Novel radiopaque ethanol injection: physicochemical properties, animal experiments, and clinical application in vascular malformations.

BACKGROUND: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue. METHODS: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection. RESULTS: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up. CONCLUSION: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs. TRIAL REGISTRATION: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.

Assessing volatile organic compounds exposure and chronic obstructive pulmonary diseases in US adults.

Background: Volatile organic compounds (VOCs) are a large group of chemicals widely used in People's Daily life. There is increasing evidence of the cumulative toxicity of VOCs. However, the association between VOCs and the risk of COPD has not been reported. Objective: We comprehensively evaluated the association between VOCs and COPD. Methods: Our study included a total of 1,477 subjects from the National Health and Nutrition Examination Survey, including VOCs, COPD, and other variables in the average US population. Multiple regression models and smooth-curve fitting (penalty splines) were constructed to examine potential associations, and stratified analyses were used to identify high-risk groups. Results: We found a positive association between blood benzene and blood o-xylene concentrations and COPD risk and identified a concentration relationship between the two. That is, when the blood benzene and O-xylene concentrations reached 0.28 ng/mL and 0.08 ng/mL, respectively, the risk of COPD was the highest. In addition, we found that gender, age, and MET influence the relationship, especially in women, young people, and people with low MET. Significance: This study revealed that blood benzene and blood o-xylene were independently and positively correlated with COPD risk, suggesting that long-term exposure to benzene and O-xylene may cause pulmonary diseases, and providing a new standard of related blood VOCs concentration for the prevention of COPD.

Ethanol Embolization of Chest Wall Arteriovenous Malformations: Four-Year Findings.

OBJECTIVES: To summarize the clinical characteristics and investigate the efficacy of ethanol embolotherapy in the treatment of chest well arteriovenous malformation (AVM). Treatment-associated complications were also explored. MATERIALS AND METHODS: Between March 2017 and August 2021, 32 consecutive patients (mean age, 23.7 years; age range, 5-54 years) who underwent ethanol embolotherapy for chest well AVMs under general anesthesia were included in this study. Embolization was performed through a direct puncture, transarterial catheterization, or a combination of the 2 procedures. The mean follow-up duration after the last treatment was 18.0 months (range, 3-42 months). The degree of devascularization on follow-up (assessed using angiography or computed tomography), and the clinical signs and symptoms of AVMs were evaluated as the therapeutic outcomes. The major and minor complications associated with the procedures were recorded. RESULTS: A total of 103 embolization procedures (mean, 3.2; range, 2-7) comprising 101 ethanol embolization and 2 coil embolizations were performed on 32 patients with chest wall AVMs. The AVM nidus was accessed through the transarterial approach alone in 4 patients, by direct puncture in 11, and a combined procedure in 17 patients. Overall, more than 80% of the procedures were performed using the combined approach. Complete AVM devascularization was achieved in 12 (37.5%) patients. Moreover, 76% to 99% AVM was achieved in 18 patients (56.3%), and 50% to 75% in 2 patients (6.3%). Bleeding, pain, heart failure, and cosmetic deformities were the indications for treatment. For 3 patients (3/32, 9.4%) who had bleeding, the treatment stopped the hemorrhage. Complete pain relief was reported in 8 patients (8/32, 25.0%), whereas complete relief from congestive heart failure post-embolization was observed in 5 of the 6 patients with congestive heart failure (5/6, 83.3%). Complete correction of cosmesis deformities after embolization was achieved in 10 patients (10/32, 31.3%). Two patients who underwent surgery to correct persistent deformity after embolization only showed insignificant improvement. In addition, 6 (18.8%) patients developed 13 complications including blister, necrosis, hemothorax, transient hemoglobinuria, and transient pulmonary artery hypertension. CONCLUSIONS: Ethanol embolotherapy is a safe and effective procedure for chest well AVMs. Surgery is required for some patients with residual cosmesis deformity. CLINICAL IMPACT: Currently, there is no standard treatment for chest well AVMs due to their rarity and high heterogeneity. The present study shows that thanol embolotherapy is a safe and clinically effective treatment procedure for the chest well AVMs. Transarterial embolization in combination with direct puncture embolization can reach the AVM nidus. Ethanol embolotherapy can achieve complete obliteration of the AVM nidus in the majority of patients. Surgery may still be needed to correct cosmetic deformity after embolization. The present study provides valuable evidence to inform clinical decision-making.

Management of high-output cardiac failure caused by head and neck AVMs: Percutaneous suture-assisted ethanol and coil embolotherapy.

Purpose: The aim of this study was to describe the treatment technique, outcomes, and complications of Schobinger stage IV head and neck arteriovenous malformations (HNAVMs) with associated high-output cardiac failure (HOCF) using ethanol and coils with the percutaneous suture technique. Methods: From January 2015 to December 2019, 19 patients who had HNAVMs with associated HOCF were treated first with a percutaneous suture of the remarkably dilated dominant drainage vein (RDDOV) and subsequent embolization with coils and ethanol. The percutaneous suture of RDDOV was preferred to be performed, followed by the deployment of coils and the injection of absolute ethanol via transarterial approach, direct puncture approach, or both of them. Treatment outcomes and complication rates were evaluated at follow-up. Results: A total of 19 patients who experienced HNAVMs with HOCF received 19 percutaneous suture procedures and 84 embolization procedures with ethanol and coils. Complete or >90% shunt reduction of the AVM was achieved in 16 patients. Notably, 19 patients with New York Heart Association (NYHA) stage II improved to stage I, and the symptom of dyspnea disappeared after embolization. The symptoms of five patients with bleeding disappeared. All patients presented with cosmetic concerns; Four were cured, and eight had a clearly recognizable improvement. Of note, 19 (100%) patients presented with impairment of daily life, which was resolved. The minor complications were encountered and recovered by the self. No major complications occurred. Conclusion: This study provides evidence that ethanol and coil embolotherapy is effective and safe in treating HOCF caused by HNAVMs with acceptable complications in these cases. The percutaneous suture technique for RDDOV management can act as an adjunct for embolotherapy.

Dietary magnesium intake is protective in patients with periodontitis.

Background: Periodontitis is a chronic inflammatory disease of the oral cavity characterized by inflammation of the periodontal tissue and resorption of the alveolar bone, which has a high incidence and is the main cause of tooth loss in adults. In addition to its role in promoting osteogenesis, magnesium also has a role in regulating the inflammatory response, both systemically and locally. There is growing evidence that magnesium is an important factor in maintaining the normal functioning of the body's immune system. Hypomagnesaemia can lead to a variety of chronic inflammatory diseases throughout the body, including periodontitis. Two-thirds of the US population suffers from magnesium deficiency. The connection between dietary magnesium and periodontitis is unknown. As a result, we set out to investigate the link between dietary magnesium intake and periodontitis. Methods: In this study, we collected data from the National Health and Nutrition Examination Survey (NHANES) database from 2013 to 2014. Through 24-h dietary recalls, information about food consumption was collected. We examined the association between the dietary magnesium and periodontitis using multivariable logistic regression model. Based on odds ratios (OR) and 95% confidence intervals (CIs), a strong association was detected. Results: Multivariable logistic regression analysis showed that the OR for periodontitis comparing the highest to the lowest quintile of dietary magnesium intake was 0.69 (95% CIs = 0.52~0.92). The restricted cubic spline (RCS) analysis showed that the non-linear association between dietary magnesium and periodontitis was statistically significant and that dietary magnesium supplementation reduced the prevalence of periodontitis. Conclusion: Dietary magnesium intake is associated with the prevalence of periodontitis. Dietary magnesium deficiency increases the prevalence of periodontitis.

Effect of SARS-CoV-2 infection on asthma patients.

Background: SARS-CoV-2 causes coronavirus disease 2019 (COVID-19), a new coronavirus pneumonia, and containing such an international pandemic catastrophe remains exceedingly difficult. Asthma is a severe chronic inflammatory airway disease that is becoming more common around the world. However, the link between asthma and COVID-19 remains unknown. Through bioinformatics analysis, this study attempted to understand the molecular pathways and discover potential medicines for treating COVID-19 and asthma. Methods: To investigate the relationship between SARS-CoV-2 and asthma patients, a transcriptome analysis was used to discover shared pathways and molecular signatures in asthma and COVID-19. Here, two RNA-seq data (GSE147507 and GSE74986) from the Gene Expression Omnibus were used to detect differentially expressed genes (DEGs) in asthma and COVID-19 patients to find the shared pathways and the potential drug candidates. Results: There were 66 DEGs in all that were classified as common DEGs. Using a protein-protein interaction (PPI) network created using various bioinformatics techniques, five hub genes were found. We found that asthma has some shared links with the progression of COVID-19. Additionally, protein-drug interactions with common DEGs were also identified in the datasets. Conclusion: We investigated possible links between COVID-19 and asthma using bioinformatics databases, which might be useful in treating COVID-19 patients. More studies on populations affected by these diseases are needed to elucidate the molecular mechanism behind their association.

The association of healthy eating index with periodontitis in NHANES 2013-2014.

Background: Periodontal disease is very common worldwide and is one of the main causes of tooth loss in adults. Periodontal disease is characterized by chronic inflammation that can destroy adjacent alveolar bone and lead to a loss of periodontal ligaments. Although previous studies have found that a daily diet can influence the development of periodontal disease (e.g., a diet low in carbohydrates and rich in vitamins C and D and fiber can have a protective effect). Periodontal disease may present as gingivitis or periodontitis. However, studies on the role of healthy eating index in periodontitis are lacking. The purpose of this study was to assess the association between healthy eating index and periodontitis. Methods: We analyzed data collected from participants in the National Health and Nutrition Examination Survey (NHANES), a nationally representative survey conducted in 2-year cycles from 2013 to 2014. As part of our analysis, we developed multivariate logistic regression models to examine the independent association between the healthy eating index and periodontitis. We evaluated the significance of association using odds ratios (OR) with 95% confidence intervals (95%CI). Results: Individuals with a lower total healthy eating index had a higher prevalence of periodontitis. Adjusted multivariate regression models showed that a higher healthy diet index was associated with a lower prevalence of periodontitis (OR = 0.69, 95% CI: 0.55-0.86, P < 0.05). Conclusion: The results of the study showed that dietary structure was associated with the prevalence of periodontitis. Patients with a higher healthy eating index had a lower prevalence of periodontitis. These findings will need to be confirmed by longitudinal, prospective studies in the future.

Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis.

Background: Necroptosis, a form of programmed cell death, is increasingly being investigated for its controversial role in tumorigenesis and progression. Necroptosis suppresses tumor formation and tumor development by killing tumor cells; however, the necrotic cells also promote tumor formation and tumor development via the immunosuppressive effect of necroptosis and inflammatory response caused by cytokine release. Thus, the exact mechanism of necroptosis in pan-cancer remains unknown. Methods: The data of 11,057 cancer samples were downloaded from the TCGA database, along with clinical information, tumor mutation burden, and microsatellite instability information of the corresponding patients. We used the TCGA data in a pan-cancer analysis to identify differences in mRNA level as well as single nucleotide variants, copy number variants, methylation profiles, and genomic signatures of miRNA-mRNA interactions. Two drug datasets (from GDSC, CTRP) were used to evaluate drug sensitivity and resistance against necroptosis genes. Results: Necroptosis genes were aberrantly expressed in various cancers. The frequency of necroptosis gene mutations was highest in lung squamous cell carcinoma. Furthermore, the correlation between necroptosis gene expression in the tumor microenvironment and immune cell infiltration varied for different cancers. High necroptosis gene expression was found to correlate with NK, Tfh, Th1, CD8_T, and DC cells. These can therefore be used as biomarkers to predict prognosis. By matching gene targets with drugs, we identified potential candidate drugs. Conclusion: Our study showed the genomic alterations and clinical features of necroptosis genes in 33 cancers. This may help clarify the link between necroptosis and tumorigenesis. Our findings may also provide new approaches for the clinical treatment of cancer.

Trans-ophthalmic arterial ethanol embolotherapy for arteriovenous malformations: a single-center experience.

Arteriovenous malformation (AVM)-derived ophthalmic artery (OphA) branches are not common, and their management is very challenging. We evaluated the safety and efficacy of Trans OphA ethanol embolotherapy for these lesions. We retrospectively reviewed 26 patients with AVMs fed by OphA, who underwent transOphA embolization using ethanol from February, 2015 to December, 2019. Sixty-six transOphA embolotherapy procedures (range, 1-4 procedures; mean, 2.5 procedures) were performed. Devascularization degree, visual field, visual acuity, and quality-of-life outcomes were compared and analyzed at follow up (mean, 32.6 months; month range 10-60). Complications were recorded. Twenty-five of the 26 patients (96%) reported complete or > 90% AVM devascularization while one patient (4%) showed > 70% devascularization. Eleven patients (42%) presented with visual acuity impairments; among them, 6 had improvements while 4 were completely relieved. Eight patients (30.7%) presented visual field defects, 3 had improvements while 4 were completely relieved. Ten patients (38.4%) presented with diplopia and exophthalmos with 2 being completely relieved while 6 had major improvements. Bleeding was controlled in all cases (100%). All patients (100%) exhibited cosmetic deformities with 17 being completely relieved. Moreover, all patients (100%) exhibited impaired daily life, which was resolved in 21 patients with 5 patients reporting major improvements. After endovascular treatment, there was no vision loss, death, or permanent disability in any patient. TransOphA ethanol embolotherapy is efficacious and safe for symptomatic resolution or improvement of AVMs fed by OphA with acceptable complications without the risk of visual impairment.

OAS3 is a Co-Immune Biomarker Associated With Tumour Microenvironment, Disease Staging, Prognosis, and Treatment Response in Multiple Cancer Types.

2',5'-oligoadenylate synthase (OAS) is a class of enzymes induced by interferons and mainly encoded by the OAS1, OAS2, and OAS3 genes, which activate the potential RNA enzymes to degrade viral mRNA, inhibit viral protein synthesis and promote apoptosis in virus-infected cells. OAS3 is associated with breast cancer prognosis. However, the expression and prognosis of OAS3 and tumour-infiltrating lymphocytes in pan-cancer remain unknown. In the present study, we have systematically investigated and confirmed the role of OAS3 in tumour immune infiltration, immune escape, tumour progression, response to treatment, and prognosis of different cancer types using various bioinformatics methods. The findings suggest that OAS3 is aberrantly expressed in almost all TCGA cancer types and subtypes and is associated with tumour staging, metastasis, and prognostic deterioration in different tumours. In addition, OAS3 expression is associated with the prognosis and chemotherapeutic outcomes of various cancers. In terms of immune-infiltrating levels, OAS3 expression is positively associated with the infiltration of immunosuppressive cells. These findings suggest that OAS3 is correlated with prognosis and immune-infiltrating levels.

Association of Angiogenesis Gene Expression With Cancer Prognosis and Immunotherapy Efficacy.

Background: Several new blood vessels are formed during the process of tumor development. These new blood vessels provide nutrients and water for tumour growth, while spreading tumour cells to distant areas and forming new metastases in different parts of the body. The available evidence suggests that tumour angiogenesis is closely associated with the tumour microenvironment and is regulated by a variety of pro-angiogenic factors and/or angiogenic inhibitors. Methods: In the present study, a comprehensive characterization of angiogenesis genes expression was performed in a pan-cancer analysis across the 33 human cancer types. Further, genetic data from several public databases were also used in the current study. An angiogenesis score was assigned to The Cancer Genome Atlas (TCGA) pan-cancer data, with one angiogenesis score as per sample for each tumour. Results: It was found that angiogenesis genes vary across cancer types, and are associated with a number of genomic and immunological features. Further, it was noted that macrophages and iTreg infiltration were generally higher in tumours with high angiogenesis scores, whereas lymphocytes and B cells showed the opposite trend. Notably, NK cells showed significantly different correlations among cancer types. Furthermore, results of the present study showed that a high angiogenesis score was associated with poor survival and aggressive types of cancer in most of the cancer types. Conclusion: In conclusion, the current study evidently showed that the expression of angiogenesis genes is a key feature of tumour biology that has a major impact on prognosis of patient with cancers.

Ethanol Embolization of Nasal Arteriovenous Malformations: A 10-Year, Single-Institution Experience.

PURPOSE: To summarize a 10-year, single-institution experience with ethanol embolization of nasal arteriovenous malformations (NAVMs) in 52 patients. PATIENTS AND METHODS: The present work was a retrospective study of 52 patients (aged between 1 and 67 years) with NAVMs who were treated with ethanol embolization between August 2009 and August 2019. The diagnosis of NAVMs was established based on clinical and imaging studies including ultrasound, computer tomography angiography, and digital subtract angiography. Embolization techniques used in the current study included transarterial, direct puncture, and a combination of both. The clinical and angiographic features, treatment methods, clinical outcomes, and complications were assessed within the mean period of 55.2 months (range, 1-119 months) after the last embolization. RESULTS: The total number of embolization sessions (140 embolization procedures in 52 pts) included transarterial approach (1 pt), direct puncture (2 pt), and a combination of transarterial and direct puncture (49 pts). There was a positive correlation between nidus size and treatment sessions (r = 0.780, P = 0.0005) and the amount of ethanol injected (r = 0.840, P = 0.0004). Results of the current study showed that the therapeutic outcomes were complete response in two patients (3.8%) without recurrence throughout the follow-up period (range, 1-119 months; mean, 55.2 months), and partial response in 50 patients (96.2%). A total of seven patients (13.5%) experienced one or more complications, including skin necrosis in one patient (1.9%), transient hemoglobinuria in five patients (9.6%), and skin blister in five patients (9.6%). CONCLUSION: The reported single-institution experience evidently indicated that ethanol embolotherapy has the potential to successfully devascularize NAVMs and also significantly improve symptoms and signs. Further, it was evident that the use of a combination of transarterial and direct puncture techniques has the potential to increase the rate of therapeutic response in patients with NAVMs.

Absolute Ethanol Embolization of Lip Arteriovenous Malformations: Observational Results from 10 Years of Experience.

PURPOSE: To evaluate the safety and efficacy of ethanol embolization of lip arteriovenous malformations (AVMs). MATERIALS AND METHODS: Seventy-six patients with lip AVMs were treated with 173 ethanol embolization procedures. Lip AVMs were treated with direct puncture alone in 21 patients (35 procedures, 20.2%), transarterial embolization alone in 13 patients (18 procedures, 10.4 %), and a combination of both in 60 patients (120 procedures, 69.3%). Adjunctive surgical resection was performed after embolization for cosmetic purposes based on the patient's request, including patient preference, functional impairment, and skin necrosis. The mean duration of follow-up was 30.9 months ± 27.6. The follow-up included clinic visits and telephonic questionnaires to evaluate the clinical signs and symptoms of AVMs as well as quality of life measures. RESULTS: Of 76 patients, 51 showed 100% devascularization of AVMs, as determined using arteriography, followed by 23 with 76%-99% devascularization and 2 with 50%-75% devascularization. Of the 76 patients, 40 achieved complete symptom relief and 25 achieved major improvements in cosmetic deformity after embolization. Additionally, 54 patients achieved satisfactory function and aesthetic improvement with ethanol embolotherapy alone, whereas 22 achieved similar outcomes with a combination of ethanol embolotherapy and surgical intervention. Thirty-three adverse events (including 1 major) were documented. CONCLUSIONS: Ethanol embolization of lip AVMs, as a mainstay, is efficacious in managing these lesions, with acceptable complications. Surgical resection after embolization may improve function and cosmesis in a subset of patients.

Local suture ligation-assisted percutaneous sclerotherapy for Kasabach-Merritt phenomenon-associated kaposiform haemangioendothelioma.

Kaposiform haemangioendotheliomas (KHEs) complicated by the Kasabach-Merritt phenomenon (KMP) are rare and severe neoplastic lesions often associated with locally aggressive disease, consumption coagulopathy and high mortality rates. Current regimens have yet to achieve a satisfactory therapeutic effect. Thus, an effective and minimally invasive approach for treating complex KHE/KMP cases is necessary for clinical management. The present case series describes patients with KHE/KMP who underwent local suture ligation-assisted percutaneous sclerotherapy to minimise surgical trauma and ensure effective treatment. Between September 2015 and September 2017, 3 consecutive patients with KHE/KMP underwent staged local suture ligation-assisted percutaneous sclerotherapy. Of these patients, 2 presented with medical histories of corticosteroid treatment with unsatisfactory outcomes. The patients underwent a stepwise synthetic serial therapy programme consisting of percutaneous sclerotherapy and adjunctive pharmacotherapy accompanied by a suture ligation procedure. Clinical, radiological, pathological and laboratory data were analysed to evaluate the outcomes of the therapy. All patients were successfully managed with the proposed procedure. Significant relief of clinical symptoms and improvements in haematological indicators were achieved. No recurrence or complications were observed during regular follow-up (4, 19 and 28 months). In conclusion, local suture ligation-assisted percutaneous sclerotherapy was demonstrated to be a safe and effective treatment for KHE/KMP, being minimally invasive, involving simple manipulation and providing a clear treatment benefit in certain cases. Further studies involving larger sample sizes are required to thoroughly evaluate the procedure, which can potentially be used as a novel therapeutic option for KHE/KMP treatment.