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.

N-methyl-D-aspartate receptor-mediated spinal cord ischemia-reperfusion injury and its protective mechanism.

INTRODUCTION: This study investigated the specific mechanism of N-methyl-D-aspartate (NMDA) receptor-mediated spinal cord ischemia-reperfusion by comparing the protective effects of the voltage-gated Ca2+ channel blocker nimodipine and the NMDA receptor blocker K-1024 on the spinal cord. MATERIAL AND METHODS: In this study, 42 SD rats were divided randomly into four groups: non-blocking (n = 6), normal saline (n = 12), K-1024 (n = 12) and nimodipine (n = 12). The rats in three groups (saline, K-1024, nimodipine) received an intraperitoneal injection 30 minutes before ischemia. In these three groups, 6 out of 12 rats were selected randomly to have their thoracic aorta blocked with a balloon to induce spinal cord ischemia for 10 minutes. Then, the spinal cord tissues were collected. The remaining six rats were evaluated for nerve function at 1, 2, 4 and 8 hours after reperfusion. The lumbar spinal cord was removed for histological examination. The release of neurotransmitter amino acids was observed by high-pressure liquid chromatography, and the protein expression level of neuronal nitric oxide synthase (nNOS) in the spinal cord was determined by immunohistochemistry. RESULTS: All the animals in the normal saline group and five in the nimodipine group were paralysed after ischemia. Compared with the normal saline and nimodipine groups, the rats in the K-1024 group had more normal motor neurons and better behavioural scores. In addition, the histopathology of the rats in the K-1024 group was significantly better than in the normal saline and nimodipine groups. After 10 minutes of ischemia, there was no significant difference in glutamate concentration in each group. The protein expression level of nNOS in the K-1024 group was significantly downregulated compared with the saline and nimodipine groups. At 8 hours after reperfusion, the protein expression level of nNOS in the K-1024 group was significantly upregulated compared with the normal saline group. CONCLUSIONS: The specific mechanism of the NMDA receptor blocker K-1024 in protection against spinal cord ischemia-reperfusion injury is related closely to the inhibition of NMDA receptors and the downregulation of the protein expression level of nNOS.

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.

Blood Transfusion and Acute Kidney Injury After Total Aortic Arch Replacement for Acute Stanford Type A Aortic Dissection.

AIM: To evaluate the effect of packed red blood cells (pRBCs), fresh frozen plasma (FFP), and platelet concentrate (PC) transfusions on acute kidney injury (AKI) in patients with acute Stanford type A aortic dissection (ATAAD) with total arch replacement (TAR). METHOD: From December 2015 to October 2017, 421 consecutive patients with ATAAD undergoing TAR were included in the study. The clinical data of the patients and the amount of pRBCs, FFP, and PC were collected. Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Logistic regression was used to identify whether pRBCs, FFP, and platelet transfusions were risk factors for KDIGO AKI, stage 3 AKI, and AKI requiring renal replacement therapy (RRT). RESULTS: The mean ± standard deviation age of the patients was 47.67±10.82 years; 77.7% were men; and the median time from aortic dissection onset to operation was 1 day (range, 0-2 days). The median transfusion amount was 8 units (range, 4-14 units) for pRBCs, 400 mL (range, 0-800 mL) for FFP, and no units (range, 0-2 units) for PC. Forty-one (41; 9.7%) patients did not receive any blood products. The rates of pRBC, PC, and FFP transfusions were 86.9%, 49.2%, and 72.9%, respectively. The incidence of AKI was 54.2%. Considering AKI as the endpoint, multivariate logistic regression showed that pRBCs (odds ratio [OR], 1.11; p<0.001) and PC transfusions (OR, 1.28; p=0.007) were independent risk factors. Considering KDIGO stage 3 AKI as the endpoint, multivariate logistic regression showed that pRBC transfusion (OR, 1.15; p<0.001), PC transfusion (OR, 1.28; p<0.001), a duration of cardiopulmonary bypass (CPB) ≥293 minutes (OR, 2.95; p=0.04), and a creatinine clearance rate of ≤85 mL/minute (OR, 2.12; p=0.01) were independent risk factors. Considering RRT as the endpoint, multivariate logistic regression showed that pRBC transfusion (OR, 1.12; p<0.001), PC transfusion (OR, 1.33; p=0.001), a duration of CPB ≥293 minutes (OR, 3.79; p=0.02), and a creatinine clearance rate of ≤85 mL/minute (OR, 3.34; p<0.001) were independent risk factors. CONCLUSIONS: Kidney Disease: Improving Global Outcomes-defined stage AKI was common after TAR for ATAAD. Transfusions of pRBCs and PC increased the incidence of AKI, stage 3 AKI, and RRT. Fresh frozen plasma transfusion was not a risk factor for AKI.

Early and Long-Term Follow-Up for Chronic Type B and Type Non-A Non-B Aortic Dissection Using the Frozen Elephant Trunk Technique.

Background: This study aimed to evaluate the early and long-term outcomes of a single center using a frozen elephant trunk (FET) procedure for chronic type B or non-A non-B aortic dissection. Methods: From February 2009 to December 2019, 79 patients diagnosed with chronic type B or non-A non-B aortic dissection who underwent the FET procedure were included in the present study. We analyzed operation mortality and early and long-term outcomes, including complications, survival and interventions. Results: The operation mortality rate was 5.1% (4/79). Spinal cord injury occurred in 3.8% (3/79), stroke in 2.5% (2/79), and acute renal failure in 5.1% (4/79). The median follow-up time was 53 months. The overall survival rates were 96.2, 92.3, 88.0, 79.8, and 76.2% at 1/2, 1, 3, 5 and 7 years, respectively. Moreover, 79.3% of patients did not require distal aortic reintervention at 7 years. The overall survival in the subacute group was superior to that in the chronic group (P = 0.047). Conclusion: The FET technique is a safe and feasible approach for treating chronic type B and non-A non-B aortic dissection in patients who have contraindications for primary endovascular aortic repair. The technique combines the advantages of both open surgical repair and endovascular intervention, providing comparable early and long-term follow-up outcomes and freedom from reintervention.

Comparison of Open Repair vs. the One-Stage Hybrid Extra-Anatomic Technique for Distal Aortic Arch Disease Treatment: Mid-term Outcomes With a Risk-Adjusted Analysis.

Objective: This study aims to compare the short- and mid-term outcomes of the stented elephant trunk (SET) procedure combined with supra-arch branch reconstruction and one-stage hybrid arch repair combined thoracic endovascular aortic repair (TEVAR) with extra-anatomic bypass in the management of distal arch disease. Methods: From January 2009 to January 2019, 97 patients underwent one-stage hybrid arch repair combined with TEVAR with extra-anatomic bypass (HAR group), and 206 patients underwent the SET procedure with supra-arch branch reconstruction (SET group). We used inverse-probability-of treatment weighting (IPTW) to adjust baseline differences. Results: Before IPTW adjustment, there was no significant difference in operative mortality between the two groups (5.2 vs. 1.0%, P = 0.064). The incidences of stroke, spinal cord injury (SCI), acute kidney injury (AKI), and endoleak also showed no significant differences (4.1 vs. 0.5%, P = 0.066; 2.1 vs. 1.5%, P = 1.000; 0 vs. 1.0%, P = 0.831; 6.2 vs. 1.9%, P = 0.113, respectively). After IPTW adjustment, the incidences of stroke, SCI, and AKI showed no significant differences between the two groups (1.8 vs. 1.1%, P = 0.138; 0.8 vs. 1.6%, P = 0.448; and 0 vs. 0.7%, P = 0.148, respectively). However, the HAR group tended to have higher operative mortality and incidence of endoleak than the SET group (12.4 vs. 1.3%, P = 0.01; 9.9 vs. 1.8%, P = 0.031, respectively). In the multivariate analysis, open repair decreased the risks of endoleak (odds ratio [OR], 0.171, 95% CI, 0.060-0.401; P < 0.001) and operative mortality (OR, 0.093, 95% CI, 0.027-0.238; P < 0.001). The overall survival and event-free survival of the HAR group were significantly lower than those of the SET group (P < 0.001). Conclusion: One-stage hybrid arch repair combined TEVAR with extra-anatomic bypass and the SET procedure with supra-arch branch reconstruction both provided good postoperative treatment outcomes for distal arch disease. However, hybrid arch repair increased the risks of endoleak and operative mortality. The SET procedure provided better mid-term survival than hybrid arch repair without increasing operative mortality. Carefully selecting the indications for the procedure, while receiving close long-term follow-up, may improve the survival rate of patients undergoing hybrid arch repair.

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.

One-stage hybrid procedure for distal aortic arch disease: mid-term experience at a single center.

BACKGROUND: This study analyzes the outcomes of a one-stage hybrid procedure combining thoracic endovascular aortic repair (TEVAR) with extra-anatomic bypass in patients with distal aortic arch disease. METHODS: This retrospective study collected 103 hybrid procedures combining TEVAR with extra-anatomic bypass (mean age, 62.2±9.3 years; 90 males) performed from January 2009 to January 2019 at Beijing Anzhen Hospital. We analyzed 30-day and mid-term outcomes including survival rate and the incidence of stroke, spinal cord injury (SCI), and endoleak. RESULTS: Five deaths (4.6%) occurred within 30 days, including type I endoleak in Zone 1 (n=1), hemorrhagic shock (n=1), stroke (n=2), and stent migration (n=1). Two patients developed SCI. The median follow-up time was 39.5 (interquartile range, 13.6-69.0) months. In all, 14 late deaths occurred; these were due to stroke (n=2), severe pneumonia (n=1), aortic rupture caused by type I endoleak (n=3), and sudden death (n=8). Six late endoleaks occurred including three type I and one type II in Zone 1 and two type I in Zone 2. In a competing risks analysis, the incidences of reintervention at 7 years, late death, and survival without reintervention were 8%, 22%, and 70%, respectively. In a Cox risk model, stroke (HR, 21.602; 95% CI: 2.798-166.796; P=0.003) was the only risk factor for 30-day mortality. Stroke (HR, 19.484; 95% CI: 5.245-72.380; P<0.001), SCI (HR, 15.548; 95% CI: 2.754-87.786; P=0.002), and endoleak (HR, 4.626; 95% CI: 1.068-20.040; P=0.041) were independent risk factors for long-term mortality. CONCLUSIONS: The one-stage hybrid procedure provides acceptable mid-term results with good mid-term patency of extra-anatomic bypass. Strict selection of patients suitable for hybrid repair can effectively improve the survival rate and reduce the incidence of complications. At the same time, close follow-up patients should receive close long-term follow-up after hybrid procedure.

Impact of Implementing CYP2C19 Genotype-Guided Antiplatelet Therapy on P2Y12 Inhibitor Selection and Clinical Outcomes in Acute Coronary Syndrome Patients After Percutaneous Coronary Intervention: A Real-World Study in China.

Background: CYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of clopidogrel in patients undergoing percutaneous coronary intervention for acute coronary syndrome. However, the clinical impact of implementing CYP2C19 gene-guided pharmacotherapy is unclear, especially among the Chinese population. The purpose of this study was to evaluate P2Y12 receptor inhibitor selection and clinical outcomes upon implementation of CYP2C19 genotype-guided pharmacotherapy in current clinical practice. Methods: This was a single-center observational cohort study. Adult percutaneous coronary intervention patients who received CYP2C19 genetic testing (*2, *3, *17 alleles) were included. Ticagrelor was recommended for patients with a LOF allele. Factors related to P2Y12 inhibitor selection were determined by logistic regression. The primary endpoint was major cardiac or cerebrovascular adverse events (MACCE) within 12 months. MACCE and clinically significant bleeding events (BARC ≥2) in the LOF-clopidogrel group, non-LOF-clopidogrel group, and non-LOF-ticagrelor group were compared with those in the LOF-ticagrelor group. The inverse probability of treatment weighting (IPTW) was adjusted in a Cox regression analysis to eliminate confounding factors. Results: Among 1,361 patients, 826 (60.7%) had a LOF allele. Patients with a LOF allele were more likely to be prescribed ticagrelor (multivariate-adjusted OR 1.349; 95% CI 1.040 to 1.751; p = 0.024). The MACCE rate was higher in the LOF-clopidogrel group than in the LOF-ticagrelor group (7.8 vs. 4.0%; log-rank p = 0.029; IPTW-adjusted HR 2.138; 95% CI 1.300-3.515). Compared with the LOF-ticagrelor group, the non-LOF-clopidogrel group showed no significant difference in MACCE rate (5.8 vs. 4.0%; log-rank p = 0.272; IPTW-adjusted HR 1.531; 95% CI 0.864-2.714). Among the patients treated with ticagrelor, there was no significant difference in the MACCE rate between the LOF group and non-LOF group (4.3 vs. 4.0%; log-rank p = 0.846; IPTW-adjusted HR 1.184; 95% CI 0.582-2.410). There was no significant difference in the incidence of clinically significant bleeding events among the four groups. Conclusion: This study confirms that efficiently returned CYP2C19 genotype results did partially guide cardiologists to prescribe ticagrelor for patients with a LOF allele, and that clopidogrel had a higher risk of MACCE than ticagrelor in these patients, which provides support for the implementation of CYP2C19 gene-guided antiplatelet therapy in clinical practice.

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.

Mitochondrial HTRA2 Plays a Positive, Protective Role in Dictyostelium discoideum but Is Cytotoxic When Overexpressed.

HTRA2 is a mitochondrial protein, mutations in which are associated with autosomal dominant late-onset Parkinson's disease (PD). The mechanisms by which HTRA2 mutations result in PD are poorly understood. HTRA2 is proposed to play a proteolytic role in protein quality control and homeostasis in the mitochondrial intermembrane space. Its loss has been reported to result in accumulation of unfolded and misfolded proteins. However, in at least one case, PD-associated HTRA2 mutation can cause its hyperphosphorylation, possibly resulting in protease hyperactivity. The consequences of overactive mitochondrial HTRA2 are not clear. Dictyostelium discoideum provides a well-established model for studying mitochondrial dysfunction, such as has been implicated in the pathology of PD. We identified a single homologue of human HTRA2 encoded in the Dictyostelium discoideum genome and showed that it is localized to the mitochondria where it plays a cytoprotective role. Knockdown of HTRA2 expression caused defective morphogenesis in the multicellular phases of the Dictyostelium life cycle. In vegetative cells, it did not impair mitochondrial respiration but nonetheless caused slow growth (particularly when the cells were utilizing a bacterial food source), unaccompanied by significant defects in the requisite endocytic pathways. Despite its protective roles, we could not ectopically overexpress wild type HTRA2, suggesting that mitochondrial HTRA2 hyperactivity is lethal. This toxicity was abolished by replacing the essential catalytic serine S300 with alanine to ablate serine protease activity. Overexpression of protease-dead HTRA2 phenocopied the effects of knockdown, suggesting that the mutant protein competitively inhibits interactions between wild type HTRA2 and its binding partners. Our results show that cytopathological dysfunction can be caused either by too little or too much HTRA2 activity in the mitochondria and suggest that either could be a cause of PD.

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.