Fate of the distal aorta following root replacement in Marfan syndrome: a propensity score matched study.

Objective: The aortic root is the most frequent segment involved in Marfan syndrome. However, Marfan syndrome is a systemic hereditary connective tissue disorder, and knowledge regarding the outcomes of the native distal aorta after prophylactic aortic root surgery is limited. Methods: From April 2010 to December 2020, 226 patients with Marfan syndrome and 1,200 patients without Marfan syndrome who underwent Bentall procedures were included in this study. By propensity score matching, 134 patients were assigned to each group. Clinical manifestations and follow-up data were acquired from hospital records and telephone contact. The cumulative incidence of aortic events was estimated in Marfan and non-Marfan patients with death as a competing risk. Results: Patients with and without Marfan syndrome had similar baseline characteristics after propensity score matching. Differences in the aortic root (62.25 ± 11.96 vs. 54.03 ± 13.76, P < .001) and ascending aorta (37.71 ± 9.86 vs. 48.16 ± 16.01, P < .001) remained after matching. No difference was observed in the frequency of aortic adverse events between the two groups (10.5% vs. 4.6%, P = 0.106). The cumulative incidence of aortic events was not different between Marfan and non-Marfan patients (15.03% ± 4.72% vs. 4.18% ± 2.06%, P = 0.147). Multivariate Cox regression indicated no significant impact of Marfan syndrome on distal aortic events (HR: 1.172, 95% CI: 0.263-5.230, P = 0.835). Descending and abdominal aortic diameter above normal at the initial procedure were associated with the risk of distal aortic events (HR: 20.735, P = .003, HR: 22.981, P = .002, respectively). Conclusions: New-onset events of the residual aorta in patients undergoing Bentall procedures between the Marfan and non-Marfan groups were not significantly different. Distal aortic diameter above normal at initial surgery was associated with a higher risk of adverse aortic events.

Anzhen Risk Evaluation System for Acute Aortic Syndrome (AZSCORE-AAS): protocol for a multicentre prospective cohort study in northern China.

INTRODUCTION: Acute aortic syndrome (AAS) is a group of acute and critical conditions, including acute aortic dissection (AAD), acute intramural haematoma and penetrating aortic ulcer. High mortality and morbidity rates result in a poor patient prognosis. Prompt diagnoses and timely interventions are paramount for saving patients' lives. In recent years, risk models for AAD have been established worldwide; however, a risk evaluation system for AAS is still lacking in China. Therefore, this study aims to develop an early warning and risk scoring system in combination with the novel potential biomarker soluble ST2 (sST2) for AAS. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit patients diagnosed with AAS at three tertiary referral centres from 1 January 2020 to 31 December 2023. We will analyse the discrepancies in sST2 levels in patients with different AAS types and explore the accuracy of sST2 in distinguishing between them. We will also incorporate potential risk factors and sST2 into a logistic regression model to establish a logistic risk scoring system for predicting postoperative death and prolonged intensive care unit stay in patients with AAS. ETHICS AND DISSEMINATION: This study was registered on the Chinese Clinical Trial Registry website (http://www. chictr. org. cn/). Ethical approval was obtained from the human research ethics committees of Beijing Anzhen Hospital (KS2019016). The ethics review board of each participating hospital agreed to participate. The final risk prediction model will be published in an appropriate journal and disseminated as a mobile application for clinical use. Approval and anonymised data will be shared. TRIAL REGISTRATION NUMBER: ChiCTR1900027763.

Association between preoperative serum myoglobin and acute kidney injury after Stanford Type A aortic dissection surgery.

BACKGROUND: Acute kidney injury (AKI) is a common complication after Type A aortic dissection (TAAD) surgery, and it is associated with poor outcomes. The nephrotoxic effect of myoglobin was established, but its correlation with AKI following TAAD repair still lacks sufficient evidence. We clarified the correlation between preoperative serum myoglobin (pre-sMyo) concentrations and AKI after TAAD surgery. METHOD: A retrospective analysis was performed on the perioperative data of 382 patients treated with TAAD surgery at Beijing Anzhen Hospital. AKI was defined and classified according to the criteria established by the Kidney Disease: Improving Global Outcomes Acute Kidney Injury Work Group. We attempted to determine the correlation between pre-sMyo concentrations and postoperative AKI. RESULTS: The incidences of Stage 1, 2, and 3 AKI were 37.3 % (57/153), 23.5 % (36/153), and 39.2 % (60/153), respectively. The pre-sMyo concentrations of the AKI group were significantly increased than the non-AKI group [43.1 (21.4, 107.5) vs 26.4 (18.0, 37.2), P < 0.001]. Pre-sMyo concentrations have a linear correlation with preoperative renal function-related indicators. The multivariable logistic regression analysis showed that Ln (pre-sMyo) was an independent risk factor for AKI. When the pre-sMyo concentration was at the fourth quartile [109.3 (64.8, 213.4) ng/ml], the risk of developing any-stage and severe AKI was significantly increased (OR = 4.333, 95 % CI: 2.364-7.943, P < 0.001; OR = 3.862, 95 %, CI: 2.011-7.419, P < 0.001). This difference persisted after adjustment (OR = 3.830, 95 % CI: 1.848-7.936, P < 0.001; OR = 2.330, 95 % CI: 1.045-5.199, P = 0.039). Furthermore, pre-sMyo concentrations were not affected by lower limb malperfusion, myocardial malperfusion, and cardiac tamponade. CONCLUSIONS: Increased pre-sMyo concentrations correlated with postoperative AKI in TAAD, which may increase the risk of developing any-stage AKI and severe AKI after TAAD surgery.

Surgical management and outcomes of coronary artery involvement secondary to acute type A aortic dissection: a retrospective cohort study.

Background: Coronary artery involvement (CAI) remains a fatal comorbidity in the context of acute type A aortic dissection (ATAAD). We evaluated the impact of CAI on the perioperative and short-term outcomes of patients with ATAAD who underwent total arch replacement (TAR) and frozen elephant trunk (FET) implantation and shared our surgical management experience with the involved coronary artery. Methods: In this retrospective cohort study, a total of 204 patients with ATAAD between June 2019 and December 2021 were enrolled and divided into the CAI group (n=67) and the non-CAI group (n=137). The characteristics of CAI lesions were described according to the Neri classification. Univariable and multivariable analyses were used to identify independent risk factors for in-hospital mortality. Survival analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Results: Patients in the CAI group had a longer intraoperative duration of cardiopulmonary bypass (CPB) and cross-clamp, and experienced longer mechanical ventilation time and intensive care unit stays postoperatively. Regarding perioperative outcomes, the prevalence rates of new-onset continuous renal replacement therapy requirement (23.9% vs. 10.2%, P=0.01) and in-hospital mortality (17.9% vs. 7.3%, P=0.02) were higher in the CAI group. Coronary artery malperfusion (CAM) was an independent risk factor for in-hospital mortality. Short-term survival analysis was similar between the two groups (P=0.146). Conclusions: For patients with ATAAD undergoing TAR and FET implantation, concomitant CAI may complicate surgery and increase in-hospital morbidity and mortality. CAM secondary to CAI was identified as an independent risk factor. However, short-term survival after hospital discharge was comparable between the two groups. Coronary ostium repair is quick and operable for both type A and type B lesions, while optimal management still warrants further investigation.

Risk factors and surgical prognosis in patients with aortic valve involvement caused by Takayasu arteritis.

OBJECTIVE: Aortic valve involvement is not uncommon in patients with Takayasu arteritis (TAK) and leading to poor prognosis. The aim of our study was to explore the risk factors of aortic valve involvement and to evaluate the prognosis in TAK patients with aortic valve involvement. METHOD: In this retrospective study, 172 TAK patients were divided into groups with or without aortic valve involvement to identify the risk factors. Patients who underwent aortic valve surgical treatment were followed up to assess cumulative incidence of postoperative adverse events. RESULTS: A total of 92 TAK patients (53.49%) had aortic valvular lesion. The infiltration of inflammatory cells was found in surgical specimens of aortic valve. Numano type IIb, elevated high-sensitivity C-reactive protein (hs-CRP) level, and dilation of ascending aorta and aortic root were statistically associated with aortic valvular lesion in TAK patients (OR [95%CI] 6.853 [1.685-27.875], p=0.007; 4.896 [1.646-14.561], p=0.004; 4.509 [1.517-13.403], p=0.007; 9.340 [2.188-39.875], p=0.003). The 1-, 5-, and 7-year cumulative incidence of postoperative adverse events were 14.7%, 14.7%, and 31.8%, respectively. Surgical methods (p=0.024, hazard ratio (HR) 0.082) and postoperatively anti-inflammatory therapy (p=0.036, HR 0.144) were identified as potential predictors of postoperative adverse events. CONCLUSIONS: Regularly echocardiogram screening is suggested in patients with Numano type IIb and aggressive treatment should be performed early in TAK patients. As for TAK patients with aortic valve surgery, aortic root replacement seems to be the preferred option and regular anti-inflammatory therapy may reduce the occurrence of adverse events of them.

The Parkinson's Disease-Associated Protein DJ-1 Protects Dictyostelium Cells from AMPK-Dependent Outcomes of Oxidative Stress.

Mitochondrial dysfunction has been implicated in the pathology of Parkinson's disease (PD). In Dictyostelium discoideum, strains with mitochondrial dysfunction present consistent, AMPK-dependent phenotypes. This provides an opportunity to investigate if the loss of function of specific PD-associated genes produces cellular pathology by causing mitochondrial dysfunction with AMPK-mediated consequences. DJ-1 is a PD-associated, cytosolic protein with a conserved oxidizable cysteine residue that is important for the protein's ability to protect cells from the pathological consequences of oxidative stress. Dictyostelium DJ-1 (encoded by the gene deeJ) is located in the cytosol from where it indirectly inhibits mitochondrial respiration and also exerts a positive, nonmitochondrial role in endocytosis (particularly phagocytosis). Its loss in unstressed cells impairs endocytosis and causes correspondingly slower growth, while also stimulating mitochondrial respiration. We report here that oxidative stress in Dictyostelium cells inhibits mitochondrial respiration and impairs phagocytosis in an AMPK-dependent manner. This adds to the separate impairment of phagocytosis caused by DJ-1 knockdown. Oxidative stress also combines with DJ-1 loss in an AMPK-dependent manner to impair or exacerbate defects in phototaxis, morphogenesis and growth. It thereby phenocopies mitochondrial dysfunction. These results support a model in which the oxidized but not the reduced form of DJ-1 inhibits AMPK in the cytosol, thereby protecting cells from the adverse consequences of oxidative stress, mitochondrial dysfunction and the resulting AMPK hyperactivity.

Similar Quality of Life and Safety in Patients Receiving Inpatient or Outpatient Chemotherapy: A Focus on Esophageal Squamous Cell Carcinoma.

Quality of life (QoL) is a particularly important issue for cancer patients. This study was designed to investigate the differences in QoL in esophageal squamous cell carcinoma (ESCC) patients who underwent inpatient chemotherapy (IPCT) or outpatient chemotherapy (OPCT). A total of 107 ESCC patients were enrolled, including 53 patients in the IPCT group and 54 patients in the OPCT group. The widely used and well-validated instruments European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items (EORTC QLQ-C30) and Oesophageal Cancer Module (EORTC QLQ-OES18) were used to examine the QoL of the two groups. In addition, the differences in adverse events (AEs) were evaluated. The results of QLQ C-30 analysis showed that mean global quality of life scores were similar between IPCT and OPCT groups, as were functional and symptom scales. There were no significant differences in the functional and symptom scales in the analysis of QLQ OES18 either. Most AEs of chemotherapy were grades 1-2, and the majority of patients tolerated the side effects; no statistically significant difference in AEs between these two groups was mentioned. Our study suggests that the health-related QoL and adverse events in ESCC patients who received IPCT or OPCT are similar. OPCT is reasonable and safe in clinical practice.

Insulin-like growth factor-binding protein 3 inhibits angiotensin II-induced aortic smooth muscle cell phenotypic switch and matrix metalloproteinase expression.

NEW FINDINGS: What is the central question of this study? Insulin-like growth factor 1 and its major binding protein insulin-like growth factor binding protein 3 (IGFBP3) are involved in collagen deregulation in several cardiovascular diseases: what is the role of IGFBP3 in thoracic aortic dissection and does it regulate aortic smooth muscle cells' phenotypic switch? What is the main finding and its importance? IGFBP3 inhibits aortic smooth muscle cells' phenotypic switch from a contractile to a synthetic phenotype, decreases matrix metalloproteinase 9 activation and suppresses elastin degradation. These findings provide a better understanding of the pathogenesis of thoracic aortic dissection. ABSTRACT: Thoracic aortic dissection (TAD) is characterized by aortic media degeneration and is a highly lethal disease. An aortic smooth muscle cell (AoSMC) phenotypic switch is considered a key pathophysiological change in TAD. Insulin-like growth factor binding protein 3 (IGFBP3) was found to be downregulated in aortic tissues of TAD patients. The present work aimed to study the function of IGFBP3 in AoSMCs' phenotypic switch and matrix metalloproteinase (MMP) expression. We established a mouse model of TAD by angiotensin (Ang) II infusion to ß-aminopropionitrile-administrated mice, and found decreased IGFBP3 expression accompanied by aortic dilatation and elastin degradation in vivo. Further, mouse (m)AoSMCs were isolated from mouse thoracic aorta and treated with Ang II. Ang II induced downregulation of IGFBP3 in vitro. To further study the function of IGFBP3, primary mAoSMCs were infected with adenovirus expressing IGFBP3 followed by Ang II induction. Enforced upregulation of IGFBP3 decreased MMP9 expression and activation as well as increasing tissue inhibitor of metalloproteinase (TIMP) 1 expression in Ang II-induced mAoSMCs. No difference was observed in MMP2 and TIMP3 expression. IGFBP3 suppressed subsequent Ang II-induced elastin degradation in vitro. IGFBP3 inhibited Ang II-induced mAoSMCs' phenotypic switch as evidenced by increased smooth muscle actin α-2 (ACTA2) and myosin heavy chain 11 (MYH11) expression and decreased secreted phosphoprotein 1 (SPP1) and vimentin expression. Taken together, the present study demonstrates the role of IGFBP3 in preserving AoSMCs' contractile state and reducing MMP9 activation and thus promoting elastic fibre synthesis, which provides a better understanding of the pathogenesis of TAD.

Successful repair of acute type A aortic dissection during pregnancy at 16th gestational week with maternal and fetal survival: A case report and review of the literature.

BACKGROUND: Aortic dissection during pregnancy is a rare but life-threatening event for mothers and fetuses. It often occurs in the third trimester of pregnancy and the postpartum period. Most patients have connective tissue diseases such as Marfan syndrome. Thus, the successful repair of a sporadic aortic dissection with maternal and fetal survival in the early second trimester is extremely rare. CASE SUMMARY: A 28-year-old woman without Marfan syndrome presented with chest pain at the 16th gestational week. Aortic computed tomographic angiography confirmed an acute type A aortic dissection (TAAD) with aortic arch and descending aorta involvement. Preoperative fetal ultrasound confirmed that the fetus was stable in the uterus. The patient underwent total arch replacement with a frozen elephant trunk using moderate hypothermic circulatory arrest with the fetus in situ. The patient recovered uneventfully and continued to be pregnant after discharge. At the 38th gestational week, she delivered a healthy female infant by cesarean section. After 2.5 years of follow-up, the patient is uneventful and the child's development is normal. CONCLUSION: A fetus in the second trimester may have a high possibility of survival and healthy growth after aortic arch surgery.

Neck Lymph Node Metastasis as A Poor Prognostic Factor in Thoracic Esophageal Squamous Cell Carcinoma Patients Receiving Concurrent Chemoradiotherapy: A Propensity Score-Matched Analysis.

The present study investigated the clinical impact of neck lymph node (LN) metastasis in locally advanced inoperable thoracic esophageal squamous cell carcinoma (ESCC) patients who underwent concurrent chemoradiotherapy (CCRT) with a curative intent. There were 404 ESCC patients enrolled, including 35 patients with neck LN metastasis and 369 patients without such metastasis. Through the propensity score matching method, 35 patients of the 369 patients without neck LN metastasis were matched to the 35 patients with neck LN metastasis. Progression-free survival (PFS) and overall survival (OS) were found to be significantly worse in the neck LN metastasis group compared to the full non-neck LN metastasis group (9.8 months versus 5.9 months, P < 0.001, and 18.2 months versus 9.7 months, P = 0.001) and the matched non-neck LN metastasis group (9.9 months versus 5.9 months, P = 0.006, and 19.4 months versus 9.7 months, P = 0.007). In order to determine the difference between neck LN and supraclavicular LN metastasis, seventy patients with supraclavicular LN metastasis were also selected from the 369 patients without neck LN metastasis for comparison. Subsequently, when compared to the ESCC patients with supraclavicular LN metastasis, significantly worse PFS (8.5 months versus 5.9 months, P = 0.026) and OS (17.2 months versus 9.7 months, P = 0.047) were still found in the ESCC patients with neck LN metastasis. Our study indicates that neck LN metastasis is an independent poor prognostic factor for locally advanced inoperable thoracic ESCC patients who have undergone CCRT.

The crucial role of blood VEGF kinetics in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy.

BACKGROUND: To evaluate the role of blood vascular endothelial growth factor (VEGF) kinetics in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). METHODS: A total of 97 locally advanced ESCC patients were enrolled. All the patients had their blood drawn at three time points to determine their levels of VEGF, including pre-chemotherapy (day 0), post-chemotherapy (day 5), and pre-cycle 2 chemotherapy (day 28). The VEGF levels were evaluated according to the day 0 value, day 5 value, day 28 value, day 5/day 0 ratio, day 28/day 0 ratio, and day 28/day 5 ratio. A VEGF cut-off level of 80 pg/mL was applied. RESULTS: In the analysis of progression-free survival (PFS), the patients less than 60 years old had significantly superior PFS compared to those more than 60 years old. Patients who had VEGF < 80 pg/mL at day 28 and a day 28/day 5 ratio < 1 had better PFS than those with VEGF > 80 pg/mL and a day 28/day 5 ratio > 1, respectively. In the analysis of overall survival (OS), patients with N0-1 status had significantly superior OS compared to those with N2-3 status. Furthermore, patients who had VEGF < 80 pg/mL at day 28, a day 5/day 0 ratio < 1, and a day 28/day 5 ratio < 1 had superior OS compared to those patients with VEGF > 80 pg/mL, a day 5/day 0 ratio > 1, and a day 28/day 5 ratio > 1, respectively. In the multivariate analysis, only VEGF < 80 pg/mL at day 28 and a day 28/day 5 ratio < 1 represented independent prognostic factors of superior PFS and OS. CONCLUSIONS: Our study suggests that VEGF kinetics is a prognostic factor for locally advanced ESCC patients receiving curative CCRT. For these patients, lower post-treatment VEGF levels and decreasing levels of VEGF during CCRT are significantly associated with better clinical outcomes.

The clinical impact of supraclavicular lymph node metastasis in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy.

BACKGROUND: To evaluate the clinical significance of supraclavicular lymph node (SCLN) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: We retrospectively analyzed all 369 locally advanced ESCC patients treated with CCRT between 2000 and 2015, including 70 patients with SCLN metastasis and 299 patients without SCLN metastasis. RESULTS: For these locally advanced ESCC patients treated with curative CCRT, N0-2 were significantly associated with superior progression-free survival (PFS) and overall survival (OS) in univariate and multivariable analyses. However, there were no significant differences in PFS and OS between the SCLN metastasis and non-SCLN metastasis groups; a subgroup analysis also revealed there was no significant differences in PFS and OS between patients with and without SCLN metastasis either in the N0-2 or in the N3 subgroup analysis. CONCLUSIONS: Our study suggests that SCLN metastasis is not a prognostic factor in locally advanced ESCC patients receiving curative CCRT, and that SCLNs should be considered to be regional LNs and treated with curative intent.

The prognostic significance of celiac lymph node metastasis in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy.

BACKGROUND: To evaluate the clinical outcomes of celiac lymph node (LN) metastasis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 375 stage III ESCC patients were identified, including 51 patients with celiac LN metastasis and 324 patients without celiac LN metastasis. Among these 324 patients without celiac LN metastasis, 51 were matched with the 51 patients with celiac LN metastasis using the propensity score matching method. RESULTS: Overall, the celiac LN metastasis group had worse progression-free survival (PFS) and overall survival (OS) than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For the ESCC patients with celiac LN metastasis, lower third ESCC was significantly associated with superior PFS and OS. For patients with upper/middle third ESCC, the celiac LN metastasis group had worse PFS and OS than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For patients with lower third ESCC, there were no significant differences in PFS and OS between these groups. CONCLUSIONS: Our study suggests celiac LN metastasis is a poor prognostic factor for locally advanced ESCC patients receiving curative CCRT. Among these ESCC patients with celiac LN metastasis, tumor location is a strongly prognostic factor, indicating patients with lower third ESCC have better PFS and OS than those with upper/middle third ESCC. The 6th American Joint Committee on Cancer staging system seems more favorable than 7th edition in the definition of celiac LNs for those patients.