Efficacy and safety of Ciprofol for procedural sedation and anesthesia in non-operating room settings.

STUDY OBJECTIVE: Ciprofol, a novel intravenous anesthetic, provides rapid recovery in patients undergoing colonoscopy. We aimed to examine the efficacy and safety of ciprofol in comparison with propofol for sedation or anesthesia in non-operating room settings including endoscopic submucosal dissection, endoscopic retrograde cholangiopancreatography, and flexible bronchoscopy (FB). DESIGN: Prospective, randomized, double-blind, parallel-group clinical trial. SETTING: University-affiliated teaching hospital. PATIENTS: We recruited 207 patients scheduled for an endoscopic procedure from October 2021 to December 2021. INTERVENTIONS: Patients were randomized into three groups according to the dose during induction (n = 69 each): 1) ciprofol 6 mg/kg/h, 2) ciprofol 8 mg/kg/h, or 3) propofol 40 mg/kg/h. Ciprofol or propofol was administered throughout the procedure. MEASUREMENTS: The primary outcome was the success rate of sedation or anesthesia for the procedures. Secondary outcomes included induction time, endoscope insertion time, recovery time, discharge time, incidence of drug-related adverse events (AEs), neurological and inflammatory outcomes. MAIN RESULTS: The procedure success rates in the three groups were 100%. The induction time in the 6 (3.3 ± 1.0 min) and 8 mg/kg/h (2.9 ± 0.6 min) ciprofol groups was longer than that in the propofol group (2.5 ± 0.6 min) only in patients undergoing FB (p = 0.004). The time for patients to be fully alert and discharged from the post-anesthesia care unit was comparable across the three groups (p > 0.05). The incidence of drug-related AEs in the propofol and 6 and 8 mg/kg/h ciprofol groups was 84.1%, 76.8%, and 79.7%. No pain on injection was reported by ciprofol groups. Neurological outcomes and inflammatory responses were comparable among the three groups. CONCLUSIONS: Ciprofol induced a level of sedation or anesthesia equivalent to that induced by propofol in non-operating room settings except for a prolonged induction time in patients undergoing FB. Ciprofol had a safety profile similar to that of propofol. No pain on injection was reported by ciprofol.

Altered DNA methylation pattern reveals epigenetic regulation of Hox genes in thoracic aortic dissection and serves as a biomarker in disease diagnosis.

BACKGROUND: Thoracic aortic dissection (TAD) is a severe disease with limited understandings in its pathogenesis. Altered DNA methylation has been revealed to be involved in many diseases etiology. Few studies have examined the role of DNA methylation in the development of TAD. This study explored alterations of the DNA methylation landscape in TAD and examined the potential role of cell-free DNA (cfDNA) methylation as a biomarker in TAD diagnosis. RESULTS: Ascending aortic tissues from TAD patients (Stanford type A; n = 6) and healthy controls (n = 6) were first examined via whole-genome bisulfite sequencing (WGBS). While no obvious global methylation shift was observed, numerous differentially methylated regions (DMRs) were identified, with associated genes enriched in the areas of vasculature and heart development. We further confirmed the methylation and expression changes in homeobox (Hox) clusters with 10 independent samples using bisulfite pyrosequencing and quantitative real-time PCR (qPCR). Among these, HOXA5, HOXB6 and HOXC6 were significantly down-regulated in TAD samples relative to controls. To evaluate cfDNA methylation pattern as a biomarker in TAD diagnosis, cfDNA from TAD patients (Stanford type A; n = 7) and healthy controls (n = 4) were examined by WGBS. A prediction model was built using DMRs identified previously from aortic tissues on methylation data from cfDNA. Both high sensitivity (86%) and specificity (75%) were achieved in patient classification (AUC = 0.96). CONCLUSIONS: These findings showed an altered epigenetic regulation in TAD patients. This altered epigenetic regulation and subsequent altered expression of genes associated with vasculature and heart development, such as Hox family genes, may contribute to the loss of aortic integrity and TAD pathogenesis. Additionally, the cfDNA methylation in TAD was highly disease specific, which can be used as a non-invasive biomarker for disease prediction.

Transcollateral Recanalization of an Occluded Superior Mesenteric Artery.

OBJECTIVE: To report the technique of transcollateral retrograde recanalization of a superior mesenteric artery flush occlusion. METHODS: The technique of a patient undergoing transcollateral retrograde recanalization for acute symptomatic superior mesenteric artery flush occlusion was reviewed and presented. Other adjunctive methods to facilitate the endovascular treatment of the superior mesenteric artery total occlusion lesion were also compared and discussed. RESULTS: The patient was a 47-year-old woman, acute onset of symptomatic chronic mesenteric ischemia with flush occlusion of the superior mesenteric artery which was unable to be revascularized in a routine operation. A collateral was found to connect celiac artery and superior mesenteric artery (gastroduodenal arch). The guidewire was retrograde crossed the occluded lesion via this collateral and recaptured by the catheter from the same single brachial sheath followed by balloon angioplasty and stent implantation. The patient recovered well and the symptoms completely disappeared after the procedure. CONCLUSION: The technique of retrograde recanalization through collateral pathway is an applicable alternative option for patients with superior mesenteric artery flush occlusion who have failed attempts by conventional antegrade approaches.

Identification of Lysophosphatidylcholines and Sphingolipids as Potential Biomarkers for Acute Aortic Dissection via Serum Metabolomics.

OBJECTIVES: Acute aortic dissection (AAD) is a severe clinical emergency with a high mortality, and is easily misdiagnosed in its early stage. This study aimed at discovering serum metabolomic markers with the potential to diagnose AAD and distinguish between two subtypes of AAD. METHODS: Thirty-five patients with AAD, including 20 with Stanford type A and 15 with Stanford type B were enrolled in this study, together with 20 healthy controls. All patients with AAD were admitted within 72 h of onset. Serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and the data were analysed by principal component analysis and partial least squares discriminant analysis. RESULTS: A total of 17 metabolites differing between the control and AAD groups were finally screened and identified as lysophosphatidylcholines (LPC) and sphingolipids including sphinganine, phytosphingosine, sphingomyelin, and ceramide. Compared with those in the healthy control group, LPC levels were significantly lower in both the Stanford type A and type B AAD groups. Interestingly, sphingolipids, including sphinganine, phytosphingosine, and ceramide, were remarkably reduced in the Stanford type A AAD group, but not in the Stanford type B AAD group. Subgroup analysis showed that the changes in LPC and sphingolipid levels were unrelated to hypertension or gender. CONCLUSIONS: The present results indicate that LPCs and sphingolipids are significantly altered in patients with AAD, and several sphingolipids, such as sphinganine, phytosphingosine, and ceramide, were dramatically decreased in patients with Stanford type A AAD. A combination of these two families of metabolites could serve as a potential biomarker for the diagnosis of AAD and distinguishing between Stanford type A and Stanford type B.

Application of triple-chimney technique using C-TAG and Viabahn or Excluder iliac extension in TEVAR treatment of aortic arch dilation diseases.

BACKGROUND: To report the experience of a single centre regarding the application of the triple-chimney technique using C-TAG with Viabahn or Excluder iliac extension devices for the endovascular management of aortic arch dilation diseases. METHODS: From July 2016 to August 2017, 7 patients (5 men; mean age 56.1±10.8 years) with aortic arch dilation diseases were treated with the triple-chimney technique. All patients were followed up at 1, 3, and 6 months and every 6 months thereafter. RESULTS: Six innominate arteries were deployed with Excluder iliac extensions and one with a Viabahn cover-stent. All the left common carotid arteries and left subclavian arteries were placed with Viabahn. Reverse chimney technique was applied in four patients. Three (42.0%) type I endoleaks were found on the final angiogram. Two were apparently reduced, and one disappeared after balloon dilation. The mean follow-up time was 15.7 months (9-20 months). All the type I endoleak was found disappeared within 3 months. One patient died of myocardial infarction at 6 months after discharge. No other complications such as stent-graft migration, occlusion, type II endoleak or neurological stroke occurred. CONCLUSIONS: The use of C-TAG coupled with Viabahn or Excluder iliac extension is feasible and effective for the treatment of aortic arch dilatation diseases. However, more patients and longer follow-up time are required to verify its long-term safety and efficacy.

Radical treatment of primary type B aortic dissection or after thoracic endovascular aortic repair to manage disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) secondary to type B aortic dissection is an unusual and fatal complication that has not been fully investigated. The aim of our study is to report a novel endovascular technique excluding all tears to manage DIC. From April 2017 to October 2017, we performed 2 cases of DIC complicated to type B aortic dissection using this novel radical endovascular repair technique. Clinical data of patients were collected and technical details were presented. These two cases were successfully treated with novel radical endovascular repair technique. DIC was managed and FL thrombosis was formed in these two patients. Follow-up at 6 months revealed no recurrent DIC and a stable aortic diameter with complete FL thrombosis. This endovascular repair technique that excluding all the tears is a feasible approach to prevents continuous coagulation components consumption and thus to manage DIC effectively.

A Comparative Study of the Efficacy by using Different Stent Grafts in Bell-Bottom Technique for the Treatment of Abdominal Aortic Aneurysm Concomitant with Iliac Artery Aneurysm.

BACKGROUND: Bell-bottom technique (BBT) is one method to preserve the internal iliac artery during endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) that extends to iliac artery. The data on the efficacy of this technique are still limited. We sought to evaluate the midterm efficacy of BBT by using different stent grafts in the treatment of AAA combined with iliac artery aneurysm (IAA). METHODS: From January 2011 to December 2016, AAA patients with IAA using BBT to preserve the internal iliac artery were retrospectively analyzed in our institution. Patients were followed up at 3, 6, and then every 12 months after surgery. The outcomes among 3 types of stent grafts (Zenith, Excluder, and Endurant) were compared. BBT-related end points including type Ib endoleak, IAA sac expansion, distal neck expansion, and rupture during follow-up were compared. Other events including perioperative death, any other types of endoleak, and corresponding management were also documented. RESULTS: A total of 125 patients with 141 IAAs were identified. Ninety-eight patients (78.4%) with 113 lesions (80.4%) received a median follow-up time of 38 months. The incidence of type Ib endoleak was 22.9%, 8.3%, 11.9%, and 14.2% (P = 0.19) in Zenith, Excluder, Endurant group, and total patients, respectively. The incidence of IAA sac enlargement was 17.1%, 5.6%, 7.1%, and 9.7% (P = 0.20). The incidence of IAA rupture was 8.6%, 0.0%, 0.0%, and 2.7% (P = 0.03). The incidence of IAA neck enlargement was 34.3%, 13.9%, 16.7%, and 21.2% (P = 0.07). Totally, 14 cases (10.7%) received further treatment for BBT-related issues. CONCLUSIONS: Although BBT remains a safe and effective treatment option to preserve internal iliac artery during standard EVAR with acceptable complication rates in Asians, different IAA rupture rates were found among 3 different stent grafts. Our data for the first time revealed that the type of stent grafts has influence on the final clinical outcome. Based on that, iliac extension should be selected appropriately while treating AAA-IAA.

A New Adjustable Puncture Device for In Situ Fenestration During Thoracic Endovascular Aortic Repair.

PURPOSE: To describe a new adjustable puncture system for in situ fenestration in thoracic endovascular aortic repair (TEVAR). TECHNIQUE: An adjustable puncture needle for use in conjunction with a steerable 8-F, 55-cm Fustar sheath is demonstrated in a 65-year-old man with acute complicated type B dissection involving the left subclavian artery (LSA). The puncture device features an inflatable balloon at the tip, a central lumen for 0.018-inch guidewires, and a 3-level puncture depth. After thoracic stent-graft deployment at zone 2, the needle/sheath combination was delivered from a left brachial artery access. The needle was adjusted perpendicular to the fabric of the stent-graft with the assistance of the steerable sheath. The balloon at the tip was inflated to center the needle, and the puncture depth was selected on the puncture needle system. Holding the sheath and puncture needle together, a hole was created in the graft fabric. The aperture was sequentially dilated to accommodate the mating stent selected to maintain perfusion to the LSA. This new device has been successfully applied in 6 patients treated with TEVAR for different arch pathologies. CONCLUSION: This new puncture device could assist in situ fenestration and improve the technical success rate.

Obstructive sleep apnea and risk of aortic dissection: A meta-analysis of observational studies.

Objectives Obstructive sleep apnea acts as a potential risk factor for the development of cardiovascular disease. We undertook collaborative meta-analyses to clarify the risk of aortic dissection among adults suffering obstructive sleep apnea. Methods A systematic search of the databases (PubMed, Embase, and Cochrane Library) was performed. Studies reporting on the association between obstructive sleep apnea and aortic dissection were included. Information on 424 cases of aortic dissection in 56,291 patients from one cohort, four case-controls, and two cross-sectional studies were included in this study. Results The summary suggested that patients with obstructive sleep apnea are associated with an overall significant 60% increase in the risk of aortic dissection, compared to unexposed patients (odds ratios 1.60; 95% confidence interval 1.01-2.53), with a significantly higher apnea-hypopnea index (mean difference 10.71; 95% confidence interval 7.46-13.96). Moreover, a greater relation was found between moderate-to-severe obstructive sleep apnea and aortic dissection (odds ratios 4.43; 95% confidence interval 2.59-7.59). Adverse outcomes obtained by sleep study such as oxygen desaturation index (mean difference 10.51; 95% confidence interval 7.54-13.48), average SaO2 (-1.36; 95% confidence interval -2.63 to -0.09), and minimum SaO2 (-3.63; 95% confidence interval -5.27 to -1.98) were correspondingly related to patients with aortic dissection. Conclusions Obstructive sleep apnea, especially moderate-to-severe obstructive sleep apnea, may impose an additional risk of suffering from aortic dissection with a potential mechanism including intermittent hypoxia.

Structural basis of RGD-hirudin binding to thrombin: Tyr3 and five C-terminal residues are crucial for inhibiting thrombin activity.

BACKGROUND: Hirudin is an anti-coagulation protein produced by the salivary glands of the medicinal leech Hirudomedicinalis. It is a powerful and specific thrombin inhibitor. The novel recombinant hirudin, RGD-hirudin, which contains an RGD motif, competitively inhibits the binding of fibrinogen to GPIIb/IIIa on platelets, thus inhibiting platelet aggregation while maintaining its anticoagulant activity. RESULTS: Recombinant RGD-hirudin and six mutant variants (Y3A, S50A, Q53A, D55A, E57A and I59A), designed based on molecular simulations, were expressed in Pichia pastoris. The proteins were refolded and purified to homogeneity as monomers by gel filtration and anion exchange chromatography. The anti-thrombin activity of the six mutants and RGD-hirudin was tested. Further, we evaluated the binding of the mutant variants and RGD-hirudin to thrombin using BIAcore surface plasmon resonance analysis (SPR). Kinetics and affinity constants showed that the KD values of all six mutant proteins were higher than that of RGD-hirudin. CONCLUSIONS: These findings contribute to a novel understanding of the interaction between RGD-hirudin and thrombin.

Expression, purification, and characterization of rhTyrRS.

BACKGROUND: Aminoacyl-tRNA synthetases (AARSs) catalyze the first step of protein synthesis. Emerging evidence indicates that AARSs may have additional functions, playing a role in signal transduction pathways regulating thrombopoiesis and inflammation. Recombinant human tyrosyl-tRNA synthetase (rhTyrRS) is engineered with a single amino acid substitution that unmasks its cytokine activity. An industrial production method that provides high yield as well as high purity, quality, and potency of this protein is required for preclinical research. RESULTS: We expressed codon-optimized rhTyrRS in Escherichia coli under fermentation conditions. Soluble protein was purified by a three-step purification method using cation exchange chromatography, gel filtration chromatography, and anion exchange chromatography. We also established a method to test the biological activity of rhTyrRS by measuring aminoacylation and IL-8 release in rhTyrRS-treated HL-60 cells. CONCLUSIONS: The characterization of purified rhTyrRS indicated that this protein can be used in pharmacodynamic and pharmacokinetic studies.