IL-6 signaling accelerates iron overload by upregulating DMT1 in endothelial cells to promote aortic dissection.

Aortic dissection (AD), caused by tearing of the intima and avulsion of the aortic media, is a severe threat to patient life and organ function. Iron is closely related to dissection formation and organ injury, but the mechanism of iron ion transport disorder in endothelial cells (ECs) remains unclear. We identified the characteristic EC of dissection with iron overload by single-cell RNA sequencing data. After intersecting iron homeostasis and differentially expressed genes, it was found that hypoxia-inducible factor-1α (HIF-1α) and divalent metal transporter 1 (DMT1) are key genes for iron ion disorder. Subsequently, IL-6R was identified as an essential reason for the JAK-STAT activation, a classical iron regulation pathway, through further intersection and validation. In in vivo and in vitro, both high IL-6 receptor expression and elevated IL-6 levels promote JAK1-STAT3 phosphorylation, leading to increased HIF-1α protein levels. Elevated HIF-1α binds explicitly to the 5'-UTR sequence of the DMT1 gene and transcriptionally promotes DMT1 expression, thereby increasing Fe2+ accumulation and endoplasmic reticulum stress (ERS). Blocking IL-6R and free iron with deferoxamine and tocilizumab significantly prolonged survival and reduced aortic and organ damage in dissection mice. A comparison of perioperative data between AD patients and others revealed that high free iron, IL-6, and ERS levels are characteristics of AD patients and are correlated with prognosis. In conclusion, activated IL-6/JAK1/STAT3 signaling axis up-regulates DMT1 expression by increasing HIF-1α, thereby increasing intracellular Fe2+ accumulation and tissue injury, which suggests a potential therapeutic target for AD.

Early and long-term outcomes of young adult patients ≤30 years old with acute type A aortic dissection.

OBJECTIVES: The aim of this study was to investigate the early and long-term outcomes after total arch replacement (TAR) and frozen elephant trunk (FET) implantation in adult patients ≤30 years with acute type A aortic dissection (ATAAD). METHODS: All young adult patients (≤30 years) with ATAAD who underwent TAR and FET between 2009 and 2017 were enrolled. The end points were major organ morbidity and mortality, aortic-related events and reoperation. RESULTS: The mean age of all 83 patients was 25.9 (standard deviation, 3.3) years. The in-hospital mortality was 9.64% (8/83), and 9 (10.8%) patients required re-exploration for bleeding. The aortic-related events risk was 42.7% (32/75) and the aortic reoperation risk was 17.3% (13/75). Overall survival was 85.5% [95% confidence interval (CI), 75.9-91.5%] at 5 years and 75.9% (95% CI, 63.3-84.7%) at 10 years. The cumulative incidence of aortic-related events was 35% (95% CI, 24-47%) at 5 years and 58% (95% CI, 36-75%) at 10 years; the cumulative reoperation rate was 15% (95% CI, 7.9-24%) at 5 years and 17% (95% CI, 9.2-27%) at 10 years. Marfan syndrome significantly increased the aortic-related events (P = 0.036) and reoperation (P = 0.041) risks. CONCLUSIONS: Despite extensive repair in young ATAAD patients, the late aortic dilatation and reoperation risk remain high. The TAR and FET procedures achieved satisfactory early outcomes and reduced late aortic dilatation and reoperation in young patients compared with other records. Close follow-up and aggressive early reintervention are essential for patients with aortic-related risk factors early in life.

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.

Redo Total Aortic Arch Replacement in Patients with Aortic Dissection After Open-Heart Surgery and Long-Term Follow-Up Results.

INTRODUCTION: The objectives of this study were to investigate the main treatment strategies and long-term follow-up results of aortic dissection surgery after open-heart surgery (ADSOHS) and to analyze the risk factors that cause ADSOHS. METHODS: One hundred thirty-seven patients with ADSOHS hospitalized in our hospital from January 2009 to December 2018 were selected as the research object. Long-term follow-up results, complications, mortality, and changes of cardiac function before and after operation were used to explore the value of Sun's operation. RESULTS: The length of stay in intensive care unit of these 137 patients ranged from 9.5 to 623.75 hours (average of 76.41±97.29 hours), auxiliary ventilation time ranged from 6.0 to 259.83 hours (average of 46.16±55.59 hours), and hospital stay ranged from six to 85 days (average of 25.06±13.04 days). There were seven cases of postoperative low cardiac output, 18 cases of coma and stroke, and six cases of transient neurological dysfunction. A total of 33 patients died; 19 patients died during the perioperative period, 18 died during Sun's operation and one died during other operation; and 14 patients died during follow-up (January 2021), 12 cases of Sun's operation and two cases of other operations. CONCLUSION: ADSOHS treatment strategy is of high application value, and the risk of neurological complications and mortality is low. The main risk factors are postoperative low cardiac output, coma, stroke, and transient neurological dysfunction. The extracorporeal circulation time is relatively long. Short- and long-term follow-up effects are good, and it is worthy of clinical promotion.

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.

Redo Total Aortic Arch Replacement in Patients with Aortic Dissection After Open-Heart Surgery and Long-Term Follow-Up Results

ABSTRACT Introduction: The objectives of this study were to investigate the main treatment strategies and long-term follow-up results of aortic dissection surgery after open-heart surgery (ADSOHS) and to analyze the risk factors that cause ADSOHS. Methods: One hundred thirty-seven patients with ADSOHS hospitalized in our hospital from January 2009 to December 2018 were selected as the research object. Long-term follow-up results, complications, mortality, and changes of cardiac function before and after operation were used to explore the value of Sun's operation. Results: The length of stay in intensive care unit of these 137 patients ranged from 9.5 to 623.75 hours (average of 76.41±97.29 hours), auxiliary ventilation time ranged from 6.0 to 259.83 hours (average of 46.16±55.59 hours), and hospital stay ranged from six to 85 days (average of 25.06±13.04 days). There were seven cases of postoperative low cardiac output, 18 cases of coma and stroke, and six cases of transient neurological dysfunction. A total of 33 patients died; 19 patients died during the perioperative period, 18 died during Sun's operation and one died during other operation; and 14 patients died during follow-up (January 2021), 12 cases of Sun's operation and two cases of other operations. Conclusion: ADSOHS treatment strategy is of high application value, and the risk of neurological complications and mortality is low. The main risk factors are postoperative low cardiac output, coma, stroke, and transient neurological dysfunction. The extracorporeal circulation time is relatively long. Short- and long-term follow-up effects are good, and it is worthy of clinical promotion.

Development and validation of a nomogram for postoperative severe acute kidney injury in acute type A aortic dissection.

BACKGROUND: Postoperative acute kidney injury (AKI) is a major complication associated with increased morbidity and mortality after surgery for acute type A aortic dissection (AAAD). To the best of our knowledge, risk prediction models for AKI following AAAD surgery have not been reported. The goal of the present study was to develop a prediction model to predict severe AKI after AAAD surgery. METHODS: A total of 485 patients who underwent AAAD surgery were enrolled and randomly divided into the training cohort (70%) and the validation cohort (30%). Severe AKI was defined as AKI stage III following the Kidney Disease: Improving Global Outcomes criteria. Preoperative variables, intraoperative variables and postoperative data were collected for analysis. Multivariable logistic regression analysis was performed to select predictors and develop a nomogram in the study cohort. The final prediction model was validated using the bootstrapping techniques and in the validation cohort. RESULTS: The incidence of severe AKI was 23.0% (n = 78), and 14.7% (n = 50) of patients needed renal replacement treatment. The hospital mortality rate was 8.3% (n = 28), while for AKI patients, the mortality rate was 13.1%, which increased to 20.5% for severe AKI patients. Univariate and multivariate analyses showed that age, cardiopulmonary bypass time, serum creatinine, and D-dimer were key predictors for severe AKI following AAAD surgery. The logistic regression model incorporated these predictors to develop a nomogram for predicting severe AKI after AAAD surgery. The nomogram showed optimal discrimination ability, with an area under the curve of 0.716 in the training cohort and 0.739 in the validation cohort. Calibration curve analysis demonstrated good correlations in both the training cohort and the validation cohort. CONCLUSIONS: We developed a prognostic model including age, cardiopulmonary bypass time, serum creatinine, and D-dimer to predict severe AKI after AAAD surgery. The prognostic model demonstrated an effective predictive capability for severe AKI, which may help improve risk stratification for poor in-hospital outcomes after AAAD surgery.

Massive Bleeding After Surgical Repair in Acute Type A Aortic Dissection Patients: Risk Factors, Outcomes, and the Predicting Model.

Background: Massive bleeding throughout aortic repair in acute type A aortic dissection (ATAAD) patients is a common but severe condition that can cause multiple serious clinical problems. Here, we report our findings regarding risk factors, short-term outcomes, and predicting model for massive bleeding in ATAAD patients who underwent emergent aortic repair. Methods: A universal definition of perioperative bleeding (UDPB) class 3 and 4 were used to define massive bleeding and comprehensively evaluate patients. A total of 402 consecutive patients were enrolled in this retrospective study during 2019. Surgical strategies used to perform aortic arch procedures included total arch and hemiarch replacements. In each criterion, patients with massive bleeding were compared with remaining patients. Multivariable regression analyses were used to identify independent risk factors for massive bleeding. Logistic regression was used to build the model, and the model was evaluated with its discrimination and calibration. Results: Independent risk factors for massive bleeding included male sex (OR = 6.493, P < 0.001), elder patients (OR = 1.029, P = 0.05), low body mass index (BMI) (OR = 0.879, P = 0.003), emergent surgery (OR = 3.112, P = 0.016), prolonged cardiopulmonary bypass time (OR = 1.012, P = 0.002), lower hemoglobin levels (OR = 0.976, P = 0.002), increased D-dimer levels (OR = 1.000, P = 0.037), increased fibrin degradation products (OR = 1.019, P = 0.008), hemiarch replacement (OR = 5.045, P = 0.037), total arch replacement (OR = 14.405, P = 0.004). The early-stage mortality was higher in massive bleeding group (15.9 vs. 3.9%, P = 0.001). The predicting model showed a well discrimination (AUC = 0.817) and calibration (χ2 = 5.281, P = 0.727 > 0.05). Conclusion: Massive bleeding in ATAAD patients who underwent emergent aortic repair is highly associated with gender, emergent surgery, increased D-dimer levels, longer CPB time, anemia, and use of a complex surgical strategy. Since massive bleeding may lead to worse outcomes, surgeons should choose suitable surgical strategies in patients who are at a high risk of massive bleeding.

Management of acute type A aortic dissection during COVID-19 outbreak: Experience from Anzhen.

OBJECTIVES: We seek to report our management protocol and early outcomes of acute type A aortic dissection (ATAAD) repair during the early phase of coronavirus disease 2019 (COVID-19). METHODS: From January 23 to April 30, 2020, we performed ATAAD repair for 33 patients, including three with pregnancy-related TAADs. Confirmation of COVID-19 depended on the results of two nucleic acid tests and pulmonary computed tomography scan. Based on testing results and hemodynamic stability, patients were triaged to an isolated intensive care unit or negative pressure operating room for emergency surgery. RESULTS: Mean age 50.2 ± 13.3 years and 20 were male (60.1%) and 8 patients were febrile (>37.3°C; 24.2%) and 17 were lymphopenic (51.5%). No patient was excluded from COVID-19 infection preoperatively. Extensive aortic repair with total arch replacement (TAR) was performed in 24 (72.7%), and limited proximal repair in 9 patients (27.3%). Cardiopulmonary bypass and cross-clamp times averaged 177 ± 34 and 88 ± 20 min for TAR, and 150 ± 30 and 83 ± 18 min for hemiarch, respectively. The mean operation time was 410 ± 68.3 min. Operative mortality was 6.1% (2/33). Complications included reintubation in four (12.1%), acute kidney failure in two (6.1%), and cerebral infarction in one (3.0%). No paraplegia nor re-exploration for bleeding occurred. COVID-19 was excluded in 100% eventually. No nosocomial infection occurred. Nor did any patient/surgical staff develop fever or test positive during the study period. CONCLUSIONS: The results of this study show that our management protocol based on testing results and hemodynamic stability in patients with ATAAD during the COVID-19 pandemic was effective and achieved favorable early surgical outcomes.

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.

Surgical repair of cervical aortic arch: An alternative classification scheme based on experience in 35 patients.

OBJECTIVE: Cervical aortic arch (CAA) is rare and difficult to repair. Clinical experience is limited. We report the surgical techniques and midterm outcomes in 35 patients with CAA based on an alternative classification scheme. METHODS: Of 35 patients with CAA, 30 (85.7%) had left-sided aortic arch and 5 had (14.3%) right-sided aortic arch (all 5 had a vascular ring). Mean age was 34.2 ± 13.1 years, 23 were female (65.7%), and 18 were asymptomatic (51.4%). Surgical access and procedure were chosen according to an alternative classification scheme that is based on the presence or absence of vascular ring and relationship of descending aorta to the side of the aortic arch. In the left-sided aortic arch group, aortic arch reconstruction though median sternotomy was performed in 15 patients, and distal arch and descending thoracic aortic replacement via left thoracotomy in 15 patients. In the right-sided aortic arch group, ascending-to-descending aortic bypass was done via median sternotomy in 2 patients and right thoracotomy in 1, and distal arch and descending thoracic aortic replacement via right thoracotomy in 2 patients. RESULTS: Neither death nor spinal cord injury occurred. Left recurrent laryngeal nerve injury, prolonged ventilation, and reexploration for bleeding occurred in 1 each. In 11 patients with coarctation, the upper-lower limb gradient decreased significantly postoperatively (from 34.0 ± 12.7 to 10.2 ± 2.7 mm Hg; P < .01). The diseased aortic segment was excluded in 34 patients, except 1 with residual aneurysm in the proximal descending thoracic aorta. Follow-up was complete in 100% at mean 4.4 ± 2.0 years. No late death, limb ischemia, or stroke occurred. Endovascular repair was performed in 1 patient, and ascending aortic dilation occurred in 1 patient. The residual aorta remained nondilated in 33 patients. Aortic grafts were patent in 100%, with no anastomotic leak or pseudoaneurysm. At 6 years, the incidences of death, aortic events, and event-free survival were 0%, 6.5%, and 93.5%, respectively. CONCLUSIONS: Open repair of CAA can achieve favorable early and midterm outcomes. Surgical accesses and procedures should be chosen based on type of CAA, anatomic variations and associated anomalies. Our alternative categorization scheme of CAA is intuitive and comprehensive, which may facilitate classification and surgical decision making.

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.

Synthesis and comparative biological evaluation of bifunctional ligands for radiotherapy applications of (90)Y and (177)Lu.

Zevalin® is an antibody-drug conjugate radiolabeled with a cytotoxic radioisotope ((90)Y) that was approved for radioimmunotherapy (RIT) of B-cell non-Hodgkin's lymphoma. A bifunctional ligand that displays favorable complexation kinetics and in vivo stability is required for effective RIT. New bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA for potential use in RIT were efficiently prepared by the synthetic route based on regiospecific ring opening of aziridinium ions with prealkylated triaza- or tetraaza-backboned macrocycles. The new bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA along with the known bimodal ligands 3p-C-NETA and 3p-C-DEPA were comparatively evaluated for potential use in targeted radiotherapy using ß-emitting radionuclides (90)Y and (177)Lu. The bifunctional ligands were evaluated for radiolabeling kinetics with (90)Y and (177)Lu, and the corresponding (90)Y or (177)Lu-radiolabeled complexes were studied for in vitro stability in human serum and in vivo biodistribution in mice. The results of the comparative complexation kinetic and stability studies indicate that size of macrocyclic cavity, ligand denticity, and bimodality of donor groups have a substantial impact on complexation of the bifunctional ligands with the radiolanthanides. The new promising bifunctional chelates in the DE4TA and NE3TA series were rapid in binding (90)Y and (177)Lu, and the corresponding (90)Y- and (177)Lu-radiolabeled complexes remained inert in human serum or in mice. The in vitro and in vivo data show that 3p-C-DE4TA and 3p-C-NE3TA are promising bifunctional ligands for targeted radiotherapy applications of (90)Y and (177)Lu.