Hydrogels have been applied to improve stem cell therapy and drug delivery, but current hydrogel‐based delivery methods are inefficient in clinical settings due to difficulty in handling and ...treatment processes, and low off‐the‐shelf availability. To overcome these limitations, an adhesive hyaluronic acid (HA) hydrogel patch is developed that acts as a ready‐to‐use tissue tape for therapeutic application. The HA hydrogel patches functionalized with phenolic moieties (e.g., catechol, pyrogallol) exhibit stronger tissue adhesiveness, greater elastic modulus, and increased off‐the‐shelf availability, compared with their bulk solution gel form. With this strategy, stem cells are efficiently engrafted onto beating ischemic hearts without injection, resulting in enhanced angiogenesis in ischemic regions and improving cardiac functions. HA hydrogel patches facilitate the in vivo engraftment of stem cell–derived organoids. The off‐the‐shelf availability of the hydrogel patch is also demonstrated as a drug‐loaded ready‐made tissue tape for topical drug delivery to promote wound healing. Importantly, the applicability of the cross‐linker‐free HA patch is validated for therapeutic cell and drug delivery. The study suggests that bioinspired phenolic adhesive hydrogel patches can provide an innovative method for simple but highly effective cell and drug delivery, increasing the off‐the‐shelf availability—a critically important component for translation to clinical settings.
Tissue tape hyaluronic acid (HA) hydrogel patches with catechol or pyrogallol modification exhibit significantly improved physical, mechanical, and adhesive properties over the HA solution hydrogel form. The phenolic HA hydrogel patches are ready‐to‐use for stem cell therapy and therapeutic drug delivery, increasing off‐the‐shelf availability and enabling successful therapeutic applications even without cross‐linking agents.
IMPORTANCE: Use of intravascular ultrasound (IVUS) promotes better clinical outcomes for coronary intervention in complex coronary lesions. However, randomized data demonstrating the clinical ...usefulness of IVUS are limited for lesions treated with drug-eluting stents. OBJECTIVE: To determine whether the long-term clinical outcomes with IVUS-guided drug-eluting stent implantation are superior to those with angiography-guided implantation in patients with long coronary lesions. DESIGN, SETTING, AND PARTICIPANTS: The Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) randomized, multicenter trial was conducted in 1400 patients with long coronary lesions (implanted stent ≥28 mm in length) between October 2010 and July 2014 at 20 centers in Korea. INTERVENTIONS: Patients were randomly assigned to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. MAIN OUTCOMES AND MEASURES: Primary outcome measure was the composite of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 1 year, analyzed by intention-to-treat. RESULTS: One-year follow-up was complete in 1323 patients (94.5%). Major adverse cardiac events at 1 year occurred in 19 patients (2.9%) undergoing IVUS-guided and in 39 patients (5.8%) undergoing angiography-guided stent implantation (absolute difference, −2.97% 95% CI, −5.14% to −0.79%) (hazard ratio HR, 0.48 95% CI, 0.28 to 0.83, P = .007). The difference was driven by a lower risk of ischemia-driven target lesion revascularization in patients undergoing IVUS-guided (17 2.5%) compared with angiography-guided (33 5.0%) stent implantation (HR, 0.51 95% CI, 0.28 to 0.91, P = .02). Cardiac death and target lesion–related myocardial infarction were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4%) in the IVUS-guided group and 5 patients (0.7%) in the angiography-guided group (HR, 0.60 95% CI, 0.14 to 2.52, P = .48). Target lesion–related myocardial infarction occurred in 1 patient (0.1%) in the angiography-guided stent implantation group (P = .32). CONCLUSIONS AND RELEVANCE: Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year. These differences were primarily due to lower risk of target lesion revascularization. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01308281
Abstract Objective Stent graft-induced new entry (SINE) has been increasingly observed after thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection. SINE is often life ...threatening, and reintervention is required. This study investigated risk factors for SINE after TEVAR. Methods From July 2001 to June 2013, we retrospectively analyzed data from 79 patients who underwent TEVAR for Stanford type B aortic dissection. TEVAR was performed in 17 patients ≤2 weeks (acute) after the diagnosis of aortic dissection and in the remaining 62 patients >2 weeks (chronic) after diagnosis. Forty-two of the patients underwent TEVAR with modified stent graft with an “inwardly bent” margin, and the remaining 37 underwent TEVAR with a conventional stent graft. The maximal diameter, minimal diameter, mean diameter, circumference, and area of the true lumen were analyzed. Taper ratio and oversizing ratio were evaluated and compared between the SINE and non-SINE groups, and cutoff values of taper ratio and oversizing ratio for prediction of SINE were determined using receiver-operating characteristic curve analysis. The cumulative incidence of SINE was estimated with the Kaplan-Meier method. The multivariate Cox proportional hazards model was used to identify independent predictive variables for SINE. Results SINE occurred in 21 patients (26.5%) and occurred more frequently in patients with chronic dissection than in those with acute dissection (32.3% vs 5.9%; P = .032). The Kaplan-Meier curves were significantly different ( P = .016) between these groups. The incidence of SINE events was not significantly different between the modified stent group and nonmodified stent group (23.8% vs 36.0%; P = .284). The taper ratio and oversizing ratio by maximal diameter, mean diameter, circumference, and area were significantly higher in the SINE group than in the non-SINE group, and Kaplan-Meier curves were significantly different between groups above and below optimal cutoff value ( P < .0005 to .003). According to multivariate analysis, the hazard ratios of chronic aortic dissection were 6.30 (95% confidence interval, 0.83-47.74; P = .075) to 7.80 (95% confidence interval, 1.03-59.07; P = .047). The taper ratio and oversizing ratio calculated by maximal diameter, mean diameter, circumference, and area were independent predictors of the development of SINE. Conclusions Distal oversizing of the stent graft was an independent predictor of the development of SINE. Appropriate size selection of stent graft without distal oversizing might reduce the risk of late SINE events.
Long-term data on drug-coated balloon (DCB) outcomes in complex femoropopliteal atherosclerotic lesions are limited.
The authors sought to report 5-year safety and effectiveness outcomes of a ...paclitaxel DCB for the treatment of de novo in-stent restenosis (ISR), long lesions (LL), or chronic total occlusions (CTOs) in the prespecified imaging cohorts of the IN.PACT Global Study.
The IN.PACT Global study was a prospective, international single-arm study. Assessments through 5 years included freedom from clinically driven target lesion revascularization (CD-TLR), a safety composite (freedom from device- and procedure-related death to 30 days, and freedom from major target limb amputation and freedom from clinically driven target vessel revascularization within 60 months), and major adverse events.
The prespecified imaging cohorts enrolled 132 de novo ISR, 158 LL, and 127 CTO participants. Kaplan-Meier estimates of freedom from CD-TLR through 5 years were 58.0% (ISR), 67.3% (LL), and 69.8% (CTO). The cumulative incidences of the composite safety endpoint were 56.0% (ISR), 65.7% (LL), and 69.8% (CTO). The 5-year freedom from all-cause mortality with vital status update were 81.4% (ISR), 75.2% (LL), and 78.2% (CTO). Within the ISR cohort, 15.9% of participants experienced 2 or more TLRs, compared with 9.5% and 5.5% in the LL and CTO groups, respectively.
Results demonstrate long-term safety and effectiveness of this DCB in all 3 cohorts, with low reintervention rates in the LL and CTO cohorts and no safety issues. These results support the inclusion of this DCB into the treatment algorithm for complex femoropopliteal disease.
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Background:Coronary interventions using drug-eluting stents (DESs) of left main coronary artery (LMCA) lesions have shown favorable clinical outcomes. However, duration of dual antiplatelet therapy ...(DAPT) after LMCA interventions has not yet been investigated.Methods and Results:From a multicenter Korean Multicenter Angioplasty Team (KOMATE) registry, 1,004 patients who received DES implantations for LMCA lesions and did not experience major adverse cardiovascular events (including major bleeding) for 1 year after coronary intervention were analyzed. Patients were divided into 2 groups; DAPT ≤12 (n=503) and >12 months (n=501). The primary endpoint was number of net clinical adverse events (NACEs), composite of cardiac deaths, myocardial infarctions, stent thrombosis and major bleeding events. During a 4.5-year follow-up period after LMCA interventions, the DAPT >12 months group showed a lower NACE rate than the DAPT ≤12 months group (adjusted-HR 0.53 0.29–0.99, P=0.045). For patients who maintained DAPT >12 months, rate of cardiac deaths, myocardial infarctions, and stent thrombosis events were lower than in patients who had DAPT ≤12 months (adjusted-HR 0.35 0.17–0.73, P=0.005) without increased major bleeding (P=0.402).Conclusions:For patients who can continue DAPT without major bleeding events, prolonged DAPT (>12 months) after LMCA stenting demonstrated better long-term efficacy outcomes than DAPT ≤12 months with comparable safety.
Electrophysiological phenotype development and paracrine action of mesenchymal stem cells (MSCs) are the critical factors that determine the therapeutic efficacy of MSCs for myocardial infarction ...(MI). In such respect, coculture of MSCs with cardiac cells has windowed a platform for cardiac priming of MSCs. Particularly, active gap junctional crosstalk of MSCs with cardiac cells in coculture has been known to play a major role in the MSC modification through coculture. Here, we report that iron oxide nanoparticles (IONPs) significantly augment the expression of connexin 43 (Cx43), a gap junction protein, of cardiomyoblasts (H9C2), which would be critical for gap junctional communication with MSCs in coculture for the generation of therapeutic potential-improved MSCs. MSCs cocultured with IONP-harboring H9C2 (cocultured MSCs: cMSCs) showed active cellular crosstalk with H9C2 and displayed significantly higher levels of electrophysiological cardiac biomarkers and a cardiac repair-favorable paracrine profile, both of which are responsible for MI repair. Accordingly, significantly improved animal survival and heart function were observed upon cMSC injection into rat MI models compared with the injection of unmodified MSCs. The present study highlights an application of IONPs in developing gap junctional crosstalk among the cells and generating cMSCs that exceeds the reparative potentials of conventional MSCs. On the basis of our finding, the potential application of IONPs can be extended in cell biology and stem cell-based therapies.
Objective Tibial artery calcification (TAC) is associated with increased risk of amputation and mortality in peripheral artery disease. We sought to investigate whether the severity of TAC based on ...semiquantitative analysis of computed tomography angiography (CTA) can predict outcomes of endovascular therapy in patients with critical limb ischemia. Methods We reviewed medical records of 124 patients who underwent lower extremity CTA before intervention. Based on CTA, TAC severity was categorized into three groups: minimal calcification (MC; n = 43), intermediate calcification (IC; n = 36), or extensive calcification (EC; n = 45). Immediate and late outcomes of infrapopliteal interventions were compared, and predictors of the outcomes were investigated. Results The categorized severity of target TAC correlated with the log-transformed TAC score ( r = 0.873; P < .001). The EC group was younger and had more diabetes and chronic kidney disease compared with the MC or IC group (all P < .001). The technical success was lower in the EC group (71.1%) than in the MC (95.3%) or IC (91.7%) group ( P = .001). The survival free of unplanned amputations at 2 years was significantly lower in the EC group (58.9%) than in the MC (79.0%) or IC (95.3%) group ( P < .001). Extensive TAC was an independent predictor of technical success (hazard ratio, 0.02; 95% confidence interval, 0.00-0.45; P = .014) and unplanned amputation (hazard ratio, 9.90; 95% confidence interval, 2.05-47.75; P = .004). Conclusions The categorized severity of TAC by semiquantitative analysis of CTA correlated with TAC score, and extensive TAC was associated with a lower technical success rate of angioplasty and an increased incidence of unplanned amputation.
Objectives This study sought to assess the impact of intravascular ultrasound (IVUS) guidance on clinical outcomes following drug-eluting stent implantation when treating long lesions. Background The ...role of IVUS guidance when treating long lesions has been tested during bare-metal stent, but not during drug-eluting stent, implantation. Methods A total of 543 patients treated with stents ≥28 mm in length were randomly assigned to IVUS guidance (n = 269) versus angiography guidance (n = 274). The primary endpoint was a composite of major adverse cardiac events (MACE), including cardiovascular death, myocardial infarction, target vessel revascularization, or stent thrombosis at 1 year following intervention. Results In the intention-to-treat analysis, total stent length was 32.4 mm in the IVUS-guided arm versus 32.3 mm in angiography-guided arm (p = 0.84). Adjunct post-dilation was more frequently performed in the IVUS-guided arm (54.6% vs. 44.5%, p = 0.03); post-intervention minimal lumen diameters were similar (2.55 vs. 2.55 mm, respectively, p = 0.50); and MACE occurred in 12 (4.5%) patients in IVUS-guided arm and in 20 (7.3%) patients in the angiography-guided arm (p = 0.16). However, among the 269 patients assigned to IVUS guidance, IVUS was not used in 13 patients (4.8%); conversely, in 274 patients assigned to angiography alone, 41 patients (15.0%) were treated with IVUS guidance. Therefore, in a per-protocol analysis according to actual IVUS usage, minimum lumen diameter was larger (2.58 vs. 2.51 mm, p = 0.04), and MACE rates were lower: 4.0% in the IVUS-guided arm versus 8.1% in the angiography-guided arm (p = 0.048). Conclusions A strategy of routine IVUS for drug-eluting stent implantation in long lesions did not improve the 1-year MACE rates. The IVUS use per operator decision was associated with improved results. (A New Strategy Regarding Discontinuation of Dual Antiplatelet; NCT01145079 )
Background:There are limited data comparing the outcomes of subintimal vs. intraluminal approach in the treatment of long femoropopliteal artery occlusions. The objective of this study was to ...investigate the efficacy and safety of the subintimal approach for long femoropopliteal artery occlusions.Methods and Results:From a multicenter retrospective registry cohort, we included a total of 461 patients with 487 femoropopliteal artery occlusions classified as Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) II C/D for this analysis. We compared the immediate and mid-term outcomes of subintimal vs. intraluminal approaches. There were 228 patients with 243 limbs in the subintimal group, and 233 patients with 244 limbs in the intraluminal group. Baseline clinical and lesion characteristics were comparable between the 2 groups. The technical success rate was significantly higher in the subintimal group than in the intraluminal group (95.1% vs. 89.8%, P=0.041). The clinical primary patency (67.5% vs. 73.4% at 12 months, 54.0% vs. 61.3% at 24 months; P=0.086) and target lesion revascularization (TLR)-free survival (89.5% vs. 86.3% at 12 months, 77.6% vs. 76.0% at 24 months; P=0.710) did not differ significantly between the subintimal and the intraluminal groups.Conclusions:In long femoropopliteal occlusions, the subintimal approach achieved a higher technical success rate and similar mid-term primary patency and TLR-free survival compared with intraluminal approach.
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