve holes of up in 4 mm diameter. WET accuracy is similar for both ion species, with a root mean squared error of approximately 1 mm. WET accuracy was stable (maximum of 0.1 mm increase) across beam spacings, although important under‐sampling artifacts were observed for iRads reconstructed using large beam spacings, especially for cRads. iRads of the anthropomorphic head phantom showed improved apparent contrast using cRads, especially to identify bony structures. Conclusions This work is the first investigation of image quality metrics such as spatial resolution and low contrast detectability for integrated mode cRads, with a full comparison with pRads. Enhanced image quality is obtained with cRads compared to pRads, although pRads still maintain high WET accuracy and deliver image quality within acceptable bounds.

OBJECTIVE Tobacco smoking is among the factors known to significantly augment the risk of untreated intracranial aneurysm (IA) growth and rupture. Smoking appears to have a variable effect on different endovascular treatment modalities. The impact of smoking on the safety, efficacy, and outcomes of Woven EndoBridge (WEB) device use for wide-neck IAs has not been evaluated. This study aimed to investigate the outcomes of WEB devices by smoking status. METHODS A retrospective multicenter analysis was conducted on the data of patients from 36 sites worldwide treated with the WEB device for intracranial saccular aneurysms. Patients were stratified based on smoking status (current, former, and never smokers). The Student t-test and chi-square test were performed for continuous and categorical variables, respectively. Multivariable logistic regression was used to adjust for confounders. RESULTS Of 1376 patients with available smoking status, 504 were current smokers, 358 were former smokers, and 514 were never smokers. Upon adjusting for significant confounders, no association was found between smoking and recurrence outcomes (OR 1.39, 95% CI 0.69–2.80; p = 0.36), thromboembolic and hemorrhagic complications, and mortality among IAs treated with the WEB device. There was no statistically significant difference in outcomes between former and never smokers (OR 1.23, 95% CI 0.70–2.18; p = 0.46). The location of aneurysms differed between smoking groups, with former smokers having more anterior circulation aneurysms compared with current and never smokers (99.0% vs 96.9% vs 95.3%; p = 0.01). In terms of clinical symptoms, headache and dizziness were more common in the never smokers compared with current and former smokers (13.9% vs 8.9% vs 7.7%, p = 0.01). CONCLUSIONS This large-scale study suggests no significant correlation between smoking and the recurrence of IAs treated with the WEB device. Biological studies are warranted to better understand the biological impact of smoking on the growth and rupture of treated IAs.

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT. Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75–100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (modified Rankin Scale (mRS), 0–2). Secondary outcomes included excellent functional outcome at 90 days (mRS, 0–1), mortality, and day 1 post-MT National Institutes of Health Stroke Scale (NIHSS) score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH). Results: Among 1354 patients, 150 were on pre-stroke low-dose aspirin. After applying inverse probability of treatment weighting (IPTW), aspirin use was associated with significantly better functional outcomes (mRS, 0–2: odds ratio (OR) = 1.89, 95% confidence interval (CI) = 1.14 to 3.12) and lower 90-day mortality (OR = 0.56, 95% CI = 0.32 to 1.00). The aspirin group had lower NIHSS scores on day 1 (β = −1.5, 95% CI = −2.8 to −0.27). The sICH rate was not significantly different between the groups (OR = 0.92, 95% CI = 0.60 to 1.43). Conclusions: Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.

Objectives: Every year, around 300 million surgeries are conducted worldwide, with an estimated 4.2 million deaths occurring within 30 days after surgery. Adequate patient education is crucial, but often falls short due to the stress patients experience before surgery. Large language models (LLMs) can significantly enhance this process by delivering thorough information and addressing patient concerns that might otherwise go unnoticed. Material and methods: This cross-sectional study evaluated Chat Generative Pretrained Transformer-4o’s audio-based responses to frequently asked questions (FAQs) regarding six general surgical procedures. Three experienced surgeons and two senior residents formulated seven general and three procedure-specific FAQs for both preoperative and postoperative situations, covering six surgical scenarios (major: pancreatic head resection, rectal resection, total gastrectomy; minor: cholecystectomy, Lichtenstein procedure, hemithyroidectomy). In total, 120 audio responses were generated, transcribed, and assessed by 11 surgeons from 6 different German university hospitals. Results: ChatGPT-4o demonstrated strong performance, achieving an average score of 4.12/5 for accuracy, 4.46/5 for relevance, and 0.22/5 for potential harm across 120 questions. Postoperative responses surpassed preoperative ones in both accuracy and relevance, while also exhibiting lower potential for harm. Additionally, responses related to minor surgeries were minimal, but significantly more accurate compared to those for major surgeries. Conclusions: This study underscores GPT-4o’s potential to enhance patient education both before and after surgery by delivering accurate and relevant responses to FAQs about various surgical procedures. Responses regarding the postoperative course proved to be more accurate and less harmful than those addressing preoperative ones. Although a few responses carried moderate risks, the overall performance was robust, indicating GPT-4o’s value in patient education. The study suggests the development of hospital-specific applications or the integration of GPT-4o into interactive robotic systems to provide patients with reliable, immediate answers, thereby improving patient satisfaction and informed decision-making.