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Cobb syndrome is a rare neurocutaneous disease characterized by vascular anomalies involving the skin and spinal cord at the same metamere. The most common initial symptoms are neurological manifestations such as pain, monoparesis, headache, scoliosis, and motor damage. We present two patients with Cobb syndrome and severe disease burden harboring somatic mutations in KRAS. The two patients were subsequently treated with the MEK inhibitor trametinib, indicating the potential therapeutic benefit of this treatment for patients with life-threatening Cobb syndrome who are currently considered incurable.
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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.
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Etanol , Malformaciones Vasculares , Animales , Conejos , Etanol/uso terapéutico , Etanol/farmacología , Masculino , Malformaciones Vasculares/terapia , Malformaciones Vasculares/tratamiento farmacológico , Humanos , Medios de Contraste/farmacocinética , Medios de Contraste/farmacología , Medios de Contraste/uso terapéutico , Yohexol/análogos & derivadosRESUMEN
BACKGROUND: Mandibular arteriovenous malformation (AVM) is rare. Our work aims to introduce the ethanol embolization of a patient suffering from acute oral hemorrhage induced by mandibular AVM. METHODS: A 35-year-old woman without coagulopathy underwent tooth extraction, and the acute oral bleeding occurred intraoperatively. Imaging examinations indicated the enhancement of vascular mass with bone destruction inside the mandible. Angiography finally confirmed the high blood flow nature and the diagnosis of AVM. RESULTS: During the interventional procedure, the coils were first applied into the dilated outflowing vein to slow down the blood flow rate of mandibular AVM. Absolute ethanol was injected in a multi-bolus modality to destroy the nidus of AVM. Her mandibular lesion had been stable in the 12-month re-examined angiography, no further bleeding occurred during the period. CONCLUSIONS: Ethanol embolotherapy was a less invasive, more precise, and quick-action approach managing AVM of the jaw and related emergency medicine.
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Malformaciones Arteriovenosas , Embolización Terapéutica , Etanol , Mandíbula , Hemorragia Bucal , Extracción Dental , Humanos , Femenino , Embolización Terapéutica/métodos , Adulto , Malformaciones Arteriovenosas/terapia , Malformaciones Arteriovenosas/complicaciones , Etanol/administración & dosificación , Extracción Dental/efectos adversos , Hemorragia Bucal/etiología , Hemorragia Bucal/terapia , Mandíbula/irrigación sanguínea , AngiografíaRESUMEN
BACKGROUND: Clinically, arteriovenous malformations in the buttocks (bAVMs) are extremely rare. Our study aimed to evaluate the efficacy and safety of ethanol embolotherapy in managing bAVMs. RESULTS: A total of 32 patients with bAVMs (14 females and 18 males) from 2012 to 2021 were included in this study. All patients underwent complete clinical and imaging examinations. Further, the AVMs lesions were analyzed according to Schöbinger staging and Yakes classification. Each patient had undergone a multistage ethanol embolization. The amelioration of clinical symptoms and devascularization on angiography were evaluated at regular follow-ups. In the present cohort, the 11-20 age group had the most patients (15/32; 46.88%). A total of 124 embolization procedures were performed (average 3.88 procedures per patient), and the average dose of absolute ethanol was 18.96 mL per procedure. Thirteen patients with dominant draining veins underwent additional coil deployment before ethanol embolization (13/32; 40.63%). During follow-ups, clinical improvement was found in 23 of 27 who presented with a pulsating mass (85.19%), 17 of 20 with abnormal local skin temperature (85%), 5 of 6 with bleeding (83.33%), and 5 of 5 patients treated for pain (100%). More than 75% angiographic devascularization was achieved in 18 patients (18/32; 56.25%). Finally, 12 out of 13 patients (92.31%) reduced from Schöbinger Stage III to a lower grade, and ten patients exhibited a complete response (10/32; 31.23%). There was a single serious complication of local necrosis, while neither paranesthesia nor infection was observed postoperatively. CONCLUSIONS: Ethanol embolization assisted with coils can treat bAVMs effectively and safely. The Yakes classification contributed to the optimal ethanol embolotherapy of bAVMs.
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Malformaciones Arteriovenosas , Embolización Terapéutica , Etanol , Humanos , Embolización Terapéutica/métodos , Femenino , Masculino , Etanol/uso terapéutico , Malformaciones Arteriovenosas/terapia , Nalgas/irrigación sanguínea , Adulto , Adulto Joven , Adolescente , Niño , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
A 17-year-old boy with typical neurodevelopment presented with 3 months of lower-limb weakness without a history of trauma. Physical examination, plain radiography and a T2-weighted MRI revealed a port-wine stain over the lumbar region, significant scoliosis below the cervical segment, and a multifocal flow void sign (steal phenomenon) from epidural space to dorso-lumbar spine, respectively (Figure 1). CT angiography identified an enhancing dorsal vascular mass with involvement of the spinal canal including destruction of the vertebral body determined to be extensive arteriovenous shunts on digital subtraction angiography (DSA) (Figure 2).
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Escoliosis , Canal Medular , Masculino , Humanos , Adolescente , Radiografía , Vértebras Lumbares , Espacio Epidural , Imagen por Resonancia Magnética , Angiografía de Substracción DigitalRESUMEN
PURPOSE: To investigate the efficacy and safety of interventional embolization in the treatment of frontal arteriovenous malformation (AVM). METHODS: A retrospective study was used to analyze 9 patients with frontal AVM who were treated in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The patients were treated with interventional embolization under the guidance of DSA. The scope of lesions was observed through DSA, and the injection dose of sclerosing agent was predicted so that the drug could be injected into the lesion cavity. The efficacy, adverse reactions and complications of all patients were observed and analyzed. RESULTS: Among the 9 patients, there were 7 males(77.8%) and 2 females(22.2%), aged from 1.5-20 years old. Local swelling or mass was the main reported symptom(66.7%). The blood supply arteries of the cases involved in this study included superficial temporal artery and ophthalmic artery. All patients received interventional embolization treatment under general anesthesia, a total of 19 times (each patient received 1-6 times, average 2.1 times/person), and the average single dose of absolute ethanol was 9.0 mL. A total of 80 coils (4.2 coils/time on average) were used for 5 times (80 coils/19 times) with absolute ethanol embolization. In addition, bleomycin was used 3 times, pingyangmycin was used 2 times, and 3% polydocanol was used 1 time to assist embolization. Among the 9 cases included in this study, 4 cases were cured, 3 cases were basically cured, 2 cases were improved, and the effective rate of treatment was 100%. No local or systemic complications were reported in all patients. CONCLUSIONS: In the treatment of frontal arteriovenous malformation, correct diagnosis according to clinical and imaging manifestations, and interventional embolization with anhydrous ethanol according to DSA angiography results can reduce trauma, improve symptoms, control lesions, and obtain relatively satisfactory treatment results. This scheme is safe and effective.
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Malformaciones Arteriovenosas , Embolización Terapéutica , Masculino , Femenino , Humanos , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Estudios Retrospectivos , China , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/terapia , Resultado del Tratamiento , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , EtanolRESUMEN
PURPOSE: The present work aimed to determine the different angio-architectural types of palpebral arteriovenous malformations (pAVMs) and appropriate ethanol embolotherapy for each type. MATERIALS AND METHODS: This was a multi-center comparative effectiveness research retrospectively conducted from November 2012 to October 2021. A total of 70 patients with pAVMs were included, which was classified into cystic pAVMs (n=29) and diffuse pAVMs (n=41) based on the angio-architecture. Of the included patients, 17 with cystic pAVMs and 13 with diffuse pAVMs underwent ethanol embolization combined with coils (CE). The remaining participants underwent no-coil ethanol embolization (NCE). Participants had undergone 60 months of follow-up. Normality of data was tested by the D'Agostino and Pearson test. Correlation was tested by the Pearson χ2 test. Deterioration-free survival (DFS) rate was estimated using the Kaplan-Meier survival analysis. Multivariate Cox regression models included variables that were significant at a p value<0.05 in the univariate analysis to screen the prognostic factor. RESULTS: The local symptoms of pAVMs, including pulsation, warmth, red plaque, blepharoptosis, bleeding, and visual blurring, along with the devascularizational grade of angiography were recorded before and after the respective procedures. Post-treatment complications were either evaluated at the 3-month routine follow-up or were self-reported by patients. Cystic pAVMs presented with significantly different clinical and angiographic features compared with diffuse pAVMs. With CE, patients with cystic pAVMs obtained a higher devascularizational grade (p<0.0001) and better clinical outcomes (p=0.0009) than those with diffuse pAVMs. Contrarily, with NCE, patients with diffuse pAVM had better outcomes than those with cystic pAVMs (p=0.0248). Moreover, the overall DFS rate was higher in patients with cystic pAVMs (p=0.0006). Finally, the angio-architecture of pAVMs was found to independently influence its prognosis (p=0.02). CONCLUSIONS: In pAVMs, the angio-architectural type was associated with the relative prognostic status. Ethanol embolization combined with coils was an effective method to treat cystic pAVMs, whereas NCE was more suitable for the diffuse type, further emphasizing the importance of a type-based therapeutic strategy for pAVMs. CLINICAL IMPACT: Palpebral arteriovenous malformations (pAVMs) are rare and tricky in clinical practices. The present study has divided the pAVMs into cystic and diffuse types according to their angiographic characteristics. Ethanol embolization with (CE) or without coils (NCE) was performed on both types. CE was suitable for cystic pAVMs; whereas NCE was a better choice for diffuse pAVMs. The five-year survival analyses provided evidence of the safety and efficacy of ethanol application in pAVMs. Finally, our work demonstrated that both the short- and long-term clinical outcomes of diffuse pAVMs were poor compared to those of cystic pAVM.
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OBJECTIVE: This study aimed to evaluate the outcomes of coil-assisted ethanol embolotherapy in recanalized head and neck arteriovenous malformations (HNAVMs) with dilated outflowing veins after Onyx treatment. METHODS: Thirty-six patients with HNAVMs (18 females and 18 males with a mean age of 26.83 years) who experienced recurrence after Onyx embolization from October 2007 to October 2017 were included in this study. All patients underwent complete clinical and angiographic examinations. Further, each patient was classified based on the Schobinger stage before undergoing staged ethanol embolization. All patients were followed up for 5 years in-person at an interval of 3 months after discharge. The Kaplan-Meier method was used to perform the recurrence-free survival analysis. RESULTS: Sixteen patients (44.4%) had Schobinger stage II HNAVMs, and the remaining patients had Schobinger stage III or IV (20/36 patients [55.6%]) HNAVMs. A total of 116 embolization procedures were performed, coils were applied in 107 procedures (92.2%) among patients with dilated outflowing veins. The dose of absolute ethanol was 16.39 mL per procedure in patients with Schobinger II HNAVMs, and 22.45 mL per procedure in patients with Schobinger III and IV HNAVMs (P = .024, 95% confidence interval, 1.128-5.009). During the 3-month evaluation, complete response was observed in 13 of 36 patients (36.1%), and partial response was observed in 23 of 36 patients (63.9%). The 5-year recurrence-free survival rate for patients who underwent Onyx treatment had improved 58.3% after ethanol embolization (95% confidence interval, 2.853-9.595; P < .0001). CONCLUSIONS: Coil-assisted ethanol embolotherapy could treat refractory HNAVMs with Onyx recrudescence effectively.
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Malformaciones Arteriovenosas , Embolización Terapéutica , Masculino , Femenino , Humanos , Adulto , Etanol/efectos adversos , Resultado del Tratamiento , Estudios Retrospectivos , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/terapia , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodosRESUMEN
OBJECTIVE: In the present study, we summarize our experience in locating the nidus of arteriovenous malformations (AVMs) with a dominant outflow vein (DOV) in the lower extremities and eradicating the nidus with ethanol and coils. METHODS: Twelve patients with lower extremity AVMs who underwent ethanol embolization combined with DOV occlusion from January 2017 to May 2018 were enrolled in the present study. Selective angiography was used to locate the nidus of the AVMs, which was eradicated using ethanol and coils via the direct puncture pathway. All treated patients underwent postoperative follow-up (mean, 25.5 months; range, 14-37 months). RESULTS: The 12 patients underwent a total of 29 procedures (mean, 2.4; range, 1-4) with 27 detachable coils and 169 Nester coils (Cook Medical Inc, Bloomington, IN). Of the 12 patients, 7 (58.3%) had a complete response and 5 (41.7%) a partial response. Three patients (25%) had minor complications such as blister and superficial skin ulcers during follow-up. However, they recovered spontaneously and completely. No major complications were recorded. CONCLUSIONS: Ethanol embolization combined with coil-assisted DOV occlusion has the potential to eradicate the nidus of lower extremity AVMs with acceptable complication rates.
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Malformaciones Arteriovenosas , Embolización Terapéutica , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/terapia , Etanol/efectos adversos , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Extremidad InferiorAsunto(s)
Cicatriz , Malformaciones Vasculares , Humanos , Cicatriz/etiología , Cicatriz/patología , Úlcera , CapilaresRESUMEN
BACKGROUND: Venous malformation (VM) is a kind of congenital vascular anomaly with a high incidence of recurrence, detailed pathogenesis and standard treatment of VM still lack now. Increasing evidence showed exosomal RNA plays a pivotal role in various diseases. However, the underlying mechanism of VM based on the potential differentially exosomal RNAs remains unclear. METHODS: Comparative high-throughput sequencing with serum exosomes from three VM patients and three healthy donors was used to explore differentially expressed (DE) circRNAs, DE lncRNAs, and DE mRNAs involving the formation of VM. We identified and verified DE circRNAs, DE lncRNAs, and DE mRNAs via qRT-PCR assay. We explored the potential functions of these exosomal DE non-coding RNAs via performing further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Besides, circRNA/lncRNA-miRNA-mRNA linkages were also constructed to find their potential relationships in VM. RESULTS: A total of 121 circRNAs, 53 lncRNAs, and 42 mRNAs (|log2 FC| ≥ 2.0, FDR <0.05, n = 3) were determined to be differentially expressed. QRT-PCR validated that these top-changed DE circRNAs, lncRNAs, and mRNAs had significant expression changes. Functional studies demonstrated that DE circRNAs play a pivotal role in thyroid hormone signaling pathway, DE lncRNAs function as a key regulator in MAPK signaling pathway and DE miRNAs participate in the process of hepatocellular carcinoma mostly. CONCLUSION: Our study comprehensively depicted exosomal DE non-coding RNAs networks related to the pathogenesis of VM which can provide new insight into, a novel target for treating VM.
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MicroARNs , ARN Largo no Codificante , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Circular/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Perfilación de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
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.
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PURPOSE: Here, we report our experience treating a patient with Maffucci syndrome and evaluate the outcomes resulting from surgical management combined with sclerotherapy in the treatment of head and neck venous malformations (VMs). A 19-years-old woman with multiple enchondromas and heterauxesis complained of masses in the oral cavity that had gradually increased in size and eventually affected her daily life. A tracheotomy was performed followed by traditional sclerotherapy to treat the oropharyngeal VMs. Next, we surgically excised the VMs of the oral cavity and maxillofacial skin. RESULTS: Magnetic resonance imaging indicated that the oral VMs were nearly eradicated and the oropharyngeal VMs had stabilized. The patient's appearance and normal maxillofacial region function were restored. CONCLUSION: In summary, local resection combined with sclerotherapy facilitated timely and efficient VMs removal from the head and neck region of a patient with Maffucci syndrome.
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Encondromatosis , Enfermedades Vasculares , Malformaciones Vasculares , Humanos , Femenino , Adulto Joven , Adulto , Escleroterapia/métodos , Resultado del Tratamiento , Cuello , Venas/anomalías , Malformaciones Vasculares/terapiaRESUMEN
This study aimed to examine whether the administration of losartan can prevent acute elevation of pulmonary arterial pressure (AEPAP) induced by endovascular ethanol injection and to assess its related mechanisms. Male swine were selected and performed with absolute ethanol endovascular injection. Saline was used as the negative control. Losartan was administered preoperatively. Pulmonary arterial pressure (PAP), femoral arterial pressure (FAP) and heart rate (HR) were monitored during operations. Venous plasma and pulmonary artery (PA) tissue were harvested for analyses. Protein level was detected by Western blotting and ELISA, whereas qRT-PCR was used in mRNA detection. H & E staining and immunohistochemistry were conducted to evaluate histopathology. Ethanol injection elevated PAP in swine. The concentration of RAS ligands was elevated in plasma (all P < 0.0001) but not in PA. The level of oxidative stress increased in both plasma and PA. MRNA level of AT1R (P < 0.01, 95% CI: 0.251-1.006), not AT2R increased in PA. Losartan failed to inhibit AEPAP after all sessions of ethanol injection, and partially reversed the ethanol-induced PA remodeling. The P38 MAPK was activated after ethanol injection and could be inhibited by losartan (P < 0.01, 95% CI: -0.391 to -0.164). Ethanol also promoted the translocation of the P40-PHOX/P47-PHOX/P67-PHOX complex and the activation of NOX, which was independent from RAS. Endovascular ethanol injection can induce AEPAP mainly by activating RAS and P38 MAPK signaling. Losartan can partially prevent AEPAP and vascular remodeling owing to the promotion of NOX activity by ethanol. Mechanism diagram of endovascular ethanol injection-induced acute elevation of pulmonary arterial pressure (AEPAP) partially prevented by losartan. RAS: Renin-angiotensin system; AGT: angiotensinogen; Ang I: angiotensin I; ACE: angiotensin I converting enzyme; Ang II: angiotensin II. AT1R: angiotensin II type 1 receptor. NOX2: NADPH oxidase 2. PA: pulmonary artery.
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Presión Arterial , Losartán , Masculino , Animales , Porcinos , Losartán/farmacología , Losartán/uso terapéutico , Receptor de Angiotensina Tipo 1/metabolismo , Sistema Renina-Angiotensina , Angiotensina II/farmacología , Angiotensina II/metabolismo , ARN Mensajero/metabolismo , Etanol/farmacología , Receptor de Angiotensina Tipo 2/metabolismoRESUMEN
We aimed to identify a novel prognostic biomarker for head and neck squamous cell carcinoma (HNSCC) based on tumor immunology-related alternative splicing (AS). Data for 502 HNSCC and 44 normal samples were obtained from the TCGA database and used to establish an AS-related risk model through univariate, least absolute shrinkage, and selection operator Cox regression analyses. Fresh HNSCC and normal oral tissues were surgically obtained from 44 HNSCC patients. Western blotting and quantitative reverse transcription-PCR were used to assess gene expression levels. Kaplan-Meier was performed to evaluate patients' overall survival (OS) rate. The CIBERSORT algorithm, single-sample gene set enrichment analysis, and immune checkpoint analyses were performed to compare immune activities between subgroups. The risk model was established using 10 pivotal AS events first. Collagen Type III Alpha 1 Chain (COL3A1) were screened based on |log2FC| ≥ 1 and FDR < 0.05 criteria. COL3A1 expression levels in HNSCC tissues were elevated relative to normal tissues (p < 0.001). Moreover, COL3A1 was a reliable biomarker for HNSCC patients' prognostic prediction in both cohorts (p < 0.001, p = 0.0085, respectively). COL3A1 protein (p = 0.0054) and mRNA (p < 0.0001) levels were correlated with HNSCC differentiation. Furthermore, the T stage was correlated with COL3A1 expression (p = 0.043), and COL3A1 expression was an independent prognostic predictor for HNSCC patients (p = 0.006). Compared with the risk model, COL3A1 was better at evaluating immune cell infiltrations, immune activities, and immune checkpoint gene expressions of HNSCC lesions.
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Empalme Alternativo , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Pronóstico , Neoplasias de Cabeza y Cuello/genética , Análisis de Regresión , Microambiente Tumoral/genética , Colágeno Tipo IIIRESUMEN
@#Vascular malformations, which mainly occur in the head and neck region, are a group of congenital disorders that cannot involute and dilate gradually as patients grow. Traditional therapeutic strategies for vascular malformations include laser therapy, sclerotherapy, interventional embolization, surgical resection, etc. However, for some cases with a relatively larger range of lesions, traditional therapeutic strategies might fall short of the goals. With the development of molecular genetics, gene mutations are currently recognized as the root cause of the occurrence of vascular malformations. The progression of vascular malformation lesions is further promoted by the activation of related pathways. Low-flow vascular malformations mainly involve activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, whereas high-flow vascular malformations mainly involve activation of the rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MAPKK)/extracellular-signal regulated protein kinase (ERK) pathway. Targeted drugs against relevant gene mutations and signaling pathways have also been applied in the treatment of vascular malformations, and previous studies have shown that the mTOR inhibitor rapamycin is effective and now widely used in the treatment of low-flow vascular malformations. The PI3K inhibitor alpelisib is also promising in the treatment of venous malformations, and the MAPKK inhibitor trametinib has shown good results in the treatment of arteriovenous malformations. Therefore, traditional therapies supplemented by targeted drugs may bring new breakthroughs to the treatment of vascular malformations.
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Based on the latest classification by the International Society for the Study of Vascular Anomalies in 2018, vascular malformations (VMs) can be categorized into simple, combined VMs of major named vessels, and VMs associated with other anomalies. Simple VMs include lymphatic, venous, capillary, and arteriovenous malformations (AVMs). AVMs represent disorders of direct arteriovenous shunts caused by the absence of a capillary bed between the involved arteries and veins. This abnormal vascular communication causes arterial blood to accumulate in the venous vessels, thus resulting in venous hypertension and characteristic clinical manifestations, such as pulsation, tremors, and elevated temperature. AVMs can occur sporadically or as manifestations of syndromic lesions and are considered among the most complex and challenging VMs. The diagnosis and treatment of AVMs can vary depending on the lesion location and associated clinical symptoms, thus complicating their management. Herein, we discuss peripheral AVMs in terms of their clinical manifestations, imaging examinations, and staging systems to provide a comprehensive reference for the treatment, evaluation methods, and follow-up procedures for this vascular anomaly.
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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.
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PURPOSE: Maxillary arteriovenous malformations (AVMs) are uncommon, limiting comprehensive research into standard treatment protocols. This study evaluated the management, outcomes, and clinical safety of embolization techniques for maxillary AVMs, using coils and ethanol. METHODS: In this retrospective case series, we enrolled a sample of patients with maxillary AVMs treated with embolization using coils with or without ethanol between June 2017 and July 2019. Coils were super-selectively placed into the nidus and dominant outflow vein to decrease the flow of the arteriovenous fistulas. Absolute ethanol was then injected to obliterate the nidus. Clinical follow-up was performed for all the patients, and therapeutic outcomes were measured by evaluating the degree of devascularization and symptoms. RESULTS: Ten patients were included in the present study, including 4 men (40%) and 6 women (60%), with a mean age of 18.1 years (range, 10 to 36 years). Transvenous release of coils (9 detachable coils and 143 pushable coils), either with or without absolute ethanol embolization, was used in all the patients. The amount of ethanol injected ranged from 0 to 12 mL (mean: 6.5 mL; 95% confidence interval: 3.489 to 9.511) in a single session. Seven (70%) of the 10 patients were cured, while 3 patients (30%) had partial remission. Follow-up times ranged from 26 to 42 months (median: 29.7 months). Tooth loosening and coil exposure occurred in 7 patients (70%) and healed after surgery. No major complications were noted. CONCLUSIONS: Coils and ethanol embolization have the potential to cure AVMs in the maxilla with an acceptable risk of minor complications.