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Objectives: Few evidence-based medications to improve the primary patency of arteriovenous fistulas in patients with diabetes who require hemodialysis are available. We investigated whether proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) could improve arteriovenous fistula function through pleiotropic effects in a rat model of hyperglycemia., Methods: Ex vivo effects of PCSK9i on the aorta of Sprague-Dawley (SD) rats were investigated using an organ bath system. For in vivo experiments, an abdominal aortocaval (AC) fistula was generated in SD rats (200-250 g) after inducing hyperglycemia through streptozotocin administration (80 mg/kg, intraperitoneal). Alirocumab (50 mg/kg/week, subcutaneous) was administered on the day of fistula surgery and day 7. Echocardiography, blood flow through the aorta-limb, vasomotor reactivity, and serum biochemistry were examined on D14. Furthermore, enzyme-linked immunosorbent assay and immunoblotting were performed., Results: PCSK9i induced aorta relaxation ex vivo through a potassium channel-associated mechanism. PCSK9i significantly improved blood flow and preserved endothelial function without changes in cardiac function and serum lipid levels in rats with hyperglycemia. The levels of lectin-like oxidized low-density lipoprotein receptor-1, superoxide dismutase, cyclooxygenase-2, caspase-1, and interleukin-1β were significantly reduced in the treatment group. PCSK9i decreased the ratio of phosphorylated to total p38 mitogen-activated protein kinase and extracellular signal-regulated kinase in the aorta of rats with hyperglycemia., Conclusions: Short-term treatment with PCSK9i preserved endothelial function, induced vascular dilatation, and increased blood flow in the AC fistula of rats with hyperglycemia. The pleiotropic mechanisms were associated with the suppression of oxidative stress and tissue inflammation during hyperglycemia., Competing Interests: The authors declare no conflict of interest.

Background: Venoarterial (V-A) extracorporeal membrane oxygenation (ECMO) after cardiac arrest often predisposes patients to acute brain injury (ABI), which affects survival and neurological performance. The investigation of the predictors of ABI will be beneficial for further management., Objectives: To explore the predictors and outcomes of ABI and intracerebral hemorrhage (ICH) in patients experiencing cardiac arrest and cardiopulmonary resuscitation (CPR) with V-A ECMO support., Methods: We retrospectively analyzed 150 patients who successfully weaned from V-A ECMO support after pre-ECMO CPR at our institution from January 2009 to December 2021. Short-term and long-term outcomes were evaluated. Characteristics before and during ECMO were analyzed for determining the predictors of ABI and ICH., Results: Of the 150 patients, 66 (44.0%) had ABI. ABI was associated with higher in-hospital mortality (62.1% vs. 21.4%, p < 0.0001) and poorer long-term survival after discharge (p = 0.002). Patients who survived to discharge with ABI had significantly more severe neurological deficits at discharge (84.0% vs. 42.4%, p < 0.0001) and improved little at one year after discharge (33.3% vs. 11.4%, p = 0.027). We found that CPR duration [odds ratio (OR) = 1.04, p = 0.003] was the independent risk factor for ABI, whereas lower platelet counts was the independent risk factor for ICH (OR = 0.96, p = 0.019)., Conclusions: After CPR, development of ABI during V-A ECMO support impacted survival and further neurological outcome. Longer CPR duration before ECMO set up significantly increases the occurrence of ABI. Besides, severe thrombocytopenia during ECMO support increases the possibility of ICH., Competing Interests: All the authors declare no conflict of interest.

Competing Interests: All the authors declare no conflict of interest.

Background: The optimal level of hypothermia and safe time of unilateral antegrade cerebral perfusion (uACP) in acute type A aortic dissection (ATAAD) repair remain controversial., Objectives: To analyze the association of uACP time and circulatory arrest temperature with surgical outcomes of ATAAD., Methods: We retrospectively analyzed 263 patients who had undergone ATAAD repair between 2006 and 2020 using uACP. The patients were stratified by three chronologically equivalent periods (period 1, 2006 to 2010; period 2, 2011 to 2015; period 3, 2016 to 2020) to demonstrate the decade-long evolution of surgical strategy and outcomes., Results: The mean age of the patients was 59.4 ± 12.5 years, and 68.8% were male. The hospital mortality rates were 15.1%, 12.9%, and 11.0% from period 1 to 3 (p = 0.740). The median circulatory arrest temperatures were 20, 23, and 25 °C (p < 0.001), respectively, and the median uACP times were 72, 59, and 41 minutes (p < 0.001). The incidence rates of postoperative permanent neurologic deficits were 13.2%, 10.9%, and 18.3% (p = 0.312), and those of transient neurologic deficits were 9.4%, 10.9%, and 11.9% (p = 0.936), respectively. Multivariate logistic regression analysis showed that uACP time ≥ 60 minutes was an independent predictor of hospital mortality rather than postoperative stroke. ROC curve analysis estimated an optimal cutoff value of 52 minutes of uACP time when the circulatory arrest temperature was ≥ 25 °C to predict hospital mortality (area under the curve: 0.72)., Conclusions: Unilateral antegrade cerebral perfusion time was associated with hospital mortality after ATAAD surgery. A safe threshold of 50 to 60 minutes of uACP should be considered.

Background: Prothymosin α (ProT), a polypeptide, attenuates inflammation and inhibits transforming growth factor (TGF)-β signaling in pulmonary tissues. We investigated the potential role of ProT in myocardial ischemia-reperfusion (MyoIR) injury using ProT cDNA transfer., Methods: Serum ProT levels were investigated in cardiogenic shock patients with MyoIR (n = 9). In addition, the myocardium of Sprague-Dawley rats (n = 52) was subjected to 25 min of ischemia followed by an injection of adenoviral vectors (2 × 10 9 plaque-forming units) carrying ProT or the luciferase gene, 10 min before reperfusion. Echocardiography, serum ProT, and biochemical analyses of organ functions were performed before euthanasia, 14 days after treatment. Immunohistochemistry and immunoblotting of the myocardial tissue were also performed., Results: Serum ProT levels were transiently elevated in the rats and patients early after MyoIR, which was reduced to baseline levels in control rats and patients. ProT gene transfer persistently mobilized ProT serum levels, reduced dilatation, attenuated fibrotic changes, and preserved the left ventricular ejection fraction after MyoIR. Tissue thrombospondin-1 level was abundant, and matrix metalloproteinase-2, collagen I, and collagen IV levels were decreased in the treatment group. While TGF-β protein level remained stable, ProT transduction mobilized Smad7, which counteracted TGF-β. ProT reduced tissue microRNA-223 expression, inhibited the associated interleukin-1β, and preserved RAS p21 protein activator 1 protein abundance., Conclusions: An increase in transient serum ProT levels could be a protective response in the acute stage of MyoIR. ProT gene transfer further preserved ventricular morphology and function through anti-inflammatory and anti-fibrotic effects in the subacute stage after injury.

Background: Very limited therapeutic strategies exist to prevent the primary failure of arteriovenous (AV) fistulas in patients with diabetes., Objectives: To investigate whether rosuvastatin could improve the primary patency of AV fistulas in diabetic patients with stage 5 chronic kidney disease (CKD)., Methods: This was a double-blind randomized clinical trial. From July 2012 to September 2018, patients aged between 18 and 65 years with type 2 diabetes and stage 5 CKD were randomized to receive placebo or rosuvastatin (5 mg/day) for 7 days prior to the creation of an AV fistula on the forearm until the 21 st day after surgery. Patients were followed up for 180 days after the operation. The primary composite endpoint was the development of fistula immaturity or stenosis. The secondary endpoints were changes in inflammatory markers, oxidative stress, and occurrence of postoperative complications., Results: A total of 60 patients were enrolled in the study. Rosuvastatin resulted in a 20% reduction in total cholesterol from postoperative day 0 to 28 (p = .0006). The overall rate of AV fistula failure (immaturity or stenosis) was 30%, with no significant difference between patients receiving rosuvastatin and those receiving the placebo (33.3% vs. 26.7%, p = .5731). Although not statistically significant, the administration of rosuvastatin might have increased the incidence of postoperative complications (2.99 vs. 2.39 event rate per 1000 patient-days; odds ratio, 1.33; p = .5986)., Conclusions: Rosuvastatin showed no significant beneficial effects on the primary patency of AV fistulas in diabetic patients with stage 5 CKD, but might have been associated with the risk of drug-related complications.

Background: A patent arteriovenous (AV) fistula induces activation of regional vascular endothelium and vascular shear force. Shear stress is an important physiological force in mobilizing endothelial progenitor cells (EPCs). This study aimed to explore the perioperative changes of circulating EPC levels for patients who require hemodialysis and underwent radiocephalic fistula operation., Methods: This prospective cohort study included patients who received a radiocephalic fistula surgery when they were between 25 and 65 years of age. The subjects were followed for 90 days postoperatively for any stenotic events or immaturity of the fistula. Blood samples were obtained on the day before surgery and at postoperation day (POD) 3 and 30. CD133+/KDR+ cells, defined as EPCs, were analyzed using flow cytometry. Blood flow of the fistula was followed on POD 3 and 30., Results: A total of 30 patients were enrolled in the study from July 2009 to December 2011. One patient dropped out of the study and seven patients developed a stenotic (or immature) AV fistula (7/29, 24.1%). There were positive linear relationships between EPC numbers and shear rate postoperatively, which were more significant on POD 30. In addition, postoperative mobilization of EPCs was significantly higher in patients who developed a stenotic fistula than those without., Conclusions: The mobilization of circulating EPCs correlated with a compromised arteriovenous fistula. The biological significance of increased EPC numbers need to be determined in future studies., Key Words: Arteriovenous fistula; Endothelial progenitor cells.