Metagenomic next-generation sequencing performed on blood samples for the early recognition of severe Pneumocystis pneumonia in critical hematological patients.

Severe Pneumocystis pneumonia (PCP) has a poor prognosis, and its early and precise diagnosis is difficult in immunocompromised individuals. Therefore, this study explored the diagnostic value of metagenomic next-generation sequencing (mNGS) of peripheral blood in diagnosing severe PCP in patients with hematological diseases. This prospective study analyzed the clinical manifestations, mNGS results (from the peripheral blood), traditional pathogen detection results, laboratory test results, chest computed tomography (CT) images, treatments, and outcomes of severe PCP in hematological patients who were hospitalized in the 2 centers of the Affiliated Hospital of Soochow University between September 2019 and October 2021. A total of 31 cases of hematological diseases complicated with pulmonary infections, including 7 cases of severe PCP diagnosed by mNGS performed on peripheral blood samples, were analyzed. Traditional pathogen detection methods for PCP cannot be used. In contrast, the laboratory readings for Pneumocystis jirovecii (Pj) detected within 48 hours of symptom onset by mNGS on the 7 blood samples ranged from 12 to 5873, with a median value of 43. Under the guidance of the mNGS results, preemptive antimicrobial therapy with trimethoprim/sulfamethoxazole alone or in combination with caspofungin was administered to treat Pj. After treatment, 4 patients recovered, and 3 patients died of acute respiratory failure and acute respiratory distress syndrome (ARDS). MNGS performed on peripheral blood samples is optional but can provide early recognition of severe PCP and help guide empirical treatment in critical hematological patients.

Circulating Exosomal LncRNAs as Novel Diagnostic Predictors of Severity and Sites of White Matter Hyperintensities.

Objective: Exosomal long noncoding RNAs (lncRNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lncRNAs in white matter hyperintensities (WMH). Methods: We used high-throughput sequencing to determine the differential expression (DE) profiles of lncRNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using qRT-PCR. The diagnostic potential of candidate exosomal lncRNAs was proven by binary logistic analysis and receiver operating characteristic (ROC) curves. The diagnostic value of DE exo-lncRNAs was determined by the area under the curve (AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lncRNAs in the subgroup was evaluated. Results: In our results, four DE exo-lncRNAs were identified, and ROC curve analysis revealed that exo-lnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities. Conclusion: Plasma exosomal lncRNAs have potential diagnostic value in WMH. Moreover, exo-lnc_011797 is considered to be a predictor of the severity and location of WMH.

Spinal Cord Protection of Aorto-Iliac Bypass in Open Repair of Extent II and III Thoracoabdominal Aortic Aneurysm.

BACKGROUND: Spinal cord injury (SCI) is one of the serious complications of thoracoabdominal aortic aneurysm (TAAA) repair. Cardiopulmonary bypass (CPB) and left heart bypass (LHB) are well-established extracorporeal circulatory assistance methods to increase distal aortic perfusion and prevent spinal cord ischaemia in TAAA repair. Aorto-iliac bypass, a new surgical adjunct offering distal aortic perfusion without the need of complex perfusion skills, was developed as a substitute for CPB and LHB. However, its spinal cord protective effect is unknown. METHODS: The perioperative data of 183 patients who had elective open Crawford extent II and III TAAA repair at our aortic centre from July 2011 to May 2019 were retrospectively analysed. Spinal cord protection was compared between the aorto-iliac bypass group (n=106) and the extracorporeal circulatory assistance group (n=77 [65 CPB, 12 LHB]), and the risk factors for SCI in these patients were explored. RESULTS: Eleven (11) patients had postoperative SCI: five (6.5%) in the extracorporeal circulatory assistance group (four with CPB and one with LHB), and six (5.7%) in the aorto-iliac bypass group. The incidence of SCI was 6.0% (11/183 cases). There was no difference between the aorto-iliac bypass group and the extracorporeal circulatory assistance group (p=1.0), while operation time, proximal aortic clamp time, intercostal artery clamp time, and length of intensive care unit stay were all increased in the latter group. Multivariate logistic regression analysis showed that cerebrospinal fluid pressure (odds ratio [OR] 1.270; 95% confidence interval [CI] 1.092-1.478 [p=0.002]) and lowest haemoglobin on the first postoperative day (OR 0.610; 95% CI 0.416-0.895 [p=0.011]) were the independent predictors of SCI in TAAA repair. CONCLUSIONS: Spinal cord protection of aorto-iliac bypass is comparable to that of CPB and LHB in open TAAA repair.

Novel Insights into the Potential Diagnostic Value of Circulating Exosomal IncRNA-Related Networks in Large Artery Atherosclerotic Stroke.

Exosomes show diagnostic and therapeutic promise as carriers of ncRNAs in diseases. LncRNAs in exosomes have been identified as being stable and avoided degradation by nucleolytic enzymes. Although lncRNAs have been confirmed to be important in cancers, no studies for exo-lncRNAs have been reported in LAA stroke. High-throughput sequencing was performed to detect the differential expression profiles of lncRNAs in five paired plasma-derived exosome samples from patients with LAA stroke and controls (matched on vascular risk factors). Exo-lncRNA-associated networks were predicted with a combination of multiple databases. The expression of the selected genes in the networks was confirmed by qRT-PCR in a validation set (LAA vs. controls = 30:30). Furthermore, ROC analysis was used to evaluate the diagnostic performance of the lncRNA-related networks. A total of 1,020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. qRT-PCR confirmed that the expression trend of differential expressed genes was consistent with RNA-seq. Furthermore, the AUCs of the lnc_002015-related network and lnc_001350-related network were 0.959 and 0.97, respectively, in LAA stroke. Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic networks for LAA stroke for the first time. The results suggested that exosomal lncRNA-related networks could be potential diagnostic tools in LAA stroke.

Roles of noncoding RNAs in the initiation and progression of myocardial ischemia-reperfusion injury.

The morbidity and mortality of myocardial ischemia-reperfusion injury (MIRI) have increased in modern society. Noncoding RNAs (ncRNAs), including lncRNAs, circRNAs, piRNAs and miRNAs, have been reported in a variety of studies to be involved in pathological initiation and developments of MIRI. Hence this review focuses on the current research regarding these ncRNAs in MIRI. We comprehensively introduce the important features of lncRNAs, circRNAs, piRNA and miRNAs and then summarize the published studies of ncRNAs in MIRI. A clarification of lncRNA-miRNA-mRNA, lncRNA-transcription factor-mRNA and circRNA-miRNA-mRNA axes in MIRI follows, to further elucidate the crucial roles of ncRNAs in MIRI. Bioinformatics analysis has revealed the biological correlation of mRNAs with MIRI. We provide a comprehensive perspective for the roles of these ncRNAs and their related networks in MIRI, providing a theoretical basis for preclinical and clinical studies on ncRNA-based gene therapy for MIRI treatment.

Mild hypothermic circulatory arrest with selective cerebral perfusion in open arch surgery.

BACKGROUND: This study aimed to evaluate whether the use of mild hypothermic circulatory arrest (HCA) with selective cerebral perfusion (SCP) in open arch procedure provides comparable perioperative results to moderate HCA for patients with dissected or degenerative arch pathologies. METHODS: Between January 2017 and September 2020, a total of 88 consecutive patients (mean age 47±11 years, 71 males) underwent open arch repair under a single surgeon at our institution with mild or moderate systemic hypothermia assisted by unilateral or bilateral SCP. Patients were divided into groups according to the nasopharyngeal temperature at the beginning of HCA: a moderate HCA group (n=47, 53.4%) and a mild HCA group (n=41, 46.6%). The postoperative mortality, morbidity, and visceral organ functions between these groups were analyzed retrospectively. RESULTS: Compared to the moderate HCA group, the mild HCA group had a significantly higher core temperature (nasopharynx: 24.4±0.8 vs. 28.5±2, P<0.001; bladder 25.9±0.9 vs. 30±1.2, P<0.001), and the incidence of major adverse events (MAE) in this group was markedly lower (21.3% vs. 4.9%, P=0.031). No differences were identified between the two groups refer to in-hospital mortality, permanent neurological deficit (PND), temporary neurological deficit (TND), and paraplegia (8.5% vs. 2.4%, P=0.366; 8.5% vs. 0, P=0.120; 6.4% vs. 7.3%, P=1.0; 4.3% vs. 2.4%, P=1.0, respectively). In the moderate HCA group, 6 patients (12.8%) developed acute renal failure needing replacement therapy, which did not occur in the mild HCA group (P=0.028). The duration of ventilator support and intensive care unit stay was shorter in the mild HCA group, as well as a decreased volume of drainage during the first 24 h and reduced platelet transfusion. CONCLUSIONS: The preliminary results of the mild HCA group with SCP applied in open arch repair, mainly in total arch replacement (TAR) and stented elephant trunk (SET) implantation for aortic dissection, were satisfactory. Furthermore, comparable inferior outcomes were obtained with mild HCA compared with that of the conventional moderate HCA strategy. These encouraging surgical and postoperative results favor this more aggressive hypothermia strategy in open arch repair.

Concomitant coronary artery bypass grafting during surgical repair of acute type A aortic dissection affects operative mortality rather than midterm mortality.

BACKGROUND: In this study, we investigated the impact of concomitant coronary artery bypass grafting (CABG) on operative and midterm mortality in patients with acute type A aortic dissection (ATAAD) undergoing surgical repair. METHODS: From January 2012 to December 2014, among 489 patients (mean age: 47.6 ± 10.4 years, 77.1% male) with ATAAD who received surgical repair at our institute, 21 patients (4.3%) underwent concomitant CABG. Isolated aortic repair was performed in the remaining 468 cases (95.7%). Coronary dissection was indicated in 15 patients (Neri classification type B in 2, type C in 13), concomitant coronary artery disease in five and coronary artery compression in one. The follow-up time was 97.3% at 44.1 ± 13.9 months. RESULTS: A total of 44 patients (9%) died from surgery, and operative mortality in the concomitant CABG group was significantly higher than that in the isolated aortic repair group (47.6%, 10/21 vs. 7.3%, 34/468; P < 0.001). Among the 11 survivors in the concomitant CABG group, no deaths occurred during the follow-up. Cox regression indicated that concomitant CABG increased the operative mortality risk by 9.2 times (HR, 9.26; 95% CI, 4.31-19.89; P < 0.001). Although it predicted a 5.2-fold increase in overall mortality (HR, 5.20; 95% CI, 2.55-10.61; P < 0.001), concomitant CABG did not affect midterm death (P = 0.996). CONCLUSIONS: Concomitant CABG carries a significant operative risk in ATAAD patients undergoing surgical repair. However, survivors may benefit from concomitant CABG and had similar midterm mortality compared with the other cases.

Development and Validation of a Plasma FAM19A5 and MRI-Based Radiomics Model for Prediction of Parkinson's Disease and Parkinson's Disease With Depression.

Background: Prediction and early diagnosis of Parkinson's disease (PD) and Parkinson's disease with depression (PDD) are essential for the clinical management of PD. Objectives: The present study aimed to develop a plasma Family with sequence similarity 19, member A5 (FAM19A5) and MRI-based radiomics nomogram to predict PD and PDD. Methods: The study involved 176 PD patients and 181 healthy controls (HC). Sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure FAM19A5 concentration in the plasma samples collected from all participants. For enrolled subjects, MRI data were collected from 164 individuals (82 in the PD group and 82 in the HC group). The bilateral amygdala, head of the caudate nucleus, putamen, and substantia nigra, and red nucleus were manually labeled on the MR images. Radiomics features of the labeled regions were extracted. Further, machine learning methods were applied to shrink the feature size and build a predictive radiomics signature. The resulting radiomics signature was combined with plasma FAM19A5 concentration and other risk factors to establish logistic regression models for the prediction of PD and PDD. Results: The plasma FAM19A5 levels (2.456 ± 0.517) were recorded to be significantly higher in the PD group as compared to the HC group (2.23 ± 0.457) (P < 0.001). Importantly, the plasma FAM19A5 levels were also significantly higher in the PDD subgroup (2.577 ± 0.408) as compared to the non-depressive subgroup (2.406 ± 0.549) (P = 0.045 < 0.05). The model based on the combination of plasma FAM19A5 and radiomics signature showed excellent predictive validity for PD and PDD, with AUCs of 0.913 (95% CI: 0.861-0.955) and 0.937 (95% CI: 0.845-0.970), respectively. Conclusion: Altogether, the present study reported the development of nomograms incorporating radiomics signature, plasma FAM19A5, and clinical risk factors, which might serve as potential tools for early prediction of PD and PDD in clinical settings.

Cardiopulmonary bypass duration is an independent predictor of adverse outcome in surgical repair for acute type A aortic dissection.

OBJECTIVE: This study aimed to investigate the relationship between the duration of cardiopulmonary bypass (CPB) and stroke or early death in patients with acute type A aortic dissection (ATAAD) receiving total aortic arch replacement with the frozen elephant trunk procedure (TAR with FET). METHODS: A retrospective cohort study of 258 consecutive patients was conducted at Beijing Anzhen Hospital from December 2014 to June 2016. Patients who received TAR with FET for ATAAD were included. An adverse outcome (AO) was defined as 30-day mortality or stroke. Additionally, an AO was compared using propensity score matching. RESULTS: The incidence of AO was 13.6% (n = 35). The 30-day mortality rate was 10.8% and the stroke rate was 9.3%. Patients were aged 47.9 ± 10.6 years old. The duration of CPB was an independent predictor of occurrence of AO after adjusting for confounding factors by multivariable logistic regression analysis (odds ratio 1.101, 95% confidence interval 1.003-1.208). In matched analysis, CPB duration remained a risk factor of AO. CONCLUSIONS: The duration of CPB is an independent predictor of AO in surgical repair for ATAAD. The underlying mechanisms of this association are important for developing improved prevention strategies.

Different hypothermic and cerebral perfusion strategies in extended arch replacement for acute type a aortic dissection: a retrospective comparative study.

BACKGROUND: The optimal hypothermic level in total arch replacement with stented elephant trunk implantation for acute type A aortic dissection (aTAAD) has not been established, and the superiority of unilateral or bilateral cerebral perfusion remains a controversial issue. Therefore, we evaluated the application of moderate hypothermic circulatory arrest (MHCA) with a core temperature of 29 °C and bilateral selective antegrade cerebral perfusion in aTAAD treated by total arch replacement with stented elephant trunk implantation. METHODS: From July 2019 to January 2020, 25 aTAAD patients underwent total arch replacement with stented elephant trunk implantation via MHCA (29 °C) and bilateral selective antegrade cerebral perfusion (modified group). Thirty-six patients treated by the same procedure with MHCA (25 °C) and unilateral selective antegrade cerebral perfusion during this period were selected as controls. RESULTS: There were no differences between the two groups of patients in terms of age, sex, incidence of hypertension, malperfusion, and pericardial effusion, although the incidence of cardiac tamponade was higher in the modified group (control 2.8%, modified 20%; P = 0.038). The lowest mean circulatory arrest temperature was 24.6 ± 0.9 °C in the control group, and 29 ± 0.8 °C in the modified group (P <  0.001). In-hospital mortality was 4.9% (3/61) for the entire cohort (control 8.3%, modified 0; P = 0.262). The incidence of permanent neurologic deficit was 4.9% (control 8.3%, modified 0; P = 0.262). There were no significant differences in the occurrence of temporary neurological deficit, renal failure, and paraplegia between groups. The rate of major adverse events in the modified group was lower (30.6% vs. 4%, P = 0.019). A shorter duration of ventilation and ICU stay was identified in the modified group, as well as a reduced volume of drainage within the first 48 h and red blood cell transfusion. CONCLUSIONS: The early results of MHCA (29 °C) and bilateral selective antegrade cerebral perfusion applied in total arch replacement with stented elephant trunk implantation for aTAAD were acceptable, providing similar inferior cerebral and visceral protection compared with that of the conventional strategy. A higher core temperature may account for the shorter duration of ventilation and ICU stay, as well as a reduced volume of drainage and red blood cell transfusion.

Sun's total arch replacement and stent elephant trunk with modified branch-first technique for patients with Stanford type A aortic dissection.

BACKGROUND: Stanford type A aortic dissection (STAAD) is a critical cardiovascular disease, and surgical procedure is the first-choice treatment. The classical surgical procedure still leads to a high mortality rate and neurological complications. In this study, we introduce a new modified Sun's procedure and investigate the association between the branch-first technique and the postoperative outcomes of patients with STAAD. METHODS: A total of 108 consecutive patients with STAAD who underwent arch replacement and stent elephant trunk procedure at Beijing Anzhen Hospital between July, 2017 and November, 2018 were included in the analysis. The patients were divided into two groups: the branch-first group and the classic group. The branch-first group and the classic group comprised 24 patients (22.2%) and 84 patients (77.8%), respectively. RESULTS: Patients in the branch-first group had a significantly shorter cardiopulmonary bypass (CPB) duration (172.4±29.9 vs. 194.9±47.4 min; P=0.035), Intensive care unit (ICU) stay [17.0 (14.6-38.2) vs. 42.1 (19.7-87.2) hours; P<0.001], and mechanical ventilation time [15.5 (11.9-40.0) vs. 19.0 (17.0-45.6) hours; P=0.018] than patients in the classic group. The branch-first was associated with a reduction in postoperative neurological complications in all models. CONCLUSIONS: The benefits of the branch-first technique, including lower CPB duration, better bilateral cerebral perfusion, and higher nasopharyngeal temperature during hypothermic arrest, contributed to a shortened recovery time for patients after surgery.

The use of cIMT as a predictor of postoperative stroke in patients undergoing surgical repair of acute type a aortic dissection.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a life-threatening condition that requires surgical intervention. Stroke remains an extremely serious adverse outcome that can occur in ATAAD patients undergoing aortic arch repair, leading to higher rates of patient mortality and decreased postoperative quality of life. In the present study, we sought to determine whether carotid intima-media thickness (cIMT) is a reliable predictor of postoperative stroke risk. MATERIALS AND METHODS: This was a prospective study of 76 patients with ATAAD undergoing aortic arch repair. For all patients, cIMT was determined preoperatively through a Doppler-based method. Incidence of different forms of neurological dysfunction, including temporary neurological dysfunction (TND) and stroke, was monitored in these patients, and the relationship between cIMT and stroke incidence was assessed using a receiver-operating characteristic (ROC) curve. Prognostic variables associated with stroke risk were further identified through univariate and multivariate analyses. RESULTS: A total of 26/76 (34.2%) patients in the present study suffered from neurological dysfunction, of whom 16 (21.0%) suffered from TND and 10 (13.2%) suffered a stroke. The remaining 50 patients (65.8%) did not suffer from neurological dysfunction. The cIMT values in the stroke, TND, and neurological dysfunction-free patients in this study were 1.12 ± 0.19 (mm), 0.99 ± 0.13 (mm), and 0.87 ± 0.13 (mm), respectively. A total of 4 patients in this cohort died during the study, including 1 in the TND group and 3 in the stroke group. An ROC curve analysis indicated that cIMT could predict stroke with an area under the curve value of 0.844 (95% CI, 0.719-0.969; p < 0.001). A multivariate analysis revealed that cIMT > 0.9 mm was independently associated with stroke risk (p = 0.018). CONCLUSION: We found that cIMT can be used to predict postoperative stroke risk in ATAAD patients undergoing aortic arch repair, with a cIMT > 0.9 mm coinciding with increased stroke risk in these patients. TRIAL REGISTRATION: ChiCTR1900022289. Date of registration 4 April 2019 retrospectively registered.

The onset of acute type A aortic dissection following recovery of type B intramural haematoma: a case report.

BACKGROUND: Aortic intramural hematoma is a life-threatening condition reported with increasing frequency. It can be classified into Stanford type A or B depending on whether the ascending or descending aorta are involved, respectively. However, the onset of acute type A aortic dissection following recovery of type B intramural haematoma is rarely reported. CASE PRESENTATION: We present an uncommon case of acute Stanford type A aortic dissection developing 3 months after recovery of type B IMH in a 47-year-old female. She complained acute chest pain. The operation was successfully done. She was in good condition and asymptomatic at a 3-month follow-up. CONCLUSIONS: Type B intramural haematoma can lead to type A aortic dissection even after totally absorbed and the primary entry has the potential to be located in the ascending aorta. Unsatisfied blood pressure control may be the underlying cause.

Renal malperfusion affects operative mortality rather than late death following acute type A aortic dissection repair.

OBJECTIVE: The aim of our study was to assess how much renal malperfusion increases the risk of early and late mortality in patients with acute type A aortic dissection (ATAAD) undergoing surgical repair. METHODS: This study included 218 patients with ATAAD undergoing surgical repair using the total arch replacement and frozen elephant trunk technique. Mean age was 47.8 ± 10.7 years and 170 were male (78.0%). Based on clinical symptoms and computed tomographic angiography (CTA) findings, 48 patients were diagnosed with preoperative renal malperfusion (22.0%). Clinical data were compared between two groups. The impact of renal malperfusion on operative and late mortality were evaluated with Cox regression. RESULTS: Patients with renal malperfusion experienced significantly higher incidences of persistent postoperative acute kidney injury (AKI; 10/48, 20.8% vs 7/170, 4.1%; p < 0.001) and transient AKI (10/48, 20.8% vs 8/170, 4.7%; p = 0.001) as well as operative mortality (22.9%, 11/48 vs 8.3%, 14/170; p = 0.023). Five-year survival was significantly lower in the renal malperfusion group (72.9% vs 87.0%, p = 0.003). Renal malperfusion was the risk factor for operative mortality (hazard ratio, HR, 2.74; 95% CI, 1.07-6.99; p = 0.035) and overall mortality (HR, 2.64; 95% CI, 1.23-5.67; p = 0.013) but did not predict late death (HR, 2.46; 95% CI, 0.65-9.35; p = 0.187). CONCLUSION: Renal malperfusion increases the risk of operative mortality by 3 times but did not affect late death in patients undergoing acute type A dissection repair.

Supra-aortic vessel reconstruction in total arch replacement for acute type A dissection: Comparison of en bloc and separate graft techniques.

OBJECTIVE: To compare the outcomes of the en bloc and branched graft techniques for supra-aortic vessel reconstruction in total arch replacement (TAR) for acute type A aortic dissection (ATAAD). METHODS: In 53 ATAAD patients with intact supra-aortic arch vessels undergoing TAR, the arch vessels were reconstructed using the branched graft technique in 35 patients and en bloc technique in 18, i.e. reimplantation of the innominate artery and the left carotid artery (LCA) and transposition of left subclavian artery to LCA. The early and mid-term outcomes were compared between two groups. RESULTS: The selective antegrade cerebral perfusion time in en bloc group was significantly longer (33 ± 10 vs 24 ± 7 min, p = 0.001). Operative mortality was 5.7% (3/53), including 1 and 2 in the en bloc and branched graft groups, respectively (5.6% vs 5.7%, p = 0.981). Stroke occurred in 1 patient. No spinal cord injury occurred. At mean 4.3 ± 1.6 years, clinical and CT follow-up were complete in 100% and 86% (43/50). No cerebrovascular accidents or upper extremity claudication occurred. There were 4 deaths and 1 reintervention in follow-up. Survival was 88.6% and 88.9% at 3 months, and 83.3% and 88.6% at 6 months, 3 and 5 years in the en bloc and branched graft groups, respectively (p = 0.597). The arch vessels were patent in 100% (43/43) without stenosis or aneurysm. CONCLUSIONS: The modified en bloc technique could achieve comparable early and mid-term outcomes to the branched graft technique in patients undergoing TAR for ATAAD. This approach may be an alternative technique for ATAAD patients with intact supra-aortic arch vessels.

Associations of CXCL16, miR­146a and miR­146b in atherosclerotic apolipoprotein E­knockout mice.

Atherosclerosis is the primary cause of cardiovascular and cerebrovascular diseases. Recent studies have revealed that C­X­C motif chemokine ligand 16 (CXCL16), microRNA (miR)­146a and miR­146b may have important roles in atherosclerotic diseases. However, the associations of CXCL16, miR­146a and miR­146b in atherosclerotic diseases in vivo remain unclear. Previous studies have demonstrated that miR­146a and miR­146b may negatively regulate the toll like receptor (TLR4)/nuclear factor (NF)­κB signaling pathway to repress the inflammatory response. The present study investigated the associations of CXCL16, miR­146a and miR­146b in atherosclerotic apolipoprotein E (ApoE)­/­ mice in vivo. The expression levels of CXCL16, TLR4/NF­κB signaling pathway, miR­146a and miR­146b in the control and atherosclerotic ApoE­/­ mice were investigated via reverse transcription­quantitative polymerase chain reaction and western blot analysis. The present study demonstrated that the expression of CXCL16 was significantly upregulated in atherosclerotic ApoE­/­ mice compared with control ApoE­/­ mice. The expression levels of TRL4, interleukin­1 receptor­associated kinase 1, tumor necrosis factor receptor associated factor 6, NF­κB, tumor necrosis factor­α and interleukin­1ß were also significantly upregulated in atherosclerotic ApoE­/­ mice compared with control mice. However, the present study revealed that the expression levels of miR­146a and miR­146b were significantly downregulated in atherosclerotic ApoE­/­ mice compared with control ApoE­/­ mice. Overall, the results of the present study suggested that CXCL16 may regulate the TRL4/NF­κB/CXCL16 signaling pathway, and that miR­146a and miR­146b may negatively regulate CXCL16 via this pathway in atherosclerosis in vivo.

In vitro and in vivo evaluation of a small-caliber coaxial electrospun vascular graft loaded with heparin and VEGF.

INTRODUCTION: To date, clinically available expanded polytetrafluoro-ethylene (ePTFE) vascular grafts are suboptimal for reconstructing small caliber (D < 6 mm) arteries, owing to thrombosis in early and restenosis in late stage. Our aim in this preliminary study was to fabricate a nano-fibrous vascular graft which was biofunctionalized with VEGF165 and heparin. The short term performance was evaluated both in vitro and in vivo. METHOD: Four-mm caliber grafts were prepared by the coaxial-elctrospun technique, which consisted of poly(l-lactide-co-caprolactone) [P(LLA-CL)] collagen and elastin. Heparin and endothelial cell growth factor-165 (VEGF165) were encapsulated in the core of the fibrous. Controlled release of the heparin and VEGF165 were evaluated for 28 days. Endothelial cells were cultured on the electrospun grafts or ePTFE grafts as controls. The cellular adhesion, proliferation and morphology were examined. Electrospun or ePTFE grafts were randomly implanted into a rabbit infrarenal aortic replacement model (n = 30) for 28 days without any antiplatelet therapy. At the termination, all grafts were examined by Doppler ultrasound and then evaluated with histology and scanning electron microscopy. RESULTS: The cumulative release amount of heparin (6.93 ± 1.03 mg) and VEGF165 (22.17 ± 5.56 µg) during 28 days were measured. Endothelial cells cultured on electrospun grafts showed significantly higher attachment efficiency and proliferation compared to the ePTFE ones (P < 0.001). At 2 h more ECs had attached to the P(LLA-CL)/Collagen/Elatin grafts (83.26 ± 8.02%) compared to P(LLA-CL) (67.07 ± 4.16%) and ePTFE (46.87 ± 8.85%). ECs proliferated faster on VEGF loaded grafts (O.D = 2.9 ± 1.2, n = 12) compared to ePTFE (O.D = 1.7 ± 1.0, n = 12). The patency was significantly higher in electrospun grafts (86.6%) than ePTFE grafts (40.0%) (P = 0.021). Correspondingly, the microscope images of electrospun implants showed little thrombus when compared with the ePTFE implants. CONCLUSION: Biofunctionalized electrospun graft showed surgical properties, hemocompatibility and higher short-term patency compared with the ePTFE grafts. Despite good early performances, profound study should be designed for long-term evaluation.

Endovascular repair of residual intimal tear or distal new entry after frozen elephant trunk for type A aortic dissection.

BACKGROUND: In patients with type A dissection, residual dissection and new distal entry tears following the frozen elephant trunk (FET) procedure adversely affect long-term prognosis. Management include open and endovascular repair, while clinical experience is limited. We evaluate the efficacy of thoracic endovascular aortic repair (TEVAR) in management of residual intimal tear or distal new entry tear following FET in patients with type A aortic dissection (TAAD). METHODS: Between May 2003 and April 2013, we performed FET and total arch replacement for 1,003 patients with TAAD. Among these, 23 patients (2.3%) required TEVAR for distal new entry (n=2) or residual intimal tear (n=21) at a mean of 2.0±1.6 years after FET. Mean age was 50.1±11.5 years. Marfan syndrome was seen in 2 patients (8.7%). RESULTS: Procedural success was 100%. The distal landing zone was above the 11th thoracic vertebra (T11) in 86.9% (20/23). Neither death nor any paraplegia or stroke occurred early after TEVAR. Follow-up was complete in 100% averaging 2.8±1.7 years (0.3-6.4). One non-Marfan patient died of distal aortic rupture at 4 months after TEVAR. No late stroke or paraplegia occurred. Survival was 95.7% (95% CI, 72.9-99.4%) at 3 and 5 years, respectively. CTA detected false lumen obliteration by thrombus around the endograft in the descending aorta in 91.3% (21/23) of patients. CONCLUSIONS: These early and midterm outcomes show the efficacy of TEVAR in obliterating the residual intimal tear or distal new entry after FET in patients with TAAD. TEVAR may be an alternative approach to distal new entry or residual intimal tear following FET for patients with TAAD.

Type A aortic dissection with arch entry tear: Surgical experience in 104 patients over a 12-year period.

OBJECTIVE: To evaluate the efficacy of the frozen elephant trunk (FET) and total arch replacement (TAR) technique (FET + TAR) in the management of type A aortic dissection (TAAD) with arch entry tear. METHODS: Clinical outcomes were analyzed for 104 TAAD patients with arch entry tear undergoing FET + TAR at 4.7 ± 3.5 days from symptom onset and compared with 728 TAAD patients with entry tears in elsewhere. The mean patient age was 49.3 ± 9.3 years, compared with 45.6 ± 10.8 years in other TAAD patients (P < .001). There were 84 men (80.8%). Hypertension was seen in 84.6% (88/104). RESULTS: Operative mortality was 8.6% (9/104). Spinal cord injury occurred in 3 cases (2.9%), stroke in 2 (1.9%), renal failure in 4 (3.8%) and limb ischemia in 2 (1.9%). Follow-up was 100% (95/95) at mean 5.6 ± 2.6 years (range 1.3-11.6). Late death occurred in 2 cases (1.9%). Survival and freedom from late adverse events were 89.2% (95% confidence interval [CI], 81.3%-93.9%) and 85.0% (95% CI, 76.3%-90.8%) at 8 years, respectively. Both the stented and unstented distal aortic segments showed significant trends of false lumen shrinkage and true lumen expansion over time (P < .001). Of the 65 CT scans at mean 4.6 ± 2.9 years postoperatively, the false lumen was completely obliterated in 63. Risk factors for arch entry tear were hypertension (odds ratio [OR], 2.091; 95% CI, 1.186-3.687; P = .011) and age (OR, 1.025; 95% CI, 1.002-1.048; P = .032). CONCLUSIONS: TAAD with arch entry tear was treated safely and durably by FET + TAR. Although patients with arch entry tear were somewhat older than other patients, operative mortality was not substantially higher despite their older age and arch location of entry tear. These results argue favorably for the use of the FET + TAR technique in the management of TAAD patients with arch entry tears.