Del-Nido cardioplegia in cardiac surgery for elderly patients: a propensity score-matched analysis.

OBJECTIVES: To compare the safety and efficacy of del-Nido cardioplegia (DNC) with traditional 4:1 cold blood cardioplegia (CBC) in coronary artery bypass grafting and/or valve surgeries in elderly patients. METHODS: The present study is a retrospective case-series study that included 302 consecutive patients aged 70 years and over who underwent on-pump valve surgery and/or coronary artery bypass graft (CABG). DNC was administered to 90 patients and CBC to 212 patients. After propensity-score matching, 89 pairs were compared. The safety and efficacy were analyzed between the two groups. RESULTS: The DNC group had a similar mortality (3.4% vs. 5.6%, OR = 0.79, P = 0.720) and extracorporeal membrane oxygenation (ECMO) implantation rate (1.1% vs. 2.2%, OR = 0.75, P = 1.000) to the CBC group, a lower incidence of postoperative intra-aortic balloon pump (IABP) implantation (1.1% vs. 9.0%, OR = 0.54, P = 0.034) and a higher left ventricular ejection fraction (LVEF) at discharge (60 (56-64) % vs. 57 (51-62)%, P = 0.007). The estimated glomerular filtration rate (eGFR) in the DNC group was higher when the patient was transferred to the intensive care unit (79.4 (65.0-94.3) ml/min/1.73m2 vs. 77.2 (59.8-88.7) ml/min/1.73m2, P = 0.014), but no significant differences were identified after 24 h. The serum lactate values of the DNC group were significantly lower than those of the CBC group (0 h: 2.7 (2.0-3.2) vs. 3.2 (2.4-4.4), P = 0.001; 3 h: 3.2 (2.0-4.8) vs. 4.8 (2.8-6.6), P < 0.001; 6 h: 3.5 (2.2-5.4) vs. 5.8 (3.4-8.4), P < 0.001; 9 h: 3.4 (2.0-7.0) vs. 5.5 (2.9-8.3), P = 0.005). There were no differences between the two groups in respect of lactate levels at 12 h and thereafter. Postoperative creatinine kinase-MB concentrations were similar between the two groups. CONCLUSIONS: Del-Nido cardioplegia is safe and effective in elderly patients undergoing CABG and/or valve surgery.

Outcomes of minimally invasive isolated tricuspid valve reoperation after left-side valve surgery: A single-center experience.

Background: Late severe tricuspid regurgitation (TR) after left-side valve surgery (LSVS) is not uncommon. However, the tricuspid valve has been deemed the forgotten valve because the isolated TR is well tolerated with medication, and reoperation has a higher rate of adverse events. With the advancement of minimally invasive techniques, isolated tricuspid valve reoperation (ITVR) via totally endoscopy or transcatheter approach brings the tricuspid valve into spotlight. Our aim is to report the safety and efficacy of minimally invasive ITVR using endoscopic and transcatheter approaches. Methods: From October 2020 to October 2021, 21 patients with LSVS history and secondary massive TR underwent minimally invasive ITVR in our institution. Baseline characteristics, surgical outcomes and follow-up results were analyzed, and data between the totally endoscopy approach and the transcatheter approach were compared. Results: Of the 21 cases, totally endoscopic isolated tricuspid valve surgery (EITVS) accounts for 16 (76.2%) cases, with 14 tricuspid valvuloplasty cases, and 2 tricuspid valve replacement cases; the remaining 5 (23.8%) cases underwent transcatheter tricuspid valve replacement (TTVR). The mean age was (60.0 ± 8.4) years, with 15 (71.4%) being female. Minimally invasive ITVR procedures were 100% successfully performed in all patients without any perioperative mortality, sternotomy conversion, or reoperation. During the median follow-up of 16.8 months (IQR, 13.0-20.6 months), New York Heart Association Class improved significantly from baseline (P = 0.004). TR severity was significantly improved during postoperative and follow-up period (both P < 0.001). Compared with the EITVS group, the TTVR group had a higher clinical risk score [8.00 (8.00, 9.00) vs. 5.00 (3.25, 5.00), P = 0.001], but a higher success rate in reducing TR to less than grade 1+ (100 vs. 43.8%, P = 0.045) at follow-up. Conclusion: In our series, minimally invasive ITVR, including EITVS and TTVR, is a safe and feasible option for severe TR after LSVS, and presents excellent early outcomes in selected patients. TTVR is a reliable alternative for patients with high surgical risk. To improve the results of ITVR, it is necessary to improve patient's preoperative status or perform reoperation before the onset of significant right heart failure. Further studies with a larger sample size and a longer follow-up period are awaited.

Novel hKDR mouse model depicts the antiangiogenesis and apoptosis-promoting effects of neutralizing antibodies targeting vascular endothelial growth factor receptor 2.

Vascular endothelial growth factor receptor 2 (VEGFR2)/KDR plays a critical role in tumor growth, diffusion, and invasion. The amino acid sequence homology of KDR between mouse and human in the VEGF ligand-binding domain was low, thus the WT mice could not be used to evaluate Abs against human KDR, and the lack of a suitable mouse model hindered both basic research and drug developments. Using the CRISPR/Cas9 technique, we successfully inserted different fragments of the human KDR coding sequence into the chromosomal mouse Kdr exon 4 locus to obtain an hKDR humanized mouse that can be used to evaluate the marketed Ab ramucirumab. In addition, the humanized mAb VEGFR-HK19 was developed, and a series of comparative assays with ramucirumab as the benchmark revealed that VEGFR-HK19 has higher affinity and superior antiproliferation activity. Moreover, VEGFR-HK19 selectively inhibited tumor growth in the hKDR mouse model but not in WT mice. The most important binding epitopes of VEGFR2-HK19 are D257, L313, and T315, located in the VEGF binding region. Therefore, the VEGFR2-HK19 Ab inhibits tumor growth by blocking VEGF-induced angiogenesis, inflammation, and promoting apoptosis. To our best knowledge, this novel humanized KDR mouse fills the gaps both in an animal model and the suitable in vivo evaluation method for developing antiangiogenesis therapies in the future, and the newly established humanized Ab is expected to be a drug candidate possibly benefitting tumor patients.

Totally endoscopic aortic valve replacement: Techniques and early results.

Objective: To demonstrate the technical details of total endoscopic aortic valve replacement using a standard prosthesis, compare the clinical effect and safety of endoscopic aortic valve replacement and traditional aortic valve replacement. Methods: From 2020 to 2021, 60 consecutive patients underwent elective isolated aortic valve replacement (AVR). They were divided into two groups: the total endoscopic AVR group (TE-AVR group, 29 patients, nine women, aged 51.65 ± 11.79 years), and the traditional full-sternotomy group (AVR group, 31 patients, 13 women, aged 54.23 ± 12.06 years). Three working ports were adopted in the TE-AVR procedure. Results: No patient died in either group. The cardiopulmonary bypass (CPB) time and aortic cross-clamp (ACC) time in the TE-AVR group were longer than those in the AVR group (CPB time: 177.6 ± 43.2 vs. 112.1 ± 18.1 min, p < 0.001; ACC time: 118.3 ± 29.7 vs. 67.0 ± 13.2 min, p < 0.001). However, the mechanical ventilation duration (14.2 ± 9.3 vs. 24.0 ± 18.9 h, p = 0.015) and postoperative hospital stay (6.0 ± 1.7 vs. 8.0 ± 4.5 days, p = 0.025) were shorter in patients of TE-AVR group than those of AVR group. Although the ICU stay (55.1 ± 26.9 vs. 61.5 ± 44.8 h, p = 0.509) and post-operative chest drainage of the first 24 h (229.8 ± 125.0 vs. 273.2 ± 103.2 ml, p = 0.146) revealed no statistical difference, there was a decreasing trend in the TE-AVR group. Among the patients of the TE-AVR group, two patients were converted to thoracotomy because of mild to moderate paravalvular leakage identified by intraoperative transesophageal echocardiography. Conclusion: Total endoscopic aortic valve replacement is safe and feasible, with less trauma and quicker recovery.

Degradation behaviors and in-vivo biocompatibility of a rare earth- and aluminum-free magnesium-based stent.

Biodegradable stents can provide scaffolding and anti-restenosis benefits in the short term and then gradually disappear over time to free the vessel, among which the Mg-based biodegradable metal stents have been prosperously developed. In the present study, a Mg-8.5Li (wt.%) alloy (RE- and Al-free) with high ductility (> 40%) was processed into mini-tubes, and further fabricated into finished stent through laser cutting and electropolishing. In-vitro degradation test was performed to evaluate the durability of this stent before and after balloon dilation. The influence of plastic deformation and residual stress (derived from the dilation process) on the degradation was checked with the assistance of finite element analysis. In addition, in-vivo degradation behaviors and biocompatibility of the stent were evaluated by performing implantation in iliac artery of minipigs. The balloon dilation process did not lead to deteriorated degradation, and this stent exhibited a decent degradation rate (0.15 mm/y) in vitro, but divergent result (> 0.6 mm/y) was found in vivo. The stent was almost completely degraded in 3 months, revealing an insufficient scaffolding time. Meanwhile, it did not induce possible thrombus, and it was tolerable by surrounding tissues in pigs. Besides, endothelial coverage in 1 month was achieved even under the severe degradation condition. In the end, the feasibility of this stent for treatment of benign vascular stenosis was generally discussed, and perspectives on future improvement of Mg-Li-based stents were proposed.

Mitral valve replacement via minimally invasive totally thoracoscopic surgery versus traditional median sternotomy: a propensity score matched comparative study.

BACKGROUND: To compare surgical outcomes after mitral valve replacement via either minimally invasive thoracoscopic (MIs) or traditional median sternotomy (MS) surgery and determine the short- and mid-term clinical outcomes of the MI approach. METHODS: All patients who received either MIs (n=405) or MS (n=691) mitral valve replacement surgery at the Guangdong Cardiovascular Institute between January 2012 and July 2015 were analyzed for outcome differences due to surgical approach using propensity score matching. The best 202 matches from the MI group and the MS group were analyzed. The clinical data of the two groups were collected, including preoperative cardiac function, operative data, postoperative complications, and follow-up. RESULTS: A final total of 404 patients were included in this study after propensity score matching; the MIs group and the MS group each contained 202 patients. The two groups were similar in age, weight, pathological changes, and surgical approach. Compared with the MS group, the MIs group had a longer cardiopulmonary bypass time (P<0.001), aortic cross-clamping time (P<0.001), and total procedure time (P<0.001). There were no significant differences between the groups regarding in-hospital mortality, stroke, pneumonia, acute renal failure, arrhythmia, and chylothorax. The MS group had significantly more patients with poor wound healing than the MIs group (P=0.004). The MI group had a lower rate of transfusion (P=0.037), shorter ventilation time (P=0.041), shorter ICU stay (P=0.033), reduced chest tube drainage and length of chest tube stay (P<0.001), and shorter hospital stay (P<0.001). There was no significant difference between the groups in hospital re-admission for bleeding, but the total hospitalization cost was higher in the MIs group (P=0.002). The mean follow-up was 26.59±12.33 months, the 1-year postoperative survival rate was 98.86%, and the overall survival rate was 97.44%. Compared with the MS group, the MIs group recovered earlier (P<0.05), and returned to work or study earlier (P<0.05). More patients in the MIs group were satisfied with the wound (P<0.001). The MS group had a higher incidence of postoperative osteomyelitis than the MIs group (P=0.028). There were no significant differences between groups in rates of mortality, stroke, pacemaker, reoperation, or 36-item Short Form Health Survey score. CONCLUSIONS: Compared with the MS approach, the MIs method of mitral valve replacement has longer cardiopulmonary bypass time and aortic cross-clamp time; however, it does not increase the risk of mortality and complications. Furthermore, MIs causes less trauma, fewer transfusions, less wound infection, faster recovery, faster return to work or study, and greater satisfaction with the incision in the mid-term. MI cardiac surgery is safe, effective, and feasible.

Endogenous controls of gene expression in N-methyl-N-nitrosourea-induced T-cell lymphoma in p53-deficient mice.

BACKGROUND: Real-time polymerase chain reaction (PCR) has become an increasingly important technique for gene expression profiling because it can provide insights into complex biological and pathological processes and be used to predict disease or treatment outcomes. Although normalized data are necessary for an accurate estimation of mRNA expression levels, several pieces of evidence suggest that the expression of so-called housekeeping genes is not stable. This study aimed to validate reference genes for the normalization of real-time PCR in an N-methyl-N-nitrosourea (MNU)-induced T-cell lymphoma mouse model. METHODS: T-cell lymphomas were generated in p53-deficient mice by treatment with 37.5 mg/kg MNU. Thymus and spleen were identified as the primary target organs with the highest incidences of lymphomas. We analyzed the RNA expression levels of eight potential endogenous reference genes (Gapdh, Rn18s, Actb, Hprt, B2M, Rplp0, Gusb, Ctbp1). The expression stabilities of these reference genes were tested at different time points after MNU treatment using geNorm and NormFinder algorithms. RESULTS: A total of 65% of MNU-treated mice developed T-cell lymphomas, with the spleen and thymus as the major target organs. All candidate reference genes were amplified efficiently by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Gene stability evaluation after MNU treatment and during lymphomagenesis revealed that Ctbp1 and Rplp0 were the most stably expressed genes in the thymus and spleen, respectively. RT-PCR of thymus RNA using two additional sets of primer confirmed that Ctbp1 was the most stable of all the candidate reference genes. CONCLUSIONS: We provided suitable endogenous controls for gene expression studies in the T-cell lymphoma model.

Surgical ablation for persistent atrial fibrillation in concomitant cardiac surgery: mid-long-term result.

OBJECTIVES: Surgical ablation is an option for patients with atrial fibrillation (AF) undergoing concomitant cardiac surgery. This study aims to evaluate the outcome of surgical ablation during concomitant cardiac surgery and to identify the independent predictors for a primary end-point consisting of AF or atrial flutter (AFL) recurrence, death, permanent pacemaker implantation and necessity for anti-arrhythmic drugs and the effects of reintervention for AF/AFL recurrence. METHODS: A retrospective analysis was performed for 1028 patients who underwent surgical ablation during concomitant cardiac surgery from October 2004 to April 2015. Nine hundred and twenty-seven of 1017 (91.2%) discharged patients were followed up. Sixty-three recurrent patients received reintervention. Predictors of ablation failure were identified using univariate analysis and the Cox regression model. RESULTS: The mean follow-up length was 29.0 ± 22.7 months. The New York Heart Association class, ejection fraction, left atrial and right atrial diameters and left ventricular end-diastolic diameter were improved at follow-up compared with the preoperative status. The rate of freedom from the primary end-point at 1, 2 and 3 years was 86.8, 79.4 and 68.3%. Independent predictors of reaching the primary end-point were AF/AFL at discharge, preoperative right atrial diameter, hypertension, diabetes and smoking. The rate of sinus rhythm without anti-arrhythmic drugs at 12, 24 and 36 months after reintervention was 78.3, 62.8 and 49.9%, respectively. CONCLUSIONS: Surgical ablation has a high success rate and may improve cardiac function postoperatively. AF/AFL at discharge, preoperative right atrial diameter, hypertension, diabetes and smoking are the major independent predictors for ablation failure. Reintervention in AF/AFL recurrent patients can achieve a favourable clinical outcome.