Development and validation of a prediction model for postoperative ischemic stroke following total arch replacement and frozen elephant trunk under mild hypothermia.

Background: Early identification of postoperative ischemic stroke among patients with acute DeBakey type I aortic dissection (ADIAD) is of great significance to taking timely effective treatment. We aimed to develop and validate a prediction model for postoperative ischemic stroke in ADIAD patients who underwent total arch replacement (TAR) and frozen elephant trunk (FET) under mild hypothermia. Methods: ADIAD patients who underwent TAR and FET between January 2017 and April 2023 were enrolled in our study. Preoperative and intraoperative variables were selected using pairwise comparisons, the Least Absolute Shrinkage and Selection Operator (LASSO), and logistic regression to construct a prediction model for postoperative ischemic stroke. The accuracy and calibration of the model were assessed using 1000 bootstrap resamples for internal validation, with the area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow test. The AUC was also used to evaluate the model's accuracy in the validation cohort. Results: The development cohort included 246 patients. The mean [standard deviation (SD)] age of patients in the cohort was 50.7 (11.2) years, 196 (79.7%) were men, and 22 (8.9%) were diagnosed with postoperative ischemic stroke. The validation cohort included 73 patients with a mean (SD) age of 52.5 (11.9) years, 58 (79.5%) were men and 3 (4.1%) were diagnosed with postoperative ischemic stroke. Three variables out of the initial 40 potential predictors were included in the final prediction model: the platelet count [odd ratio (OR), 0.992; 95% confidence interval (CI), 0.983-1.000], the presence of innominate artery dissection (OR, 3.400; 95% CI, 1.027-11.260), and the flow of selective cerebral perfusion (OR, 0.147; 95% CI, 0.046-0.469). The mean AUC in the development cohort was 0.77 (95% CI, 0.68-0.87), and calibration was checked with the Hosmer-Lemeshow test (P = 0.78). In the validation cohort, the AUC was 0.98 (95% CI, 0.94-1.00). A prediction model and a clinical impact curve were developed for practical purposes. Conclusions: In this study, we have developed a prediction model with competent discriminative ability and calibration. This model can be used for early assessment of the risk of postoperative ischemic stroke in patients with ADIAD following TAR and FET under mild hypothermia.

Total Arch Replacement With Frozen Elephant Trunk Using a NEW "Brain-Heart-First" Strategy for Acute DeBakey Type I Aortic Dissection Can Be Performed Under Mild Hypothermia (≥30°C) With Satisfactory Outcomes.

BACKGROUND: Total arch replacement (TAR) with Frozen elephant trunk (FET) treatment of acute DeBakey type I aortic dissection (ADIAD) is complicated, carries a high complication/mortality risk and remains controversial on the optimal hypothermic level, cerebral perfusion and visceral organ protection strategy. We developed a new strategy named "Brain-Heart-first" in which the surgical procedures and the management of cardiac perfusion/cerebral protection during Cardiopulmonary bypass (CPB) were redesigned, and TAR with FET technique can be performed under mild hypothermia with satisfactory outcomes. OBJECTIVE: Our aims were to describe a new surgical strategy under mild hypothermia (≥30°C) for the treatment of ADIAD and to report the operative outcomes of 215 patients. METHODS: We conducted a retrospective analysis of 215 consecutive cases of ADIAD treated with our new strategy. RESULTS: The durations of CPB, aortic cross-clamping, antegrade cerebral perfusion, operation, mechanical ventilation support, and Intensive Care Unit stay were 139.7 ± 52.3 min, 55.6 ± 27.4 min, 14.1 ± 3.1 min, 6.0 ± 1.7 h, 40.0 h and 4.0 d, respectively. The 30-day mortality was 9.8%, with cerebral stroke occurring in nine patients (4.2%), paraplegia in one patient (0.5%) and postoperative renal injury requiring dialysis in 21 patients (9.8%). The blood transfusion of red blood cells and fresh frozen plasma during surgery and the first 24 h after surgery was 4.0 u and 200.0 ml, respectively. CONCLUSIONS: The Brain-Heart-first strategy can be widely used with low technical and resource requirements and provides a safe alternative for conventional TAR with FET technique in ADIAD patients with satisfactory operative results.

Type A Aortic Dissection During COVID-19 Pandemic: Report From Tertiary Aortic Centers in the United States and China.

Coronavirus disease 2019 (COVID-19) has substantially disrupted many processes of care related to emergency cardiac conditions, while there has been no clinical guidance regarding the management of type A aortic dissection. A retrospective multicenter study involving 52 consecutive patients (mean age 52.3, 28.9% women) with type A aortic dissection during COVID-19 pandemic was conducted at tertiary aortic centers in Michigan, Wuhan and Changsha (China). Twenty-four (46.2%) were considered clinically suspicious for COVID-19 based on radiographic lung lesions (70.8%) followed by dyspnea (25.0%), cough (12.5%), and fever (12.5%). Overall, 47 (90.4%) underwent an operation and 5 (9.6%) managed nonoperatively. All suspected patients underwent a reverse-transcriptase-polymerase-chain-reaction at arrival, whereas 82.1% in the nonsuspected (P = 0.054). Among the 24 patients either nonoperatively managed or whose operation was delayed for >24 hours, only 1 (4.2%) died. A total of 3 (6.4%) operated patients had a positive reverse-transcriptase-polymerase-chain-reaction at various timings, including 1 nonsuspected patient preoperatively and 2 with very recent COVID-19 infection. The first patient died of respiratory failure despite uneventful surgical repair and maximal medical management. The postoperative course of both patients with recent COVID-19 was characterized by severe coagulopathy requiring massive transfusions and prolonged ICU stay. However, both survived to hospital discharge. In light of the possible dismal outcomes associated with dual diagnoses of type A aortic dissection/COVID-19 and the higher-than-expected number of asymptomatic carriers, all type A dissection patients should be immediately tested for COVID-19. Surgical interventions in patients recovered from recent COVID-19 may be safe.

LOXL1-AS1/miR-515-5p/STAT3 Positive Feedback Loop Facilitates Cell Proliferation and Migration in Atherosclerosis.

Existing research has elucidated the critical role of long noncoding RNAs (lncRNAs) in the progression of multiple human cardiovascular diseases, including atherosclerosis (AS). Nonetheless, whether long noncoding RNA LOXL1 antisense RNA 1 (LOXL1-AS1) regulates the biological functions in AS is exceedingly limited. In this research, we detected through reverse transcription-quantitative polymerase chain reaction that LOXL1-AS1 expression was markedly upregulated in patients with AS. The role of LOXL1-AS1 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) was unmasked by functional assays. Moreover, knockdown of LOXL1-AS1 exerted suppressive effect on proliferation and migration whereas accelerated apoptosis in VSMCs and HUVECs. Molecular mechanism assays revealed that signal transducer and activator of transcription 3 (STAT3) functioned as a transcription activator of LOXL1-AS1 in VSMCs and HUVECs. In addition, miR-515-5p was manifested to bind with LOXL1-AS1 (or STAT3) in VSMCs and HUVECs. Furthermore, LOXL1-AS1 could elevate STAT3 expression by sponging miR-515-5p in VSMCs and HUVECs. More importantly, rescue assays delineated that inhibited expression of miR-515-5p or elevated expression of STAT3 could reverse the restraining effect of LOXL1-AS1 depletion on the progression of AS in HUVECs. All these findings revealed the role of a LOXL1-AS1/miR-515-5p/STAT3 positive feedback loop in AS.

An innovative arch-first surgical procedure under moderate hypothermia for acute type A aortic dissection.

BACKGROUND: We hypothesized that the arch-first procedure without extra devices under moderate-to-mild systemic hypothermia during acute type A aortic dissection is safe and efficient and will improve patient outcome compared with the standard total arch replacement technique. METHODS: From December 2014 to February 2017, 89 patients were enrolled in this study, 52 of whom underwent conventional deep hypothermic circulatory arrest (DHCA, 24.2±0.71 °C) using the antegrade cerebral perfusion surgical procedure (Group A) and 37 of whom underwent the "arch-first" technique with moderate (27.4±1.1 °C) systemic hypothermia during antegrade cerebral perfusion (Group B). The clinical data, surgical and postoperative data, complications, and mortality of the two groups were analyzed. RESULTS: The cardiopulmonary bypass (171.3±40.0 min) and awakening time (7.0 hours) was significantly decreased in Group B. Two patients died 30 d after surgery (5.4%, two of 37) in Group B. The incidence of transient neurologic deficit (2.7%) and distal organ complications (5.4%) was lower in Group B. CONCLUSIONS: In patients with acute type A aortic dissection involving the arch, the innovative arch-first surgical procedure could provide feasible and safe treatment outcomes, which brings us closer to the goal of performing surgery with moderate-to-mild systemic hypothermia with better cerebral, distal organ, and survival outcomes.

The methylation of Notch1 promoter mediates the osteogenesis differentiation in human aortic valve interstitial cells through Wnt/ß-catenin signaling.

Aortic valve interstitial cells (AVICs) have the potential to undergo calcification, which has been regarded as a critical issue during the pathology of calcific aortic valve disease (CAVD). In the past decade, epigenetics, in particular, DNA methylation dysregulation, has been reported to play a vital role in the occurrence and development of CAVD. In the present study, the expression of Notch1, which can inhibit the osteogenesis differentiation of valve interstitial cells, was downregulated whereas the expression of methyltransferases was upregulated in CAVD tissues, suggesting the potential role of DNA methylation in Notch1 expression and CAVD progression. As revealed by DNA extraction and bisulfite sequencing polymerase chain reaction (PCR), the methylation level in Notch1 promoter was much higher in CAVD tissues and human AVICs on Day 14 of osteogenesis differentiation induction. The silence of Notch1 intercellular domain (NICD) promoted while the treatment of demethylation agent, 5-Aza-dC, inhibited the osteogenesis differentiation. Moreover, NICD overexpression significantly suppressed the transcriptional activity of ß-catenin on TCF4, and the expression of osteogenesis differentiation factors, indicating the involvement of Wnt/ß-catenin signaling in Notch1 modulating the osteogenesis differentiation in human AVICs (hAVICs). Taken together, Notch1 promoter methylation leads to a decreased Notch1 expression and subsequent decreased release of NICD in the nucleus of hAVICs, therefore promoting the activation of Wnt/ß-catenin signaling and the expression of osteogenesis differentiation factors, finally promoting the osteogenesis differentiation in hAVICs. DNA methylation might act as an important bridge to link epigenetic variation and CAVD progression.

Untreated distal intimal tears may be associated with paraplegia after total arch replacement and frozen elephant trunk treatment of acute Stanford type A aortic dissection.

OBJECTIVE: To investigate the possible overlooked causes of early postoperative paraplegia, a severe complication of acute Stanford type A aortic dissection (ATAAD) after total arch replacement and frozen elephant trunk (FET). METHODS: We reviewed the clinical data and perioperative aortic computed tomography angiography records of 110 consecutive patients with ATAAD who underwent total arch replacement and FET (12 cm) between December 2014 and September 2017 and investigated the possible risk factors related to early postoperative paraplegia. RESULTS: Paraplegia occurred in 5 (4.5%) patients. No significant differences were found between patients with and without paraplegia in terms of sex, age, medical history, cardiopulmonary bypass time, antegrade cerebral perfusion time, rectal temperature during antegrade cerebral perfusion, postoperative hypotension, maximum first 24-hour vasoactive-inotropic score, upper-lower pressure gradient, or false lumen thrombosis. Postoperative aortic computed tomography angiography showed a "cutoff" phenomenon in the lower descending aorta in 4 of the 5 patients. Univariate logistical analysis showed that paraplegia was associated with the "cutoff" phenomenon (P < .05). The patients with a distance ≥30 mm from the distal end of the stent to the first untreated intimal tear had significantly greater rates of the "cutoff" phenomenon and paraplegia than those with the distance <30 mm (P < .05). CONCLUSIONS: Total arch replacement and FET is safe and feasible for ATAAD involving the descending aorta. Early postoperative paraplegia is associated with the "cutoff" phenomenon in the lower descending aorta. The position of the first untreated intimal tear may be related with the occurrence of the "cutoff" phenomenon and paraplegia.

Case report: surgical removal of a migrated needle in right ventricle of an intravenous drug user.

BACKGROUND: Illicit drug use has become an increasing public health and social concern in the past decades worldwide. Intravenous injection has an elevated risk of infection. Needle embolism is a rare complication of intravenous drug users, Retained broken needles can lead to local complications, such as infection, but they also have the potential to embolize to heart or lung, and lead to serious complications. METHOD: We reported a rare case of an intravenous drug user which a retained broken needle fragments in the inferior wall of the right ventricle. RESULTS: We performed a successful surgery and give our comments and recommendations for illicit drug use worldwide and in China. CONCLUSIONS: Illicit Drug use becomes a global problem because of its health and social harmfulness. To help drug addicts and provide prevention and treatment services are the obligations and responsibilities of all medical workers.

DNA methylation dysregulations in valvular atrial fibrillation.

BACKGROUND: The epigenetic changes underlying the development of atrial fibrillation (AF) remain incompletely understood. Limited evidence suggests that abnormal DNA methylation might be involved in the pathogenesis of AF. In the present study, we evaluated the methylation status of genomic DNA from myocardial tissue in AF patients and sinus rhythm (SR) patients systematically. HYPOTHESIS: DNA methylation dysregulations will be associated with valvular AF. METHODS: Right atrial myocardial tissue was obtained from rheumatic valvular patients who had undergone valve replacement surgery (SR group, n = 10; AF group, n = 10). The global DNA methylation level, the promoter methylation level of the natriuretic peptide receptor-A gene (NPRA), and its correlation with the mRNA expression level of DNA methyltransferase genes were detected. RESULTS: The global DNA methylation level was significantly higher in the AF group than in the SR group (P < 0.05). The NPRA mRNA expression was decreased and the NPRA gene was hypermethylated in the AF group (P < 0.05). Meanwhile, the NPRA mRNA expression level has a negative correlation with the mean methylation level in the promoter region of the NPRA gene. CONCLUSIONS: DNA methylation dysregulations may be relevant in the pathogenesis of AF. DNA methyltransferase 3B likely plays an essential role in the DNA methylation dysregulations in AF.

DNA methylation dysregulations in rheumatic heart valve disease.

BACKGROUND: The epigenetic changes underlying the development of rheumatic heart valve disease (RHVD) remain incompletely understood. Limited evidence suggests that abnormal DNA methylation might be involved in the pathogenesis of RHVD. In the present study, we evaluated the DNA methylation dysregulations from myocardial tissue in RHVD patients systematically. METHODS: Right atrial myocardial tissue obtained from rheumatic valvular patients who had undergone valve replacements surgery (n = 73) and were compared to healthy controls (n = 4). the promoter methylation level of Intercellular adhesion molecule-1 (ICAM-1) gene and its correlation with ICAM-1 mRNA expression level, the global DNA methylation level and its correlation with age and mRNA expression level of DNA methyltransferase (DNMT) genes were detected. RESULTS: The ICAM-1 mRNA expression was increased (healthy control vs. NHYA III, 0.70 ± 0.19 vs. 4.38 ± 3.19, p = 0.011; NYHA IIvs. NHYA III, 2.60 ± 1.99 vs. 4.38 ± 3.19, p = 0.008) and the ICAM-1 gene was hypomethylated in RHVD patients (healthy controls vs. NYHA II, 0.120 ± 0.011 vs. 0.076 ± 0.057, p = 0.039; healthy control vs. NHYA III, 0.120 ± 0.011 vs. 0.041 ± 0.022, p < 0.001; NYHA IIvs. NHYA III, 0.076 ± 0.057 vs. 0.041 ± 0.022, p < 0.001). Meanwhile, The ICAM-1 mRNA expression level has negative correlation with the mean methylation level in the promoter region of ICAM-1 gene (r = -0.459, p < 0.001). The global DNA methylation levels was significantly increased in RHVD patients than in healthy controls (healthy control vs. NHYA III, 0.77 ± 0.28 vs. 2.09 ± 1.20, p = 0.017; NYHA IIvs. NHYA III, 1.57 ± 0.78 vs. 2.09 ± 1.20, p = 0.040) and had positive correlation with age (r = 0.326, p = 0.005), especially for older age group (≥ 60 years). DNMT1 likely plays an essential role in the DNA dysregulations in RHVD patients. CONCLUSIONS: Our analysis revealed that DNA methylation dysregulations may be relevant in the pathogenesis of RHVD.

Apelin attenuates the osteoblastic differentiation of aortic valve interstitial cells via the ERK and PI3-K/Akt pathways.

Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.

Procalcitonin as a diagnostic marker of ventilator-associated pneumonia in cardiac surgery patients.

The aim of the present study was to assess whether procalcitonin (PCT) can be used as a diagnostic marker for ventilator-associated pneumonia (VAP) in cardiac surgery patients. Between January 2012 and June 2013, a total of 92 patients were recruited and divided into non-VAP (59 patients) and VAP (33 patients) groups. The preoperative and postoperative characteristics of the patients were recorded. Serum levels of PCT, interleukin (IL)-6 and C-reactive protein (CRP) were measured using an electrochemiluminescence immunoassay. Subsequently, receiver operating characteristic curves of the PCT, IL-6 and CRP levels were constructed. In addition, associations between the sequential organ failure assessment (SOFA) scores and the serum levels of PCT, IL-6 and CRP in the VAP patients were analyzed. No statistically significant difference was observed between the non-VAP and VAP patients in the occurrence of postoperative complications. However, the SOFA scores (days 1 and 7), the duration of stay in the intensive care unit and the mechanical ventilation time were all significantly higher in the VAP group when compared with the non-VAP group (P<0.05). The optimum PCT cut-off value for VAP diagnosis on day 1 was 5.0 ng/ml, with a sensitivity of 91% and a specificity of 71%. The serum PCT levels on days 1 and 7 were found to correlate positively with the SOFA scores (r=0.54 and r=0.66 for days 1 and 7, respectively). Therefore, the results suggested that serum PCT may be used as diagnostic marker for VAP in patients following cardiac surgery.

A rare case of primary pulmonary artery myofibroblastic sarcoma--imaging and pathologic features.

Primary myofibroblastic sarcomas of the pulmonary artery are very uncommon, but early detection is critical. Common clinical symptoms include shortness of breath, chest discomfort, and syncope. Patients diagnosed with a pulmonary tumor have a high risk of fatal pulmonary embolism. In this case study, we identified and diagnosed pulmonary artery myofibroblastic sarcoma in a young man by its imaging and pathologic characters. Surgery to excise the tumor was successfully performed and the operation was considered to have improved his prognosis. Postoperative examinations did not show any evidence of residual tumor, recurrence, or metastasis in the lungs or cardiac tissue. Based on the results of this case study, we concluded that the imaging and pathologic features of primary pulmonary artery myofibroblastic sarcoma can assist physicians in making a prompt diagnosis and an immediate surgical and treatment plan to greatly improve prognosis.

[A new triple-branched aortic arch covered stent graft in DeBakey Type I aortic dissection].

OBJECTIVE: To explore the effect of a new triple-branched aortic arch covered stent graft on DeBakey Type I aortic dissection, and to assess its efficacy in comparison with traditional surgery. METHODS: From January 2010 to November 2010, 38 patients of DeBakey Type I aortic dissection were treated surgically in the Second Xiangya Hospital of Central South University, in which 16 operations used triple-branched aortic arch covered stent grafts (stent graft group, SG group), 22 operations used traditional 4 sides branches aortic arch grafts (arch graft group, AG group). RESULTS: Compared with AG group, the cardiopulmonary bypass time[(138.1± 56.42) vs (179.21± 67.64) min], the clamp time [(98.56±28.08) vs (134.36±46.46) min] and the selective cerebral perfusion time[(27.3±14.76) vs (48.74±18.22) min] in SG group were obviously shortened(P<0.05). The volume of drainage 24 hours after operation in SG group also reduced[(608.93±308.15) vs (899.04±437.79) mL](P<0.05). The SG group had a lower rate of recurrent laryngeal nerve injury (6.25% vs 27.3%) and duration of hospitalization[(16.15±6.68) vs (21.18±12.69) d](P<0.05). During a following-up period of 14 to 24 months,reexamination of aortic CT angiography showed that the triple-branched aortic arch covered stent graft expanded well, and attached to the wall satisfactorily, while the corresponding false lumen of the aortic artery disappeared and the distal false lumen was filled with thrombus. The life quality of patients were good. CONCLUSION: The new triple-branched aortic arch covered stent graft is appropriated for most patients with DeBakey Type I aortic dissection. Its use can simplify the aortic arch procedure,decrease the operation risk and has satisfactory results in early and middle stage after operation.

Application of triple-branched stent graft for Stanford type A aortic dissection: potential risks.

OBJECTIVES: A new surgical technique named triple-branched stent graft was developed and reported to have excellent clinical results for Stanford type A aortic dissection. However, we found some potential risks, in our experience, of this technique. We compared this technique with total arch replacement combined with stented elephant trunk implantation in patients with acute Stanford type A dissection. METHODS: Thirty-eight patients with acute Stanford type A aortic dissection underwent surgical treatment from January to November 2010. These patients were divided into two groups: patients with total arch replacement combined with stented elephant trunk implantation (Group A, n = 22) and those with ascending aorta replacement combined with open placement of triple-branched stent graft (Group B, n = 16). RESULTS: In-hospital mortality was not different in the two groups (9.1 and 6.25%, respectively). Cardiopulmonary bypass, aortic cross-clamp, circulation arrest, selective cerebral perfusion and low-body arrest times were shorter in Group B. Mechanical ventilation support, duration of intensive care unit (ICU) stay and hospitalization time were not different in the two groups. The incidence of postoperative stent graft-related complications was significantly higher in Group B. Actuarial survival rates and freedom from reoperation during the follow-up did not differ in the two groups. CONCLUSIONS: The triple-branched stent graft technique truly has some advantages in simplifying the procedure and reducing the surgical time. However, this technique has some potential risks such as postoperative stent graft shifting or kinking, which may cause occlusion, aortic disruption and malperfusion syndrome. Long-term follow-up and further multicentre clinical trials are necessary to verify their use in this setting and the design of the grafts and surgical procedure should be further refined to reduce the incidence of stent graft complications.

A successful intervention combined with surgical treatment of a pulmonary dissection secondary to an acute type B aortic dissection.

Pulmonary dissection is an acute, lethal disease to patients. Pulmonary dissection occurs secondary to type B aorta dissection in some cases, as seen in surviving patients with the development of imaging techniques. A patient presenting with pulmonary dissection secondary to an acute type B aortic dissection was treated by proper interventional therapy combined with surgical treatment, which made him survive till now. It is crucial to establish tunica intima laceration position and then design a proper treatment plan rapidly for patients affected by this condition.