Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Long-term outcomes of titanium-nitride-oxide coated stents and drug-eluting stents in acute coronary syndrome:A systematic review and meta-analysis

BACKGROUND In severe cases of coronary artery disease,percutaneous coronary intervention provide promising results.The stent used could be a drug-eluting stent(DES)or a titanium-nitride-oxide coated stent(TiNOS).AIM To compare the 5-year effectiveness and safety of the two stent types.METHODS The following systematic review and meta-analysis was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines,and PubMed/MEDLINE,Scopus,and Cochrane Central were searched from inception till August 2023.Primary outcomes were major adverse cardiac events(MACE),cardiac death,myocardial infarction(MI),cardiac death or MI,and ischemia-driven total lesion revascularization(ID-TLR).RESULTS Four randomized controlled trials(RCT),which analyzed a sum total of 3045 patients with acute coronary syndrome(ACS)after a median follow-up time of 5 years were included.Though statistically insignificant,an increase in the ID-TLR was observed in patients receiving TiNOSs vs DESs.In addition,MI,cardiac death and MI,and definite stent thrombosis(DST)were significantly decreased in the TiNOS arm.Baseline analysis revealed no significant results with meta-regression presenting non-ST elevated MI(NSTEMI)as a statistically significant covariate in the outcome of MACE.CONCLUSION TiNOS was found to be superior to DES in terms of MI,cardiac death or MI,and DST outcomes,however,the effect of the two stent types on ID-TLR and MACE was not significant.A greater number of studies are required to establish an accurate comparison of patient outcomes in TiNOS and DES.

Prolonged dual antiplatelet therapy after drug-eluting stent implantation improves long-term prognosis for acute coronary syndrome:five-year results from a large cohort study

BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of China.METHODS:We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013.Patients were divided into four groups based on DAPT duration:standard DAPT group(11-13 months,n=1,568)and prolonged DAPT groups(13-18 months[n=308],18-24 months[n=2,125],and>24 months[n=1,186]).Baseline characteristics and 5-year clinical outcomes were recorded.RESULTS:Baseline characteristics were similar across the four groups.Among the four groups,those with prolonged DAPT(18-24 months)had the lowest incidence of major adverse cardiovascular and cerebrovascular events(MACCEs)(14.1%vs.11.7%vs.9.6%vs.24.2%,P<0.001),all-cause death(4.8%vs.3.9%vs.2.1%vs.2.6%,P<0.001),cardiac death(3.1%vs.2.6%vs.1.4%vs.1.9%,P=0.004),and myocardial infarction(MI)(3.8%vs.4.2%vs.2.5%vs.5.8%,P<0.001).The incidence of bleeding was not different among the four groups(9.9%vs.9.4%vs.11.0%vs.9.4%,P=0.449).Cox multivariable analysis showed that prolonged DAPT(18-24 months)was an independent protective factor for MACCEs(hazard ratio[HR]0.802,95%confidence interval[CI]0.729-0.882,P<0.001),all-cause death(HR 0.660,95%CI 0.547-0.795,P<0.001),cardiac death(HR 0.663,95%CI 0.526-0.835,P<0.001),MI(HR 0.796,95%CI 0.662-0.957,P=0.015),and target vessel revascularization(HR 0.867,95%CI 0.755-0.996,P=0.044).Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs.CONCLUSION:For patients with ACS after DES,appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.

Meta-analysis of outcomes from drug-eluting stent implantation in infrapopliteal arteries

BACKGROUND Percutaneous drug-eluting stent implantation(DESI)is an emerging and promising treatment modality for infrapopliteal artery diseases(IPADs).This systematic review and meta-analysis summarizes and quantitatively analyzes the outcomes of DESI in IPADs considering the hazard ratio(HR),which is a more accurate and appropriate outcome measure than the more commonly used relative risk and odds ratio.AIM To explore the superiority of drug-eluting stents(DESs)vs traditional treatment modalities for IPADs.METHODS The following postoperative indicators were the outcomes of interest:All-cause death(ACD)-free survival,major amputation(MA)-free survival,target lesion revascularization(TLR)-free survival,adverse event(AE)-free survival,and primary patency(PP)survival.The outcome measures were then compared according to their respective HRs with 95%confidence intervals(CIs).The participants were human IPAD patients who underwent treatments for infrapopliteal lesions.DESI was set as the intervention arm,and traditional percutaneous transluminal angioplasty(PTA)with or without bare metal stent implantation(BMSI)was set as the control arm.A systematic search in the Excerpta Medica Database(Embase),PubMed,Web of Science,and Cochrane Library was performed on November 29,2022.All controlled studies published in English with sufficient data on outcomes of interest for extraction or conversion were included.When studies did not directly report the HRs but gave a corresponding survival curve,we utilized Engauge Digitizer software and standard formulas to convert the information and derive HRs.Then,meta-analyses were conducted using a random-effects model.RESULTS Five randomized controlled trials and three cohort studies involving 2639 participants were included.The ACDfree and MA-free survival HR values for DESI were not statistically significant from those of the control treatment(P>0.05);however,the HR values for TLR-free,AE-free,and PP-survival differed significantly[2.65(95%CI:1.56-4.50),1.57(95%CI:1.23-2.01),and 5.67(95%CI:3.56-9.03),respectively].CONCLUSION Compared with traditional treatment modalities(i.e.,PTA with or without BMSI),DESI for IPADs is superior in avoiding TLR and AEs and maintaining PP but shows no superiority or inferiority in avoiding ACD and MA.

Drug-eluting fully covered self-expanding metal stent for dissolution of bile duct stones in vitro

BACKGROUND The treatment of difficult common bile duct stones(CBDS)remains a big challenge around the world.Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography.Fully covered self-expanding metal stent(FCSEMS)has gained increasing attention in the management of difficult CBDS.AIM To manufacture a drug-eluting FCSEMS,which can achieve controlled release of stone-dissolving agents and speed up the dissolution of CBDS.METHODS Customized covered nitinol stents were adopted.Sodium cholate(SC)and disodium ethylene diamine tetraacetic acid(EDTA disodium,EDTA for short)were used as stone-dissolving agents.Three different types of drug-eluting stents were manufactured by dip coating(Stent I),coaxial electrospinning(Stent II),and dip coating combined with electrospinning(Stent III),respectively.The drugrelease behavior and stone-dissolving efficacy of these stents were evaluated in vitro to sort out the best manufacturing method.And the selected stonedissolving stents were further put into porcine CBD to evaluate their biosecurity.RESULTS Stent I and Stent II had obvious burst release of drugs in the first 5 d while Stent III presented controlled and sustainable drug release for 30 d.In still buffer,the final stone mass-loss rate of each group was 5.19%±0.69%for naked FCSEMS,20.37%±2.13%for Stent I,24.57%±1.45%for Stent II,and 33.72%±0.67%for Stent III.In flowing bile,the final stone mass-loss rate of each group was 5.87%±0.25%for naked FCSEMS,6.36%±0.48%for Stent I,6.38%±0.37%for Stent II,and 8.15%±0.27%for Stent III.Stent III caused the most stone mass-loss no matter in still buffer or in flowing bile,which was significantly higher than those of other groups(P<0.05).In vivo,Stent III made no difference from naked FCSEMS in serological analysis(P>0.05)and histopathological examination(P>0.05).CONCLUSION The novel SC and EDTA-eluting FCSEMS is efficient in diminishing CBDS in vitro.When conventional endoscopic techniques fail to remove difficult CBDS,SC and EDTA-eluting FCSEMS implantation may be considered a promising alternative.

Efficacy of intra-arterial contrast-enhanced ultrasonography during transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma

AIM To assess the usefulness of intra-arterial contrastenhanced ultrasonography(IAUS) during transarterial chemoembolization(TACE) with drug-eluting beads(DEB) for hepatocellular carcinoma(HCC).METHODS Thirty two patients with 39 HCC underwent DEB-TACE guided with IAUS, and examined by contrast-enhanced ultrasonography(CEUS) or dynamic CT after DEB-TACE were enrolled in this study. CEUS findings before DEBTACE and IAUS findings were compared. Treatments judged to be complete and incomplete for lesions were appropriate and insufficient, respectively. Findings on CEUS and/or dynamic CT performed 1, 3 and 6 mo after DEB-TACE were evaluated using m RECIST(CR/PR/SD/PD).RESULTS The treatments were complete and incomplete in 26 and 13 lesions, respectively. On imaging evaluation using CEUS and/or dynamic CT one month after treatment, 25 and 1 lesions were judged to be CR and PR, respectively, and at 6 mo after treatment, the results were CR, PR, SD and PD for 24, 1, 0 and 1 of these lesions, respectively, in the 26 completely treated lesions. Of the 13 lesions in which treatment was incomplete, the results on imaging at one month after treatment were CR, PR, SD and PD for 0, 6, 4 and 3 lesions, respectively. The overall CR rate at 6 mo after treatment was 61.5%(24/39).CONCLUSION A combination of DEB-TACE with IAUS can improve the therapeutic effects in patients with HCC.

Conventional vs drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma

Transarterial chemoembolization(TACE) is the current standard of therapy for patients with intermediatestage hepatocellular carcinoma(HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE(cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drugeluting beads(DEBs) have been imposed as novel drugdelivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEBTACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.

Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma

Transarterial chemoembolization(TACE) is a widely used standard treatment for patients with hepatocellular carcinoma(HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia(conventional TACE). Recently, drugeluting beads(DC Beads?) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads? can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads? substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drugeluting beads for the treatment of HCC and discuss future therapeutic possibilities.

Advances in the treatment of hepatocellular carcinoma using drug-eluting beads

Hepatocellular carcinoma(HCC)is one of the most common types of malignant tumor.Although radical surgery and liver transplantation are possible cures for the disease,most patients are beyond the optimum stage for radical treatment at the time of diagnosis.Transarterial chemoembolization(TACE)is the first choice of treatment for advanced HCC.Owing to the widespread use of conventional TACE(cTACE),the problems with this treatment cannot be ignored.Drug-eluting beads(DEBs),a new type of embolization material,appear to overcome the problems of cTACE,and they have other advantages such as synchronous controlled continuous drug release after chemotherapy and embolization and low blood concentrations after treatment.This review summarizes the recent advances in the use of DEB-TACE to treat HCC.

Conventional versus drug-eluting bead transarterial chemoembolization:A better option for treatment of unresectable hepatocellular carcinoma

Transarterial chemoembolization(TACE) is a minimally invasive procedure involving intra-arterial catheter-based chemotherapy to selectively administer high doses of cytotoxic drugs to the tumor bed along with ischemic necrosis induced by arterial embolization.Chemoembolization forms the essential core of management in patients with hepatocellular carcinoma(HCC) who are not suitable for curative therapies such as transplantation,resection,or percutaneous ablation.TACE of hepatic cancer(s) has proven to be helpful in achieving local tumor control,and has supported the ability to prevent tumor progression,prolong patient life,and manage patient symptoms.Recent data have demonstrated that,in patients with single-nodule HCC ≤3 cm without vascular invasion,the 5-year overall survival with TACE was found to be comparable with hepatic resection and radiofrequency ablation.Used for several years,Lipiodol continues to play a vital role as a tumor-seeking and radiopaque drug delivery vector in interventional oncology.Efforts have been made to enhance the administration of chemotherapeutic agents to tumors.Compared with conventional TACE,drug-eluting bead TACE is a fairly new drug delivery embolization technique that permits fixed dosing and has the ability to provide sustained release of anticancer agents over a period of time.The present review discusses the basic procedure of TACE and its properties,and the effectiveness of conventional and drug-eluting bead chemoembolization systems currently available or presently undergoing clinical evaluation.

Drug-eluting balloons versus new generation drug-eluting stents for the management of in-stent restenosis: an updated meta-analysis of randomized studies

Background New-generation drug-eluting stents (DES) was more effective in the treatment of in-stent restenosis (ISR) compared with the first-generation DES. Drug-eluting balloons (DEB) and new-generation DES had been available strategies in treatment of bare-metal stents/DES ISR (BMS/DES-ISR). Six new randomized trials have recently examined the angiographic outcomes and one-year clinical outcomes of DEB and new generation DES in BMS/DES-ISR. However, the optimal management for BMS/DES-ISR lesions remains controversial. Methods We searched the randomized clinical trials evaluating the angiographic outcomes and one-year clinical outcomes of DEB and new-generation DES in patients with BMS/DES-ISR. The primary endpoints were the angiographic outcomes, including the minimal luminal diameter (MLD), diameter stenosis %(DS%), late lumen loss (LLL), and binary restenosis (BR). Results A total of six randomized clinical trials with 1177 BMS/DES-ISR patients were included in our meta-analysis. For angiographic outcomes, there were significantly less MLD and more DS% with DEB compared to new-generation DES (MLD: MD =?0.18, 95% CI:?0.31– ?0.04, P < 0.001;DS%: MD = 5.68, 95% CI: 1.00–10.37, P < 0.001). Moreover, for one-year clinical outcomes, DEB was associated with a significant increase risk in target lesion revascularization (TLR)(RR = 2.93, 95% CI: 1.50–5.72, P = 0.002). However, DEB was associated with higher risks of major adverse cardiac event, target vessel revascularization, TLR, BR, and more DS% only in DES-ISR group. Conclusions DEB and new-generation DES have the similar clinical efficacy for the treatment of BMS-ISR. However, DES showed more MLD, less DS%, and a decreased risk of TLR for the treatment of DES-ISR.

Ureteral stent technology:Drug-eluting stents and stent coatings

Ureteral stents are commonly used following urological procedures to maintain ureteral patency.However,alongside the benefits of the device,indwelling stents frequently cause significant patient discomfort(pain,urgency,frequency)and can become encrusted and infected.The importance of these sequelae is that they are not only bothersome to the patient but can lead to significant morbidity,urinary retention,ureteral damage,recurrent infections,pyelonephritis and sepsis.When these problems occur,stent removal or replacement alongside antibiotic,analgesic and/or other symptom-modifying therapies are essential to successfully treat the patient.In an attempt to prevent such morbidity,numerous approaches have been investigated over the past several decades to modify the stent itself,thereby affecting changes locally within the urinary tract without significant systemic therapy.These strategies include changes to device design,polymeric composition,drug-elution and surface coatings.Of these,drug-elution and surface coatings are the most studied and display the most promise for advancing ureteral stent use and efficacy.This article reviews these two strategies in detail to determine their clinical potential and guide future research in the area.

Domestic versus imported drug-eluting stents for the treatment of patients with acute coronary syndrome

BACKGROUND:The application of coronary stents,especially drug-eluting stents(DESs),has made percutaneous coronary intervention(PCI) one of important therapeutic methods for CHD. DES has reduced the in-stent restenosis to 5%–9% and signifi cantly improved the long-term prognosis of patients with CHD. The study aimed to investigate the long-term eff icacy and safety of domestic drugeluting stents(DESs) in patients with acute coronary syndrome(ACS).METHODS:All patients with ACS who had undergone successful percutaneous coronary intervention(PCI) in the First Aff iliated Hospital of Zhengzhou University from July 2009 to December 2010 were included in this study. Patients were excluded from the study if they were implanted with bare metal stents or different stents(domestic and imported DESs) simultaneously. The included patients were divided into two groups according to different stents implanted:domestic DESs and imported DESs.RESULTS:In the 1 683 patients of this study,1 558(92.6%) patients were followed up successfully for an average of(29.1±5.9) months. 130(8.3%) patients had major adverse cardiovascular events(MACEs),including cardiac death in 32(2.1%) patients,recurrent myocardial infarction in 16(1%),and revascularization in 94(6%). The rates of cardiac death,recurrent myocardial infarction,revascularization,in-stent restenosis,stent thrombosis and other MACEs were not signif icantly different between the two groups(all P>0.05). Multivarite logistic regression revealed that diabetes mellitus(OR=1.75,95%CI:1.09–2.82,P=0.021),vascular numbers of PCI(OR=2.16,95%CI:1.22–3.83,P=0.09) and PCI with left main lesion(OR=9.47,95%CI:2.96–30.26,P=0.01) were independent prognostic factors of MACEs. The Kaplan-Meier method revealed that there was no significant difference in cumulative survival rates and survival rates free from clinical events between the two groups(all P>0.05).CONCLUSIONS:The incidences of clinical events and cumulative survival rates are not statistically different between domestic DESs and imported DESs. Domestic DES is effective and safe in the treatment of patients with ACS.

Drug-eluting beads transarterial chemoembolization sequentially combined with radiofrequency ablation in the treatment of untreated and recurrent hepatocellular carcinoma

BACKGROUND Drug-eluting beads transarterial chemoem-bolization(DEB-TACE)has the advantages of slow and steady release,high local concentration,and low incidence of adverse drug reactions compared to the traditional TACE.DEBTACE combined with sequentially ultrasound-guided radiofrequency ablation(RFA)therapy has strong anti-cancer effects and little side effects,but there are fewer related long-term studies until now.AIM To explore the outcome of DEB-TACE sequentially combined with RFA for patients with primary hepatocellular carcinoma(HCC).METHODS Seventy-six patients with primary HCC who underwent DEB-TACE sequentially combined with RFA were recruited.Forty patients with untreated HCC were included in Group A,and 36 patients with recurrent HCC were included in Group B.In addition,40 patients with untreated HCC who were treated with hepatectomy were included in Group C.The serological examination,preoperative magnetic resonance imaging examination,and post-treatment computed tomography enhanced examination were performed for all patients.The efficacy was graded as complete remission(CR),partial remission(PR),stable disease and progressive disease at the 3rd,6th,and 9th.All patients were followed up for 3 years and their overall survival(OS),disease-free survival(DFS)were assessed.RESULTS The efficacy of Group A and Group C was similar(P>0.05),but the alanine aminotransferase,aspartate aminotransferase and total bilirubin of Group A were lower than those of Group C(all P<0.05).The proportions of CR(32.5%),PR(37.5%)were slightly higher than Group A(CR:27.5%,PR:35%),but the difference was not statistically significant(χ2=0.701,P=0.873).No operationalrelated deaths occurred in Group A and Group C.The OS(97.5%,84.7%,and 66.1%)and the DFS(75.0%,51.7%,and 35.4%)of Group A at the 1st,2nd,and 3rd year after treatment were similar with those of Group C(OS:90.0%,79.7%,and 63.8%;DFS:80.0%,59.7%,and 48.6%;P>0.05).The OS rates in Group A and Group B(90%,82.3%,and 66.4%)were similar(P>0.05).The DFS rates in Group B(50%,31.6%,and 17.2%)were lower than that of Group A(P=0.013).CONCLUSION The efficacy of DEA-TACE combined with RFA for untreated HCC is similar with hepatectomy.Patients with recurrent HCC could get a longer survival time through the combined treatment.

Five-year clinical outcomes of first-generation versus second-generation drug-eluting stents following coronary chronic total occlusion intervention

Background There are limited data comparing long-term clinical outcomes between first-generation (1G) and second-generation (2G) drug-eluting stents (DESs) in patients who underwent successful percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) lesion. Methods A total of 840 consecutive patients who underwent PCI with DESs for CTO lesion from January 2004 to November 2015 were enrolled. Finally, a total of 324 eligible CTO patients received 1G-DES (Paclitaxel-eluting stent or Sirolimus-eluting stent, n = 157) or 2G-DES (Zotarolimus-eluting stent or Everolimus-eluting stent, n = 167) were enrolled. The clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death, recurrent myocardial infarction (re-MI), total repeat revascularization [target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR]. We investigated the 5-year major clinical outcomes between 1G-DES and 2G-DES in patient who underwent successful CTO PCI. Results After propensity score matched (PSM) analysis, two well-balanced groups (111 pairs, n = 222, C-statistic = 0.718) were generated. Up to the 5-year follow-up period, the cumulative incidence of all-cause death, re-MI, TLR, TVR and non-TVR were not significantly different between the two groups. Finally, MACE was also similar between the two groups (HR = 1.557, 95% CI: 0.820–2.959, P = 0.176) after PSM. Conclusions In this study, 2G-DES was not associated with reduced long-term MACE compared with 1G-DES following successful CTO revascularization up to five years.

Duration of dual antiplatelet treatment in the era of next generation drug-eluting stents

Current percutaneous coronary intervention guidelines recommend dual antiplatelets(aspirin 100 mg + clopidogrel 75 mg daily) for at least 12 mo following drugeluting stent(DES) implantation if patients are not at high risk of bleeding.Several reports have tried to shorten the dual antiplatelet therapy to 3-6 mo,especially following next-generation DES implantation,for cost-effectiveness.However,the clinical results are inconsistent and the data regarding next-generation DESs limited.In this report,recently published important pivotal reports regarding the optimal duration of dual antiplatelets following DES implantation are summarized.

Use of Initial Modified RECIST Tumor Response Evaluation Criteria for Predicting Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization with Drug-Eluting Beads

Introduction: Transarterial chemoembolization (TACE) reduces tumor growth and increases survival in patients with hepatocellular carcinoma (HCC). Drug-eluting beads (DEB) deliver slow-release chemotherapy and reduce systemic toxicity during TACE. This study correlated initial tumor response according to modified RECIST (mRECIST) criteria and 1-year survival in patients with HCC treated with TACE-DEB, and identified predictors of tumor response. Methods: Fifty-two patients with HCC received TACE-DEB loaded with doxorubicin 75 mg during a 6-month period. Tumor response was evaluated 1 month after the procedure according to mRECIST criteria. Results: Most patients were cirrhotic and etiology of liver disease was hepatitis C in 26/52 (50%). Similar numbers of patients had Barcelona Clinic Liver Cancer (BCLC) A and BCLC B disease. Most patients had one nodule (66%). Complete response (CR) was achieved in 12/52 (23%), partial response in 19/52 (37%), stable disease in 4/52 (8%) and progressive disease in 17/52 (32%). Largest HCC ≤58 mm and BCLC stage A were associated with CR. The 1-year survival was 74%, with survival rates of 95% and 56% in the BCLC A and B groups, respectively. Variables reflecting tumor extension were associated with better survival. CR according to mRECIST criteria was a predictor of better 1-year survival (100% vs. 64%, P < 0.05). Conclusion: BCLC A and CR according to mRECIST criteria predict improved 1-year survival in patients with HCC treated with TACE-DEB. Further studies are needed to evaluate other predictors of survival and to determine if tumor response predicts long-term survival.

From oral formulations to drug-eluting implants:using 3D and 4D printing to develop drug delivery systems and personalized medicine

Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown extensively.In short,personalized medicine is a term that describes medical treatment that is tuned to the individual.One possible way to realize personalized medicine is 3D printing.When using materials that can be tuned upon stimulation,4D printing is established.In recent years,many studies have been exploring a new field that combines 3D and 4D printing with therapeutics.This has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an individual.Moreover,the first 3D printed drug,Spritam®,has already found its way to the clinic.This review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.

Revisiting endovascular treatment in below-the-knee disease. Are drug-eluting stents the best option？

Patients with below-the-knee arterial disease are primarily individuals suffering from critical limb ischemia(CLI), while a large percentage of these patients are also suffering from diabetes or chronic renal failure or both. Available data from randomized controlled trials and their meta-analysis demonstrated that the use of infrapopliteal drug-eluting stents(DES), in short-to medium-length lesions, obtains significantly better results compared to plain balloon angioplasty and bare metal stenting with regards to vascular restenosis, target lesion revascularization, wound healing and amputations. Nonetheless, the use of this technology in every-day clinical practice remains limited mainly due to concerns regarding the deployment of a permanent metallic scaffold and the possibility of valid future therapeutic perspectives. However, in the majority of the cases, these concerns are not scientifically justified. Large-scale, multicenter randomized controlled trials, investigating a significantly larger number of patients than those already published, would provide more solid evidence and consolidate the use of infrapopliteal DES in CLI patients. Moreover, there is still little evidence on whether this technology can be as effective for longer below-the-knee lesions, where a considerable number of DES is required. The development and investigation of new, longer balloon-expanding or perhaps selfexpanding DES could be the answer to this problem.

Efficacy of Short-term Dual Antiplatelet Therapy after Implantation of Second-generation Drug-eluting Stents:A Meta-analysis and Systematic Review

Objective The benefit of short-term dual antiplatelet therapy(DAPT) following second-generation drug-eluting stents implantation has not been systematically evaluated. To bridge the knowledge gap,we did a meta-analysis to assess the efficacy of ≤6 months versus ≥12 months DAPT among patients with second-generation drug-eluting stents. Methods We searched online databases and identified randomized controlled trials that assess the clinical impact of short-term DAPT(≤6 months) published before March 3,2016. The efficacy endpoints included the incidence of all-cause death,myocardial infarction,cerebrovascular accidents,and definite or probable stent thrombosis. Safety endpoint defined as major bleeding was also evaluated and discussed. Results We included 5 trials that randomized 9473 participants(49.8%,short-term DAPT duration vs. 50.2%,standard duration). A total of 9445(99.7%) patients reported the efficacy endpoints,and the safety endpoint was available from 4 studies(n=8457). There was no significant difference in efficacy endpoints between short-term and standard DAPT duration(≥12 months) [risk ratio(RR) 0.96; 95% confidence intervals(CI),0.80-1.15]. Short-term DAPT duration did not significantly increase the individual risk of all-cause death,myocardial infarction,cerebrovascular accidents,or definite or probable stent thrombosis. Although short-term DAPT obviously reduced risk of major bleeding compared with standard DAPT(RR 0.53; 95% CI,0.29-0.96),significant publication bias was found when accessing the safety endpoint of the 4 studies(Egger's test,P=0.009). Conclusions The efficacy of short-term DAPT was comparable with that of standard duration DAPT.DAPT less than 6 months may be appropriate for patients receiving second-generation drug-eluting stents implantation.