MEK inhibitors for the treatment of extracranial arteriovenous malformations

Arteriovenous malformations(AVMs)are serious congenital vascular anomalies in which the arteries connect directly with veins without capillaries.This condition will continue to worsen without proper intervention and cause ulcers,repeated hemorrhages,and even cardiac insufficiency.Primary treatment options for AVMs include surgery and interventional treatment;however,they are associated with high risk and recurrence rates.Recent studies revealed that excessive activation of the Ras/MAPK pathway can induce the formation and development of peripheral AVM,whereas MEK inhibitors can effectively control nidus progression,making them a potential novel treatment for AVM.This review provides an up-to-date overview of correlated laboratory and clinical research to provide information for further research and clinical practice.

Absolute ethanol embolization for treatment of peripheral arteriovenous malformations

Arteriovenous malformations(AVMs)are aggressive congenital high-flow vascular anomalies,in which the feeding artery and draining vein are connected through fistulas without normal capillary networks.In severe cases,the condition may cause swelling,ulceration,bleeding,and even heart failure.Various treatment options are available for AVMs,including laser,surgical resection,embolization,and targeted drug therapy.With the development of endovascular treatment technology,absolute ethanol embolization of AVMs has become one of the first-line therapies owing to its sustained efficacy and low recurrence rate.However,administration of this therapy is challenging and may lead to serious complications if inappropriately managed.In this article,we reviewed and summarized previous clinical articles,literature reviews,and clinical trial data to comprehensively describe clinical manifestations of AVMs,the mechanism of ethanol embolotherapy,key points in treatment and management of complications,and issues that need to be addressed.We expect to provide a reliable information reference source for clinical physicians and researchers.

Bleomycin inhibits CLEC14A to attenuate the progression of extracranial arteriovenous malformations

Background:We previously reported that interstitial injection of bleomycin(BLM)reduces the size of early-stage extracranial arteriovenous malformation(AVM).Here,we sought to investigate the potential mechanism of BLM in treating extracranial AVM.Methods:Samples of human extracranial AVM(n=3)with no pharmacological treatment were harvested.AVM endothelial cells were isolated and cultured in primary cell culture.The transcriptome was examined using RNAsequencing,and differentially expressed C-type lectin domain family 14 member A(CLEC14A)was validated at the transcriptomic and protein levels.Immunocytochemical staining of CLEC14A was performed in samples of human extracranial AVM,with and without BLM treatment.Results:Through second-generation sequencing,we found that the expression of 5689 genes were differentially increased or decreased following 24-h BLM stimulation.We found that CLEC14A may play an important role in the progression of AVM and can be inhibited by BLM treatment.Conclusion:BLM inhibited CLEC14A expression to attenuate the progression of AVM.

Systemic Hemodynamic Changes in Low-Dose Ethanol Embolotherapy for Soft-Tissue Arteriovenous Malformations

Background Ethanol embolotherapy is considered an optimal choice for the treatment of arteriovenous malformations(AVMs);however,there are some complications associated with this treatment.This study aimed to prospectively investigate systemic hemodynamic changes in high-flow AVMs using ethanol embolotherapy.Methods From September 2012 to September 2014,34 male patients and 26 female patients with AVMs who underwent embolotherapy(100 sessions in total)with absolute ethanol were included in this study.Invasive systolic blood pressure(SBP)and heart rate(HR)were recorded before and after each injection and throughout the procedure.Differences between the initial and highest SBP(ΔmaxSP)and HR values(ΔmaxHR),as well as the initial and final SBP(ΔSP)and HR(ΔHR)values,were analyzed.We aimed to explore the potential association between these values and the amount of ethanol that was used.Results The total ethanol used was variable(0.01–0.40 mL/kg;mean,0.20 mL/kg).SBP and HR increased after ethanol injection in most sessions(91 in 100 sessions).SBP decreased in 9 sessions(9 in 100 sessions),while HR,oxygen saturation,and end-tidal CO2 decreased in one of the 9 sessions.ΔmaxSP andΔmaxHR averaged 38.4 mmHg and 27.8 bpm,respectively(both P<0.05),whileΔSP andΔHR averaged 3.4 mmHg and 4.0 bpm,respectively(both P<0.05).ΔmaxSP andΔmaxHR were positively correlated with the total dose of ethanol injected.Conclusions Elevations in SBP and HR during ethanol embolotherapy are common,temporary,and most likely pain-mediated;these increases tend to be positively correlated with ethanol dose.Hypotension may be regarded as an acute complication of ethanol embolotherapy.Hypotension combined with bradycardia,oxygen desaturation,and decreased end-tidal CO2 may be a potential predictor of cardiovascular collapse.

A Fast and Effective Surgical Method for a Painful Skin Lesion

Background Eccrineangiomatoushamartoma(EAH)is a rare benign disease that comprises vascular and eccrine malformations.Pain is one of the most common symptoms and surgical resection is generally required.Objective To report a novel surgical technique that can alleviate severe pain caused by a large lesion in an EAH patient.Methods On magnetic resonance imaging(MRI),a subcutaneous abnormal signal was detected in the right hip and groin area of an 18-year-old male.The lesion was carefully elevated from the normal tissue above the plane of the deep fascia and was sutured in situ.Additionally,a small sample of the central lesion tissue was collected for histological examination.Results The visual analog scale score of pain decreased from 9 points to 2 points at 1week and to 0 points at 2 weeks after the surgery.The only complication observed was local numbness,which recovered spontaneously.No recurrence of pain was observed after 1 year of surgery.Histological findings demonstrated that the numbers of eccrine sweat glands and abnormal vessels decreased post-surgery.Conclusion The surgical procedure used in our case may represent a novel,easy,safe,and effective option for the treatment of a large,severely painful EAH.

Intralesional Interstitial Injection of Bleomycin for Management of Extracranial Arteriovenous Malformations in Children

Background Despite many advances in the treatment for extracranial arteriovenous mal­formations(AVMs),they still result in tedious dissection and potential unacceptable com­plications,particularly in children.Therefore,this study aimed to investigate the efficacy and safety of intralesional interstitial injection of bleomycin for the treatment of children with AVMs.Methods A total of 10 children(6 boys and 4 girls)with AVMs were treated with serial interstitial bleomycin injections between May 2014 and January 2017.Maximum single doses of 15 U and 1 U/kg per session were administered for six sessions at a 1-month inter­val.Therapeutic effectiveness was evaluated and classified into four categories:complete response(CR),partial response(PR),no response,and worsening at 3 months after the last session.Further clinical follow-up outcomes were classified as improved,stable,or aggra­vated.Adverse events were recorded according to the Society of Interventional Radiology classification.Results All 10 children completed the sessions and follow-ups.CR occurred in 3(30%)patients,PR in 6(60%),and no response in 1(20%).Minor complications(class A)included maculopapular rash,bulla,vomiting,and hyperpigmentation,whereas no major complications occurred.Conclusion Intralesional interstitial injection of bleomycin is a feasible approach for the treatment of AVMs in children and provides safe and effective outcomes.This method may be an earlier treatment alternative in children to prevent potential destructive progression,considering the serious complications of currently available therapeutic methods.

Flame Burn Injury in Yichang of China:the Trends,Complications,and Risk Factor Analysis

Background A flame burn is an injury of body tissues,including respiratory tract damage,due to exposure to a flame or its dense smoke.Flame burns cause some of the most physically and psychologically devastating forms of trauma.Compared to scald burns,flame burn patients have a higher mortality rate and a higher frequency of multiorgan failure.The purpose of this research was to investigate the trends,complications,and mortality risk factors of flame burns at the Department of Plastic and Burn Surgery(DPBS)of the People’s Hospital of China Three Gorges University(PHCTGU).Methods A retrospective analysis of 48 flame burn patients—accounting for 8.3%of the 576 burn victims admitted for burns at the PHCTGU from February 1,2010,to September 30,2019—was performed after collecting information from the Burns Registry of the said hospital.Results The proportion of patients with flame burns was 8.3%(n=48).The mean total body surface area(TBSA)affected was 27.6%.The mean duration of hospitalization was 32.5 days.The etiologies of the flame burns were as follows:gas explosions(21,43.8%),ethanol(8,16.7%),charcoal fire(7,14.6%),petrol explosions(4,8.3%),wooden houses(4,8.3%),and others,including dust,cigarette lighter,and burning incense,accounting for 8.3%of cases(4).Finally,42(87.5%)patients were treated and discharged,and 6(12.5%)patients died.Complications included scarring in 38(90.5%)patients,severe scar contractures on different parts of the body in 25(60.0%)patients,scar ulcer in 6(14.3%)patients,keloids in 3(7.1%)patients,and scar cancer in 1(2.4%)patient.Multiple complications occurred in the same patient.The only risk factor for mortality that was identified was TBSA(P=0.043).Conclusions Our study revealed that a small population(8.3%)was injured by flame burns,but 6 deaths were recorded.Society must continually enhance safeguard procedures to flames and strengthen education to protect life and avoid severe complications.