Nanomedicines Promote Cartilage Regeneration in Osteoarthritis by Synergistically Enhancing Chondrogenesis of Mesenchymal Stem Cells and Regulating Inflammatory Environment.

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of the articular cartilage and inflammation. Mesenchymal stem cells' (MSCs) transplantation in OA treatment is emerging, but its clinical application is still limited by the low efficiency in oriented differentiation. In our study, to improve the therapeutic efficiencies of MSCs in OA treatment by carbonic anhydrase IX (CA9) siRNA (siCA9)-based inflammation regulation and Kartogenin (KGN)-based chondrogenic differentiation, the combination strategy of MSCs and the nanomedicine codelivering KGN and siCA9 (AHK-CaP/siCA9 NPs) was used. In vitro results demonstrated that these NPs could improve the inflammatory microenvironment through repolarization of M1 macrophages to the M2 phenotype by downregulating the expression levels of CA9 mRNA. Meanwhile, these NPs could also enhance the chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) by upregulating the pro-chondrogenic TGF-ß1, ACAN, and Col2α1 mRNA levels. Moreover, in an advanced OA mouse model, compared with BMSCs alone group, the lower synovitis score and OARSI score were found in the group of BMSCs plus AHK-CaP/siCA9 NPs, suggesting that this combination approach could effectively inhibit synovitis and promote cartilage regeneration in OA progression. Therefore, the synchronization of regulating the inflammatory microenvironment through macrophage reprogramming (CA9 gene silencing) and promoting MSCs oriented differentiation through a chondrogenic agent (KGN) may be a potential strategy to maximize the therapeutic efficiency of MSCs for OA treatment.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

Ferritin-based nanomedicine for disease treatment.

Ferritin is an endogenous protein which is self-assembled by 24 subunits into a highly uniform nanocage structure. Due to the drug-encapsulating ability in the hollow inner cavity and abundant modification sites on the outer surface, ferritin nanocage has been demonstrated great potential to become a multi-functional nanomedicine platform. Its good biocompatibility, low toxicity and immunogenicity, intrinsic tumor-targeting ability, high stability, low cost and massive production, together make ferritin nanocage stand out from other nanocarriers. In this review, we summarized ferritin-based nanomedicine in field of disease diagnosis, treatment and prevention. The different types of drugs to be loaded in ferritin, as well as drug-loading methods were classified. The strategies for site-specific and non-specific functional modification of ferritin were investigated, then the application of ferritin for disease imaging, drug delivery and vaccine development were discussed. Finally, the challenges restricting the clinical translation of ferritin-based nanomedicines were analyzed.

The Global and Regional Prevalence of Abdominal Aortic Aneurysms: A Systematic Review and Modeling Analysis.

OBJECTIVE: To estimate the global and regional prevalence and cases of abdominal aortic aneurysms (AAAs) in 2019 and to evaluate major associated factors. BACKGROUND: Understanding the global prevalence of AAA is essential for optimizing health services and reducing mortality from reputed AAA. METHODS: PubMed, MEDLINE, and Embase were searched for articles published until October 11, 2021. Population-based studies that reported AAA prevalence in the general population, defined AAA as an aortic diameter of 30 mm or greater with ultrasonography or computed tomography. A multilevel mixed-effects meta-regression approach was used to establish the relation between age and AAA prevalence for high-demographic sociodemographic index and low-and middle-sociodemographic index countries. Odds ratios of AAA associated factors were pooled using a random-effects method. RESULTS: We retained 54 articles across 19 countries. The global prevalence of AAA among persons aged 30 to 79 years was 0.92% (95% CI, 0.65-1.30), translating to a total of 35.12 million (95% CI, 24.94-49.80) AAA cases in 2019. Smoking, male sex, family history of AAA, advanced age, hypertension, hypercholesterolemia, obesity, cardiovascular disease, cerebrovascular disease, claudication, peripheral artery disease, pulmonary disease, and renal disease were associated with AAA. In 2019, the Western Pacific region had the highest AAA prevalence at 1.31% (95% CI, 0.94-1.85), whereas the African region had the lowest prevalence at 0.33% (95% CI, 0.23-0.48). CONCLUSIONS: A substantial proportion of people are affected by AAA. There is a need to optimize epidemiological studies to promptly respond to at-risk and identified cases to improve outcomes.

A hybrid metal-organic framework nanomedicine-mediated photodynamic therapy and hypoxia-activated cancer chemotherapy.

The hypoxic tumor microenvironment and photodynamic therapy (PDT)-aggravated hypoxia compromise the anticancer efficacy of chemotherapy, immunotherapy, and PDT. Thus, sophisticated nanomedicines that can activate their anticancer capability in situ in response to specific stimuli need to be developed. This study aimed to construct a hybrid nanomedicine that activated chemotherapy by inducing hypoxia, which synergized with PDT to promote antitumor outcomes, contrary to the strategies focusing on reversing tumor hypoxia. The hybridization of a porphyrin metal-organic framework (MOF) and gold nanoparticles (AuNPs) enhanced the stability of the hybrid nanomedicine against the phosphate in blood, thereby preventing the premature drug release during blood circulation. The surface modification with polyethylene glycol (PEG) markedly increased the tumor accumulation of the hybrid MOF nanomedicine, which encapsulated a hypoxia-activated prodrug (tirapazamine, TPZ), by enhancing its colloidal stability and pharmacokinetics. The loaded TPZ was rapidly released from the nanomedicine in response to the concentrated intracellular phosphate after cellular uptake, and was then converted into a potent anticancer drug in a hypoxic microenvironment exacerbated by continuous O2 consumption during PDT. In vitro and in vivo experiments demonstrated that the synergistic PDT and hypoxia-activated chemotherapy exhibited enhanced antitumor therapeutic efficiency and superior antimetastatic effect, and effectively ablated the tumor without recurrence. Therefore, the sophisticated nanomedicine reported here, which eliminated cancer cells by inducing a hypoxic tumor microenvironment, showed translational potential in future therapeutic development.

Research Progress of Ponticulus Posticus: A Narrative Literature Review.

Study Design: Narrative review. Objective: The purpose of this review was to consolidate the current literature related to ponticulus posticus (PP) and to improve the systematic understanding of this anatomical variant of atlas among spine surgeons. Methods: Articles reviewed were searched in PubMed, Ovid MEDLINE, and Embase. All articles of any study design discussing on PP were considered for inclusion. Two independent authors read article titles and abstracts and included appropriate articles. The relevant articles were studied in full text. Results: A total of 113 literatures were reviewed and consolidated in this narrative review. These articles are roughly divided into the following five subcategories: (1) epidemiology, (2) pathology and anatomy, (3) clinical presentation, (4) surgical significance, and (5) radiographic examination. Conclusion: The PP is non-negligible with a high prevalence. The PP compresses the V3 segment of the artery, the suboccipital nerve, and the venous plexus, consequently contributing to the incidence of neurological pathologies. When a PP is observed or suspected on a lateral radiograph, we recommend that a computed tomography (CT) scan of a patient who is about to receive a C1 lateral mass screw (C1LMS) should be performed, which could determine a safe entry point and the right trajectory of screw insertion.

Icariin-Loaded Hydrogel Regulates Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and Promotes Cartilage Repair in Osteoarthritis.

Intra-articular injection of mesenchymal stem cells is a potential therapeutic strategy for cartilage protection and symptom relief for osteoarthritis (OA). However, controlling chondrogenesis of the implanted cells in the articular cavity remains a challenge. In this study, hydrogels containing different concentrations of icariin were prepared by in situ crosslinking of hyaluronic acid and Poloxamer 407. This injectable and thermoresponsive hydrogel, as a 3D cell culture system, showed good biocompatibility with chondrocytes and bone marrow mesenchymal stem cells (BMSCs), as well as promoted proliferation and chondrogenesis of BMSCs through the Wnt/ß-catenin signaling pathway. Intra-articular injection of this kind of BMSC-loaded composite hydrogel can significantly prevent cartilage destruction by inducing chondrogenic differentiation of BMSCs, and relieve pain through regulating the expression of inflammatory cytokines (e.g., IL-10 and MMP-13) in the OA model. Incorporating BMSCs into this novel icariin-loaded hydrogel indicates a more superior efficacy than the single BMSC injection, which suggests a great potential for its application in OA.

Efficacy and safety of rivaroxaban in patients with inferior vena cava filter placement without anticoagulation contraindications (EPICT): a prospective randomised controlled trial study protocol.

INTRODUCTION: Inferior vena cava (IVC) filters are commonly used in patients with venous thromboembolism to prevent fatal pulmonary embolism, but the thrombosis risk increases after filter placement. Warfarin is a widely anticoagulant, but long-term monitoring and dose adjustments are required. Anticoagulation with rivaroxaban is more straightforward as it dose not require laboratory monitoring. This study compares the efficacy and safety of rivaroxaban and warfarin as an in anticoagulation therapy for patients with IVC filter placement. METHODS AND ANALYSIS: This is a multicentre, randomised controlled trial. In total, 200 patients with deep vein thrombosis (DVT) with IVC filter implantation from 10 hospitals will be recruited. The patients will be randomised to the experimental group (rivaroxaban) or the control group (nadroparin overlapped with warfarin). The primary outcomes include death of any cause, pulmonary embolism (PE)-related death, bleeding and recurrent PE/DVT. The secondary outcomes include the percentage of other vascular events, IVC filter retrieval failure and net clinical benefits. This study aims to provide reliable, verification for the efficacy and safety of rivaroxaban antithrombotic therapy after IVC filter placement. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (approval number: (2019) 295). The results will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals TRIAL REGISTRATION NUMBER: NCT04066764.

Effect of miR-215 on the Expression of Tumor Suppressor Gene Rb1 in Retinoblastoma Cell Lines.

BACKGROUND: Effect of miR-215 on the expression of tumor suppressor gene retinoblastoma (Rb)1 in Rb cell lines was investigated. METHODS: A total of 128 patients were selected. The expression of miR-215 in cancer and adjacent healthy tissues of the 128 patients was detected by reverse transcription-quantitative PCR (RT-qPCR). HXO-Rb44 and Y79 cell lines were transfected with miR-215 analogs or miR-215 inhibitors, and the expression of Rb1 protein in the cell lines was detected by western blotting. RESULTS: The expression of miR-215 in the adjacent healthy tissues of patients was significantly lower than that in cancer tissues (P<0.001). The expression of miR-215 in Y79 and HXO-Rb44 cells was significantly higher than that in APRE-19 cells (P<0.001). The expression of miR-215 in HXO-Rb44 cells was significantly higher than that in Y79 cells (P<0.001). The expression of miR-215 was statistically different from the degree of differentiation and nerve infiltration (P<0.05). The expression of Rb1 in cancer tissues was significantly lower than that in adjacent tissues (P<0.001), the expression of APRE-19 was significantly higher than that in Y79 and HXO-Rb44 cells (P<0.001), and the expression of Rb1 in HXO-Rb44 cells was significantly higher than that in Y79 cells (P<0.05). There was a negative correlation between miR-215 and Rb1 in the tissues of patients, and Rb1 expression decreased with the increase of miR-215 (r=-0.576, P<0.001). CONCLUSION: miR-215 is highly expressed in Rb cell lines, and is related to the clinicopathological features of this disease.

TRIM28 and TRIM27 are required for expressions of PDGFRß and contractile phenotypic genes by vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) in the normal arterial media continually express contractile phenotypic markers which are reduced dramatically in response to injury. Tripartite motif-containing proteins are a family of scaffold proteins shown to regulate gene silencing, cell growth, and differentiation. We here investigated the biological role of tripartite motif-containing 28 (TRIM28) and tripartite motif-containing 27 (TRIM27) in VSMCs. We observed that siRNA-mediated knockdown of TRIM28 and TRIM27 inhibited platelet-derived growth factor (PDGF)-induced migration in human VSMCs. Both TRIM28 and TRIM27 can regulate serum response element activity and were required for maintaining the contractile gene expression in human VSMCs. At the same time, TRIM28 and TRIM27 knockdown reduced the expression of PDGF receptor-ß (PDGFRß) and the phosphorylation of its downstream signaling components. Immunoprecipitation showed that TRIM28 formed complexes with TRIM27 through its N-terminal RING-B boxes-Coiled-Coil domain. Furthermore, TRIM28 and TRIM27 were shown to be upregulated and mediate the VSMC contractile marker gene and PDGFRß expression in differentiating human bone marrow mesenchymal stem cells. In conclusion, we identified that TRIM28 and TRIM27 cooperatively maintain the endogenous expression of PDGFRß and contractile phenotype of human VSMCs.

Role of Programmed Cell Death 4 (PDCD4)-Mediated Akt Signaling Pathway in Vascular Endothelial Cell Injury Caused by Lower-Extremity Ischemia-Reperfusion in Rats.

BACKGROUND We aimed to investigate the role of PDCD4-mediated Akt signaling pathway in vascular endothelial cell injury caused by ischemia-reperfusion in the lower extremities. MATERIAL AND METHODS Ten rats were used as control, while 50 rats were used for creating disease models and were assigned to 5 groups: model group (no injection), NC group (injected with vectors containing PDCD negative control sequence), sh-PDCD4 group (injected with vectors containing sh-PDCD4 sequence), IGF-1 group (injected with IGF-1), and sh-PDCD4+IGF-1 group (injected with IGF-1 and vectors containing sh-PDCD4 sequence). RESULTS Compared with the control group, the expression levels of PDCD4 mRNA and protein, as well as levels of circulating endothelial cells, von Willebrand factor, thrombomodulin, and malondialdehyde, increased in the other 5 groups, while the mRNA and protein expression levels of Akt and eNOS, the protein expression levels of p-Akt and p-eNOS, and superoxide dismutase content decreased in these groups (all P<0.05). Compared with the model group, the sh-PDCD4 and sh-PDCD4+1GF-1 groups had lower mRNA and protein expressions of PDCD4 (all P<0.05), whereas the IGF-1 group had similar levels (all P>0.05). These 3 groups had lower levels of circulating endothelial cells, von Willebrand factor, thrombomodulin, and malondialdehyde, and higher mRNA and protein expressions of Akt and eNOS, protein expressions of p-Akt and p-eNOS, and superoxide dismutase content (all P<0.05). The NC group did not differ from the model group (all P>0.05). CONCLUSIONS PDCD4 gene silencing can activate the Akt signaling pathway and attenuate vascular endothelial cell injury caused by ischemia-reperfusion in the lower extremities in rats.

Single-Stage Treatment of AngioJet Rheolytic Thrombectomy and Stenting for Iliac Vein Compression Syndrome with Secondary Acute Iliofemoral Deep Vein Thrombosis.

BACKGROUND: We sought to evaluate the feasibility, safety, and effectiveness of single-stage endovascular treatment with AngioJet rheolytic thrombectomy followed by stenting for iliac vein compression syndrome (IVCS) with secondary acute iliofemoral deep vein thrombosis (DVT). METHODS: We conducted a multiple-center prospective nonrandomized study to enroll patients with left-sided acute iliac-common femoral DVT secondary to IVCS. We performed AngioJet rheolytic thrombectomy followed by stenting to evaluate the success rate, periprocedural complications, hospital stay, clinical outcomes, and stent-patency rate. RESULTS: A prospective cohort study of 19 consecutive patients diagnosed with IVCS and secondary acute iliac-common femoral DVT from October 2014 to April 2017 was conducted. The technique success rate was 94.7%, and the mean procedure time was 77 minutes. The 1-year primary and secondary patency rate was 84.2% and 94.7%, respectively. CONCLUSIONS: Single-staged endovascular treatment with AngioJet rheolytic thrombectomy and stenting is feasible, safe, and effective for IVCS with secondary acute iliofemoral DVT.

One-Step Reduction and Surface Modification of Graphene Oxide by 3-Hydroxy-2-Naphthoic Acid Hydrazide and Its Polypropylene Nanocomposites.

3-Hydroxy-2-naphthoic acid hydrazide (HNH), a new reductant and modifier, was applied to reduce and modify graphene oxide (GO) in a one-step process. The obtained HNH reduced graphene oxide (HNH-rGO) was characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), Raman spectroscopy, X-ray photoelectron spectroscopic (XPS) and Fourier transform infrared spectra (FTIR). The results demonstrated that GO was successfully reduced to graphene and the surface of HNH-rGO was grafted with HNH. The interlayer space was increased from 0.751 nm to 1.921 nm, and its agglomeration was much more attenuated compared with GO. HNH-rGO/polypropylene and graphene/polypropylene composites were synthesized through melt-blending method. The viscosity was enhanced with increased addition of graphene and surface modified graphene demonstrated stronger rheological behavior improving effect than the untreated graphene.

Percutaneous Revascularization for Atherosclerotic Renal Artery Stenosis: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Percutaneous revascularization (PR) of atherosclerotic renal artery stenosis (RAS) improves patency in the renovascular disease. However, whether PR is associated with additional clinical benefits in the patients with atherosclerotic RAS remains controversial. We conducted a meta-analysis to evaluate the outcomes of PR versus medication alone for atherosclerotic RAS. METHODS: We compiled an electronic database of prospective, randomized, controlled trials related to the efficacy of PR versus medication for RAS. The standardized mean difference (SMD) or relative risk ratios (RRs) were estimated with 95% confidence intervals (CI) based on an intention-to-treat analysis. We considered the following outcomes: changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), reduction in antihypertension medication, serum creatinine, worsening renal failure, mortality, stroke, and congestive heart failure. RESULTS: Seven trials with a total of 1916 patients (937 with PR, 979 with medication alone) were analyzed. The changes in SBP/DBP from baseline were similar between the 2 groups (changes in SBP: P = 0.69; changes in DBP: P = 0.15). PR treatment led to a statistically significant decrease in the number of antihypertensive medications compared with medical management alone (SMD -0.18, 95% CI -0.27 to -0.10, P < 0.001). The pooled RR for deteriorating renal function, congestive heart failure, or stroke showed no significant difference. CONCLUSION: PR is equally effective to medical management in the treatment of RAS. Therefore, patients with atherosclerotic RAS along with hypertension or chronic kidney disease should receive medical therapy to control blood pressure, but they should not be considered for a renal artery stent.

Endovascular treatment for symptomatic iliac vein compression syndrome: a prospective consecutive series of 48 patients.

BACKGROUND: We sought to assess the prevalence of iliac vein compression syndrome (IVCS) in patients with unilateral left lower limb chronic venous disease and evaluate the feasibility and effectiveness of endovascular treatment for IVCS. METHODS: We conducted a prospective cohort study of 48 consecutive patients diagnosed with IVCS between December 2008 and May 2012. We divided the patients into 2 groups: thrombotic IVCS (n = 12) and nonthrombotic IVCS (n = 36). We evaluated the perioperative, 30-day, and 1-year outcomes of endovascular treatment. We estimated the stent patency rate using the Kaplan-Meier method. RESULTS: The prevalence of IVCS within our cohort was 14.8% (48/324). The technical success rate of the endovascular treatment was 95.8%. There was no death, pulmonary embolism, or contrast-induced nephropathy among the patients. The 1-year primary patency rate was 93.0%. There was no significant difference between the thrombotic and nonthrombotic IVCS groups (P = 0.156). Perioperative complications were minor and improved quickly. The median pain level recorded on a visual analogue scale declined from 4.5 to 1.2 (P < 0.05) in the thrombotic ICVS group and from 3.3 to 0.3 (P < 0.05) in the nonthrombotic ICVS group. The edema relief rates in the thrombotic and nonthrombotic ICVS groups were 81.8% and 58.5%, respectively. The cumulative recurrence free ulcer healing rate was 71.4% 12 months after treatment. CONCLUSIONS: IVCS is more common than previously thought among patients with unilateral left lower limb chronic venous disease. Endovascular therapy, a minimally invasive approach to treating venous lesions, is a feasible and effective treatment for left-sided IVCS and has a high technical success rate and an acceptable complication profile.

Preoperative versus intraoperative endoscopic sphincterotomy in patients with gallbladder and suspected common bile duct stones: system review and meta-analysis.

BACKGROUND: Conducting preoperative versus intraoperative endoscopic sphincterotomy in patients with gallbladder and suspected common bile duct stones remains controversial. We conducted a meta-analysis to evaluate the outcomes of preoperative endoscopic sphincterotomy (POES) versus intraoperative endoscopic sphincterotomy (IOES). METHODS: We searched multiple electronic databases for prospective, randomized, controlled trials related to safety and effectiveness of POES versus IOES. Relative risk ratios (RRs) were estimated with 95 % confidence intervals (CI) based on an intention-to-treat analysis. We considered the following outcomes: clearance rate, postprocedural complications, and hospital stay. RESULTS: Five trials with 631 patients (318 with POES, 313 with IOES) were analyzed. Although the overall rates of common bile duct stone clearance were similar between POES and IOES (RR 0.96, 95 % CI 0.91-1.01; p = 0.13), the failure rate of common bile duct cannulation during endoscopic retrograde cholangiopancreatography (ERCP) was significantly higher for IOES (RR 2.54, 95 % CI 1.23-5.26; p = 0.01). The pooled RR after POES for overall complication rates was similar to that for IOES (RR 1.56, 95 % CI 0.94-2.59; p = 0.09). However, compared with IOES, the RR risk of ERCP-related complications was significantly higher for POES (RR 2.27, 95 % CI 1.18-4.40, p = 0.01), especially in the patients at high risk of developing post-ERCP pancreatitis. There was no significant difference in morbidity after laparoscopic cholecystectomy or required subsequent open surgery between the two groups. In the subgroup analyses, the RR risks of post-ERCP pancreatitis were significantly higher for POES (RR 4.85, 95 % CI 1.41-16.66, p = 0.01), and mean hospital stay was longer in the POES group (RR 2.22, 95 % CI 1.98-246; p < 0.01). However, the rates of bleeding, perforation, cholangitis, cholecystitis, and gastric ulceration did not differ significantly between POES and IOES. CONCLUSIONS: With regard to the stone clearance and overall complication rates, POES is equal to IOES in patients with gallbladder and common bile duct stones. However, IOES is associated with a reduced incidence of ERCP-related pancreatitis and results in a shorter hospital stay.

Endovascular management of ascending aortic pathology.

BACKGROUND: Endovascular treatment of the ascending aorta is particularly challenging because of the anatomic features of this aortic segment. Only patients without connective tissue disorders, clinically relevant aortic regurgitation or stenosis, or concomitant coronary artery disease can be considered for an endovascular procedure. We report our results in a series of patients with aneurysms or intramural hematoma, penetrating ulcers, or floating thrombus who were scheduled for stent grafting. METHODS: Only patients with ascending aortic pathology who were unfit for open surgery were treated with an endograft. When preoperative computed tomography imaging showed severe calcification of the aortic arch or thrombus lining, temporary clamping of the carotid arteries before wire and catheter introduction was performed. An extracorporeal bypass from the right groin to both carotid arteries with a roller pump was established and maintained during the procedure. The endograft was placed across the aortic valve into the left ventricle and deployed in a retrograde fashion. At the end of the procedure, ventriculography and, if necessary, coronary angiography was performed to rule out any damage to the left ventricle or the valve apparatus. RESULT: Eleven patients were scheduled for stent graft exclusion of ascending aortic pathology. In five cases because of discrepancies in length measurements and sizing, the thoracic endograft was cut to length intraoperatively after partial deployment on the operating table and reloaded to avoid covering of the innominate artery. The mean length of the ascending aorta covered was longer in aneurysm patients than in those with dissection. An 81-year-old patient presented with a type Ia leak. The distal landing zone in one patient was enlarged by debranching. One patient died after wire perforation of the left ventricle, and one patient sustained a cerebral stroke. Combined morbidity and mortality was 18%, and the technical success rate was 91%. CONCLUSIONS: Stent grafting of the ascending aorta is technically feasible but should be reserved for selected high-risk patients only, preferably in centers where vascular specialists cooperate closely with interventional cardiologists. Cardiac surgery with cardiopulmonary bypass is still the gold standard to treat ascending aortic aneurysms. Stent graft exclusion of more advanced and complex ascending aortic pathology should be performed only in centers with the necessary experience in transvalvular cardiac procedures.