An eighth note.

Venous stenosis is the most common cause of arteriovenous fistula (AVF) failure in hemodialysis patients. For patients with AVF stenosis, the pressure over the antecedent part of the AVF stenotic lesion will increase if arterial inflow is sufficient. We report a chronic hemodialysis patient who received an angiographic examination for the juxta-anastomosis stenosis of his AVF. A unique feature of a collateral venous branch antecedent to the stenotic lesion was noted, resembling a musical sign as the "eighth note." After percutaneous transluminal angioplasty, the eighth note attenuated markedly at once. Of note, the eighth note sign is not seen frequently, and thus we postulate that the formation of an eighth note sign on the radiocephalic fistula should fulfill the following requirements, including a sufficient arterial inflow, an adjacent collateral branch close enough to the arteriovenous anastomosis, a severe juxta-anastomotic stenotic lesion, and an intact ulnar venous drainage system.

Pentraxin 3 Predicts Arteriovenous Fistula Functional Patency Loss and Mortality in Chronic Hemodialysis Patients.

INTRODUCTION: Viable vascular access is the lifeline for hemodialysis patients. In the nondialysis population, emerging evidence suggests that circulating pentraxin 3 (PTX3), neutrophil gelatinase-associated lipocalin (NGAL), and chitinase-3-like protein 1 (CHI3L1) are associated with cardiovascular inflammation and endothelial injury. However, predictive values of these three biomarkers on arteriovenous fistula (AVF) outcomes are unknown. METHODS: This prospective observational cohort study enrolled 135 hemodialysis patients using AVF and then followed them for 3 years. Plasma levels of PTX3, NGAL, and CHI3L1 were measured. Patients were followed up prospectively for two clinical outcomes, including AVF functional patency loss and death. Cox proportional hazards regression models were used to analyze hazard ratios for the commencement of AVF functional patency loss and mortality. RESULTS: Among 135 patients, the mean age was 66.0 ± 15.7 years old and 48.1% were male. The plasma level of PTX3, NGAL, and CHI3L1 was 2.8 ± 2.3 ng/mL, 349.2 ± 111.4 ng/mL, and 185.5 ± 66.8 ng/mL, respectively. During a 3-year follow-up period, the plasma level of PTX3 was an independent predictor for AVF functional patency loss (per 1 ng/mL increase, HR 1.112 [95% CI: 1.001-1.235], p = 0.048). Besides, patients with higher plasma levels of PTX3 were more likely to suffer from cardiovascular mortality (per 1 ng/mL increase, HR 1.320 [95% CI: 1.023-1.703], p = 0.033), infectious mortality (per 1 ng/mL increase, HR 1.394 [95% CI: 1.099-1.769], p = 0.006), and all-cause mortality (per 1 ng/mL increase, HR 1.233 [95% CI: 1.031-1.476], p = 0.022). CONCLUSIONS: The plasma level of PTX3, not NGAL or CHI3L1, was associated with higher risks of AVF functional patency loss in chronic hemodialysis patients, showing its value in reflecting AVF endothelial dysfunction. Furthermore, PTX3 also predicts mortality in chronic hemodialysis patients.

Clinical Effect of Revascularization Strategies and Pharmacologic Treatment on Long-Term Results in Patients with Advanced Peripheral Artery Disease with TASC C and D Femoropopliteal Lesions.

Background: This study was to assess the clinical outcome and associated parameters of endovascular therapy (EVT group) and bypass surgery (bypass group) in patients with long femoropopliteal TransAtlantic Inter-Society Consensus II (TASC II) C and D peripheral artery disease (PAD). Methods: 187 patients who underwent successful EVT or bypass surgery were assessed. The endpoints included the events of cardiovascular disease (CVD) and lower-extremity amputation (LEA), 3-year primary patency, and 3-year amputation-free survival (AFS). Results: The 3-year primary and secondary patency rates were better in the bypass group (P=0.007 and P=0.039, respectively), while the incidences of LEA, new CVD events, and mortality were comparable between groups. Weighted multivariate Cox analyses showed that cilostazol treatment (hazard ratio (HR): 0.46, 95% confidence interval (CI): 0.3-0.72, P=0.001), statin treatment (HR: 0.54, 95% CI: 0.33-0.9, P=0.014), and direct revascularization (DR) (HR: 0.47, 95% CI: 0.29-0.74, P=0.001) were predictive factors of 3-year primary patency. Kaplan-Meier curve analyses of time-to-primary cumulative AFS showed that nondiabetes mellitus, mild PAD, and cilostazol and statin treatment were correlated with a superior 3-year AFS (log rank test, P=0.001, P < 0.001, P=0.009, and P=0.044, respectively). Conclusions: Endovascular stenting based on the angiosome concept and bypass surgery provide comparable benefits for the treatment of long, advanced femoropopliteal lesions after a short follow-up period, whereas cilostazol therapy for more than 3 months, aggressive treatment of dyslipidemia, and surgical revascularization were associated with higher primary patency.

Tumor Necrosis Factor-Alpha Exacerbates Viral Entry in SARS-CoV2-Infected iPSC-Derived Cardiomyocytes.

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.

Outcome of drug-eluting balloon angioplasty versus endarterectomy in common femoral artery occlusive disease.

OBJECTIVE: Common femoral artery (CFA) occlusive disease remains a debatable site for endovascular therapy, and the outcome of drug-eluting balloon (DEB) angioplasty in treating CFA occlusive disease is largely unknown. This study compared the efficacy, safety, and short-term patency rate of DEB angioplasty and femoral endarterectomy for treatment of CFA occlusive disease. METHODS: From March 2013 to June 2016, there were 100 patients with symptomatic CFA occlusive disease who were retrospectively reviewed. Forty patients were treated with DEB angioplasty and 60 were treated with femoral endarterectomy. Each patient received regular follow-up. Patency rate, ankle-brachial index, target lesion revascularization, and adverse events were assessed. RESULTS: Technical success was 100% in all patients. The DEB group had a lower 1-year primary patency rate (75.0% vs 96.7%; P = .003), but the secondary patency rate was similar between the two groups (97.5% vs 98.3%; P = 1.000). At 2-year follow-up, the primary patency was lower in the DEB group (57.1%) than in the endarterectomy group (94.1%; P = .001), whereas the secondary patency rate had no significant difference (90.5% vs 97.1%; P = 1.000). Both groups had significant improvement in ankle-brachial index. Freedom from target lesion revascularization was lower in the DEB group both at 1 year (75.0% vs 96.7%; P = .003) and at 2 years (57.1% vs 94.1%; P = .001). There was no significant difference in the incidence of complications and adverse events. CONCLUSIONS: Femoral endarterectomy has a better primary patency rate compared with DEB angioplasty in treating CFA occlusive disease without significant increase in complications. In patients not suitable for endarterectomy, DEB angioplasty provides a similar secondary patency rate and could be considered an alternative treatment.

Edge Stenosis After Covered Stenting for Long Superficial Femoral Artery Occlusive Disease: Risk Factor Analysis and Prevention With Drug-Coated Balloon Angioplasty.

PURPOSE: To report a retrospective analysis of risk factors for edge restenosis after Viabahn stent-graft treatment of superficial femoral artery (SFA) occlusive disease and determine any protective effect of drug-coated balloons (DCBs) used at the time of stent-graft implantation. METHODS: Between October 2011 and July 2016, 110 patients (mean age 73.3±7.6 years; 78 men) were treated with the Viabahn stent-graft for long SFA occlusions. Thirty-eight (34.5%) patients had DCB reinforcement at the distal edge of the stent-graft. For analysis, the population was divided into groups of no edge stenosis patients (n=88; mean lesion length 22.4±4.2 cm) and edge stenosis patients (n=22; mean lesion length 23.5±5.7 cm). The clinical outcomes, ankle-brachial indices, computed tomography angiography findings, and patency were compared at a minimum of 12 months. Logistic regression analysis was employed to determine risk factors for edge stenosis; the results are presented as the odds ratio (OR) and 95% confidence interval. RESULTS: No differences in clinical or procedural characteristics were identified except the higher incidence of diabetes (p=0.008) and greater need for retrograde access (p=0.033) in the edge stenosis group. DCB reinforcement reduced the incidence of edge stenosis (p=0.021) and target lesion revascularization (TLR; p=0.010) and resulted in a significantly higher 1-year primary patency rate (92.1% vs 76.4%, p=0.042). However, multivariate analysis revealed only poor distal runoff (OR 0.31, 95% CI 0.11 to 0.83, p=0.020) as a predictor of edge stenosis. CONCLUSION: The risk of edge stenosis after Viabahn implantation was higher in patients with poor distal runoff. DCB reinforcement over the distal edge reduced edge stenosis, decreased 1-year TLR, and improved 1-year primary patency.

Endovascular and Hybrid Revascularization for Complicated Aorto-Iliac Occlusive Disease: Short-Term Results in Single Institute Experience.

BACKGROUND: Treatment for extensive aortoiliac occlusive disease (AIOD) includes endovascular interventions, hybrid procedures and surgical reconstruction. This study evaluated the short-term outcomes of endovascular and hybrid procedures in patients with Trans-Atlantic Inter-Society Consensus II (TASC-II) D AIOD lesions. MATERIALS AND METHODS: From January 2013 to June 2015, 41 patients with TASC-II D AIOD lesions who underwent revascularization at our institute were retrospectively included. Nineteen underwent endovascular procedures and 22 underwent hybrid procedures with a postoperative surveillance program for at least 1 year. Patient demographics and short-term outcomes were analyzed. RESULTS: The procedural success rate in all patients was 100%. The accumulative postoperative complication rate was 20.2%, and the major complication was acute kidney injury (14.6%). The time of freedom from target lesion revascularization was 18.9 months. The primary patency rates in the endovascular group were 89.5% and 84.2% at 1 and 2 years, respectively, compared to 95.5% at 1 and 2 years in the hybrid group; however, the difference was not significant (p = 0.234). The secondary patency rates were 94.7% and 93% at 1 and 2 years, respectively, in the endovascular group, and 95.5% and 94% at 1 and 2 years, respectively, in the hybrid group; however, the differences was not significant (p = 0.916). CONCLUSIONS: Our study revealed that endovascular and hybrid procedures are favorable treatment choices for patients with TASC-II D AIOD lesions. In patients with multilevel steno-occlusive lesions, hybrid procedures improved distal runoff flow and reduced the complexity of endovascular procedures.

Real-World Comparison of Drug-Eluting and Bare-Metal Stents in Superficial Femoral Artery Occlusive Disease with Trans-Atlantic Intersociety Consensus B Lesions: A 2-Year, Single-Institute Study.

BACKGROUND: Endovascular stenting has surpassed bypass surgery to become the first-line treatment for superficial femoral artery (SFA) occlusive disease, and various types of stents including bare-metal stents (BMSs), covered stents, and drug-eluting stents (DESs), have been approved for treatment. This retrospective, single-institute study compared the short-term, real-world outcomes of BMSs and DESs for treating SFA occlusive disease. METHODS: A retrospective chart review was used to enroll 94 patients who received a DES (n = 24) or BMS (n = 70) between 2009 and 2014. All patients had SFA occlusive disease with critical limb ischemia and an intermediate length of SFA occlusion [Trans-Atlantic Intersociety Consensus (TASC)-II B lesions] and were regularly followed for 2 years. All patient characteristics, procedural details, and outcomes were recorded. RESULTS: The 1-year primary patency rates in the BMS and DES groups were 71.4% and 87.5% (p = 0.169), respectively, and the corresponding 2-year rates were 61.4% and 79.2% (p = 0.139). The target lesion revascularization rate was 38.6% versus 20.8% (p = 0.139), the in-stent restenosis rate was 22.9% versus 0% (p = 0.009), the major limb amputation rate was 4.3% versus 0% (p = 0.568), the peripheral arterial disease-related mortality rate was 8.6% versus 0% (p = 0.332), and the all-cause mortality rate was 11.4% versus 0% (p = 0.109), respectively. CONCLUSIONS: The 2-year results revealed higher safety, superior efficacy, and greater clinical benefits of DESs than BMSs for treating TASC-II B SFA occlusive disease. However, more cases and long-term follow-up are warranted.

Genotype polymorphisms of genes regulating nitric oxide synthesis determine long-term arteriovenous fistula patency in male hemodialysis patients.

OBJECTIVES: Nitric oxide (NO) is a pivotal vasoactive substance modulating arteriovenous fistula (AVF) patency for hemodialysis (HD). Since genetic background could be the predicting factor of AVF malfunction, we aimed to investigate whether the NO-related genotype polymorphisms determine AVF survival rates. METHODS: This is a retrospective, observational, multi-center study involving eight HD units in Taiwan, enrolled 580 patients initiating maintenance HD via AVFs. Genotype polymorphisms of NO-biosynthesis regulating enzymes (DDAH-1, DDAH-2, eNOS and PRMT1) were compared between HD patients with (n = 161) and without (n = 419) history of AVF malfunction. Subgroup analyses by gender were performed to evaluate the genetic effect in difference sexes. RESULTS: In overall population, statistically significant associations were not found between AVF malfunction and the genetic polymorphisms. In the male subgroup (n = 313), a single nucleotide polymorphism (SNP) of PRMT1, rs10415880 (IVS9-193 A/G), showed a significant association with AVF malfunction. Male patients with AA/AG genotype had inferior AVF outcomes compared to GG genotype, regarding primary patency (70.6% vs. 40.9%, p = 0.001), assisted primary patency (81.0% vs. 58.4%, p < 0.001) and secondary patency (83.7% vs. 63.3%, p < 0.001) at a 5-year observation period. From multivariate Cox regression model, the AA/AG genotypes of PRMT1 were an independent risk factor for AVF malfunction in men (HR: 4.539, 95% CI 2.015-10.223; p < 0.001). However, such associations were not found in women. CONCLUSIONS: rs10415880, the SNP of PRMT1 could be a novel genetic marker associated with AVF malfunction risk in male HD patients. Those with AA and AG genotypes of rs10415880 may predict a poorer long-term patency of AVF.

Aliskiren Inhibits Neointimal Matrix Metalloproteinases in Experimental Atherosclerosis.

BACKGROUND: The renin-angiotensin system (RAS) plays an important role in atherosclerosis. Acting via the angiotensin II receptor, type 1, oxidative stress increases and contributes to endothelial dysfunction and vascular inflammation. Renin exerts effects through a renin receptor causing an increase in the efficiency of angiotensinogen cleavage and facilitates angiotensin II (Ang II) generation and action on cell surfaces. Ang II enhances proliferation and migration of vascular smooth muscle cells, indicating a direct involvement of the RAS in smooth muscle cell proliferation during neointimal formation. Aliskiren, a direct renin inhibitor, is a new oral antihypertensive drug. However, the role of the direct renin inhibitor in neointimal formation and vascular matrix metalloproteinases remains unclear. METHODS: To investigate the effects of aliskiren on the expression of vascular matrix metalloproteinases, we evaluated the aortic neointimal formation of high-cholesterol-fed animals after vascular injury in vivo and the cellular function of the tumor necrosis factor-α stimulated human aortic smooth muscle cells in vitro. Thereafter, we evaluated vascular expression (by western blot), activity (by gelatin zymography) and molecular pathway. RESULTS: In this study we demonstrated that aliskiren reduced neointimal hyperplasia in hypercholesterolemic rabbits after vascular injury and the expression of matrix metalloproteinases in the neointima. Aliskiren also inhibited the expression and activities of matrix metalloproteinases on tumor necrosis factor-α (TNF-α)-stimulated human aortic smooth muscle cells via the mitogen-activated protein kinase pathway. CONCLUSIONS: The present study showed that aliskiren inhibited the expression of vascular matrix metalloproteinases. With these results, we have better clarified the potential role of renin inhibitors in human atherosclerosis.

Rivaroxaban, a factor Xa inhibitor, improves neovascularization in the ischemic hindlimb of streptozotocin-induced diabetic mice.

BACKGROUND: Factor Xa inhibitor is used for preventing venous thromboembolism (VTE) in adult patients receiving orthopedic operation. However, the role of factor Xa inhibitor, rivaroxaban, in angiogenesis is still unknown. METHODS AND RESULTS: Streptozotocin (STZ)-induced diabetic mice with model of hind-limb ischemia, were divided into non-diabetic control, diabetic control, and low- and high-dose rivaroxaban treatment groups, in order to evaluate the effect of rivaroxaban in angiogenesis. Doppler perfusion imaging showed that blood flow recovery was significantly increased, and more capillary density occurred in the rivaroxaban treatment group. In vitro studies, human endothelial progenitor cells (EPCs) treated with rivaroxaban had significant functional improvement in migration and senescence under hyperglycemic conditions. Rivaroxaban also increased endothelial nitric oxide synthase (eNOS) as well as vascular endothelial growth factor (VEGF) expressions in hyperglycemia-stimulated EPCs. CONCLUSIONS: Rivaroxaban promoted vessel formation in diabetic mice and improved endothelial progenitor cell function under hyperglycemic conditions. These effects may be associated with enhancement of expression of eNOS and VEGF.

Percutaneous pharmacomechanical thrombectomy offers lower risk of post-thrombotic syndrome than catheter-directed thrombolysis in patients with acute deep vein thrombosis of the lower limb.

BACKGROUND: Despite optimal anticoagulant therapy, patients with proximal deep vein thrombosis (DVT) will often develop post-thrombotic syndrome (PTS). Early thromboreduction can potentially decrease the risk of PTS by restoring venous patency and preserving valvular function. This study was undertaken to compare the efficacy and treatment outcomes of patients with acute proximal DVT of the lower limb who underwent either catheter-directed thrombolysis (CDT) or percutaneous pharmacomechanical thrombectomy (PMT). METHODS: Thirty-nine patients with acute proximal DVT of the lower limb who were diagnosed by Wells' Score, PMT or CDT was chosen depending on the patient. They underwent early thromboreduction, and 3 died postoperatively in less than 12 months, while 2 were removed for not following-up. Thirty-four patients, 16 in PMT and 18 in CDT, were followed up for more than 1 year. Venous Registry Index (VRI) was used to evaluate the postprocedural patency, while PTS was assessed using the Villalta scale. RESULTS: The technical success was 100% in both the groups, without any 30-day mortality. VRI changed from 13.1 ± 4.3 preoperatively to 2.4 ± 1.5 postoperatively in the PMT group, and from 11.8 ± 2.4 to 3.6 ± 2.2 in the CDT group. Thrombolysis rate was 81.5 ± 8.5% and 67.7 ± 21.0% in the PMT and CDT groups, respectively (P = 0.059). There were no differences in complications, thrombus score, and VRI between the 2 groups. Primary patency rate at 1 year was 93.8% in the PMT group and 88.9% in the CDT group (P = 0.648). The Villalta scale was 2.1 ± 3.0 in the PMT group and 5.1 ± 4.1 in the CDT group (P = 0.030). CONCLUSIONS: Both PMT and CDT are effective treatment modalities in patients with acute proximal DVT. Compared with CDT, PMT provides similar treatment success, but with lower risk of PTS at 1-year follow-up.

Systemic vascular resistance predicts high-output cardiac failure in patients with high-flow arteriovenous fistula.

AIMS: Patients with high-flow arteriovenous (AV) access are at risk of developing high-output cardiac failure (HOCF) and subsequent hospitalization. However, diagnosing HOCF is challenging and often requires invasive procedures. The role of systemic vascular resistance (SVR) in diagnosing HOCF is underestimated, and its predictive value is limited. Our study aims to identify non-invasive risk factors for HOCF to facilitate early diagnosis and timely surgical interventions. METHODS AND RESULTS: We included 109 patients with high-flow AV access who underwent serial echocardiography. The retrospective cohort was divided into two groups based on their hospitalization due to HOCF. The two groups were matched for age and gender. After a mean follow-up of 25.1 months, 19 patients (17.4%) were hospitalized due to HOCF. The two groups had similar baseline characteristics. However, the HOCF group had a higher value of vascular access blood flow (Qa) (2168 ± 856 vs. 1828 ± 617 mL/min; P = 0.045). Echocardiographic analysis revealed that the HOCF group had more pronounced left ventricular diastolic dysfunction (E/e': 21.1 ± 7.3 vs. 16.2 ± 5.9; P = 0.002), more severe pulmonary hypertension (right ventricular systolic pressure: 41.4 ± 16.7 vs. 32.2 ± 12.8; P = 0.009), a higher Doppler-derived cardiac index (CI) (4.3 ± 0.8 vs. 3.7 ± 1.1; P = 0.031), and a lower Doppler-derived estimated SVR (eSVR) value (5.5 ± 0.3 vs. 6.9 ± 0.2; P = 0.002) than the non-HOCF group. Using multivariable Cox regression analysis, a low eSVR value (<6) emerged as an independent predictor of HOCF hospitalization with a hazard ratio of 9.084 (95% confidence interval, 2.33-35.39; P = 0.001). Receiver operating characteristic curve analysis indicated that CI/eSVR values more accurately predicted HOCF hospitalization [sensitivity: 94.7%, specificity: 51.0%, area under the curve (AUC): 0.75, P < 0.001] than the Qa/cardiac output ratio (AUC: 0.50, P = 0.955), Qa values ≥ 2000 mL/min (AUC: 0.60, P = 0.181), and Qa values indexed for height in metres (AUC: 0.65, P = 0.040). CONCLUSIONS: In patients with high-flow AV access, low eSVR values obtained through non-invasive Doppler echocardiography were associated with a high rate of HOCF hospitalizations. Therefore, routine eSVR screening in these patients might expedite the diagnosis of HOCF.

Safety and efficiency of femoral artery access closure using QuikClot Combat Gauze in patients with severe arterial calcification of access sites.

Background: In order to achieve better hemostasis of puncture holes in the femoral artery (FA) after an endovascular procedure, this study evaluated the effect and safety of manual compression (MC) with QuikClot Combat Gauze (QIC) and with mechanical compression (using a C-clamp) of the common access site, the FA, in patients with peripheral arterial occlusive disease (PAOD) combined with anterior femoral artery calcification (AFAC). Methods: We prospectively reviewed 100 patients receiving either MC with QIC or mechanical compression (control group) after endovascular intervention for PAOD plus AFAC from February 2014 to September 2018 in a single unit, which was assessed using computerized tomography angiography (CTA). Results: The mean time to completion of hemostasis was 30±0 minutes in the control group and 18±2.20 minutes in the QIC group (P<0.001). The time to ambulation of the QIC and control groups was 4.38±0.46 and 4.86±0.30 hours (P<0.001), respectively. Eight (16%) patients in the control group had hematoma, as compared with one patient (2%) in the QIC group (P=0.031), while sixteen (32%) patients in the control group had ecchymosis, as compared with four (8%) in the QIC group (P=0.005). Use of QIC and coronary artery disease (CAD) were identified as independent factors correlated with an increased risk of minor complications. Conclusions: QIC facilitated effective and safe hemostasis in patients with PAOD and AFAC.

miR-548j-5p regulates angiogenesis in peripheral artery disease.

Peripheral artery disease (PAD) is a vascular disease involving diffuse atherosclerosis, and is associated with increased cardiovascular mortality and morbidity. Critical limb ischemia (CLI) is the most severe complication of PAD. In addition to medical and interventional treatment, therapeutic angiogenesis is a novel therapy for PAD. Circulating microRNAs (miRNAs) are considered key regulators of gene expression, but their role in ischemic-induced angiogenesis is poorly-characterized. There is currently a limited understanding of the specific miRNAs associated with PAD. To determine the regulation of miRNAs, we obtained miRNA profiles using RNA isolated from patients with PAD and a control group. The effects of specific miRNAs on angiogenesis were evaluated by assessing the in vitro angiogenic function of endothelial progenitor cells (EPCs), performing an in vivo angiogenesis assay, and employing a mouse hindlimb ischemic model. Our results demonstrated that circulating miR-548j-5p was significantly reduced in patients with PAD as compared with the controls. miR-548j-5p promoted EPC angiogenesis by enhancing migration and tube formation. The endothelial nitric oxide synthase (NOS) and stromal cell-derived factor (SDF)-1 signaling pathways appeared to be potential targets of miR-548j-5p. Furthermore, the results of a directed in vivo angiogenesis assay of EPCs and a hindlimb ischemia mouse model demonstrated that miR-548j-5p enhanced the capillary density and blood flow recovery in hindlimb ischemia. In conclusion, our data indicated that up-regulation of miR-548j-5p promotes angiogenesis in ischemic tissue and may represent a novel therapeutic approach for PAD.

Far-Infrared Therapy Improves Arteriovenous Fistula Patency and Decreases Plasma Asymmetric Dimethylarginine in Patients with Advanced Diabetic Kidney Disease: A Prospective Randomized Controlled Trial.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and plays a significant role in the pathogenesis of arteriovenous fistula (AVF) dysfunction. The aim of this study is to evaluate the effect of far-infrared (FIR) therapy on the maturation and patency of newly-created AVFs in patients with advanced diabetic kidney disease (DKD) as well as the concurrent change in plasma ADMA. The study enrolled 144 participants with advanced DKD where 101 patients were randomly allocated to the FIR therapy group (N = 50) and control group (N = 51). Patients receiving FIR therapy had a decreased AVF failure rate within 12 months (16% versus 35.3%; p = 0.027); decreased incremental change of ADMA concentration at the 3rd and 12th month; increased AVF blood flow at the 1st, 3rd, and 12th month; increased 3-month physiologic maturation rate (88% versus 68.6%; p = 0.034); increased 1-year unassisted AVF patency rate (84% versus 64.7%; p = 0.017); and increased clinical AVF maturation rate within 12 months (84% versus 62.7%; p = 0.029) compared to the control group. The study demonstrates that FIR therapy can reduce the incremental changes in plasma ADMA concentration, which may be associated with the improvement of AVF prognosis in patients with advanced DKD.

Effects of Postoperative Percutaneous Coronary Intervention, Pharmacologic Treatment, and Predisposing Factors on Clinical Outcomes in Patients With and Without Type 2 Diabetes Along With Critical Limb Ischemia.

PURPOSE: Critical limb ischemia (CLI) has been identified as being connected to rates of cardiovascular mortality and lower extremity amputation (LEA). This prospective study investigated the effects of percutaneous coronary intervention (PCI), pharmacologic treatment, and predisposing factors on clinical outcomes in patients with and without type 2 diabetes mellitus (DM) along with CLI after endovascular intervention. METHODS: 249 consecutive patients with CLI (Fontaine stages III-IV) received pharmacologic treatment after successful endovascular intervention. Their primary patency rates of infrapopliteal lesions and cardiovascular and amputation events during a 36-month follow-up period were assessed. FINDINGS: Patients with DM were more likely to be younger (P = 0.026); 50% (n = 63), 42.9% (n = 54), 52.4% (n = 66), and 77% (n = 97) of DM patients had arterial calcification, end-stage renal disease, diabetic neuropathy, and Fontaine stage IV (P < 0.001, P < 0.001, P < 0.001, and P = 0.019, respectively). The primary patency rates were 61%, 48.8%, and 42.3% at 12, 24, and 36 months, in the patients without DM (P = 0.034, P = 0.013, and P = 0.005). Patients with DM had higher risks of 36-month coronary artery disease, cerebrovascular accident, mortality, and LEA (P = 0.005, P = 0.042, P = 0.042, and P < 0.001). Patients with CLI receiving long-term cilostazol treatment had a better primary patency and amputation-free survival, and a lower risk of mortality at 36 months (P < 0.001, P < 0.001, and P = 0.001). Statin use was associated with 36-month amputation-free survival but not with primary patency (P = 0.032 and P = 0.088). Subgroup multivariate Cox analyses showed that primary patency was independently associated with long-term cilostazol treatment, PCI in the first postoperative year, and direct revascularization in the DM group, whereas in the control group, long-term cilostazol treatment was the main independent factor. The risk of amputation was independently associated with a high high-sensitivity chronic reactive protein level, diabetic neuropathy, sole use of an oral hypoglycemic agent, and lack of supervised exercise. IMPLICATIONS: Long-term cilostazol treatment, aggressive management of dyslipidemia, and meticulous assessment and prevention of postoperative unstable coronary artery disease should be considered in CLI patients with and without DM to maximize clinical outcomes. PCI in the first postoperative year may be a predisposing factor for patency failure in patients with CLI, especially those with DM. A large-scale prospective randomized trial should be conducted to confirm these findings (TVGH IRB No. 2013-08-020B).

Long-Term Cilostazol Treatment and Predictive Factors on Outcomes of Endovascular Intervention in Patients with Diabetes Mellitus and Critical Limb Ischemia.

INTRODUCTION: Despite improvements in endovascular interventions and multidisciplinary approaches, improving clinical outcomes and increasing limb salvage have become increasingly challenging. This prospective study investigated the associations of cilostazol treatment with clinical outcomes and predictive factors in patients with diabetes mellitus (DM) and critical limb ischemia (CLI) after endovascular revascularization of the affected angiosome. METHODS: In this study, 172 consecutive patients with CLI (Fontaine levels III-IV) received cilostazol treatment after successful endovascular intervention according to the angiosome concept, and their primary patency rates and cardiovascular and amputation events during a 24-month follow-up period were assessed. RESULT: The 24-month primary patency rate, mortality rate, and amputation rate were better in the patients under long-term cilostazol treatment (P < 0.001, P = 0.029, and P = 0.014). Weighted multivariate Cox analyses with a propensity scoring-based method showed that long-term cilostazol treatment [hazard ratio (HR) 0.2, 95% confidence interval (CI) 0.11-0.36, P < 0.001], direct revascularization (DR) (HR 0.46, 95% CI 0.28-0.74, P = 0.002), and supervised exercise (HR 0.4, 95% CI 0.24-0.66, P < 0.001) were independently associated with primary patency. Patients with lower-extremity amputation (LEA) had a higher risk of coronary artery disease (CAD) and mortality. Cellulitis and neuropathy were independently associated with LEA events (cellulitis: HR 2.89, 95% CI 1.66-5.05, P < 0.001; neuropathy: HR 2.2, 95% CI 1.31-3.7, P = 0.003). CONCLUSION: Our results showed that patients with DM who received cilostazol treatment for more than 3 months had significantly better outcomes and decreased amputation and mortality rates after DR, and cellulitis and neuropathy were highly associated with the risk of limb loss. A large-scale randomized trial should be conducted in the future to confirm these results. TRIAL REGISTRATION: Taipei Veterans General Hospital (TVGH) IRB no. 2013-08-020B. Registered 30 August 2013.

Hemodialysis vascular access care during the COVID-19 pandemic.

Dialysis patients are more vulnerable and susceptible to the severe coronavirus disease 2019 (COVID-19) infection due to multiple comorbidities. Since Taiwan has the highest incidence and prevalence of treated end-stage kidney disease worldwide, it is crucial to act in advance to prevent a potential disaster. In the face of the COVID-19 pandemic, we implement proactive infection control measures to prevent it from spreading without sacrificing the dialysis care quality. In this article, we focused on hemodialysis vascular access (HVA) care in particular. As a life-line of hemodialysis (HD) patients, HVA care has a profound impact on the patient's quality of dialysis and life. Specifically, in our facility, the working and office areas of the HD units are separated to reduce cross-infection. All elective procedures for HVA are postponed, and operating rooms equipped with a negative-pressure anteroom are used for the suspected or confirmed COVID-19 patients. Herein, we share how we modified our HVA care policy not only to prevent our patients from COVID-19 infection but also to maintain the quality of HVA care.

Catastrophic complication of stent perforation in a uremic patient with acute myocardial infarction.

Catheter-induced coronary artery dissection is a rare but devastating complication of coronary angiography and percutaneous coronary intervention (PCI). Complications during PCI include coronary artery dissection, intramural hematoma, coronary artery perforation, and occlusion of branch vessels. Stent perforation is more unusual and potentially fatal. Here, we report a 68-year-old uremic woman who underwent primary PCI for her acute myocardial infarction. Unfortunately, dissection of the left proximal coronary artery by a guide catheter, followed by stent implantation, resulted in stent perforation through the middle left coronary artery and severe laceration of the left coronary orifice. Cardiogenic shock leading to cardiac arrest occurred. Emergency coronary artery bypass grafting and aortomy for left coronary orifice repair were conducted. The patient's postoperative course was uneventful, and she was discharged 15 days after surgery. From the successful outcome in this patient, we speculate that both better selection of patients and lesions for angioplasty and surgical standby may prove to be life-saving and effectively decrease subsequent mortality for patients experiencing devastating complications during PCI.