Overexpression of 14-3-3ζ primes disease recurrence, metastasis and resistance to chemotherapy by inducing epithelial-mesenchymal transition in NSCLC.

The prognosis of non-small cell lung cancer (NSCLC) is disappointing because disease recurrence and distant metastasis inevitably occurred. The aim of the present study is to identify novel biomarkers predicting tumor recurrence and metastasis. The 14-3-3ζ protein has been extensively described as a tumor promoter in a panel of solid tumors, including NSCLC. However, there is a big gap regarding the knowledge between 14-3-3ζ and NSCLC recurrence. In this study, we found that overexpression of 14-3-3ζ was more frequent in NSCLC tumor tissues with tumor recurrence. By using scratch healing assay and transwell assay, we demonstrated that NSCLC cells with high expression of 14-3-3ζ gained increased motile and invasive capacity, whereas siRNA-mediated knockdown of endogenous 14-3-3ζ abrogated cancer cell dissemination. Intriguingly, we found that NSCLC cells underwent epithelial-mesenchymal transition (EMT) after the induction of 14-3-3ζ in vitro and in vivo. These findings could be readily recaptured in clinical setting since we showed that NSCLC tumor specimen with high expression of 14-3-3ζ revealed biological features of EMT. Overexpression of 14-3-3ζ also enhanced the phosphorylation of Akt and promoted the proliferation of NSCLC cell lines. In agreement with this notion, we reported that NSCLC cells with high expression of 14-3-3ζ became resistant to chemotherapy-induced apoptosis. These findings strongly suggested that 14-3-3ζ as a novel biomarker predicting risks of disease recurrence and screening 14-3-3ζ status may be a promising approach to select patients who experienced high risks of cancer recurrence and resistance to chemotherapy.

Surgical treatment of type A acute aortic dissection with cerebral malperfusion: a systematic review.

OBJECTIVES: Type A acute aortic dissection (TAAAD) complicated with cerebral malperfusion (CM) is a life-threatening condition associated with high mortality, poor outcomes, and the optimal surgical management remains controversial. The aim of this review was to report the current results of surgical interventions of these patients. METHODS: A systematic review was performed using PubMed and MEDLINE search for cases underwent surgical repair for TAAAD with CM. Demographics, neurological symptom, the time from onset of symptoms to operation, operation data, mortality, neurological outcome, and follow-up were reviewed. RESULTS: A total of 363 patients with mean age of 65.7 ± 13 years underwent surgical repair for TAAAD with CM were identified in 12 retrospective studies. In-hospital mortality was 20.1%. Mean duration of follow-up was 40.1 ± 37.6 months. The involved supra-aortic branch vessels were RCCA (n = 99), LCCA (n = 25), B-CCA (n = 52), CCA (n = 131), IA (n = 19), and LSA (n = 8). Time from onset of neurological symptoms to surgery was 13.3 h. Antegrade and/or retrograde cerebral perfusion were applied. Postoperatively, improved, unchanged and worsened neurological status was occurred in 54.3%, 27.1%, and 8.5%, respectively in 199 patients. CONCLUSION: The outcomes of surgical treatment of TAAAD complicated with CM indicate acceptable early mortality and morbidity. It is reasonable to perform lifesaving surgery on these patients. Early central surgical repair and reperfusion of brain may improve the outcomes.

Extracorporeal membrane oxygenation in trauma patients: a systematic review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has evolved considerably over the past two decades and has been gradually utilized in severe trauma. However, the indications for the use of ECMO in trauma remain uncertain and the clinical outcomes are different. We performed a systematic review to provide an overall estimate of the current performance of ECMO in the treatment of trauma patients. MATERIALS AND METHODS: We searched PubMed and MEDLINE databases up to the end of December 2019 for studies on ECMO in trauma. The PRISMA statement was followed. Data on demographics of the patient, mechanism of injury, injury severity scores (ISS), details of ECMO strategies, and clinical outcome were extracted. RESULTS: A total of 58 articles (19 retrospective reports and 39 case reports) were deemed eligible and included. In total, 548 patients received ECMO treatment for severe trauma (adult 517; children 31; mean age of adults 34.9 ± 12.3 years). Blunt trauma (85.4%) was the primary injury mechanism, and 128 patients had traumatic brain injury (TBI). The mean ISS was 38.1 ± 15.0. A total of 71.3% of patients were initially treated with VV ECMO, and 24.5% were placed on VA ECMO. The median time on ECMO was 9.6 days, and the median time to ECMO was 5.7 days. A total of 60% of patients received initially heparin anticoagulation. Bleeding (22.9%) and thrombosis (19%) were the most common complications. Ischemia of the lower extremities occurred in 9 patients. The overall hospital mortality was 30.3%. CONCLUSIONS: ECMO has been gradually utilized in a lifesaving capacity in severe trauma patients, and the feasibility and advantages of this technique are becoming widely accepted. The safety and effectiveness of ECMO in trauma require further study. Several problems with ECMO in trauma, including the role of VA-ECMO, the time to institute ECMO, and the anticoagulation strategy remain controversial and must be solved in future studies.

3D printing in adult cardiovascular surgery and interventions: a systematic review.

3D printing in adult cardiac and vascular surgery has been evaluated over the last 10 years, and all of the available literature reports benefits from the use of 3D models. In the present study, we analyzed the current applications of 3D printing for adult cardiovascular disease treated with surgical or catheter-based interventions, including the clinical medical simulation of physiological or pathology conducted with 3D printing in this field. A search of PubMed and MEDLINE databases were supplemented by searching through bibliographies of key articles. Thereafter, data on demographic, clinical scenarios and application, imaging modality, purposes of using with 3D printing, outcomes and follow-up were extracted. A total of 43 articles were deemed eligible and included. 296 patients (mean age: 65.4±14.2 years; male, 58.2%) received 3D printing for cardiac and vascular surgery or conditions [percutaneous left atrial appendage occlusion (LAAO), TAVR, mitral valve disease, aortic valve replacement, coronary artery abnormality, HOCM, aortic aneurysm and aortic dissection, Kommerell's diverticulum, primary cardiac tumor and ventricular aneurysm]. Eight papers reported the utility of 3D printing in the medical simulator and training fields. Most studies were conducted starting in 2014. Twenty-six was case report. The major scenario used with 3D printing technology was LAAO (50.3%) and followed by TAVR (17.6%). CT and echocardiography were two main imaging techniques that were used to generate 3D-printed heart models. All studies showed that 3D-printed models were helpful for preoperative planning, orientation, and medical teaching. The important finding is that 3D printing provides a unique patient-specific method to assess complex anatomy and is helpful for intraoperative orientation, decision-making, creating functional models, and teaching adult cardiac and vascular surgery, including catheter-based heart surgery.

Cox-maze III procedure for atrial fibrillation during valve surgery: a single institution experience.

OBJECTIVES: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in patients with heart valve disease. Our aim was to summarize our experience and evaluate the efficacy and safety of the Cox maze III procedure combined with valve surgery in patients with AF. METHODS: A retrospective, observational analysis was performed for all consecutive patients underwent maze III procedure combined with valve surgery between October 2015 and June 2019. In this trial, we used a monopolar radiofrequency (RF) ablation in addition to cut and sew technique to treat AF. RESULTS: 66 patients (37 female, 56.1%) with persistent or long-lasting persistent AF associated with valve disease were identified. The mean age was 54.2 ± 8.4 years (range, 30 to 73 years). Overall hospital mortality was 3.0%. The duration of cardiopulmonary bypass and aortic cross clamping was 175.4 ± 32.9 and 115.6 ± 22.8 min respectively. The first 24 h drainage was 488.6 ± 293.3 ml. The postoperative hospital stay was 14.8 ± 8.3 days. The postoperative incidence of permanent pacemaker implantation, reoperation for bleeding, renal failure required hemodialysis, and stroke was 4.5, 1.5, 4.5% and 0 respectively. The frequency of sinus rhythm was 91.7, 93.1, 94.7, 93.3 and 89.5% at 1, 3, 6, 12, and 24 months respectively. CONCLUSIONS: The Cox-Maze III procedure is safe in the surgical treatment of AF associated with valve disease, and efficacious for sinus rhythm maintenance, with low morbidity and mortality.

Mercaptoethanol Protects the Aorta from Dissection by Inhibiting Oxidative Stress, Inflammation, and Extracellular Matrix Degeneration in a Mouse Model.

BACKGROUND The aims of this study were to investigate the effects of mercaptoethanol treatment on the expression of mediators of oxidative stress, inflammation, and extracellular matrix (ECM) degeneration in a mouse aortic dissection (AD) model. MATERIAL AND METHODS Twenty-four 8-month-old C57BL/6J mice were divided into three groups and studied for two weeks: 1) the aortic dissection (AD) Model group (N=8) underwent intraperitoneal injection of angiotensin II (Ang II) (5 ml/kg) three times every 24 h; 2) the mercaptoethanol Treated group (N=8) were given oral mercaptoethanol (2.5 mM); the Normal group (N=8) underwent intraperitoneal injection of noradrenaline (5 mg/kg) three times every 24 h. Sections of mouse aorta were prepared for histology with hematoxylin and eosin (H&E) staining; immunohistochemistry was performed to detect levels of: nuclear factor (erythroid-derived 2)-like 2 (NFE2L2), nuclear factor κB (NF-κB), p65, superoxide dismutase-1 (SOD1), glutamate cysteine ligase catalytic subunit (GCLC), tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and matrix metalloproteinase-9 (MMP9). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) evaluated mRNA expression of SOD1, GCLC, TNF-α, IL-1ß, and MMP9. RESULTS Mercaptoethanol treatment inhibited Ang II-induced aortic dissection in AD mice, as shown histologically. Mercaptoethanol treatment reduced the expression levels of NFE2L2, NF-κB, p65, TNF-α, IL-1ß and increased the expression levels of SOD1, MMP9, and GCLC. CONCLUSIONS In an AD mouse model, mercaptoethanol treatment inhibited thoracic and abdominal aortic dissection and reduced aortic tissue expression of mediators of oxidative stress and inflammation and increased the activation of ECM signaling pathways.