Background—: Appropriate surgical management of type A dissection is a critical factor for achieving satisfactory outcome, but the choice of optimal procedure is controversial. We retrospectively reviewed our experience with aortic arch replacement for type A dissection involving the arch. Methods and Results—: Excluding 14 cases of subtotal or total aortic replacement, 411 of 544 patients with type A dissection (stented elephant trunk=291, conventional surgical repair=120) underwent aortic arch replacement between January 2003 and September 2008. In-hospital mortality was 3.09% (9 of 291) for stented (acute=4.73%, 7 of 148; chronic=1.40%, 2 of 143) and 5.00% (6 of 120) for conventional repairs (acute=6.06%, 4 of 66; chronic=3.70%, 2 of 54). Spinal cord injury was 2.41% (7 of 291) in the stented and 0.83% (1 of 120) in the conventional group. The overall prevalence of stroke was 1.95% (8 of 411) (stented=2.41%, 7 of 291; conventional=0.83, 1 of 120). Secondary intervention was 2.34% (5 of 214) for acute dissection (stented=1 and conventional=4; P =0.031) and 3.05% (6 of 197) for chronic dissection (stented=4 and conventional=2; P =0.661) during follow-up. Obliteration of the false lumen around the stented elephant trunk occurred in 94.2% (130 of 138) of patients with acute dissection and in 92.0% (126 of 137) of patients with chronic dissection. Conclusions—: Total arch replacement combined with stented elephant trunk implantation demonstrated the superiority of the combination of the surgical and interventional approaches while avoiding the weaknesses associated with the individual methods. The encouraging surgical results could enable this procedure to become the new “standard” therapy for type A dissection involving repair of the aortic arch.

Purpose: This study aimed to determine a maximum tolerated dose (MTD) and recommended dose for disease-directed studies of necitumumab (IMC-11F8), a fully human IgG₁ monoclonal antibody directed at the epidermal growth factor receptor, and to characterize the safety profile, pharmacokinetics, preliminary antitumor activity, and immunogenicity of necitumumab. Experimental Design: Patients with advanced solid malignancies were treated with 100 to 1,000 mg (flat dosing) necitumumab followed by a 2-week pharmacokinetics sampling period, before beginning 6-week cycles of therapy. Results: Sixty patients received necitumumab weekly (29 patients) or every other week (31 patients). Two patients receiving 1,000 mg every 2 weeks experienced dose-limiting toxicities (DLT; grade 3 headache), accompanied by grade 3 nausea and vomiting in one patient. Occurring hours after the initial dose, these DLTs established 800 mg as the MTD. Mild dose-related skin toxicity was the most common drug-related toxicity (80%). One patient in each arm experienced grade 3 acneform rash, which responded to oral antibiotics and topical therapy. Toxicity was similar on both schedules. Necitumumab exhibited saturable elimination and nonlinear pharmacokinetics. At 800 mg (both arms), its half-life was approximately 7 days. All patients treated with ≥600 mg necitumumab achieved target trough concentrations (≥40 μg/mL). Antibodies against necitumumab were not detected. Partial response and stable disease were experienced by 2 and 16 patients, respectively. Conclusion: Well tolerated, necitumumab is associated with preliminary evidence of antitumor activity, and achieves biologically relevant concentrations throughout the dosing period. The recommended dose of necitumumab for further clinical development is 800 mg (flat dose) weekly or every 2 weeks based on the clinical setting. Clin Cancer Res; 16(6); 1915–23

Thoracic aortic surgery and cardiopulmonary bypass are both associated with development of postoperative acute kidney injury. In this study, we undertook to investigate the relationship between cardiopulmonary bypass time and postoperative acute kidney injury in patients undergoing thoracic aortic surgery for acute DeBakey Type I aortic dissection. All patients receiving thoracic aortic surgery for acute DeBakey Type I aortic dissection in Beijing Anzhen hospital from December 2015 to April 2017 were included. Cardiopulmonary bypass time was recorded during surgery. Acute kidney injury was defined based on the Kidney Disease Improving Global Outcomes criteria. A total of 115 consecutive patients were eventually analyzed. The overall incidence of acute kidney injury was 53.0% (n = 61). The average age was 47.8 ± 10.7 years; 74.8% were male. Mean cardiopulmonary bypass time was 211 ± 56 min. In-hospital mortality was 7.8%. Multivariate logistic regression revealed that cardiopulmonary bypass time was independently associated with the occurrence of postoperative acute kidney injury after adjust confounding factors (odds ratio = 1.171; 95% confidence interval: 1.002–1.368; P = 0.047). Cardiopulmonary bypass time is independently associated with an increased hazard of acute kidney injury after thoracic aortic surgery for acute DeBakey Type I aortic dissection. Further understanding of the mechanism of this association is crucial to the design of preventative strategies.

Background: This meta-analysis aims to investigate the effects of postoperative acute kidney injury (AKI) on 30-day postoperative outcomes and the independent risk factors for postoperative AKI in patients with type A acute aortic dissection (TAAD). Methods: Relevant reports published between January 1, 2011 and May 31, 2017 were searched in multiple electronic literature databases. A total of seven eligible articles were included in the meta-analysis. Results: Postoperative AKI was associated with 249% increase in 30-day postoperative mortality [odds ratio (OR): 3.49; 95% confidence interval (CI): 2.17–5.59; P<0.0001]. Subgroup analysis revealed that patients with stage II/III AKI showed 445% increase in 30-day postoperative mortality compared with the control group (OR: 5.45; 95% CI: 2.87–10.36; P<0.0001). Postoperative AKI was also associated with 143%, 432%, and 126% increase in the incidences of 30-day postoperative stroke, bleeding, and respiratory complications, respectively. Notably, high body mass index (BMI), advanced age, and perioperative sepsis were independent risk factors for postoperative AKI in patients with TAAD. Conclusions: This meta-analysis firstly provided clinical evidence showing the adverse effects of postoperative AKI on 30-day postoperative outcomes in patients with TAAD and identified high BMI, advanced age, and perioperative sepsis as the independent risk factors for postoperative AKI. These findings suggest that preventive or therapeutic methods to effectively manage postoperative AKI may improve 30-day postoperative outcomes in patients with TAAD.