A model with multiple intracranial aneurysms: possible hemodynamic mechanisms of aneurysmal initiation, rupture and recurrence.

BACKGROUND: Hemodynamic factors play an important role in aneurysm initiation, growth, rupture, and recurrence, while the mechanism of the hemodynamic characteristics is still controversial. A unique model of multiple aneurysms (initiation, growth, rupture, and recurrence) is helpful to avoids the confounders and further explore the possible hemodynamic mechanisms of aneurysm in different states. METHODS: We present a model with multiple aneurysms, and including the states of initiation, growth, rupture, and recurrence, discuss the proposed mechanisms, and describe computational fluid dynamic model that was used to evaluate the likely hemodynamic effect of different states of the aneurysms. RESULTS: The hemodynamic analysis suggests that high flow impingement and high WSS distribution at normal parent artery was found before aneurysmal initiation. The WSS distribution and flow velocity were decreased in the new sac after aneurysmal growth. Low WSS was the risk hemodynamic factor for aneurysmal rupture. High flow concentration region on the neck plane after coil embolization still marked in recanalized aneurysm. CONCLUSIONS: Associations have been identified between high flow impingement and aneurysm recanalization, while low WSS is linked to the rupture of aneurysms. High flow concentration and high WSS distribution at normal artery associated with aneurysm initiation and growth, while after growth, the high-risk hemodynamics of aneurysm rupture was occurred, which is low WSS at aneurysm dome.

Evaluation of the EMBOPIPE flow diverter device: in vivo and in vitro experiments.

BACKGROUND: Although flow diverter device (FDD) has brought revolutionized advances in endovascular treatment of intracranial aneurysms, it also presents considerable drawbacks as well, as the innovation for novel device has never stopped. This preclinical research aims to evaluate the safety and efficacy of a newly developed FDD, the EMBOPIPE, through in vivo and in vitro experiments. METHODS: Aneurysms were induced in 20 New Zealand white rabbits which were randomized to three follow-up groups according to the time elapsed after EMBOPIPE implantation (28, 90, and 180 days). Additional EMBOPIPEs were implanted in the abdominal aorta to cover the renal artery in nine rabbits. Angiography was performed immediately after device placement in all groups. Aneurysm occlusion, patency of renal arteries, and pathological outcomes were assessed. For the in vitro experiments, we measured the thrombogenic potential of EMBOPIPEs (n = 5) compared with bare stents (n = 5) using the Chandler loop model. Evaluation indicators were the platelet counts, macroscopic observations and scanning electron microscopy. RESULTS: EMBOPIPEs were successfully deployed in 19 of 20 rabbit aneurysms (95.0%). The rates of complete or near-complete aneurysm occlusion were 73.3%, 83.3%, and 100% in the 28-, 90-, and 180-day groups, respectively. All renal arteries covered by EMBOPIPEs remained patent, and the mean difference in renal artery diameter before and after the device placement in the three groups was 0.07 mm, 0.10 mm, and 0.10 mm, respectively (p = 0.77). Renal pathology was normal in all cases. The pathological findings of the aneurysms were as follows: thickened and adequate neointimal coverage at the aneurysm neck, minimal inflammatory response, near-complete smooth muscle cell layer, and endothelialization along the device. In vitro experiments showed that the platelet counts were significantly higher in EMBOPIPE blood samples than in bare stent samples and that platelet adhesion to the device was lower in the EMBOPIPE stent struts compared with bare stent struts through macroscopic observations and scanning electron microscopy. CONCLUSIONS: The EMBOPIPE can achieve high rates of aneurysm occlusion while maintaining excellent branch artery patency. It exhibited wonderful pathological results. This novel device with phosphorylcholine surface modification could reduce platelet thrombus attached to the stent struts.

Left ventricular global longitudinal strain using a novel fully automated method: A head-to-head comparison with a manual layer-specific strain and establishment of normal reference ranges.

BACKGROUND: A novel automated method for measuring left ventricular (LV) global longitudinal strain (GLS) along the endocardium has advantages in terms of its rapid application and excellent reproducibility. However, it remains unclear whether the available normal range for conventional GLS using the manual method is applicable to the automated GLS method. This study aimed to compare automated GLS head-to-head with manual layer-specific GLS, and to identify whether a specialized normal reference range for automated GLS is needed and explore the main determinants. METHODS: In total, 1683 healthy volunteers (men, 43%; age, 18-80 years) were prospectively enrolled from 55 collaborating laboratories. LV GLS was measured using both manual layer-specific and automated methods. RESULTS: Automated GLS was higher than endocardial, mid-myocardial, and epicardial GLS. Women had a higher automated GLS than men. GLS had no significant age dependency in men, but first increased and then decreased with age in women. Accordingly, sex- and age-specific normal ranges for automated GLS were proposed. Moreover, GLS appeared to have different burdens in relation to dominant determinants between the sexes. GLS in men showed no dominant determinants; however, GLS in women correlated with age, body mass index, and heart rate. CONCLUSIONS: Using the novel automated method, was LV GLS higher than when using the manual GLS method. The normal ranges of automated GLS stratified according to sex and age were provided, with dominant determinants showing sex disparities that require full consideration in clinical practice.

Wound microenvironment self-adaptive all-in-one hydrogel for rapid healing of the diabetic wound.

The natural healing of diabetic wounds is collectively impeded by multiple factors, including hyperglycemia, angiogenesis disorders, acute oxidative stress, and prolonged inflammation. Although considerable effort has been devoted to solving these problems, the treatment of diabetic wounds remains a major clinical obstacle. In light of this, we developed an innovative wound microenvironment self-adaptive hydrogel to promote the healing of diabetic wounds. The hydrogel was constructed by the crosslinking of 3-aminobenzeneboronic acid (PBA)-modified gelatin (Gel) and polyvinyl alcohol (PVA) by borate ester bonds, which showed high responsiveness to glucose. Meanwhile, the liposomes that encapsulated metformin, L-arginine, and L(+)-ascorbic acid were incorporated into the hydrogel framework. The hydrogel@lipo composite demonstrated shape adaptability, glucose responsiveness, and all-in-one capability, thereby effectively improving the intricate microenvironment of diabetic wounds. In vitro and in vivo experiments demonstrated the ability of hydrogel@lipo to mitigate oxidative stress, enhance angiogenesis, and attenuate inflammatory responses. Consequently, the hydrogel@lipo could accelerate diabetic wound healing (within two weeks). The cumulative findings strongly suggest the potential of hydrogel@lipo as a highly promising therapeutic dressing for advancing diabetic wound recovery.

Risk of unruptured aneurysms in subarachnoid hemorrhage patients with multiple intracranial aneurysms: a multicenter, longitudinal, comparative study from China.

BACKGROUND: In aneurysmal subarachnoid hemorrhage patients with multiple intracranial aneurysms (aSAH-MIA patients), the risk of secondary unruptured intracranial aneurysms is inconsistent. This study aimed to explore the risk of unruptured aneurysms in Chinese aSAH-MIA patients. METHODS: The medical records and angiographic images of aSAH-MIA patients from eight cerebrovascular centers in China were retrospectively reviewed and analyzed. Patients with a single unruptured intracranial aneurysm (UIA) and no prior aSAH were used as controls. Propensity score matching (PSM) was employed to balance the differences in age, gender, aneurysm size, aneurysm site, and follow-up duration between the two groups. RESULTS: The study included 267 unruptured aneurysms from 204 aSAH-MIA patients and 769 single UIA. After PSM, 201 aneurysms were enrolled in the aSAH-MIA group and 201 aneurysms in the control group. The mean follow-up was 2.2 years. Thirty-four aneurysm instability events (28 growth and 6 rupture, 16.9%) occurred during follow-up in the aSAH-MIA group and 16 instability events (13 growth and 3 rupture, 8%) occurred in the control group. Risk factors for aneurysmal instability were aneurysm irregularity (OR 2.53; 95% CI 1.18 to 4.31), higher size ratio (OR 1.23; 95% CI 1.37 to 4.39), and middle cerebral artery location (OR 1.86; 95% CI 1.03 to 3.17). The risk of aneurysmal instability was substantially elevated in the aSAH-MIA group (HR 2.07; 95% CI 1.12 to 3.02). CONCLUSIONS: Unruptured aneurysms in Chinese aSAH-MIA patients exhibited higher risks of growth and rupture than in patients with a single UIA. Middle cerebral artery location, higher size ratio and irregular shape were associated with higher risk of growth or rupture.

Appraising the causal association among depression, anxiety and intracranial aneurysms: Evidence from genetic studies.

BACKGROUND: The risk of intracranial aneurysms (IAs) is increased in individuals with depression and anxiety. This indicates that depression and anxiety may contribute to the development of physical disorders. Herein, to investigate the association between genetic variants related to depression and anxiety and the risk of IA, two-sample Mendelian randomization was performed. METHODS: The genome-wide association study (GWAS) comprised genome-wide genotype data of 2248 clinically well-characterized patients with anxiety and 7992 ethnically matched controls from four European countries. Sex-specific summary-level outcome data were obtained from the GWAS of IA, including 23 cohorts with a total of 10,754 cases and 306,882 controls of European and East Asian ancestry. To improve validity, five varying Mendelian randomization techniques were used in the analysis, namely Mendelian randomization-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. RESULTS: The inverse variance weighted results indicated the causal effect of depression on IA (P = 0.03, OR = 1.32 [95 % CI, 1.03-1.70]) and unruptured IA (UIA) (P = 0.02, OR = 1.68 [95 % CI, 1.08-2.61]). However, the causal relationship between depression and subarachnoid hemorrhage (SAH) was not found (P = 0.16). We identified 43 anxiety-associated single-nucleotide polymorphisms as genetic instruments and found no causal relationship between anxiety and IA, UIA, and SAH. LIMITATIONS: Potential pleiotropy, possible weak instruments, and low statistical power limited our findings. CONCLUSION: Our MR study suggested a possible causal effect of depression on the increased risk of UIAs. Future research is required to investigate whether rational intervention in depression treatment can help to decrease the societal burden of IAs.

Pipeline Embolization Device for intracranial aneurysms presenting with mass effect: a large Chinese cohort.

BACKGROUND: Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding, relieves symptoms and improve the quality of life for patients. This study aimed to assess the safety and efficacy of Pipeline Embolization Device (PED, Covidien/Medtronic, Irvine, CA) treatment for intracranial aneurysms presenting with mass effect in real-world settings. METHODS: We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation. The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up (3-36 months). We conducted multivariate analysis to identify factors associated with mass effect relief. Subgroup analyses by aneurysm location, size and form were also performed. RESULTS: This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0% (162/218). The postoperative mass effect deterioration rate was 9.6% (21/218). During a median follow-up period of 8.4 months, the mass effect relief rate was 71.6% (156/218). Notably, immediate aneurysm occlusion following treatment was significantly associated with mass effect relief (OR 0.392, 95% CI, 0.170 to 0.907, p=0.029). Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms, while dense embolism impeded symptom relief in aneurysms<10 mm and saccular aneurysms. CONCLUSIONS: Our data confirmed the efficacy of PED in relieving mass effect. The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms. TRIAL REGISTRATION NUMBER: NCT03831672.

Pipeline embolization device versus Atlas stent assisted coiling for intracranial aneurysm treatment: a retrospective, propensity score matched study with a focus on midterm outcomes and hospital costs.

BACKGROUND: Stent assisted coiling (SAC) and flow diverters (FDs) are common endovascular treatments for wide necked cerebral aneurysms, but studies comparing the new generation Atlas SAC and FDs are scarce. We performed a propensity score matched (PSM) cohort study to compare the Atlas SAC and the pipeline embolization device (PED) for proximal internal carotid artery (ICA) aneurysms. METHODS: Consecutive ICA aneurysms treated at our institution with either the Atlas SAC or PED were studied. PSM was used to control for age, sex, smoking, hypertension, and hyperlipidemia, and the rupture status, maximal diameter, and neck size of the aneurysm (aneurysms >15 mm and non-saccular aneurysms were excluded). Midterm outcomes and hospital costs were compared between these two devices. RESULTS: A total of 309 patients with 316 ICA aneurysms were included. Following PSM, 178 aneurysms treated with the Atlas SAC and PED were matched (n=89 in each group). Aneurysms treated with the Atlas SAC required a slightly longer procedure time, but had lower hospital costs than those treated with the PED (115.2±24.6 vs 102.4±40.8 min, P=0.012; $27 650.2±$6961.4 vs $34 107.0±$3707.2, P<0.001). Atlas SAC and PED treatments showed equivalent aneurysm occlusion rates (89.9% vs 86.5%, P=0.486), complication rates (5.6% vs 11.2%, P=0.177), and a favorable functional outcome (96.6% vs 97.8%, P=1.0) at follow-up (8.2±3.0 vs 8.4±4.2 months, P=0.652). CONCLUSION: In this PSM study, midterm outcomes of the PED and Atlas SAC in the treatment of ICA aneurysms were similar. However, SAC required a longer operation time, and the PED may increase the economic cost of inpatients in Beijing, China.

Fermentation characteristics and microbial community composition of wet brewer's grains and corn stover mixed silage prepared with cellulase and lactic acid bacteria supplementation.

OBJECTIVE: The objective of this study was to investigate how cellulase or/and lactic acid bacteria (LAB) affected the fermentation characteristic and microbial community in wet brewer's grains (WBG) and corn stover (CS) mixed silage. METHODS: The WBG was mixed thoroughly with the CS at 7:3 (w/w). Four treatment groups were studied: i) CON, no additives; ii) CEL, added cellulase (120 U/g fresh matter [FM]), iii) LAB, added LAB (2×106 cfu/g FM), and iv) CLA, added cellulase (120 U/g FM) and LAB (2×106 cfu/g FM). RESULTS: All additive-treated groups showed higher fermentation quality over the 30 d ensiling period. As these groups exhibited higher (p<0.05) LAB counts and lactic acid (LA) content, along with lower pH value and ammonia-nitrogen (NH3-N) content than the control. Specifically, cellulase-treated groups (CEL and CLA) showed lower (p<0.05) neutral detergent fiber and acid detergent fiber contents than other groups. All additives increased the abundance of beneficial bacteria (Firmicutes, Lactiplantibacillus, and Limosilactobacillus) while they decreased abundance of Proteobacteria and microbial diversity as well. CONCLUSION: The combined application of cellulase and LAB could effectively improve the fermentation quality and microbial community of the WBG and CS mixed silage.

Redirecting Antigens by Engineered Photosynthetic Bacteria and Derived Outer Membrane Vesicles for Enhanced Cancer Immunotherapy.

Significant strides have been made in the development of cancer vaccines to combat malignant tumors. However, the natural immunosuppressive environment within tumors, known as the tumor microenvironment (TME), hampers the uptake and presentation of antigens by antigen-presenting cells (APCs) within the tumor itself. This limitation results in inadequate activation of immune responses against cancer. In contrast, immune cells in peritumoral tissue maintain their normal functions. In this context, we present an interesting approach to enhance cancer immunotherapy by utilizing engineered photosynthetic bacteria (PSB) and their outer membrane vesicles (OMVPSB) to capture and transport antigens to the outer regions of the tumor. We modified PSB with maleimide (PSB-MAL), which, when exposed to near-infrared (NIR) laser-mediated photothermal therapy (PTT), induced extensive cancer cell death and the release of tumor antigens. Subsequently, the NIR-phototactic PSB-MAL transported these tumor antigens to the peripheral regions of the tumor under NIR laser exposure. Even more intriguingly, PSB-MAL-derived OMVPSB-MAL effectively captured and delivered antigens to tumor-draining lymph nodes (TDLNs). This facilitated enhanced antigen presentation by mature and fully functional APCs in the TDLNs. This intricate communication network between PSB-MAL, the OMVPSB-MAL, and APCs promoted the efficient presentation of tumor antigens in the tumor periphery and TDLNs. Consequently, there was a notable increase in the infiltration of cytotoxic T lymphocytes (CTLs) into the tumor, triggering potent antitumor immune responses in both melanoma and breast cancer models. This cascade of events resulted in enhanced suppression of tumor metastasis and recurrence, underscoring the robust efficacy of our approach. Our interesting study, harnessing the potential of bacteria and OMVs to redirect tumor antigens for enhanced cancer immunotherapy, provides a promising path toward the development of personalized cancer vaccination strategies.

DNA methylation regulator-mediated modification patterns and risk of intracranial aneurysm: a multi-omics and epigenome-wide association study integrating machine learning, Mendelian randomization, eQTL and mQTL data.

BACKGROUND: Intracranial aneurysms (IAs) pose a significant and intricate challenge. Elucidating the interplay between DNA methylation and IA pathogenesis is paramount to identify potential biomarkers and therapeutic interventions. METHODS: We employed a comprehensive bioinformatics investigation of DNA methylation in IA, utilizing a transcriptomics-based methodology that encompassed 100 machine learning algorithms, genome-wide association studies (GWAS), Mendelian randomization (MR), and summary-data-based Mendelian randomization (SMR). Our sophisticated analytical strategy allowed for a systematic assessment of differentially methylated genes and their implications on the onset, progression, and rupture of IA. RESULTS: We identified DNA methylation-related genes (MRGs) and associated molecular pathways, and the MR and SMR analyses provided evidence for potential causal links between the observed DNA methylation events and IA predisposition. CONCLUSION: These insights not only augment our understanding of the molecular underpinnings of IA but also underscore potential novel biomarkers and therapeutic avenues. Although our study faces inherent limitations and hurdles, it represents a groundbreaking initiative in deciphering the intricate relationship between genetic, epigenetic, and environmental factors implicated in IA pathogenesis.

Catalytic Tunable Black Phosphorus/Ceria Nanozyme: A Versatile Oxidation Cycle Accelerator for Alleviating Cisplatin-Induced Acute Kidney Injury.

Oxidative stress is one leading inner cause of acute kidney injury (AKI) induced by cisplatin (DDP). Therefore, inhibiting oxidative stress is an important strategy to prevent the occurrence of DDP-induced AKI. Herein, a pH-selective "oxidative cycle accelerator" based on black phosphorus/ceria catalytic tunable nanozymes (BP@CeO2 -PEG) to effectively and persistently scavenge ROS for alleviating DDP-induced AKI is demonstrated. The BP@CeO2 -PEG nanozymes show pH-dependent multi-enzymatic activities, which are beneficial for selectively scavenging the excess ROS in renal tissues. In the neutral environment of kidneys, BP@CeO2 -PEG nanozymes can accelerate its catalytic "oxidative cycle" by increasing the ratio of Ce3+ /Ce4+ and improving the regeneration of ATP, effectively removing DDP-induced ROS. In addition, BP@CeO2 -PEG nanozymes can suppress the oxidative stress-triggered renal tubular epithelial cell apoptosis by inhibiting the PI3K/Akt signaling pathway. However, in the acidic environment of cancers, the presence of H+ inhibits the conversion of Ce4+ to Ce3+ , which in turn disrupts the oxidative cycle, resulting in the loss of ROS scavenging ability and ensuring the antitumor effect of DDP. Conclusively, the nanozymes offer an excellent antioxidant for alleviating cisplatin-induced AKI and extensive use in other ROS-based injuries.

Normal reference values for mitral annular plane systolic excursion by motion-mode and speckle tracking echocardiography: a prospective, multicentre, population-based study.

AIMS: Mitral annular plane systolic excursion (MAPSE) is a simple and reliable index for evaluating left ventricular (LV) systolic function, particularly in patients with poor image quality; however, the lack of reference values limits its widespread use. This study aimed to establish the normal ranges for MAPSE measured using motion-mode (M-mode) and two-dimensional speckle tracking echocardiography (2D-STE) and to explore its principal determinants. METHODS AND RESULTS: This multicentre, prospective, cross-sectional study included 1952 healthy participants [840 men (43%); age range, 18-80 years] from 55 centres. MAPSE was measured using M-mode echocardiography and 2D-STE. The results showed that women had a higher MAPSE than men and MAPSE decreased with age. The age- and sex-specific reference values for MAPSE were established for these two methods. Multiple linear regression analyses revealed that MAPSE on M-mode echocardiography correlated with age and MAPSE on 2D-STE with age, blood pressure (BP), heart rate, and LV volume. Moreover, MAPSE measured by 2D-STE correlated more strongly with global longitudinal strain compared with that measured using M-mode echocardiography. CONCLUSION: Normal MAPSE reference values were established based on age and sex. BP, heart rate, and LV volume are potential factors that influence MAPSE and should be considered in clinical practice. Normal values are useful for evaluating LV longitudinal systolic function, especially in patients with poor image quality, and may further facilitate the use of MAPSE in routine assessments.

A biodegradable hollow nanoagent enables a boosted chemodynamic therapy by simultaneous autophagy inhibition and macrophage reeducation.

Various therapeutic strategies, including chemotherapy, radiotherapy, photothermal therapy (PTT), and immunotherapy have been applied in cancer therapy. However, intrinsic or acquired therapeutic resistance is the main obstacle that attenuates the treatment effect of the therapeutic reagents used in these strategies. Studies have shown that autophagy and immunosuppressive tumor-associated macrophages (TAMs), as internal and external resistance mechanisms, would significantly compromise the effectiveness of cancer treatment. Therefore, selectively blocking the autophagy and repolarizing TAMs to anti-tumor phenotype (M1) will be effective for cancer treatments. Herein, an ambidextrous strategy that simultaneously inhibited autophagy and reeducated TAMs to promote anti-tumor therapy meditated by the iron-based nanocarriers was reported. The released Fe (II) ion reacted with the released artemisinin (ART) to produce ROS for chemodynamic therapy (CDT). The chloroquine (CQ) was used to inhibit autophagy in cancer cells and reset TAMs from the M2 phenotype to the M1 phenotype, eliminating the resistance of cancer cells and realizing an augmented therapeutic effect. This work provides a promising way for augmenting therapeutic efficiency by simultaneously interfering with two critical therapeutic resistance mechanisms.

Use of Tirofiban to Prevent Ischemic Events in Patients with CYP2C19 Loss-of-Function Alleles during Flow Diversion of Intracranial Aneurysm: A Multicenter Cohort Study.

To analyze the effect of tirofiban on ischemic events in CYP2C19 loss-of-function (LOF) allele carriers during pipeline embolization device (PED) implantation. Demographic information, imaging data, ischemic complications, CYP2C19 genotyping, and platelet function test results were collected from patients with PED-treated intracranial aneurysms at three centers. Multivariate logistic regression was used to analyze risk factors for ischemic events. Patients were grouped according to LOF alleles and antiplatelet drugs, the baseline information of LOF allele carriers and non-carriers were compared, and the efficacy of tirofiban was analyzed by comparing the incidence of ischemic events in each group. In total, 278 patients were included in the study, 24 of whom had an ischemic event. 157 (56.5%) patients carried the LOF allele and were more likely to develop resistance to clopidogrel (P < 0.001) and hypertension (P = 0.010). Multivariate logistic regression analysis revealed that the independent risk factors for ischemic events were age of > 55 years (OR = 3.308, P = 0.028), LOF alleles (OR = 3.960, P = 0.036), and clopidogrel nonresponsiveness (OR = 3.301, P = 0.014). For LOF allele carriers, prophylactic use of tirofiban after PED implantation helped to reduce ischemic events (4.3% vs. 16.4%, P = 0.039). This study supports CYP2C19 genotyping before flow diversion because LOF alleles increase the risk of ischemic events. Prophylactic use of tirofiban may help reduce ischemic events in LOF allele carriers.

RNA-cleaving DNAzymes for accurate biosensing and gene therapy.

RNA-cleaving DNAzymes, which are single-stranded catalytic DNA, have attracted considerable attention in bioanalysis and biomedical applications because of their high stability, high catalytic activity, easy synthesis, easy functionalization, and modification. By incorporating these DNAzymes with amplification systems, the sensing platforms can be used to detect a series of targets with high sensitivity and selectivity. In addition, these DNAyzmes possess therapeutic potential by cutting the mRNA in cells and viruses to regulate the expression of the corresponding proteins. This review systematically summarizes the applications of RNA-cleaving DNAzymes in recent years, explaining the uniqueness and superiority of RNA-cleaving DNAzymes in biosensing and gene therapy. Finally, this review extends the discussion to the challenges and perspectives of applying RNA-cleaving DNAzyme as a diagnostic and therapeutic agent. This review provides the researchers with valuable suggestions and promotes the development of DNAzymes for accurate analysis, early diagnosis, and effective therapy in medicine and their broader applications beyond biomedicine.

Learning curve in pipeline embolization device: results from the pipeline embolization device in China post-market multicentre registry study.

BACKGROUND: Intracranial aneurysms pose a significant health issue, affecting 3-5% of the adult population. The pipeline embolization device (PED) has emerged as a promising treatment for these lesions. This study aimed to investigate the impact of operator experience on complication and poor outcome rates, as well as the learning curve for PED. METHODS: A total of 217 patients were consecutively enroled from four eligible centres and divided into three groups based on the number of procedures performed: group 1 (first 10 procedures), group 2 (11-20 procedures), and group 3(>20 procedures). Major complications include operation-related ischaemic or haemorrhagic events and mass effect deterioration. Poor outcome was defined as a modified Rankin Scale score greater than 2 at discharge. Cumulative summation (CUSUM) analysis was generated to assess the learning curve according to major complications and poor outcome. RESULTS: The study found that major complications and poor outcomes occurred in 5.1% and 2.3% of cases, respectively. The rate of major complications decreased from 10.0% in group 1 to 2.9% in group 3 ( P =0.053), while the rate of poor outcomes decreased from 7.5% in group 1 to 0.7% in group 3 ( P =0.015). Multivariable regression analysis adjusted for covariates showed that operator experience was associated with a lower rate of poor outcomes ( P =0.034). CUSUM analysis demonstrated that the learning curve for avoiding major complications and poor outcomes required 27 (mean=13) and 40 (mean=20) cases, respectively. CONCLUSIONS: These findings suggest that PED treatment requires a learning curve of 40 cases to achieve reproducibility regarding complications and functional results. Additionally, major complications and poor outcomes significantly decreases after the first 20 procedures. CUSUM analysis can serve as a useful tool for monitoring and assessing surgical performance.

Could statin improve outcomes after pipeline embolization for intracranial aneurysms in a real-world setting?

Background: Several pharmacological pathways have revealed statin to have a positive role in patients with for intracranial aneurysms. However, prior studies regarding the association between statin use and patients' outcomes after pipeline embolization device (PED) treatment were not completely supportive. Objectives: To investigate whether statin medication following PED treatment would improve the outcomes of intracranial aneurysm patients in a real-world setting. Design: A retrospective multicenter cohort study. Methods: Patients were selected from the PLUS registry study conducted from November 2014 to October 2019 across 14 centers in China. The population was divided into two groups: those who received statin medication after the PED treatment and those who did not receive statin medication after PED treatment. Study outcomes included angiographic evaluation of aneurysm occlusion, parent arteries stenosis, ischemic and hemorrhage complications, all-cause mortality, neurologic mortality, and functional outcome. Results: 1087 patients with 1168 intracranial aneurysms were eligible; 232 patients were in the statin user group and the other 855 were in the non-statin user group. For the statin user group versus the non-statin user group, no significant difference was found for the primary outcomes of complete occlusion of aneurysm (82.4% versus 84.2%; p = 0.697). Of the secondary outcomes, none had a significant difference including stenosis of parent arteries ≥ 50% (1.4% versus 2.3%; p = 0.739), total subarachnoid hemorrhage (0.9% versus 2.5%; p = 0.215), all-cause mortality (0.0% versus 1.9%; p = 0.204), neurologic mortality (0.0% versus 1.6%; p = 0.280), excellent (95.5% versus 97.2%; p = 0.877), and favorable (98.9% versus 98.4%; p = 0.933) functional outcomes. The total ischemic complication rate (9.0% versus 7.1%; p = 0.401) was higher but not significant in the statin user group. The propensity score-matched cohort showed similar results. Results of binary multivariable logistic regression analysis and propensity score-matched analysis both showed that statin usage was not independently associated with an increased rate of complete occlusion or any other secondary outcomes. Subgroup analysis found the same result in patients who did not use statin before the procedure. Conclusion: Among patients with intracranial aneurysms, statin use after the PED treatment was not significantly associated with better angiographic and clinical outcomes. Well-designed studies are needed to further confirm this finding.

Development and validation of a deep learning model for prediction of intracranial aneurysm rupture risk based on multi-omics factor.

OBJECTIVE: The clinical ability of radiomics to predict intracranial aneurysm rupture risk remains unexplored. This study aims to investigate the potential uses of radiomics and explore whether deep learning (DL) algorithms outperform traditional statistical methods in predicting aneurysm rupture risk. METHODS: This retrospective study included 1740 patients with 1809 intracranial aneurysms confirmed by digital subtraction angiography at two hospitals in China from January 2014 to December 2018. We randomly divided the dataset (hospital 1) into training (80%) and internal validation (20%). External validation was performed using independent data collected from hospital 2. The prediction models were developed based on clinical, aneurysm morphological, and radiomics parameters by logistic regression (LR). Additionally, the DL model for predicting aneurysm rupture risk using integration parameters was developed and compared with other models. RESULTS: The AUCs of LR models A (clinical), B (morphological), and C (radiomics) were 0.678, 0.708, and 0.738, respectively (all p < 0.05). The AUCs of the combined feature models D (clinical and morphological), E (clinical and radiomics), and F (clinical, morphological, and radiomics) were 0.771, 0.839, and 0.849, respectively. The DL model (AUC = 0.929) outperformed the machine learning (ML) (AUC = 0.878) and the LR models (AUC = 0.849). Also, the DL model has shown good performance in the external validation datasets (AUC: 0.876 vs 0.842 vs 0.823, respectively). CONCLUSION: Radiomics signatures play an important role in predicting aneurysm rupture risk. DL methods outperformed conventional statistical methods in prediction models for the rupture risk of unruptured intracranial aneurysms, integrating clinical, aneurysm morphological, and radiomics parameters. KEY POINTS: • Radiomics parameters are associated with the rupture risk of intracranial aneurysms. • The prediction model based on integrating parameters in the deep learning model was significantly better than a conventional model. • The radiomics signature proposed in this study could guide clinicians in selecting appropriate patients for preventive treatment.