High-Dose Drug-Coated Balloon Versus Polymer-Based Drug-Eluting Stent for Femoropopliteal Artery Disease Treatment.

PURPOSE: Clinical trials have demonstrated that high-dose drug-coated balloon (HD-DCB) and polymer-based drug-eluting stent (PB-DES) treatments for femoropopliteal (FP) artery disease have favorable outcomes. However, which one would be better remained unrevealed. METHODS: This study used the databases of 2 large-scale multicenter prospective drug-coated balloon (DCB) and drug-eluting stent (DES) registries. The study included 2470 patients with symptomatic FP lesion treated with IN.PACT Admiral DCB or Eluvia DES at 69 centers. A propensity-score-based paired analysis was conducted. Primary endpoint was 1-year restenosis rate. Secondary endpoints were 1-year reocclusion rate, target lesion revascularization (TLR), acute thrombosis, bypass conversion, major amputation, major adverse limb event (MALE), and all-cause death. RESULTS: A total of 1535 patients were treated with HD-DCB, and 935 patients were treated with PB-DES. The propensity-score matching extracted 678 pairs, with no remarkable intergroup difference in baseline characteristics. The 1-year restenosis rate was significantly lower in the PB-DES group than in the HD-DCB group (16.0% vs 22.0%, p=0.016). The other endpoints (reocclusion rate, TLR, acute thrombosis, bypass conversion, major amputation, MALE, and all-cause death) did not differ between the groups. No baseline characteristics had any significant interaction effect on the association of HD-DCB vs PB-DES with restenosis risk (all p>0.05). CONCLUSIONS: This study demonstrated that the 1-year TLR, reocclusion rate, and other endpoints did not differ between the PB-DES group and the HD-DCB group despite the lower restenosis in the PB-DES group. CLINICAL IMPACT: One-year restenosis rate was significantly lower in the polymer-based DES group than in the high-dose DCB group for foemoropopliteal disease. However, there is no difference in the other endpoints between two groups.

Multicenter Registry of Common Femoral Artery Disease Treated With Endovascular Revascularization Using Interwoven Nitinol Stents: An Observational Retrospective Study.

PURPOSE: Surgical thromboendarterectomy has been the gold standard treatment for common femoral artery (CFA) disease. However, endovascular therapy (EVT) is conducted in certain patients with CFA lesions because of multiple comorbidities. The interwoven nitinol stent (IWS) has been developed to prevent stent fracture. Thus, this study aimed to evaluate the feasibility of EVT using IWS for CFA lesions in clinical practice. MATERIALS AND METHODS: This retrospective multicenter registry analyzed patients who had symptomatic lower-extremity artery disease due to CFA lesions and underwent EVT using IWS between 2019 and 2021. The primary endpoint was restenosis 2 years after EVT. RESULTS: This study enrolled a total of 177 patients with 196 CFA lesions. The 2-year estimate of freedom from restenosis was 88.0%. The 2-year freedom rates from the target-lesion revascularization, major amputation, and all-cause death were 92.9%, 99.0%, and 75.2%, respectively. The clinical features significantly associated with restenosis risk were the reference vessel diameter (RVD, per 1.0 mm, hazard ratio [HR], 0.24 [0.08-0.70]; p=0.009), external iliac artery (EIA) involvement (HR=4.03 [1.56-10.4]; p=0.004), superficial femoral artery (SFA) involvement (HR=3.05 [1.00-9.25]; p=0.049), body mass index (BMI; per 1.0, HR=0.85 [0.73-0.99]; p=0.032), occlusion of deep femoral arteries (DFAs) at baseline (HR=7.89 [2.04-30.5]; p=0.003), and chronic limb-threatening ischemia (CLTI, HR=2.63 [1.02-6.78]; p=0.045). Their significant association was also confirmed by the random survival forest analysis. During a median follow-up of 12.0 months, guiding sheaths were inserted via CFAs implanted IWSs in 73 cases (37.2%), and no patients had cannulation-related complications, such as failed hemostasis, fracture of IWS, and stent occlusion. CONCLUSIONS: Endovascular therapy using IWS in CFA lesions showed acceptable 2-year patency rates at 88.0% and might preserve the arterial access via the ipsilateral CFAs. Small RVD, involving EIA and SFA lesions, emaciation, occluded DFA, and CLTI are associated with poor 2-year patency rates following EVT, thus, IWS implantation in CFA lesions may be an option for patients unsuitable for surgical revascularization. CLINICAL IMPACT: This retrospective multicenter registry enrolled 177 patients with 199 CFA lesions treated with EVT using interwoven nitinol stents, because surgical thromboendarterectomy was difficult due to their multiple comorbidities. The 2-year estimate of freedom from restenosis was acceptable at 88.0%. The 2-year freedom rate from major amputation was also high at 99.0%. Moreover, during a median follow-up of 12.0 months, guiding sheaths were inserted via CFAs implanted IWSs in 73 cases, and no patients had cannulation-related complications such as failed hemostasis, fracture of IWS, and stent occlusion.

Changes in Tablet Color Due to Light Irradiation: Photodegradation of the Coating Polymer, Hypromellose, by Titanium Dioxide.

The color of the tablets and capsules produced by pharmaceutical companies is important from the perspectives of product branding and counterfeiting. According to some studies, light can change tablet color during storage. In this study, tablets comprising amlodipine besylate (AB), a well-known light-sensitive drug, were coated with commonly used coating materials and exposed to light. Compared to the tablets that were not exposed to light, the color of those exposed to light changed over time. In fact, a faster and more pronounced color change was observed in the tablets exposed to light; however, the amount of AB did not decrease significantly in these tablets. The coating materials and their amounts were varied to clarify the materials involved in the color change. Based on the results, titanium dioxide and hypromellose may be involved in the color change process. As titanium dioxide is a photocatalyst, it may induce or promote chemical changes in hypromellose upon light irradiation. Overall, care should be exercised during selection of the coating polymer because titanium dioxide may promote photodegradation of the coatings while protecting the tablet's active ingredient from light.

Dual Antiplatelet Alternatives are Associated With Increased Stroke and Death After Transcarotid Revascularization.

OBJECTIVE: To define the risks associated with the replacement of dual antiplatelets for alternate medication regimens. BACKGROUND: Patients undergoing transcarotid artery revascularization (TCAR) for atherosclerotic disease in the Vascular Quality Initiative database from September 2016 to June 2022 were included. In all, 29,802 TCAR procedures were captured between 2016 and 2022, consisting of 24,651 (82.7%) maintained on dual antiplatelet therapy (DAPT) and 5151 (17.3%) on alternative regimens. METHODS: Patients maintained on DAPT were compared with those on alternative regimens consisting of any combination of single antiplatelet monotherapy and/or anticoagulation. RESULTS: On univariable analysis, patients on alternative medications were more likely to experience in-hospital death, ipsilateral stroke, any stroke, and transient ischemic attacks compared with patients in the DAPT group. The mortality rate was higher at 1 year in the alternative cohort (4.7% vs 7.0%, P <0.01). The use of alternate medication regimens was associated with increased odds of stroke and the composite outcome of in-hospital stroke/death compared with DAPT. There was also a significant association between alternative medication use and increased odds of in-hospital transient ischemic attack, immediate stent occlusion, and return to the operating room. At 1 year, there was no significant difference in the incidence of stroke between the 2 groups. However, the use of alternate regimens was associated with higher 1-year of mortality after multivariable adjustment. CONCLUSIONS: Patients not maintained on DAPT after TCAR experienced an increased risk of stroke and death in the perioperative and follow-up periods. Increased surgeon vigilance is required to ensure compliance with dual antiplatelets as recommended.

Propensity-score-matched analysis of dual antiplatelet treatment and alternative antiplatelet regimens after transcarotid revascularizations.

OBJECTIVE: Dual antiplatelet therapy (DAPT) continues to be the preferred medication regimen after the placement of a carotid stent using the transcarotid revascularization (TCAR) technique despite a dearth of quality data. Therefore, this investigation was performed to define the risks associated with antiplatelet choice. METHODS: We queried all patients who underwent TCAR captured by the Vascular Quality Initiative from September 2016 to June 2022, to determine the association between antiplatelet choice and outcomes. Patients maintained on DAPT were compared with those receiving alternative regimens consisting of single antiplatelet, anticoagulation, or a combination of the two. A 1:1 propensity-score match was performed with respect to baseline comorbidities, functional status, anatomic/physiologic risk, medications, and intraoperative characteristics. In-hospital and 1-year outcomes were compared between the groups. RESULTS: During the study period, 29,802 procedures were included in our study population, with 24,651 (82.7%) receiving DAPT and 5151 (17.3%) receiving an alternative antiplatelet regimen. A propensity-score match with respect to 29 variables generated 4876 unique pairs. Compared with patients on DAPT, in-hospital ipsilateral stroke was significantly higher in patients receiving alternative antiplatelet regimens (1.7% vs 1.1%, odds ratio [95% confidence interval]: 1.54 [1.10-2.16], P = .01), whereas no statistically significant difference was noted with respect to mortality (0.6% vs 0.5%, 1.35 [0.72-2.54], P = .35). A composite of stroke/death was also more likely in patients receiving an alternative regimen (2.4% vs 1.7%, 1.47 [1.12-1.93], P = .01). Immediate stent thrombosis (2.75 [1.16-6.51]) and a nonsignificant trend toward increased return to the operating room were more common in the alternative patients. Conversely, the incidence of perioperative myocardial infarction was lower in the alternative regimen group (0.4% vs 0.7%, 0.53 [0.31-0.90], P = .02). At 1 year after the procedure, we observed an increased risk of mortality (hazard ratio [95% confidence interval]: 1.34 [1.11-1.63], P < .01) but not stroke (0.52 [0.27-0.99], P = .06) in patients treated with an alternative medication regimen. CONCLUSIONS: This propensity-score-matched analysis demonstrates an increased risk of in-hospital stroke and 1-year mortality after TCAR in patients treated with an alternative medication regimen instead of DAPT. Further studies are needed to elucidate the drivers of DAPT failure in patients undergoing TCAR to improve outcomes for carotid stenting patients.

Predictors of 30-Day Stroke and Death After Transcarotid Revascularization.

INTRODUCTION: Much of the previous robust analyses of the results associated with transcarotid revascularization (TCAR) derives from industry-sponsored trials or the Vascular Quality Initiative (VQI). This investigation was performed to identify preoperative predictors of 30-day stroke and death using institutional databases. METHODS: A retrospective analysis was performed of carotid revascularization databases created at two high-volume TCAR centers and maintained independently of the VQI carotid module between December 2015 and December 2021. The primary outcome of interest was a composite of perioperative (30-day) stroke and death. Univariate regression analyses, followed by multivariate regression analyses, were performed to identify potential predictors of adverse events. RESULTS: During the study period, 750 TCAR procedures were performed at our combined health systems, resulting in 24 (3.2%) individuals who experienced either stroke and/or death in the perioperative period. Of these, we observed nine (1.2%) mortality events and 18 (2.4%) strokes. On univariate analysis, candidate protectors of stroke/death were found to be coronary artery disease (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.18-1.01; P = 0.05) and protamine reversal (0.51; 0.21-1.21; P = 0.15). Candidate predictors of the primary outcome were anticoagulant usage (3.03; 1.26-7.24; P = 0.01), postprocedural debris in the filter (2.30; 0.97-5.43; P = 0.06), symptomatic carotid lesion (2.03; 0.90-4.50), and cardiac arrhythmia (1.98; 0.80-4.03; P = 0.14). On multivariate analysis, two predictors remained, cardiac arrhythmia (4.21; 1.10-16.16; P = 0.04) and symptomatic carotid lesion (14.49; 1.80-116.94; P = 0.01). CONCLUSIONS: A symptomatic carotid lesion, and to a lesser extent cardiac arrhythmia, are strong predictors of 30-day stroke/death after TCAR. Surgeons should be cognizant of the increased risk of adverse events in the perioperative period in these patients.

Multicenter, retrospective registry of isolated atherosclerotic popliteal arteries treated with endovascular revascularization.

Isolated atherosclerotic popliteal lesions (IAPLs) have been considered challenging. This study aimed to investigate the efficacy of endovascular therapy (EVT) using the newer devices for IAPLs. This retrospective multicenter registry analyzed patients with lower extremity artery disease having IAPLs who underwent EVT using the newer devices between 2018 and 2021. The primary outcome was primary patency 1 year after EVT. A total of 392 consecutive patients undergoing EVT for IAPLs were enrolled. The Kaplan-Meier analysis showed that the primary patency and the freedom from target lesion revascularization were 80.9% and 87.8% 1 year after EVT, respectively. The multivariate Cox proportional hazards regression analysis showed that the clinical features that were independently associated with restenosis risk were drug-coated balloon (DCB) use for younger age (< 75 years old; adjusted hazard ratio, 3.08 [95% confidence interval 1.08-8.74]; P = 0.035), non-ambulatory status (2.74 [95% confidence interval 1.56-4.81]; P < 0.001), cilostazol use (0.51 [95% confidence interval 0.29-0.88]; P = 0.015), severe calcification (1.86 [95% confidence interval 1.18-2.94]; P = 0.007), and small external elastic membrane (EEM) area measured by intravascular ultrasound (IVUS) (< 30 mm2) (2.07 [95% confidence interval 1.19-3.60]; P = 0.010). From the univariate analysis, among patients treated with DCB, younger patients (n = 141) were associated with more comorbidities including smoking (P < 0.001), diabetes mellitus (P < 0.001), end-stage renal disease (P < 0.001), history of revascularization (P = 0.046) and small EEM area (P = 0.036), compared to older patients (n = 140). Moreover, smaller post-procedural minimum lumen area measured by IVUS after DCB dilatation was observed in younger patients (12 ± 4 vs. 14 ± 4 mm2, P = 0.033). This retrospective study demonstrated that the current EVT provided an acceptable 1-year primary patency rate in patients with IAPLs. The primary patency was lower following DCB in younger patients, likely due to the higher rates of comorbidities in this patient population.

Prediction of postprocedural filter debris after transcarotid revascularization.

OBJECTIVE: Transcarotid revascularization (TCAR) is a technique in which cerebral flow reversal is utilized as embolic protection during carotid stenting. The presence, or absence, of filter debris created during TCAR could potentially be a surrogate to characterize carotid lesions at high risk for embolization and, therefore, explored in this investigation. METHODS: A retrospective review of TCARs performed within the Indiana University and Memorial Hermann (McGovern Medical School at UTHealth) Health Systems to capture demographics and preoperative variables. A mixed effect multivariate logistic regression model was created to discern the best predictors of intraoperative filter debris. RESULTS: During the study period, from December 2015 to December 2021, we captured filter debris status in 693 of 750 patients containing 323 cases of filter embolization at case completion. With respect to demographics and indications, we found a higher incidence of neck radiation (2.7 vs. 7.1%, p = 0.01) and a more pronounced Charlson Comorbidity Index (CCI; 5.3 ± 0.3 vs 5.7 ± 0.3, p < 0.01) in the filter debris cohort while contralateral carotid occlusion (6.6 vs. 2.9%, p = 0.05) and clopidogrel usage (87.3 vs. 80.1%, p = 0.03) were less common. Longer intraoperative flow reversal (8.0 ± 1.2 vs 10.5 ± 1.2, p < 0.01) and fluoroscopy time (4.0 ± 0.6 vs 5.1 ± 0.6, p < 0.01) were also seen in those with filter debris. These findings remained when a mixed effect univariate logistic regression model was used to account for differences in filter debris reporting between locations. After multivariable modeling, we found that reverse flow time and CCI remained predictive of filter debris while the presence of a contralateral carotid occlusion was still protective. CONCLUSION: In our combined experience, the creation of visible filter debris after TCAR seems to be independently associated with extended reverse flow time and elevated CCI while a contralateral carotid occlusion was protective.

Transcarotid revascularization in obese patients.

OBJECTIVE: Transcarotid revascularization (TCAR) is a minimally invasive hybrid surgical carotid stenting technique which utilizes cerebral flow reversal as embolic protection during carotid lesion manipulation. This investigation was performed to define the perioperative risks associated with this operation in the obese patient. METHODS: A retrospective review of tandem carotid revascularization databases maintained at two high-volume health systems was performed to capture all TCARs performed between 2015 and 2022. A threshold of body mass index of 35 kg/m2 defined the "obese" patient. Demographics, intraoperative, perioperative, and follow-up characteristics were compared using univariate analysis. RESULTS: We performed 793 TCAR procedures that qualified for study inclusion within the prespecified time. After applying our obesity definition, 129 patients qualified as obese and were compared to the remainder. There were no significant differences in baseline demographics as comparable Charlson Comorbidity Indices were noted between groups; however, obese patients had a significantly higher prevalence of hypertension, hyperlipidemia, and diabetes. Intraoperative, case complexity in the obese patients did not seem to be increased, as measured by operative time (68.4 ± 23.0 vs 64.2 ± 25.8 min, p = 0.09), fluoroscopic time (4.9 ± 3.2 vs 4.6 ± 3.6 min, p = 0.38), and estimated blood loss (40.6 ± 49.0 vs 46.6 ± 49.4 min, p = 0.22). Similarly, no disparities were observed with respect to ipsilateral stroke (3.1 vs. 1.7%, p = 0.29), contralateral stroke (0 vs. 0.2%, p > 0.99), death (0 vs. 1.1%, p = 0.61), and stroke/death (3.1 vs. 3.0%, p > 0.99) in the 30-day perioperative period. Both cohorts were followed for approximately 1 year (12.0 ± 13.4 vs 11.6 ± 13.4 months, p = 0.76). During this period, rates of ipsilateral stroke (3.1% vs. 2.7%, p > 0.99), contralateral stroke (1.1 vs. 0.8%, p > 0.99), and death (4.7 vs. 6.2%, p = 0.68) were similar. CONCLUSIONS: TCAR performed in the obese population was not more challenging by intraoperative characteristics and did not result in a statistically higher incidence of adverse events in the perioperative phase.

Transcarotid artery revascularization is safe in necks with anatomy hostile for carotid endarterectomy.

OBJECTIVE: The outcomes associated with transcarotid revascularization (TCAR) have proved to be noninferior to the historical results established for carotid endarterectomy (CEA). Therefore, TCAR has been increasingly offered to patients with neck anatomy hostile for traditional CEA. The present investigation was completed to evaluate whether a difference exists for patients undergoing TCAR in de novo anatomy with unviolated surgical planes compared with those undergoing TCAR in necks with hostile anatomy. METHODS: The demographic data and outcomes were captured at two high-volume TCAR institutions from December 2015 to December 2021 via a query of two parallel, prospectively maintained, carotid intervention databases at these two health institutions. A hostile neck anatomy was defined as a history of previous ipsilateral neck radiation, oncologic dissection, or CEA. Univariate analysis was performed to compare the two cohorts at an α of 0.05. RESULTS: During the inclusion period, the data from 750 TCARs were captured, including 108 procedures in hostile neck anatomy and 642 in de novo necks. No significant differences were found in the baseline comorbidity burden using the Charlson comorbidity index or the indication for revascularization. Intraoperatively, no significant increase in case complexity was observed with respect to those with a hostile neck, except for the operative time, which was 10% longer (69.5 vs 63.4 minutes; P = .01). The flow reversal and fluoroscopic times, blood loss, radiation exposure, and contrast use were identical. Postoperatively, no differences were observed between the hostile and de novo necks with respect to stroke (0.9% vs 2.5%; P = .49), myocardial infarction (0.9% vs 0.2%; P = .27), and death (0% vs 1.5%; P = .37). Additionally, hematoma formation and the need for reintervention did not seem to vary between the two groups. Similarly, no differences in the two cohorts were noted during follow-up. CONCLUSIONS: According to the findings from our large, dual-institutional series, the performance of TCAR in surgical fields traditionally hostile for CEA was not associated with increased intraoperative complexity or postoperative morbidity.

Results associated with the health system-wide adoption of transcarotid revascularization.

BACKGROUND: In the present report, we have detailed the results derived from the adoption of transcarotid artery revascularization (TCAR) at a large health system based in the United States. METHODS: A retrospective review was performed of a prospectively maintained database capturing all carotid stents deployed using the ENROUTE neuroprotection device (Silk Road Medical, Sunnyvale, CA) and cerebral flow reversal. The demographics, intraoperative findings, and postoperative results were tabulated and reported. RESULTS: From September 2017 to December 2021, 429 TCAR procedures were attempted within the Memorial Hermann Health System. Preoperatively, all the patients were either asymptomatic with >70% stenosis (66.9%) or symptomatic with >50% stenosis (33.1%). The degree of stenosis was determined using computed tomography angiography and/or duplex ultrasound. We achieved a technical success rate of 99.1%, with the failures attributed to an inability to cross the lesion, an inability to track the stent, visualization of a flow-limiting dissection, and stent maldeployment for one patient each. During the 30-day perioperative period, nine strokes (2.3%) had occurred, three of which had occurred after discharge from the index operation and before the end of the 30-day period. No patient had experienced myocardial infarction. Five patients had died in the perioperative period. Three of the deaths were related to stroke, and two were attributed to cardiopulmonary events secondary to aspiration and likely pulmonary embolus. The mean follow-up after TCAR was 14.5 ± 12.0 months. During the follow-up period, two patients had required reintervention for in-stent stenosis. Ipsilateral to the implanted carotid stent, the overall (including perioperative) stroke incidence was 2.5%. Contralateral to the stent, the stroke incidence was 0.8%. The myocardial infarction rate was 0.8% during follow-up. Mortality in our study population was 5.1% during the follow-up period. CONCLUSIONS: After adoption of TCAR across the Memorial Hermann Health System, we found this procedure to be safe and efficacious with minimal perioperative risks comparable to the historically reported results associated with alternative carotid interventions.

Impact of Baseline and Postprocedural Intravascular Ultrasound Findings on 1-Year Primary Patency After Drug-Coated Balloon Treatment of Femoropopliteal Lesions.

PURPOSE: Drug-coated balloons (DCBs) are commonly used for endovascular treatment of femoropopliteal lesions. Here, we employed intravascular ultrasound (IVUS) to investigate the predictors of restenosis after DCB treatment. METHODS: This retrospective and single-center study was performed to examine 1-year primary patency after DCB treatment and to identify the risk factors for restenosis by analyzing clinical characteristics, angiographic findings, and IVUS measurements. We included 111 consecutive patients undergoing DCB treatment for de novo femoropopliteal lesions at our hospital from July 2018 to March 2020. RESULTS: The primary patency rate was found to be 80.0% at 1 year. The Cox proportional hazard multivariate analysis revealed that restenosis was independently associated with chronic total occlusion (CTO; p < 0.001), circumferential calcification (p = 0.023), and smaller postprocedural minimum lumen area (MLA; p = 0.036). Furthermore, receiver operating characteristic curve analysis showed that the cutoff value of postprocedural MLA to prevent restenosis was 12.7 mm2, with an area under the curve of 0.774 (p< 0.001). The multivariate analysis indicated that patients with a postprocedural MLA below 12.7 mm2 (n = 44) had a significantly smaller distal reference vessel size (p < 0.001) compared to those with a postprocedural MLA over 12.7 mm2 (n = 67). CONCLUSIONS: Restenosis after DCB treatment was shown to correlate with CTO, circumferential calcification, and postprocedural MLA as evaluated by IVUS. Moreover, smaller vessel sizes might represent a particular challenge to the DCB strategy due to the difficulty of restoring a sufficient postprocedural lumen area by balloon dilatation.

Retrospective Multicenter Comparison Between Viabahn Covered Stent-Grafts and Supera Interwoven Nitinol Stents for Endovascular Treatment in Severely Calcified Femoropopliteal Artery Disease: The ARMADILLO Study (Adjusted Retrospective coMparison of scAffolDs In caLcified LesiOns).

PURPOSE: The previous single-arm registries showed the acceptable primary patency after endovascular therapy (EVT) using covered stent-graft (CSG) and Supera interwoven nitinol stent (Supera peripheral stent [SPS]) in calcified femoropopliteal lesions. The aim of this study was to compare the safety and efficacy between CSG and SPS in calcified femoropopliteal lesions in clinical practice. MATERIALS AND METHODS: We retrospectively analyzed 341 cases who had Rutherford class 2 to 6 peripheral artery disease and underwent EVT with either CSG (n=137) or SPS (n=204) for femoropopliteal lesions with bilateral calcification in fluoroscopic image, based on the Peripheral Arterial Calcium Scoring System (PACSS) classification, between April 2017 and February 2021 at 7 cardiovascular centers in Japan. RESULTS: After propensity score (PS) matching, the final study population consisted of 150 matched patients with no remarkable intergroup difference in baseline characteristics. The primary patency at 1 year was not statistically different between CSG and SPS groups (81.4% vs 71.2%, p=0.32). There was also no significant difference in freedom from target lesion revascularization (82.8% vs 77.6%, p=0.28) and overall survival rate (88.6% vs 87.2%, p=0.81). The stratification analysis demonstrated that advanced age, current smoking, diabetes mellitus, and PACSS grade 4 had a significant interaction on the association of CSG versus SPS implantation with restenosis (interaction p<0.05). CONCLUSIONS: In patients with bilaterally calcified femoropopliteal lesions, 1-year primary patency was not significantly different between treatments using CSG and SPS after the PS matching. CLINICAL IMPACT: Covered stent-graft (CSG) and Supera interwoven nitinol stent (SPS) are reliable endovascular devices in calcified femoropopliteal lesions. This retrospective multicenter study compared the clinical outcomes between the two devices. After propensity score matching, 150 matched patients with no remarkable intergroup difference in baseline characteristics. The primary patency at 1 year was not statistically different between the CSG and SPS group (81.4% vs. 71.2%, p=0.32). There was also no significant difference in freedom from target lesion revascularization (82.8% vs. 77.6%, p=0.28) and overall survival rate (88.6% vs 87.2%, p=0.81). The two devices showed the similar efficacy in calcified femoropopliteal lesions.

Topical Xerostomia Treatment with Hyaluronate Sheets Containing Pilocarpine.

Sjogren's syndrome and radiation therapy for head and neck cancers are often accompanied by xerostomia. Oral pilocarpine (PCP) to treat xerostomia produces systemic side effects, such as runny nose and lacrimation. To improve the therapeutic efficacy of PCP and reduce the aforementioned side effects, we developed a topical delivery system for PCP using freeze-dried sheets of hyaluronic acid (HA). The advantages of HA sheets over conventional oral formulations were examined through in vivo pharmacokinetic and pharmacodynamic studies after their application to oral tissues and salivary glands. The concentration of PCP in the submucosal tissue of the oral cavity was determined using the microdialysis (MD) method after buccal application of HA sheets containing PCP to hamsters. The concentration of PCP in the MD outflow was quite low after gastric administration, whereas the PCP concentration in plasma was high. In contrast, after buccal application of HA sheets containing PCP, the concentration of the drug in the MD outflow increased, despite the negligible concentration in plasma. These findings indicated that both enhancement of saliva secretion and the avoidance of systemic side effects could be achieved through buccal administration of PCP-loaded HA sheets. In addition, the pharmacodynamic study showed that when compared with intravenous and gastric administration, salivary application of HA sheets containing PCP resulted in similar volumes of saliva secretion and reduced lacrimal secretions. In conclusion, freeze-dried HA sheets allow for the development of a novel buccal delivery system with enhanced therapeutic efficacy and safety to treat xerostomia.

Institutional Experiences with Transfemoral Compared to Transcarotid Stenting.

BACKGROUND: Transcarotid artery revascularization (TCAR) is a new surgical technique that is gaining popularity over the transfemoral method (TF-CAS) as the preferred strategy to deliver a carotid stent. This investigation was performed to evaluate the real-world perioperative and long-term outcomes of both techniques at the health system level. METHODS: A retrospective review of prospectively maintained carotid revascularization databases were performed at 2 high-volume TCAR centers in the United States to extract consecutive TF-CAS and TCAR procedures. The characteristics and outcomes associated with these 2 modalities were compared at the preoperative and perioperative points by univariate methods. The Kaplan-Meier methodology was utilized to calculate the long-term stroke and death trends. RESULTS: From 2008-2021, 1,058 carotid stents were implanted at our institutions, consisting of 750 TCARs and 308 TF-CAS procedures. Patients undergoing TF-CAS were older (68.2 ± 0.6 vs. 73.1 ± 0.3 years, P < 0.01) and unhealthier by Charlson Comorbidity Index (4.9 ± 0.1 vs. 5.5 ± 0.1, P < 0.01). Additionally, TF-CAS patients had more high-risk anatomic characteristics, such as restenosis after previous carotid surgery (27.0% vs. 9.5%, P < 0.01), previous ipsilateral neck surgery (38.8% vs. 11.5%, P < 0.01), irradiated ipsilateral field (20.4% vs. 4.5%, P < 0.01), and a contralateral carotid occlusion (10.4% vs. 4.6%, P < 0.01). The incidence of symptomatic lesions was the same (40.1% vs. 36.9%, P = 0.35). Within the operating room, TCAR outperformed TF-CAS with respect to operative time (83.2 ± 2.6 vs. 64.3 ± 0.9 min, P < 0.01), radiation exposure (769.9 ± 144.3 vs. 232.7 ± 19.1 mGys, P < 0.01), fluoroscopic time (17.8 ± 1.1 vs. 4.5 ± 0.1 min, P < 0.01), and contrast volume (75.2 ± 2.4 vs. 22.6 ± 0.4 mLs, P < 0.01). In the 30-day perioperative period, ipsilateral stroke (2.8% vs. 2.3%, P = 0.65), contralateral stroke (1.0% vs. 0.1%, P = 0.07), and death (1.0% vs. 1.2%, P > 0.99) were similar between modalities. None of these endpoints, including a composite of stroke and death (4.8% vs. 3.6%, P = 0.38), reached statistical significance. Additionally, we found no differences with respect to stroke-free survival between modalities during follow-up by Kaplan-Meier analysis (P = 0.30). CONCLUSIONS: In this combined experience from 2 large health systems, TCAR was associated with less intraoperative complexity, as measured by operative time, radiation exposure, and contrast volume. Although stroke and death seemed to be less frequent in patients undergoing transcervical stenting, this did not reach statistical significance.

Transcarotid Revascularization Associated Extended Reverse Flow Duration is Not a Harbinger of Poor Perioperative Outcomes.

BACKGROUND: Transcarotid revascularization (TCAR) is a carotid stenting technique in which an external shunt between the common carotid artery and femoral vein is created to induce cerebral flow reversal as protection against procedure-related plaque embolism. We completed this analysis to determine if prolonged cerebral flow reversal was associated with adverse perioperative outcomes. METHODS: A retrospective review of a combined carotid revascularization database separately maintained at 2 high-volume TCAR health systems was completed. Procedures with captured intraoperative reverse flow duration was included, stratified into two cohorts at a cut-off of 8 mi, and examined with univariate analysis. RESULTS: Within the predesignated study period, 800 patients received a carotid stent via the TCAR technique at Indiana University Health (n = 350) and Memorial Hermann Health Systems (n = 450). In 132 of these procedures, the duration of reverse flow time was not captured and, therefore, excluded from further analysis. Using our prespecified cutoff for extended reverse flow duration (ERFD), we generated 256 cases, leaving an additional 412 procedures completed with a short reverse flow duration. Baseline comorbidities were comparable with respect to individual diagnoses but the overall disease burden in ERFD patients was slightly higher by Charlson Comorbidity Index (5.3 ± 0.1 vs. 5.7 ± 0.1, P = 0.02). With respect to indications and high anatomic risk criteria, both groups were similar, with exception of the presence of a surgically inaccessible carotid bifurcation, which was more frequent in the ERFD procedures (5.3% vs. 10.2%, P = 0.02). Intraoperatively, more blood loss (40.9 ± 2.2 vs. 48.9 ± 2.9 mLs, P = 0.03), operative time (55.2 ± 0.8 vs. 76.3 ± 1.6 min, P < 0.01), radiation (126.3 ± 17.5 vs. 281.9 ± 28.5 mGys, P < 0.01), contrast volume (19.9 ± 0.4 vs. 26.9 ± 0.9 mLs, P < 0.01), and fluoroscopy time (3.3 ± 0.8 vs. 6.3 ± 0.3 min, P < 0.01) were noted in the patients with extended flow reversal. However, this did not increase the risk of stroke (2.7% vs. 2.0%, P = 0.61), myocardial infarction (0.5% vs. 0%, P = 0.53), or death (1.2% vs. 0.4%, P = 0.41) in the 30-day perioperative period. CONCLUSIONS: Extended cerebral flow reversal, defined here as greater than 8 min, was not associated with increased risk of stroke, myocardial infarction, or death in this institutionally derived series.

Adverse events are not increased with trainee participation in transcarotid revascularization.

OBJECTIVE: To determine whether a vascular surgery trainee's participation in transcarotid revascularization (TCAR), a new technology, affects patient safety and outcomes. DESIGN: Retrospective, institutional review of our carotid database was performed. Patients who underwent TCAR were stratified based on whether a vascular trainee was present during the procedure. Relevant demographics, comorbidities, anatomical indication, perioperative courses, and adverse events in the postoperative period were captured for statistical analysis. SETTING: Data were obtained from affiliated Memorial Hermann Hospitals in Houston, Texas. PARTICIPANTS: All patients who underwent TCAR from September 2017 to January 2022 were included. RESULTS: Of 486 patients who underwent TCAR, 173 (35.6%) were performed in the presence of a trainee, and 313 (64.4%) were performed without a trainee. Subjects in the trainee cohort had more challenging anatomy, defined as a higher rate of carotid bifurcation above C2, restenotic disease, previous ipsilateral neck dissection, and neck radiation. The trainee cohort had higher rates of estimated blood loss (61.1 ± 66 vs. 35.5 ± 39 mL, p < 0.01), longer operative time (64.8 ± 30.3 vs. 57.9 ± 20.4 min, p < .01), longer cerebral blood flow reversal time (8.9 ± 6.1 vs. 7.9 ± 6.6 min, p = .01), and higher contrast administration (25.7 ± 12.0 vs. 21.1 ± 9.4 mL, p < .01). The ability to achieve technical success was similar between the two cohorts. There was no difference in the rates of cranial nerve palsy, ipsilateral stroke, hematoma, and stent thrombosis. Hospital length of stay, death (0% vs. 1.6%, p = .10), and stroke (1.1% vs. 2.8%, p = .22) were also similar between the two cohorts. CONCLUSION: Vascular surgery trainee's involvement during TCAR did not increase adverse outcomes, such as stroke and death, in the perioperative period. The results presented herein should encourage other teaching institutions to provide surgical trainees with supervised, hands-on experience during TCAR.

Fixed compared to mobile imaging arms for transcarotid artery revascularization.

OBJECTIVE: Transcarotid artery revascularization (TCAR) is a new surgical option for carotid artery stenosis. While this procedure is optimally performed in hybrid operating rooms (OR), it is currently unclear whether it could be safely performed using portable, C-arm fluoroscopy with equivalent results. The aim of this study is to determine whether there are differences in intraoperative and perioperative outcomes stratified by imaging modality. METHODS: A retrospective review of all TCAR procedures attempted within our health system was performed, capturing all cases between September 2017 and May 2022. Procedures were divided into 2 cohorts, based on whether they were performed in a hybrid OR or with portable, C-arm in a standard OR. Patient demographics, intraoperative results, and postoperative outcomes were compared using univariate strategies. RESULTS: A total of 503 patients were included for review, of which 422 were performed in a hybrid OR (84%) and 81 were performed using a portable C-arm (16%). Intraoperatively, an increased estimated blood loss (47.7 ± 54.7 vs 26.1 ± 26.9 mLs, p < 0.01) and operative time was found in the cases performed in a hybrid OR. However, the fluoroscopy time was lower (4.0 ± 2.6 vs 5.2 ± 5.8 min, p = 0.01) in the setting of advanced intraoperative imaging. Postoperatively, we found no differences with respect to myocardial infarction (0.2% vs. 0%, p > 0.99), stroke (2.4% vs. 2.5%, p = 0.96), or death (0.7% vs. 2.5%, p = 0.15) between groups. CONCLUSIONS: While there are some intraoperative variabilities between TCAR performed in hybrid versus standard ORs, postoperative outcomes are comparable. Therefore, the lack of a hybrid room should not be a deterrent to the adoption of TCAR.

Novel bicyclic pyrazoles as potent ALK2 (R206H) inhibitors for the treatment of fibrodysplasia ossificans progressiva.

Mutant activin receptor-like kinase-2 (ALK2) is associated with the pathogenesis of fibrodysplasia ossificans progressiva, making it an attractive target for therapeutic intervention. We synthesized a new series of bicyclic pyrazoles and evaluated their mutant ALK2 enzyme inhibitory activities, leading to the identification of 8 as the most potent inhibitor. This compound showed moderate microsomal metabolic stability and human ether-a-go-go related gene (hERG) safety. In C2C12 cells carrying mutant ALK2 (R206H), 8 efficiently inhibited the bone morphogenetic protein (BMP)-induced alkaline phosphatase activity.

Freshwater mussels (Bivalvia: Unionidae) from the rising sun (Far East Asia): phylogeny, systematics, and distribution.

Freshwater mussels (Bivalvia: Unionidae) is a diverse family with around 700 species being widespread in the Northern Hemisphere and Africa. These animals fulfill key ecological functions and provide important services to humans. Unfortunately, populations have declined dramatically over the last century, rendering Unionidae one of the world's most imperiled taxonomic groups. In Far East Asia (comprising Japan, Korea, and Eastern Russia), conservation actions have been hindered by a lack of basic information on the number, identity, distribution and phylogenetic relationships of species. Available knowledge is restricted to studies on national and sub-national levels. The present study aims to resolve the diversity, biogeography and evolutionary relationships of the Far East Asian Unionidae in a globally comprehensive phylogenetic and systematic context. We reassessed the systematics of all Unionidae species in the region, including newly collected specimens from across Japan, South Korea, and Russia, based on molecular (including molecular species delineation and a COI + 28S phylogeny) and comparative morphological analyses. Biogeographical patterns were then assessed based on available species distribution data from the authors and previous reference works. We revealed that Unionidae species richness in Far East Asia is 30% higher than previously assumed, counting 43 species (41 native + 2 alien) within two Unionidae subfamilies, the Unioninae (32 + 1) and Gonideinae (9 + 1). Four of these species are new to science, i.e. Beringiana gosannensissp. nov., Beringiana fukuharaisp. nov., Buldowskia kamiyaisp. nov., and Koreosolenaia sitgyensisgen. & sp. nov. We also propose a replacement name for Nodularia sinulata, i.e. Nodularia breviconchanom. nov. and describe a new tribe (Middendorffinaiini tribe nov.) within the Unioninae subfamily. Biogeographical patterns indicate that this fauna is related to that from China south to Vietnam until the Mekong River basin. The Japanese islands of Honshu, Shikoku, Kyushu, Hokkaido, and the Korean Peninsula were identified as areas of particularly high conservation value, owing to high rates of endemism, diversity and habitat loss. The genetically unique species within the genera Amuranodonta, Obovalis, Koreosolenaiagen. nov., and Middendorffinaia are of high conservation concern.