Management of Eisenmenger syndrome by cardiac defect closure combined bilateral lung transplantation with intraoperative venoarterial ECMO support.

BACKGROUND: Optimal surgical treatment for Eisenmenger syndrome in adult congenital heart disease remains in debate. CASE REPORT: We report a case of a 22-year-old female with Eisenmenger syndrome secondary to ventricular septum defect (VSD), who underwent cardiac defect closure combined with bilateral lung transplantation in our center. The patient had an uncorrected peri-membranous VSD and subsequently developed severe pulmonary hypertension. We patched the defect under cardiopulmonary bypass. Then a sequential bilateral lung transplantation was performed with venoarterial extracorporeal membrane oxygenation support. The patient had a good postoperative recovery and remained well at follow-up at 1 year. To conclude, cardiac defect repair combined bilateral lung transplantation may be a feasible option for selected patients with Eisenmenger Syndrome.

Antibiotic-loaded bone cement fixation technique combined with bilateral pectoralis major muscle flaps tension-free management for sternal infection after midline sternotomy.

INTRODUCTION: Deep sternal wound infection (DSWI) after midline sternotomy of cardiac surgery is a challenging complication that affects the outcome of surgery. This study aims to assess the clinical effectiveness of the antibiotic-loaded bone cement fixation technique combined with bilateral pectoralis major muscle flaps tension-free management in the treatment of DSWI. METHODS: We retrospectively analyzed 5 patients with DSWI who underwent antibiotic-loaded bone cement combined with bilateral pectoralis major muscle flaps for chest wall reconstruction after sternotomy for cardiac surgery in a tertiary hospital in China from January 2020 to December 2021. The clinical and follow-up data were retrospectively analyzed. RESULTS: All patients had no perioperative mortalities, no postoperative complications, 100% wound healing, and an average hospital stay length of 24 days. The follow-up periods were from 6 to 35 months (mean 19.6 months). None of the cases showed wound problems after initial reconstruction using antibiotic-loaded bone cement combined with bilateral pectoralis major muscle flaps. CONCLUSIONS: We report our successful treatment of DSWI, using antibiotic-loaded bone cement fixation technique combined with bilateral pectoralis major muscle flaps tension-free management. The clinical and follow-up results are favorable.

Glucocorticoid receptor ß regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of ß-catenin/TCF transcriptional activity.

Astrocytes react to central nervous system (CNS) injury and participate in gliotic responses, imparting negative, as well as positive effects on axonal regeneration. Despite the considerable biochemical and morphological changes astrocytes undergo following insult, and the known influence of steroids on glial activation, details surrounding glucocorticoid receptor expression and activity are lacking. Such mechanistic information is essential for advancing and enhancing therapies in the treatment of CNS injuries. Using an in vitro wound-healing assay, we found glucocorticoid receptor ß (GRß), not GRα, is upregulated and acts as a regulator of gliosis after injury. In addition, our results suggest that GRß interacts with ß-catenin and is a necessary component for proliferation and migration in both injured astrocytes and glioma cells. Further analysis indicated GRß/ß-catenin interaction as a key modulator of astrocyte reactivity through sustained Wnt/ß-catenin/TCF signaling in its dominant-negative effect on GRα mediated trans-repression by a GSK-3ß-independent manner. These findings expand our knowledge of the mechanism of GRß action in promoting astrocyte proliferation and migration following injury and in glioma. This information furthers our understanding the function of glucocorticoid receptor in CNS injury and disease, as well as in the basic biochemical responses astrocytes undergo in response to injury and glioma pathogenesis.

Using antibiotic-loaded bone cement for a patient with deep sternal wound infection after cardiac surgery.

A 67-year-old male presented with sternal dehiscence following open cardiac surgery. Extensive debridement and attempted closure failed, and the wound had since been managed with vacuum-assisted closure therapy, with little progress. We treated him with antibiotic-loaded bone cement to repair the wound defect. After 3 weeks, the wound healed with excellent result. To our knowledge, this is the first report of antibiotic-loaded bone cement for deep sternal wound infection.

The combined application of antibiotic-loaded bone cement and vacuum sealing drainage for sternal reconstruction in the treatment of deep sternal wound infection.

BACKGROUND: Deep sternal wound infection (DSWI) is a rare but serious complication after median sternotomy, and treatment success depends mainly on surgical experience. Traditional treatment methods for DSWI include complete debridement, vacuum sealing drainage wound therapy and sometimes transposition of muscle flap. This study aimed to evaluate the utility of antibiotic-loaded bone cement combined with vacuum sealing drainage on DSWI and explore the effect of this treatment on lung function. METHODS: Between January 2018 and December 2019, we treated 12 patients suffering a mediastinitis and open thorax using antibiotic-loaded bone cement combined with vacuum sealing drainage. Subsequently, the blood and local concentration of antibiotic were measured. The patient characteristics, pulmonary function, were retrospectively analyzed. Subjects were followed up for 12 months. RESULTS: There were no intraoperative deaths. All patients' healing wounds were first-stage healing without complications and reoperation, the mean hospital stay was 20.2 ± 3.5 days. Local vancomycin concentrations largely exceeded the ones needed for their efficacy while little antibiotic was found in the blood. Pulmonary function testing was improved 2 weeks after the operation. No infection reoccurred in12-month follow-up. CONCLUSIONS: The antibiotic-loaded bone cement combined with vacuum sealing drainage might be an effective method for the sternal reconstruction of deep sternal wound infection and it can improve the patient's lung function in a short time.

[Concomitant use of peripheral veno-venous extracorporeal membrane oxygenation (VV-ECMO) and central veno-arterial ECMO during lung transplantation for coronavirus disease 2019 patients].

OBJECTIVE: To summarize the strategy of using extracorporeal membrane oxygenation (ECMO) support during lung transplantation from 2 coronavirus disease 2019 (COVID-19) with end-stage respiratory failure. METHODS: Two COVID-19 with end-stage respiratory failure patients were admitted to Nanjing Medical University Affiliated Wuxi People's Hospital in March 2020. As the homoeostasis and vital signs could not be maintained in balance by conventional treatments, lung transplantations were performed. Here, detail information about combined application of peripheral veno-venous ECMO (VV-ECMO) and central veno-arterial ECMO (CVA-ECMO) during the operation will be discussed. RESULTS: Case 1: 59 years old, 172 cm height, 72 kg weight, who received mechanical ventilation for 22 days, tracheotomy tube for 17 days, and VV-ECMO support for 7 days. Case 2: 72 years old, 178 cm height, 71 kg weight, who received mechanical ventilation for 19 days, tracheotomy tube for 17 days, and VV-ECMO support for 18 days. As both of them have severe COVID-19-associated respiratory failure, and the recovery was determined to be unlikely, lung transplantations were performed. Severe pulmonary arterial hypertension (PAH) and cardiac insufficiency were found during the operation. Based on preoperative VV-ECMO, CVA-ECMO was added. The concomitant use of peripheral VV-ECMO and CVA-ECMO offered satisfied intraoperative oxygenation and cardiopulmonary status,the operations run smoothly, and the CVA-ECMO was successfully removed, no ECMO-related complications occurred. CONCLUSIONS: The combined use of VV-ECMO and CVA-ECMO is an optimal strategy in the end-stage ARDS patients with severe PAH and cardiac insufficiency, which can offer benefits on respiratory and cardiac functions simultaneously, and ensure surgery safety.

Antibiotic-loaded bone cement combined with vacuum sealing drainage to treat deep sternal wound infection following cardiac surgery: the first case report.

BACKGROUND: Deep sternal wound infection (DSWI) is a rare but serious complication after median sternotomy, and treatment success depends mainly on surgical experience. Here we first present a case of a patient successfully treated for antibiotic-loaded bone cement (ALBC) combined with vacuum sealing drainage (VSD) of DSWI. CASE PRESENTATION: This case report presented a patient who underwent open heart surgery, and suffered postoperatively from a DSWI associated with enterococcus cloacae. Focus debridement combined with ALBC filling and VSD was conducted in stage I. Appropriate antibiotics were started according to sensitivity to be continued for 2 weeks until the inflammatory markers decreased to normal. One month after the surgery, patient's wound was almost healed and was discharged from hospital with a drainage tube. Two months after the stage I surgery procedure, the major step was removing the previous ALBC, and extensive debridement in stage II. The patient fully recovered without further surgical treatment. CONCLUSIONS: The results of this case suggest that ALBC combined with VSD may be a viable and safe option for deep sternal wound reconstruction.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis.

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Downregulation of BK channel function and protein expression in coronary arteriolar smooth muscle cells of type 2 diabetic patients.

Aims: Type 2 diabetes (T2D) is strongly associated with cardiovascular morbidity and mortality in patients. Vascular large conductance Ca2+-activated potassium (BK) channels, composed of four pore-forming α subunits (BK-α), and four regulatory ß1 subunits (BK-ß1), are densely expressed in coronary arterial smooth muscle cells (SMCs) and play an important role in regulating vascular tone and myocardial perfusion. However, the role of BK channels in coronary microvascular dysfunction of human subjects with diabetes is unclear. In this study, we examined BK channel function and protein expression, and BK channel-mediated vasodilation in freshly isolated coronary arterioles from T2D patients. Methods and results: Atrial tissues were obtained from 16 patients with T2D and 25 matched non-diabetic subjects during cardiopulmonary bypass procedure. Microvessel videomicroscopy and immunoblot analysis were performed in freshly dissected coronary arterioles and inside-out single BK channel currents was recorded in enzymatically isolated coronary arteriolar SMCs. We found that BK channel sensitivity to physiological Ca2+ concentration and voltage was downregulated in the coronary arteriolar SMCs of diabetic patients, compared with non-diabetic controls. BK channel kinetics analysis revealed that there was significant shortening of the mean open time and prolongation of the mean closed time in diabetic patients, resulting in a remarkable reduction of the channel open probability. Functional studies showed that BK channel activation by dehydrosoyasaponin-1 was diminished and that BK channel-mediated vasodilation in response to shear stress was impaired in diabetic coronary arterioles. Immunoblot experiments confirmed that the protein expressions of BK-α and BK-ß1 subunits were significantly downregulated, but the ratio of BK-α/BK-ß1 was unchanged in the coronary arterioles of T2D patients. Conclusions: Our results demonstrated for the first time that BK channel function and BK channel-mediated vasodilation were abnormal in the coronary microvasculature of diabetic patients, due to decreased protein expression and altered intrinsic properties of BK channels.

A prospective evaluation of apolipoprotein M gene T-778C polymorphism in relation to coronary artery disease in Han Chinese.

OBJECTIVES: Apolipoprotein M (apoM) is important for the formation of pre-beta-high-density lipoprotein (HDL) and cholesterol efflux in macrophages. It is demonstrated that single-nucleotide polymorphism (SNP) T-778C of apoM gene is related to type 2 diabetes in Han Chinese. In the present study, we investigated the possible association of apoM polymorphism in relation to coronary artery disease (CAD) in Han Chinese. DESIGN AND METHODS: This case-controlled study consisted of 118 CAD patients who were diagnosed angiographically to have at least 30% stenosis, and 255 unrelated subjects who were used as control. ApoM gene polymorphism in the proximal promoter region was analyzed by PCR-RFLP and serum lipid levels were also measured. RESULTS: It is indicated that CAD patients had increased frequency of C allele on apoM T-778C compared to the controls (14.8% vs. 6.9%, P=0.0008). Multivariable logistic regression analysis indicated that odds ratios (ORs) for all subjects with apoM CC+CT genotypes and C allele were 1.9 (95% CI=1.1-2.9, P<0.0001) and 1.9 (95% CI=1.3-3.2, P<0.0001), respectively. The plasma total cholesterol (TC) levels were significantly higher in individuals with CC or CT genotype than those with TT genotype in both CAD patients and controls. CONCLUSIONS: The present findings suggest that the C allele at nucleotide -778 in the apoM gene is a risk factor for genetic susceptibility to CAD and is also associated with TC levels in Han Chinese.

Injection of cardiac stem cells prolongs the survival of cardiac allograft rats.

Cardiac c-kit+ cells isolated from cardiac explant-derived cells modestly improve cardiac functions after myocardial infarction; however, their full potential has not yet been realized. The present study was undertaken to determine the isolation and culture of c-kit+ cardiac stem cells (CSCs), and the roles of myocardial injection of CSCs on the survival of rat cardiac allograft. Recipient Sprague-Dawley rats were transplanted with hearts from Wistar rats. In the in vitro experiment, c-kit+ cells were isolated from mouse heart fragment culture by magnetic cell sorting. CSCs expressed of cardiomyocyte specific protein cardiac troponin I, α smooth muscle actin and von Willebrand factor in conditioned culture. CSC injection increased graft survival of cardiac allograft rats. The effects of CSCs on increase in graft survival of cardiac allograft rats were blocked by stromal-derived factor-1 (SDF-1) knockdown. The expression of SDF-1 was increased after CSC injection into the cardiac of cardiac allograft rats. These results indicate that CSC injection into the cardiac prolongs graft survival of cardiac allograft rats. SDF-1 plays an important role in the effects of CSCs on the graft survival of cardiac allograft rats.

Expression pattern of apolipoprotein M during mouse and human embryogenesis.

Apolipoprotein M (apoM) is a recently discovered human apolipoprotein predominantly present in high-density lipoprotein (HDL), and in minor proportions in triglyceride-rich lipoprotein (TGRLP) and low-density lipoprotein (LDL). The gene encoding apoM is present in all mammalian genomes. The identity of the apoM gene of human, rat and mouse is over 80%. However, the (patho)physiological functions of apoM are unknown yet. In the present study, we investigated apoM expression patterns during mouse and human embryogenesis. ApoM transcripts were detectable in mouse embryos from day 7.5 to day 18.5. ApoM was expressed at low levels at day 7.5, its expression increased significantly at day 9.7, decreased at day 10.5, and then increased continually up to day 18.5. ApoM-positive cells appeared mainly in liver of day-12 embryos as detected by in situ hybridization. In day-15 embryos, apoM was expressed in both liver and kidney. During human embryogenesis, apoM was mainly expressed in liver and kidney and little was found in small intestine as determined by mRNA array of human fetal normal tissues. ApoM was also detected in stomach and skeletal muscle in early stages of embryogenesis (3-5 months).

Dysfunctional co-expression network analysis of familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an inherited disorder of blood lipid metabolism characterized by high serum low-density lipoprotein cholesterol levels and premature coronary artery disease. In this study, we used a system biology approach to identify co-expressed gene pairs that were potentially involved in the progression of FH and constructed a conserved co-expression network using these genes. A total of 4232 co-expressed relationships were identified and we verified the significance by random permutation. FH patients showed differences in lipoprotein and cholesterol metabolism in circulating monocytes and lymphocytes compared to healthy controls. We hope our study could aid in understanding of FH and could provide the basis for FH biomarker identification.

Magnolol induces apoptosis via activation of both mitochondrial and death receptor pathways in A375-S2 cells.

Magnolol inhibited proliferation of human malignant melanoma A375-S2 cells. The drug induced oligonucleosomal fragmentation of DNA in A375-S2 cells and increased caspase-3, 8, 9 activities followed by the degradation of caspase-3 substrates, inhibitor of caspase dependent DNase (ICAD) and poly-(ADP-ribose) polymerase (PARP). Pan-caspase inhibitor (z-VADfmk), caspase-3 inhibitor (z-DEVD-fmk), capase-8 inhibitor (z-IETD-fmk), caspase-9 inhibitor (z-LEHD-fmk) and caspase-10 inhibitor (z-AEVD-fmk) inhibited magnolol-induced A375-S2 cell apoptosis. The level of anti-apoptotic mitochondrial protein Bcl-2 was up-regulated while the level of pro-apoptotic protein Bax was down-regulated. Taken together, our results indicate that magnolol induces apoptosis by activation of both mitochondrial and death receptor pathways in A375-S2 cells.

Evaluation of apolipoprotein M as a biomarker of coronary artery disease.

OBJECTIVE: To investigate the possible role of apolipoprotein M (ApoM) in the development of coronary artery disease (CAD). DESIGN AND METHODS: Case-controlled study, which consisted of 118 CAD patients and 255 unrelated subjects used as control group. Plasma concentration of ApoM was determined by dot blot, severity of CAD was expressed with Gensini score or the numbers of lesioned coronary arteries, and serum lipid levels were also measured. RESULTS AND DISCUSSION: Our study shows the mean level of plasma ApoM is 1.3757+/-0.1493 ODu mm(-2) in CAD patients, while it is 1.3502+/-0.1288 ODu mm(-2) in control group, and there are significant differences in plasma level of ApoM between two groups (t=0.032, P<0.05). Concentration of plasma ApoM is positively associated with plasma total cholesterol (r=0.38, P=0.025), high density lipoprotein cholesterol (r=0.29, P=0.03), low density lipoprotein cholesterol (r=0.16, P=0.03) and apolipoproein A-I (r=0.24, P=0.03). Multiple logistic and linear regression analysis showed that plasma concentration of ApoM did not correlate either with the number of lesioned coronaries or the Gensini score after adjusted for conventional cardiovascular risk factors (P>0.05, respectively). CONCLUSION: The findings suggest that ApoM could not be an independent risk factor but a biomarker of CAD.