Successful surgical repair in an older adult with supracardiac total anomalous pulmonary venous connection: A case report.

Total anomalous pulmonary venous connection (TAPVC) is a rare, cyanotic and critical congenital heart disease where the entire left and right pulmonary veins fail to drain into the left atrium directly. Also, TAPVC-induced tissue hypoxia gradually worsens after birth. Thus, timely surgical repairs are recommended once diagnosed, particularly with pulmonary venous drainage obstruction(s). Nonetheless, in sporadic cases, patients with TAPVC survive to adulthood with no surgical treatment. Herein, we report a 46-year-old female with TAPVC, where the four pulmonary veins drain into to the innominate vein (IV) via the vertical vein. The patient developed palpitations and non-anginal chest pain following routine activities for over three months. The patient had a successful surgical correction with excellent postoperative recovery.

Organ damage evaluation in a temperature-controlled circulatory arrest rat model.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) is commonly used in adult aortic surgery and pediatric complex congenital heart disease, and is associated with pathophysiological changes and postoperative complications. Here, a temperature-controlled circulatory arrest model in rats was established to study the suitable temperature of circulatory arrest by investigating the damage to body organs under different temperatures. METHODS: Thirty Sprague‒Dawley rats were randomly divided into 5 equal groups for DHCA experiments: I (15-20 °C), II (20-25 °C), III (25-30 °C), IV (normothermic cardiopulmonary bypass), and V (sham operation group). Blood gas analysis, homodynamic parameters, and intervals of cardiac recovery were measured at different time points in all groups. Morphological changes in intestinal tissue were observed under light and electron microscopes. Oxidative stress was measured by MPO activity, MDA, and SOD content. Tissue damage was confirmed by serum detection of ALT, AST, BUN, Cr, and LDH. To examine the inflammatory response, cytokines, including IL-1, IL-4, IL-10, IFN-γ, and TNF-α, were detected. RESULTS: The extracorporeal circulation technique caused damage to the body; the degree of the damage caused by the circulatory arrest technique may be related to circulating temperature, with the least amount of damage occurring at 20-25 °C compared to 15-20 °C and 25-30 °C. Ischemia and hypoxia can cause intestinal tissue damage, which manifests primarily as a loss of the intestinal mucosal barrier. Ischemic intestinal damage caused by DHCA was not associated with inflammation. CONCLUSION: The study provides new insights into the pathophysiologic mechanisms of DHCA.

Risk factors for venoarterial-extracorporeal membrane oxygenation related nosocomial infection in children after cardiac surgery. / 儿童心脏术后静脉-åŠ¨è„‰ä½“å¤–è†œè‚ºæ°§åˆç›¸å ³åŒ»é™¢å† æ„ŸæŸ“çš„å±é™©å› ç´ .

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is an extracorporeal life support strategy for the treatment of critically ill children with reversible heart and lung failure, increasingly being used in patients with low cardiac output after cardiac surgery. However, the mortality of patients is closely related to the complications of ECMO, especially bleeding, thrombosis, and infection, ECMO-related nosocomial infection has become a challenge to the success of ECMO. This study aims to analyze the incidence and risk factors for venoarterial-ECMO (VA-ECMO)-related nosocomial infections in children after cardiac surgery. METHODS: We retrospectively collected the data of patients who underwent VA-ECMO treatment after pediatric cardiac surgery in the Second Xiangya Hospital of Central South University from July 2015 to March 2021, and divided them into an infected group and a non-infected group. The clinical characteristics of the 2 groups of patients, VA-ECMO-related nosocomial infection factors, pathogenic microorganisms, and patient mortality were compared. Logistic regression was used to analyze the risk factors for nosocomial infection related to VA-ECMO after cardiac surgery. RESULTS: Of the 38 pediatric patients, 18 patients (47.37%) had VA-ECMO related nosocomial infection, served as the infected group, including 7 patients with blood infections and 11 respiratory tract infections. Gram-negative pathogens (16 strains, 88.9%) were the main bacteria, such as Acinetobacter baumannii (6 strains), Klebsiella pneumoniae (3 strains), and Stenotrophomonas maltophilia (3 strains). Compared with the non-infected group (n=20), the infection group had longer time of cardiopulmonary bypass, time of myocardial block, and time of VA-ECMO assistance (All P<0.05). Multivariate logistic regression analysis showed that time of cardiopulmonary bypass (OR=1.012, 95% CI 1.002 to 1.022; P=0.021) was an independent risk factor for ECMO-related nosocomial infection. The number of surviving discharges in the infected group was less than that in the non-infected group (1 vs 11, P<0.05). CONCLUSIONS: Cardiopulmonary bypass time is an independent risk factor for VA-ECMO-related nosocomial infection in children after cardiac surgery. Shortening the duration of extracorporeal circulation may reduce the incidence of VA-EMCO-related nosocomial infections in children after cardic surgery. The occurrence of VA-ECMO-related nosocomial infections affects the number of patient's discharge alive.

Nosocomial Infections During Extracorporeal Membrane Oxygenation in Pediatric Patients: A Multicenter Retrospective Study.

Objective: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients with respiratory and/or cardiac failure. This study aimed to investigate the epidemiology and risk factors of nosocomial infection (NI) in pediatric patients who underwent ECMO for respiratory and/or circulatory failure. Methods: Medical records for patients that were administered underwent ECMO support at Xiangya Second Hospital of Central South University, The Sixth Medical Center of PLA General Hospital, and Children's Hospital Affiliation of Zhengzhou University, from September 2012 to December 2019 were retrospectively reviewed. Clinical data of the patients who developed NI were collected and analyzed. Univariate and multivariate logistic regressions were performed to identify the independent predictive factors of NI during ECMO. Results: A total of 54 first episodes of NI were identified in the 190 patients on ECMO, including 32 cases of respiratory tract infections, 20 cases of bloodstream infections, and 2 cases of surgical site wound infections. Gram-negative pathogens were the dominant pathogens isolated, accounting for 92.6% of the NI. The incidence of ECMO-related NI was 47.6 cases per 1,000 ECMO days. In the univariate logistic regression, ECMO mode, ECMO duration, ICU duration, and peritoneal dialysis were associated with the development of NI in patients with ECMO support. However, in the multivariate analysis, only ECMO duration (OR = 2.46, 95%CI: 1.10, 5.51; P = 0.029), ICU duration (OR = 1.35, 95%CI: 1.05, 1.59; P = 0.017) and peritoneal dialysis (OR = 2.69, 95%CI: 1.08, 5.73; P = 0.031) were the independent predictive factors for NI during ECMO support. Conclusion: This study identified the significant correlation between ECMO-related NI and ECMO duration, ICU duration, and peritoneal dialysis. Appropriate preventive measures are needed for hospitals to reduce the incidence of ECMO in pediatric patients.

Individualized right ventricular outflow tract reconstruction using autologous pulmonary tissue in situ for the treatment of pulmonary atresia with ventricular septum defect.

OBJECTIVE: The study aims to evaluate the feasibility and effectiveness of an individualized procedure for right ventricular outflow tract (RVOT) reconstruction in pulmonary atresia with ventricular septal defect (PA-VSD). METHODS: RVOT was reconstructed using autologous pulmonary artery tissue preserved in situ as the posterior wall and a bovine jugular vein patch (BJVP) as the anterior wall in patients with PA-VSD (observation group). The size of the BJVP made from a bovine jugular vein conduit (BJVC) was individually calculated using a formula based on the child's weight and the size of the autologous pulmonary artery (the diameter of BJVC DB⁢J⁢V⁢C = Dt⁢h⁢e⁢o⁢r⁢e⁢t⁢i⁢c⁢a⁢l-W⁢z^-4π). Its effect was then compared with the conventional modified Rastelli procedure based on the BJVC (control group). RESULTS: A total of 22 patients that underwent the new procedure were simultaneously compared with the 25 patients in the control group. No deaths occurred in both groups. Notably, there were no significant differences in mechanical ventilation, ICU and postoperative residence, cardiopulmonary bypass, and aortic cross-clamp time. In the follow-up, which spanned for 8-12 years (mean 9.2 years), only four cases with moderate regurgitation were noted in the observation group without obstruction. In the control group, two patients had a conduit replacement. Three patients suffered from anastomotic stenosis, which was corrected by balloon dilatation. CONCLUSION: Individualized RVOT reconstruction with autologous pulmonary tissue preserved in situ as the posterior wall is adequate for treating PA-VSD.

Clinical Application of Individualized Pulmonary Bi-Orifice for the Reconstruction of Right Ventricular Outflow Tract in Tetralogy of Fallot.

Objective: The study aims to establish a new method in the Tetralogy of Fallot (ToF) called the pulmonary valve bi-orifice method (pulmonary annular sparing with an individualized autologous pericardial patch; thus, two orifices are formed at the level of the pulmonary valve annulus) to reconstruct the right ventricular outflow tract (RVOT). Methods: A retrospective analysis of 128 TOF patients from October 2009 to June 2018 with severe pulmonary valve dysplasia who underwent transvalvular annular patch (TAP) procedure (control group) or an individualized pulmonary valve bi-orifice procedure (observation group) were studied. The RVOT for each patient in the observation group was individually reconstructed per the patient's weight and the size of the autologous pulmonary valve using the bi-orifice method; however, increasing the cross-sectional area of the pulmonary valve annulus without destroying its integrity. The result was then compared to the control group, where TAP procedures were applied to evaluate the short to mid-term outcome(s). An in vitro simulation test was used to verify the anti-regurgitation mechanism of the new method. Results: The in vitro simulation test indicated that the anti-regurgitation mechanism was completed by the pericardial patch and the autologous pulmonary valve movement toward each other. Thus, for clinical applications, patients in both groups were compared. The results showed no significant differences in cardiopulmonary bypass and aortic cross-clamp time, mechanical ventilation, and ICU and post-operative residence between the two groups. During the follow-up period (3- to 12-years), 14 patients in the observation group had mild regurgitation after surgery (22.2%), while 10 patients had moderate pulmonary regurgitation (15.8%) with no right ventricular (RV) dilation. On the other hand, 22 patients (39.6%) had moderate to severe regurgitation in the control group, while left pulmonary artery stenosis occurred in one patient. In the control group, six patients (9.2%) with severe RV dilation were reoperated. Conclusion: Individualized pulmonary valve bi-orifice procedure is a safe and excellent method for reconstructing RVOT in ToF.

Novel role of PKR in palmitate-induced Sirt1 inactivation and endothelial cell senescence.

Endothelial cell senescence is regarded as a vital characteristic of cardiovascular diseases. Elevated palmitate (PA) is an independent risk factor of cardiovascular diseases, but its role in endothelial cell senescence is currently unknown. During the course of studying the prosenescent role of PA, we discovered a key role of dsRNA-dependent protein kinase [protein kinase R (PKR)] in endothelial senescence. Exposure of human umbilical vein endothelial cells (HUVECs) to PA-induced cell senescence is characterized by increased levels of senescence-associated ß-galactose glucosidase activity, excessive production of reactive oxygen species production, impaired cellular proliferation, and G1 phase arrest. This phenomenon is associated with an increase of PKR autophosphorylation and decreased activity of sirtuin 1 (Sirt1), a pivotal antisenescent factor. PKR inactivation by PKR siRNA or its phosphorylation inhibitor 2-aminopurine significantly attenuated PA-induced HUVEC senescence by reversing Sirt1 activity and its downstream signaling. Moreover, to study the regulatory mechanism between PKR and Sirt1, we found that PKR promotes JNK activation to inhibit Sirt1 activity and that this effect could be reversed by the JNK inhibitor SP600125. These findings provide evidence that PKR mediates PA-induced HUVEC senescence by inhibiting Sirt1 signaling. Our study provides novel insights into the actions and mechanisms of PKR in endothelial senescence. NEW & NOTEWORTHY This study first provides a novel observation that dsRNA-dependent protein kinase (PKR) mediates palmitate-induced sirtuin 1 inactivation and subsequent human umbilical vein endothelial cell senescence. Most importantly, these new findings will provide a potential therapeutic strategy to improve free fatty acid-induced endothelial senescence by targeting PKR in cardiovascular diseases.

Krüppel-like factor 4 promotes c-Met amplification-mediated gefitinib resistance in non-small-cell lung cancer.

Gefitinib has been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met-overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of ß-catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression.