Metformin Therapeutic Targets for Aortic Aneurysms: A Mendelian Randomization and Colocalization Study.

Background: Identifying effective pharmacological interventions to prevent the progressive enlargement and rupture of aortic aneurysms (AAs) is critical. Previous studies have suggested links between metformin use and a decreased incidence of AAs. In this study, we employed Mendelian randomization (MR) to investigate causal effects of metformin's targets on AA risk and to explore the underlying mechanisms underlying these effects. Methods: To examine the relationship between metformin use and AA risk, we implemented both two-sample MR and multivariable MR analyses. Utilizing genetic instrumental variables, we retrieved cis-expression quantitative trait loci (cis-eQTL) data for potential targets of metformin from the Expression Quantitative Trait Loci Genetics Consortium (eQTLGen) Consortium and Genotype-Tissue Expression (GTEx) project. Colocalization analysis was employed to ascertain the probability of shared causal genetic variants between single nucleotide polymorphisms (SNPs) associated with eQTLs and AA. Results: Our findings reveal that metformin use reduces AA risk, exhibiting a protective effect with an odds ratio (OR) of 4.88 × 10 - 3 (95% confidence interval [CI]: 7.30 × 10 - 5 -0.33, p = 0.01). Furthermore, the protective effect of type 2 diabetes on AA risk appears to be driven by metformin use ( OR MVMR = 1.34 × 10 - 4 , 95% CI: 3.97 × 10 - 8 -0.45, p = 0.03). Significant Mendelian randomization (MR) results were observed for the expression of two metformin-related genes in the bloodstream: NADH:ubiquinone oxidoreductase subunit A6 (NDUFA6) and cytochrome b5 type B (CYB5B), across two independent datasets ( OR CYB5B = 1.35, 95% CI: 1.20-1.51, p = 2.41 × 10 - 7 ; OR NDUFA6 = 1.12; 95% CI: 1.07-1.17, p = 1.69 × 10 - 6 ). The MR analysis of tissue-specific expression also demonstrated a positive correlation between increased NDUFA6 expression and heightened AA risk. Lastly, NDUFA6 exhibited evidence of colocalization with AA. Conclusions: Our study suggests that metformin may play a significant role in lowering the risk of AA. This protective effect could potentially be linked to the mitigation of mitochondrial and immune dysfunction. Overall, NDUFA6 has emerged as a potential mechanism through which metformin intervention may confer AA protection.

Endovascular comprehensive treatment of post-traumatic superior mesenteric arteriovenous fistula: case report and literature review.

Background: Superior mesenteric arteriovenous fistula is a rare and difficult complication after abdominal trauma. Utilizing comprehensive endovascular treatment represents an effective approach to managing this condition. Case presentation: We report a case involving a 53-year-old female with a history of trauma who presented with complaints of abdominal pain, malaise, and melena. A computed tomographic scan revealed the presence of a superior mesenteric arteriovenous fistula. The fistula was occluded using four Interlock detachable coils, and a covered stent was positioned over the arteriovenous fistula in the superior mesenteric artery. Following endovascular treatment, the patient's abdominal pain and melena symptoms disappeared. Conclusion: Utilizing covered stents and Interlock detachable coils for endovascular treatment of a superior mesenteric arteriovenous fistula proves to be both feasible and highly effective.

New-onset postoperative atrial fibrillation after pulmonary endarterectomy is associated with adverse outcomes.

Background: New-onset postoperative atrial fibrillation (POAF) is a common complication after pulmonary thromboendarterectomy (PEA), yet the risk factors and their impact on prognosis remain poorly understood. This study aims to investigate the risk factors associated with new-onset POAF after PEA and elucidate its underlying connection with adverse postoperative outcomes. Methods: A retrospective analysis included 129 consecutive chronic thromboembolic pulmonary hypertension (CTEPH) patients and 16 sarcoma patients undergoing PEA. Univariate and multivariate analyses were conducted to examine the potential effects of preoperative and intraoperative variables on new-onset POAF following PEA. Propensity score matching (PSM) was then employed to adjust for confounding factors. Results: Binary logistic regression revealed that age (odds ratio [OR] = 1.041, 95% confidence interval [CI] = 1.008-1.075, p = 0.014) and left atrial diameter[LAD] (OR = 1.105, 95% CI = 1.025-1.191, p = 0.009) were independent risk factors for new-onset POAF after PEA. The receiver operating characteristic (ROC) curve indicated that the predictive abilities of age and LAD for new-onset POAF were 0.652 and 0.684, respectively. Patients with new-onset POAF, compared with those without, exhibited a higher incidence of adverse outcomes (in-hospital mortality, acute heart failure, acute kidney insufficiency, reperfusion pulmonary edema). Propensity score matching (PSM) analyses confirmed the results. Conclusion: Advanced age and LAD independently contribute to the risk of new-onset POAF after PEA. Patients with new-onset POAF are more prone to adverse outcomes. Therefore, heightened vigilance and careful monitoring of POAF after PEA are warranted.

Efficacy and safety of mechanochemical ablation versus laser ablation in the treatment of primary great saphenous vein reflux: A randomized, open, parallel controlled clinical trial.

OBJECTIVE: To evaluate the efficacy of a new mechanochemical ablation (MOCA) device versus endovenous laser ablation (EVLA) for primary great saphenous vein (GSV) reflux. MATERIALS AND METHODS: Prospectively analyze the demographics, treatment detail and outcomes data of 57 primary GSV reflux patients. Patients were randomly assigned to MOCA or EVLA group with random envelope method. Primary endpoint was 6-month closure rate of GSV. Secondary endpoint including technical success rate, the venous clinical severity score (VCSS), chronic venous insufficiency questionnaire (CIVIQ-20) score and visual analogue scale (VAS) for pain. RESULTS: The procedures were well tolerated according to the VAS score. The 6-month closure rate was 85.71% in MOCA and 96.55% in EVLA group (p = .194). Significant changes were observed in regard of VCSS and CIVIQ-20 score at 6-month follow-up. Skin paresthesia occurred in 0 in MOCA and 5 in EVLA group. CONCLUSION: The new MOCA device is safe and effective in treating primary great saphenous vein reflux. The 6-month closure rate is non-inferior compared with EVLA. However, the long-term results need further follow-up.

Risk factor and correlation between postoperative serum myoglobin and acute kidney injury after pulmonary endarterectomy.

Background: Acute kidney injury (AKI) is a common and life-threatening complication following pulmonary endarterectomy (PEA). Our study aimed to investigate the risk factors associated with AKI and evaluate the correlation between serum myoglobin (sMb) levels and postoperative AKI. Methods: We conducted a retrospective study involving 134 patients who underwent PEA at China-Japan Friendship Hospital. AKI was defined and staged according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results: During the study period, the incidence of postoperative AKI was 57.5%, and the associated mortality rate was 6.0%. Severe AKI was found to be significantly associated with worse short-term outcomes (P<0.05). Logarithmically transformed postoperative day (POD) 0 sMb levels were significantly associated with AKI [odds ratio (OR) =5.174; 95% confidence interval (CI), 2.307-11.603; P<0.001] and severe AKI (OR =4.605; 95% CI, 1.510-14.048; P=0.007), also had independent predictive value [area under the curve (AUC) =0.776 in AKI and AUC =0.737 in severe AKI]. The optimal cut-off values were 370.544 ng/mL for AKI and 419.473 ng/mL for severe AKI. Furthermore, albumin concentration was found to play a protective role in the development of severe AKI (OR =0.838; 95% CI, 0.716-0.980; P=0.027) when higher than 40.350 g/L. Conclusions: Our findings suggest that a high concentration of POD0 sMb may increase the risk of developing AKI following PEA surgery. Increasing albumin concentration could serve as an effective preventive measure against AKI.

Identification of key pyroptosis-related genes and microimmune environment among peripheral arterial beds in atherosclerotic arteries.

Atherosclerosis is a chronic inflammatory disease characterized with innate and adaptive immunity but also involves pyroptosis. Few studies have explored the role of pyroptosis in advanced atherosclerotic plaques from different vascular beds. Here we try to identify the different underlying function of pyroptosis in the progression of atherosclerosis between carotid arteries and femoral. arteries. We extracted gene expression levels from 55 advanced carotid or femoral atherosclerotic plaques. The pyroptosis score of each sample was calculated by single-sample-gene-set enrichment analysis (ssGSEA). We then divided the samples into two clusters: high pyroptosis scores cluster (PyroptosisScoreH cluster) and low pyroptosis scores cluster (PyroptosisScoreL cluster), and assessed functional enrichment and immune cell infiltration in the two clusters. Key pyroptosis related genes were identified by the intersection between results of Cytoscape and LASSO (Least Absolute Shrinkage and Selection Operator) regression analysis. Finally, all key pyroptosis related genes were validated in vitro. We found all but one of the 29 carotid plaque samples belonged to the PyroptosisScoreH cluster and the majority (19 out of 26) of femoral plaques were part of the PyroptosisScoreL cluster. Atheromatous plaque samples in the PyroptosisScoreL cluster had higher proportions of gamma delta T cells, M2 macrophages, myeloid dendritic cells (DCs), and cytotoxic lymphocytes (CTLs), but lower proportions of endothelial cells (ECs). Immune full-activation pathways (e.g., NOD-like receptor signaling pathway and NF-kappa B signaling pathway) were highly enriched in the PyroptosisScoreH cluster. The key pyroptosis related genes GSDMD, CASP1, NLRC4, AIM2, and IL18 were upregulated in advanced carotid atherosclerotic plaques. We concluded that compared to advanced femoral atheromatous plaques, advanced carotid atheromatous plaques were of higher grade of pyroptosis. GSDMD, CASP1, NLRC4, AIM2, and IL18 were the key pyroptosis related genes, which might provide a new sight in the prevention of fatal strokes in advanced carotid atherosclerosis.

Clinical outcomes and predictors of bleomycin polidocanol foam sclerotherapy treatment response in venous malformations.

OBJECTIVE: To evaluate the safety and efficacy of bleomycin polidocanol foam (BPF) sclerotherapy for venous malformations (VMs) and analyze the associated clinical outcomes and predictors. METHODS: We retrospectively assessed BPF sclerotherapy outcomes in 138 patients with VMs. We analyzed pain levels, lesion volume reduction, and subjective perception of response. Logistic regression analysis was performed to identify potential predictors of treatment outcome. Additionally, we carefully monitored and recorded complications. RESULTS: There was a notable average reduction in lesion volume by 78.50% ± 15.71%. The pain numerical rating scale (NRS) score decreased from 4.17 ± 2.63 prior to treatment to 1.05 ± 1.54 afterward, and 70.3% of the patients experienced effective relief after a single BPF treatment. Multivariate analysis revealed that a high baseline NRS (odds ratio [OR]: 4.026) and elevated activated partial thromboplastin time (APTT, OR: 1.200) were positive predictors of pain reduction. Additionally, a high baseline NRS score (OR: 1.992) and elevated thrombocytocrit (PCT, OR: 2.543) were positive predictors of incomplete postoperative pain relief. Minor complications occurred in 31 (22.46%) patients. CONCLUSION: BPF sclerotherapy is safe and effective for VMs, resulting in significant reduction in lesion volume, improved symptoms, and minimal complications. APTT and PCT levels are important predictors of pain outcomes following BPF treatment.

Comparison of bleomycin polidocanol foam vs electrochemotherapy combined with polidocanol foam for treatment of venous malformations.

OBJECTIVE: This study aims to investigate the difference in safety and efficacy between two treatments for venous malformations (VMs), electrochemotherapy combined with polidocanol foam (ECP) and bleomycin polidocanol foam (BPF), providing alternative therapies for VMs. METHODS: We conducted a retrospective review of 152 patients with VMs treated with ECP and BPF. Pre- and post-treatment magnetic resonance images (MRIs) were collected, and clinical follow-up assessments were performed. Imaging results were used to calculate lesion volume changes. Clinical outcomes included changes in pain and improvements in perceived swelling. Patients were followed up at 1 week and 6 months after surgery. All emerging complications were documented in detail. RESULTS: Of the 152 patients, 87 (57.2%) received BPF treatment, and 65 (42.8%) received ECP treatment. The most common location of VMs was the lower extremities (92/152; 60.2%), and the most common symptom was pain (108/152; 71.1%). Forty-three patients had previously undergone therapy in the BPF group (43/87; 49.4%), whereas 30 patients had received prior treatment in the ECP group (30/65; 46.2%). The study found that the percentage of lesion volume reduction in the BPF group was not significantly different from that in the ECP group (75.00% ± 17.85% vs 74.69% ± 8.48%; P = .899). ECP was more effective when the initial lesion volume was greater than 30 mL (67.66% ± 12.34% vs 73.47% ± 8.00%; P = .048). Patients treated with BPF had significantly less posttreatment pain than those treated with ECP, in different baseline lesion size. In the overall sample, pain relief was significantly higher in the BPF group than in the ECP group (4.21 ± 1.19 vs 3.57 ± 0.76; P = .002). However, there was no difference in pain relief between the two groups for the treatment of initially large VMs (4.20 ± 0.94 vs 3.70 ± 0.87; P = .113). The ECP group was significantly more likely to develop hyperpigmentation (5/87; 5.75% vs 11/65; 16.92%; P = .026) and swelling (9/87; 10.34% vs 16/65; 24.62%; P = .019) 1 week after surgery than the BPF group. CONCLUSIONS: Our study demonstrates that both BPF and ECP are effective treatments for VMs, with BPF being a safer option. ECP is a better choice for patients with the initial lesion volume greater than 30 mL, but it is more likely to lead to early swelling and hyperpigmentation.

Untargeted plasma metabolome identifies biomarkers in patients with extracranial arteriovenous malformations.

Objective: This study aimed to investigate the plasma metabolic profile of patients with extracranial arteriovenous malformations (AVM). Method: Plasma samples were collected from 32 AVM patients and 30 healthy controls (HC). Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was employed to analyze the metabolic profiles of both groups. Metabolic pathway enrichment analysis was performed through Kyoto Encyclopedia of Genes and Genomes (KEGG) database and MetaboAnalyst. Additionally, machine learning algorithms such as Least Absolute Shrinkage and Selection Operator (LASSO) and random forest (RF) were conducted to screen characteristic metabolites. The effectiveness of the serum biomarkers for AVM was evaluated using a receiver-operating characteristics (ROC) curve. Result: In total, 184 differential metabolites were screened in this study, with 110 metabolites in positive ion mode and 74 metabolites in negative mode. Lipids and lipid-like molecules were the predominant metabolites detected in both positive and negative ion modes. Several significant metabolic pathways were enriched in AVMs, including lipid metabolism, amino acid metabolism, carbohydrate metabolism, and protein translation. Through machine learning algorithms, nine metabolites were identify as characteristic metabolites, including hydroxy-proline, L-2-Amino-4-methylenepentanedioic acid, piperettine, 20-hydroxy-PGF2a, 2,2,4,4-tetramethyl-6-(1-oxobutyl)-1,3,5-cyclohexanetrione, DL-tryptophan, 9-oxoODE, alpha-Linolenic acid, and dihydrojasmonic acid. Conclusion: Patients with extracranial AVMs exhibited significantly altered metabolic patterns compared to healthy controls, which could be identified using plasma metabolomics. These findings suggest that metabolomic profiling can aid in the understanding of AVM pathophysiology and potentially inform clinical diagnosis and treatment.

Hyperuricemia promotes the progression of atherosclerosis by activating endothelial cell pyroptosis via the ROS/NLRP3 pathway.

Hyperuricemia closely correlates with the development of atherosclerosis, but little is known of the mechanism by which atherosclerosis progression occurs in hyperuricemia. Atherosclerosis appears to involve pyroptosis, an emerging mechanism of proinflammatory regulated cell death. This study tested the hypothesis that pyroptosis underlies the relationship between hyperuricemia and atherosclerosis, using ApoE-/- mice (a model of atherosclerosis), human umbilical vein endothelial cells (HUVECs), and human atherosclerotic arterial samples. We found that hyperuricemia can aggravate the aortic atherosclerotic plaque-load in ApoE-/- mice and promote endothelial cell pyroptosis. Additionally, hyperuricemia can increase the levels of serum inflammatory factors (including IL-1ß and IL-18). Exposure to lipopolysaccharide plus a high concentration of soluble uric acid (≥12 mg/dL) induced cell pyroptosis in HUVECs, as evidenced by increased expression of pyroptosis-related proteins and elevated release of lactate dehydrogenase (a marker of tissue damage). Further, MCC950, a selective nucleotide-binding oligomerization domain (NOD)-like receptor 3 (NLRP3) inflammasome inhibitor, and N-acetyl- l-cysteine, an antioxidant, attenuated HUVEC pyroptosis by inhibiting activation of the NLRP3 inflammasome and production of intracellular reactive oxygen species (ROS). Finally, we detected significantly higher expression of pyroptosis-associated proteins in carotid specimens from patients with hyperuricemia. Collectively, our findings suggest that hyperuricemia can aggravate endothelial cell pyroptosis in aortic atherosclerotic plaques, promoting the development of atherosclerosis. Additionally, a high concentration of soluble uric acid can trigger the activation stage of the NLRP3 inflammasome, mediating endothelial cell pyroptosis, and this process is regulated by the cellular ROS level.

Embolo/sclerotherapy for the treatment of hand arteriovenous malformations: a single-center retrospective cohort experience.

Purpose: To retrospectively report our preliminary experience of treating hand arteriovenous malformations (AVMs) with embolo/sclerotherapy. Materials and methods: Retrospectively review the demographics, treatment detail, outcome data, and complications of 13 consecutive patients with hand AVMs from January 2018 to December 2021. We embolize the dominant outflow vein with elastic coils and then use absolute ethanol or polidocanol for intravascular sclerotherapy and bleomycin for interstitial sclerotherapy. Results: Yakes type II presents in four lesions, type IIIa in six, and type IIIb in three. A total of 29 treatment episodes were conducted for the 13 patients (1 episode for 3 patients, 2 for 4 patients, and 3 for 6 patients; the repeated treatment rate was 76.9%). The mean stretched length of coils for 1 treatment episode was 95 cm. The mean absolute ethanol dosage was 6.8 ml (range 4-30 ml). In addition, 10 ml of 3% polidocanol foam was injected and interstitial sclerotherapy with 150,000 IU bleomycin was performed on every patient. The post-operative arterial-dominant outflow vein pressure index (AVI) increased in the 29 procedures (6.55 ± 1.68 vs. 9.38 ± 2.80, P < 0.05). The Mann-Whitney U test showed that the post-operative AVI was higher in patients without re-intervention (P < 0.05). Local swelling occurred after all the procedures. Blistering occurred in 6 of the patients in 13 (44.8%) of the 29 procedures. Superficial skin necrosis occurred in 3 of the patients in 5 (17.2%) of the 29 procedures. The swelling, blistering, and superficial skin necrosis recovered within 4 weeks. No finger amputation occurred. The follow-up time was 6 months. The 6-month assessment of clinical improvement after the last treatment episode showed that 2 patients were cured, 10 were improved, and 1 remained unchanged. With regard to angiographic evaluation, 9 showed partial response and 4 complete response. Conclusion: Embolo/sclerotherapy can be effective and safe for hand AVM. The AVI increased significantly after embolo/sclerotherapy, and the index may be valuable in predicting recurrence in further study.

Role of the Global Limb Anatomic Staging System in predicting outcomes of chronic limb-threatening ischemia in patients treated by drug-coated balloons.

Background: The Global Limb Anatomic Staging System (GLASS) was proposed to assess the procedural complexity and technical failure rate and stratify the anatomic pattern of chronic limb-threatening ischemia (CLTI). However, more evidence is needed to validate the GLASS in staging outcomes after endovascular therapy in patients with CLTI treated with drug-coated balloons (DCBs). This study aims to evaluate the role of the GLASS in predicting outcomes of CLTI patients treated with DCBs. Methods: This multicenter, retrospective cohort study enrolled patients with CLTI treated with DCBs from July 2016 to June 2019. GLASS stages were assigned for every limb. The limb-based patency (LBP) rate, clinically driven target lesion revascularization (CD-TLR) rate, clinical improvement, and safety endpoints were analyzed and compared across the GLASS stages over 12 months of follow-up. Risk factors for the loss of LBP were identified using Cox regression analysis. Results: A total of 90 limbs were enrolled, with 55 (61.1%) having isolated femoropopliteal lesions and 35 (38.9%) having femoropopliteal and infrapopliteal lesions. Of the limbs, 17 (18.9%), 12 (13.3%), and 61 (67.8%) were assigned to GLASS stages I, II, and III, respectively. The Kaplan-Meier estimate of the 12-month LBP was 65.4%, and no difference was found among the different stages (stage I 81.1%; stage II 85.2%; stage III 54.4%; P=0.080). The LBP was lower in stage III than in stages I and II combined (stage I and II 83.5%; stage III 54.4%; P=0.027). Similar results were found for the freedom from CD-TLR rates among the different stages. The ankle-brachial index values improved from 0.42±0.29 to 0.78±0.35 at follow-up (P<0.001). The rates of mortality, any amputation, and major amputation were similar among the groups. GLASS stage III and coronary heart disease were identified as independent risk factors for the loss of LBP at 12 months. Conclusions: The 1-year LBP and freedom from CD-TLR rates were lower in GLASS stage III than in stages I and II. The GLASS classification could predict the outcomes of CLTI patients with femoropopliteal lesions treated with DCB.

Comparison of polidocanol foam versus bleomycin polidocanol foam for treatment of venous malformations.

OBJECTIVE: The objective of this research was to retrospectively investigate the difference of safety and efficacy between polidocanol foam and bleomycin polidocanol foam (BPF) in the treatment of venous malformations (VMs), and provide clinical evidence for the application of BPF for VMs. METHODS: Patients with VMs treated with polidocanol foam and BPF were included between July 2018 and July 2020. The VM tissue involvements and symptoms were collected. The treatment outcomes were evaluated by the clinical improvement of symptoms and the degree of devascularization on ultrasound examination or magnetic resonance imaging. Patients were followed up for 1, 3, and 6 months after the sclerotherapy. Immediate and delayed complications were closely followed and recorded. RESULTS: A total of 51 patients were included, including 34 females and 17 males with a mean age of 26.8 years (range, 5-65 years). The most commonly involved sites were lower extremities (31/60 [51.7%]) and the most common symptom was pain (33/51 [64.7%]). Fifty-four sclerotherapies were performed with a mean of 1.06 ± 0.24 sessions (range, 1-2 sessions) per patient. The reduction percentage of lesion volume in the BPF group was significantly higher than the polidocanol foam group (79.4 ± 1.6% vs 55.7 ± 6.1%; P < .001). Patient satisfaction scores in the BPF group were significantly higher than the polidocanol foam group (7.2 ± 1.1 vs 5.7 ± 0.8; P < .001). No major complication was observed in either group. Cardiovascular and Interventional Radiological Society of Europe (CIRSE) grade 1 complications occurred in 5 of 21 patients in the BPF group and 7 of 30 patients in the polidocanol foam group, CIRSE grade 2 complications occurred in 5 of 21 patients in the BPF group and 4 of 30 patients in the polidocanol foam group; there were no significant differences between the two groups. CONCLUSIONS: BPF is a safe and effective sclerosant for VMs, showing better efficacy and similar safety as commonly used mild sclerosants. It could be a promising agent to treat VMs or other slow-flow vascular malformations.

Inhibition of mitochondrial fission alters neo-intimal hyperplasia via PI3K/Akt signaling in arteriovenous fistulas.

BACKGROUND/OBJECTIVE: Arteriovenous fistulas (AVFs) are the preferred vascular access for hemodialysis of patients with end-stage renal disease. However, there is a high incidence of AVF failures caused by insufficient outward remodeling or venous neo-intimal hyperplasia formation. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play an important role in many cardiovascular diseases. Abnormal VSMC proliferation and migration could be abolished by inhibition of mitochondrial division. METHOD: We found that abnormal proliferation and migration of VSMCs and increased mitochondrial fission were associated with AVF stenosis in patients. We also investigated the mechanisms, particularly the role of mitochondrial dynamics, underlying these VSMC behaviors. In vitro, we observed that inhibition of mitochondrial fission and Akt phosphorylation can diminish proliferation and migration of VSMCs induced by platelet-derived growth factor-BB (PDGF-BB). In vivo, daily intraperitoneal injections of mitochondrial division inhibitor 1 (Mdivi-1) decreased VSMC proliferation and reduced AVF wall thickness in a rat AVF model. CONCLUSION AND RESULT: Our results suggest that inhibition of mitochondrial fission improves AVF patency by reducing wall thickening through the PI3K/Akt signaling pathway. Therefore, inhibition of mitochondrial fission has the clinical potential to improve AVF patency.

Radiomics Signature of Epicardial Adipose Tissue for Predicting Postoperative Atrial Fibrillation after Off-Pump Coronary Artery Bypass Surgery.

Background: Postoperative new atrial fibrillation (POAF) is a commonly observed complication after off-pump coronary artery bypass surgery (OPCABG), and models based on radiomics features of epicardial adipose tissue (EAT) on non-enhanced computer tomography (CT) to predict the occurrence of POAF after OPCABG remains unclear. This study aims to establish and validate models based on radiomics signature to predict POAF after OPCABG. Methods: Clinical characteristics, radiomics signature and features of non-enhanced CT images of 96 patients who underwent OPCABG were collected. The participants were divided into a training and a validation cohort randomly, with a ratio of 7:3. Clinical characteristics and EAT CT features with statistical significance in the multivariate logistic regression analysis were utilized to build the clinical model. The least absolute shrinkage and selection operator (LASSO) algorithm was used to identify significant radiomics features to establish the radiomics model. The combined model was constructed by integrating the clinical and radiomics models. Results: The area under the curve (AUC) of the clinical model in the training and validation cohorts were 0.761 (95% CI: 0.634-0.888) and 0.797 (95% CI: 0.587-1.000), respectively. The radiomics model showed better discrimination ability than the clinical model, with AUC of 0.884 (95% CI: 0.806-0.961) and 0.891 (95% CI: 0.772-1.000) respectively for the training and the validation cohort. The combined model performed best and exhibited the best predictive ability among the three models, with AUC of 0.922 (95% CI: 0.853-0.990) in the training cohort and 0.913 (95% CI: 0.798-1.000) in the validation cohort. The calibration curve demonstrated strong concordance between the predicted and actual observations in both cohorts. Furthermore, the Hosmer-Lemeshow test yielded p value of 0.241 and 0.277 for the training and validation cohorts, respectively, indicating satisfactory calibration. Conclusions: The superior performance of the combined model suggests that integrating of clinical characteristics, radiomics signature and features on non-enhanced CT images of EAT may enhance the accuracy of predicting POAF after OPCABG.

Immune-mediated inflammatory diseases and risk of venous thromboembolism: A Mendelian randomization study.

Introduction: Immune-mediated inflammatory diseases (IMIDs) have been associated with an increased risk of venous thromboembolism (VTE) in multiple observational studies. However, a direct causally relation between IMIDs and VTE remains unclear to date. Here, we used Mendelian randomization (MR) analysis to investigate causal associations between IMIDs and VTE. Methods: We collected genetic data from published genome-wide association studies (GWAS) for six common IMIDs, specifically inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriasis (PSO), and systemic lupus erythematosus (SLE); and summary-level data for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen database. Two-sample MR analysis using inverse variance weighting (IVW) was performed to identify causal associations between IMIDs and VTE/DVT/PE, and sensitivity analyses were implemented for robustness. Results: IVW analysis showed a causal relationship between genetically predicted UC (one type of IBD) and the risk of VTE (OR = 1.043, 95% CI: 1.013-1.073, p = 0.004) and DVT (OR = 1.088, 95% CI: 1.043-1.136, p < 0.001), but we found no evidence of causality between UC and PE (OR = 1.029, 95% CI: 0.986-1.074, p = 0.19). In addition, no associations were observed between total IBD, CD, RA, SLE, or PSO and VTE/DVT/PE. Sensitivity analysis found no evidence for horizontal pleiotropy. Conclusion: This MR study provides new genetic evidence for the causal relationship between IMIDs and the risk of VTE. Our findings highlight the importance of active intervention and monitoring to mitigate VTE risk in patients with IBD, in particular those presenting with UC.

Preoperative pulmonary vascular resistance and neutrophil-to-lymphocyte ratio predict the demand of extracorporeal membrane oxygenation after pulmonary endarterectomy.

BACKGROUND: Acute respiratory and circulatory collapse might occasionally happen after pulmonary endarterectomy (PEA). We aimed to investigate the utilization of extracorporeal membrane oxygenation (ECMO) after PEA and potential risk factors. METHODS: Demographic characteristics, clinical and surgical data were collected for all patients who underwent PEA from December 2016 to June 2022. All factors were compared between patients in the ECMO group and those in the other group. The most characteristic risk factors were obtained by least absolute shrinkage and selection operator regression and support vector machine machine learning, and receiver operating characteristics (ROC) Curve analysis was performed to verify the diagnostic value of the obtained risk factors. RESULTS: A total of 117 patients underwent PEA, and 8 (6.8%) of them received ECMO treatment intraoperatively or postoperatively. There were significant differences between the two groups in terms of cardiac function, pulmonary vascular resistance (PVR), preoperative inflammation and cardiopulmonary bypass time. The PVR and neutrophil-to-lymphocyte ratio (N/L ratio) were the most characteristic risk factors with an area under the ROC curve of 0.847 (95% confidence interval [CI] = 0.7517-0.9420, p = .005) and 0.896 (95% CI = 0.803-0.989, p = .001), respectively. The ECMO group had higher PVR (1549.4 ± 600.7 vs. 952.9 ± 466.9 dyn.s.cm-5 , p = .004) and N/L ratio (6.3 ± 5.6 vs. 2.4 ± 1.7, p = .001). CONCLUSIONS: PVR and N/L ratio can correctly predict who is likely to receive ECMO treatment after PEA. Therefore, addressing the preoperative inflammatory status might be beneficial but further research is needed.

In Silico Identification of Key Genes and Immune Infiltration Characteristics in Epicardial Adipose Tissue from Patients with Coronary Artery Disease.

Background: The present study is aimed at identifying the differentially expressed genes (DEGs) and relevant biological processes and pathways associated with epicardial adipose tissue (EAT) from patients with coronary artery disease (CAD). We also explored potential biomarkers using two machine-learning algorithms and calculated the immune cell infiltration in EAT. Materials and Methods: Three datasets (GSE120774, GSE64554, and GSE24425) were obtained from the Gene Expression Omnibus (GEO) database. The GSE120774 dataset was used to evaluate DEGs between EAT of CAD patients and the control group. Functional enrichment analyses were conducted to study associated biological functions and mechanisms using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA). After this, the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) were performed to identify the feature genes related to CAD. The expression level of the feature genes was validated in GSE64554 and GSE24425. Finally, we calculated the immune cell infiltration and evaluated the correlation between the feature genes and immune cells using CIBERSORT. Results: We identified a total of 130 upregulated and 107 downregulated genes in GSE120774. Functional enrichment analysis revealed that DEGs are associated with several pathways, including the calcium signaling pathway, complement and coagulation cascades, ferroptosis, fluid shear stress and atherosclerosis, lipid and atherosclerosis, and regulation of lipolysis in adipocytes. TCF21, CDH19, XG, and NNAT were identified as feature genes and validated in the GSE64554 and GSE24425 datasets. Immune cell infiltration analysis showed plasma cells are significantly more numerous in EAT than in the control group (p = 0.001), whereas macrophage M0 (p = 0.024) and resting mast cells (p = 0.036) were significantly less numerous. TCF21, CDH19, XG, and NNAT were correlated with immune cells, including plasma cells, M0 macrophages, and resting mast cells. Conclusion: TCF21, CDH19, XG, and NNAT might serve as feature genes for CAD, providing new insights for future research on the pathogenesis of cardiovascular diseases.