Vascular endothelial growth factor on Runt-related transcript factor-2 in aortic valve cells.

BACKGROUND: Calcific aortic valve disease is associated with ageing and high mortality. However, no effective pharmacological treatment has been developed. Vascular endothelial growth factor (VEGF) and its receptor are overexpressed in the calcified aortic valve tissue. However, the role of VEGF in calcific aortic valve disease pathogenesis and its underlying mechanisms remain unclear. MATERIALS AND METHODS: Runt-related transcription factor 2 expression and calcium-related signalling were investigated in porcine valvular interstitial cells with or without human VEGF-A recombinant protein (VEGF165 , 1-100 ng/mL) treatment and/or calmodulin-dependent kinase II (CaMKII) inhibitor (KN93, 10 µmol/L) and inositol triphosphate receptor inhibitor (2-aminoethyldiphenyl borate, 30 µmol/L) for 5 days. RESULTS: VEGF165 -treated cells had higher Runt-related transcription factor 2 expression and CaMKII/ adenosine 3',5'-monophosphate response element-binding protein (CREB) signalling activation than did control cells. KN93 reduced Runt-related transcription factor 2 expression and CREB phosphorylation in VEGF165 -treated cells. The 2-aminoethyldiphenyl borate also reduced Runt-related transcription factor 2 expression in VICs treated with VEGF165 . CONCLUSION: VEGF upregulated Runt-related transcription factor 2 expression in VICs by activating the IP3R/CaMKII/CREB signalling pathway.

Toll-like receptor 4 activation modulates pericardium-myocardium interactions in lipopolysaccharide-induced atrial arrhythmogenesis.

AIMS: Inflammation plays a role in the pathogenesis of atrial fibrillation (AF). Pericarditis enhanced atrial arrhythmogenesis, but the role of the pericardium remains unclear in AF. Activation of the toll-like receptor 4 (TLR4) by binding to lipopolysaccharide (LPS) promotes cardiac electrical remodelling. In this study, we hypothesized that pericarditis may induce atrial arrhythmogenesis via pericardium-myocardium interactions by TLR4 signalling. METHODS AND RESULTS: Pericarditis was induced in rabbits by injecting LPS (1-2 mg/kg) into the pericardium. Conventional microelectrodes were used to record the action potentials of left atrial (LA) posterior walls (LAPWs) and LA appendages (LAAs) with and without attached pericardium in the control or pericarditis-induced rabbits. Cytokine array was used to measure the expression levels of proinflammatory cytokines in control and LPS-treated pericardium. Compared with the controls, the LPS-treated pericardium had higher expressions of IL-1α, IL-8, and MIP-1ß. Rapid atrial pacing-induced burst firing in LPS-treated LAPWs and LAAs, and in control LAPWs (but not in LAAs). The incidence of pacing-induced spontaneous activity and burst firing was increased by LPS-treated pericardium but was attenuated by the control pericardium. Moreover, burst firing induced by LPS-treated pericardium was blocked upon administration of the TLR4 inhibitor, TAK-242 (100 ng/mL), ryanodine receptor inhibitor (ryanodine, 3 µM), or calmodulin kinase II inhibitor (KN-93, 1 µM). CONCLUSIONS: Healthy and inflamed pericardium differently modulate LPS-induced atrial arrhythmogenesis. Targeting pericardium via TLR4 signalling may be a novel therapeutic strategy for AF.

Interleukin-33/ST2 axis involvement in atrial remodeling and arrhythmogenesis.

Interleukin (IL)-33, a cytokine involved in immune responses, can activate its receptor, suppression of tumorigenicity 2 (ST2), is elevated during atrial fibrillation (AF). However, the role of IL-33/ST2 signaling in atrial arrhythmia is unclear. This study explored the pathological effects of the IL-33/ST2 axis on atrial remodeling and arrhythmogenesis. Patch clamping, confocal microscopy, and Western blotting were used to analyze the electrical characteristics of and protein activity in atrial myocytes (HL-1) treated with recombinant IL-33 protein and/or ST2-neutralizing antibodies for 48 hrs. Telemetric electrocardiographic recordings, Masson's trichrome staining, and immunohistochemistry staining of the atrium were performed in mice receiving tail vein injections with nonspecific immunoglobulin (control), IL-33, and IL-33 combined with anti-ST2 antibody for 2 weeks. IL-33-treated HL-1 cells had a reduced action potential duration, lower L-type Ca2+ current, greater sarcoplasmic reticulum (SR) Ca2+ content, increased Na+/Ca2+ exchanger (NCX) current, elevation of K+ currents, and increased intracellular calcium transient. IL-33-treated HL-1 myocytes had greater activation of the calcium-calmodulin-dependent protein kinase II (CaMKII)/ryanodine receptor 2 (RyR2) axis and nuclear factor kappa B (NF-κB) / NLR family pyrin domain containing 3 (NLRP3) signaling than did control cells. IL-33 treated cells also had greater expression of Nav1.5, Kv1.5, NCX, and NLRP3 than did control cells. Pretreatment with neutralizing anti-ST2 antibody attenuated IL-33-mediated activation of CaMKII/RyR2 and NF-κB/NLRP3 signaling. IL-33-injected mice had more atrial ectopic beats and increased AF episodes, greater atrial fibrosis, and elevation of NF-κB/NLRP3 signaling than did controls or mice treated with IL-33 combined with anti-ST2 antibody. Thus, IL-33 recombinant protein treatment promotes atrial remodeling through ST2 signaling. Blocking the IL-33/ST2 axis might be an innovative therapeutic approach for patients with atrial arrhythmia and elevated serum IL-33.

Melatonin Inhibits NF-κB/CREB/Runx2 Signaling and Alleviates Aortic Valve Calcification.

Calcific aortic valve disease (CAVD) is linked to high mortality. Melatonin inhibits nuclear factor-kappa B (NF-κB)/cyclic AMP response element-binding protein (CREB), contributing to CAVD progression. This study determined the role of melatonin/MT1/MT2 signaling in valvular interstitial cell (VIC) calcification. Western blotting and Alizarin red staining were used to analyze NF-κB/CREB/runt-related transcription factor 2 (Runx2) signaling in porcine VICs treated with an osteogenic (OST) medium without (control) or with melatonin for 5 days. Chromatin immunoprecipitation (ChIP) assay was used to analyze NF-κB's transcription regulation of NF-κB on the Runx2 promoter. OST medium-treated VICs exhibited a greater expression of NF-κB, CREB, and Runx2 than control VICs. Melatonin treatment downregulated the effects of the OST medium and reduced VIC calcification. The MT1/MT2 antagonist (Luzindole) and MT1 receptor neutralized antibody blocked the anticalcification effect of melatonin, but an MT2-specific inhibitor (4-P-PDOT) did not. Besides, the NF-κB inhibitor (SC75741) reduced OST medium-induced VIC calcification to a similar extent to melatonin at 10 nmol/L. The ChIP assay demonstrated that melatonin attenuated OST media increased NF-κB binding activity to the promoter region of Runx2. Activation of the melatonin/MT1-axis significantly reduced VIC calcification by targeting the NF-κB/CREB/Runx2 pathway. Targeting melatonin/MT1 signaling may be a potential therapeutic strategy for CAVD.

Mechanical or biological heart valve for dialysis-dependent patients? A meta-analysis.

OBJECTIVE: The optimal selection of prosthetic heart valve for dialysis-dependent patients remains controversial. We investigated the comparative effectiveness and safety of mechanical prosthesis (MP) and bioprosthesis (BP) for these patients. METHODS: After the systematic review, we included studies that involved patients on dialysis undergoing aortic valve replacement or mitral valve replacement (MVR) and reported comparative outcomes of MP and BP. Meta-analysis was performed using random-effects model. We conducted a subgroup analysis based on the valve position and postoperative international normalized ratio (INR), which was extracted from either tables or methods of each study. A meta-regression was used to examine the effects of study-level covariates. RESULTS: We included 24 retrospective studies without randomized-controlled trials, involving 10,164 participants (MP = 6934, BP = 3230). Patients undergoing aortic valve replacement with MP exhibited a better long-term survival effectiveness (hazard ratio, 0.64; 95% confidence interval [CI], 0.47-0.86). Conversely, studies including MVR demonstrated little difference in survival (hazard ratio, 0.90; 95% CI, 0.73-1.12). A meta-regression revealed that age had little effect on long-term survival difference between MP and BP (ß = -0.0135, P = .433). MP had a significantly greater bleeding risk than did BP when INR was above 2.5 (incidence rate ratio, 10.58; 95% CI, 2.02-55.41). However, when INR was below 2.5, bleeding events were comparable (incidence rate ratio, 1.73; 95% CI, 0.78-3.82). The structural valve deterioration rate was significantly lower in MP (risk ratio, 0.24; 95% CI, 0.14-0.44). CONCLUSIONS: MP is a reasonable choice for dialysis-dependent patients without additional thromboembolic risk requiring aortic valve replacement, for its better long-term survival, durability, and noninferior bleeding risk compared with BP. Conversely, BP might be an appropriate selection for patients with MVR, given its similar survival rate and lower bleeding risk. Although our meta-regression demonstrates little influence of age on long-term survival difference between MP and BP, further studies stratifying patients based on age cut-off are mandatory.

Association between sleep disorder and atrial fibrillation: A nationwide population-based cohort study.

OBJECTIVES: Sleep disorder (SD), especially sleep apnea, and its effect on atrial fibrillation (AF) are gathering attention. However, other SDs may also play an essential role in AF. The aim of the study is to investigate the effects of other SDs on the risk of atrial fibrillation development. METHODS: This study investigated the risk of AF in people diagnosed with SD compared with that in age and sex-matched unaffected individuals. This longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) of individuals diagnosed with SD from January 1, 2001, to December 31, 2012. RESULTS: The sample consisted of 193,288 people with the SD, which include of 4406 people with sleep apnea, 73,704 people with insomnia, 107,395 people with sleep disturbance, 7,783 people with other SD, and 193,288 matched controls. A Cox proportional hazard regression was used to compute the risk of AF in people with SD and subgroup of SD, relative to that in people without SD. The AF incidences were 1.21-fold higher (95% CI 1.15-1.27) in the SD cohort, 1.19-fold higher (95% CI 0.91-1.56) in the sleep apnea cohort, 1.26-fold higher (95% CI 1.19-1.34) in the insomnia cohort, 1.15-fold higher (95% CI 1.08-1.22) in the sleep disturbance cohort, and 1.30-fold higher (95% CI 1.11-1.53) in other SDs, than in the control cohort, after age, sex, and comorbidities were adjusted. CONCLUSIONS: This nationwide population-based cohort study indicates a strong relationship between SD and incident AF, and insomnia has a higher impact on AF compared with other SD.

Galectin-3 enhances atrial remodelling and arrhythmogenesis through CD98 signalling.

AIM: Galectin-3 (Gal-3) is a biomarker of atrial fibrillation (AF) that mediates atrial inflammation. CD98 is the membrane surface receptor for Gal-3. Nevertheless, the role of the Gal-3/CD98 axis in atrial arrhythmogenesis is unclear. In this study, we investigated the effects of Gal-3/CD98 signalling on atrial pathogenesis. METHODS: Whole cell patch clamp and western blotting were used to analyse calcium/potassium homeostasis and calcium-related signalling in Gal-3-administrated HL-1 atrial cardiomyocytes with/without CD98 neutralized antibodies. Telemetry electrocardiographic recording, Masson's trichrome staining and immunohistochemistry staining of atrium were obtained from mice having received tail-vein injections with Gal-3. RESULTS: Gal-3-treated HL-1 myocytes had a shorter action potential duration, smaller L-type calcium current, increased sarcoplasmic reticulum (SR) calcium content, Na+ /Ca2+ exchanger (NCX) current, transient outward potassium current, and ultrarapid delayed rectifier potassium current than control cells had. Gal-3-treated HL-1 myocytes had greater levels of SR Ca2+ ATPase, NCX, Nav1.5, and NLR family pyrin domain containing 3 (NLRP3) expression and increased calcium/calmodulin-dependent protein kinase II (CaMKII), ryanodine receptor 2 (RyR2), and nuclear factor kappa B (NF-κB) phosphorylation than control cells had. Gal-3-mediated activation of CaMKII/RyR2 pathway was diminished in the cotreatment of anti-CD98 antibodies. Mice that were injected with Gal-3 had more atrial ectopic beats, increased atrial fibrosis, and activated NF-κB/NLRP3 signalling than did control mice (nonspecific immunoglobulin) or mice treated with Gal-3 and anti-CD98 antibodies. CONCLUSION: Gal-3 recombinant protein administration increases atrial fibrosis and arrhythmogenesis through CD98 signalling. Targeting Gal-3/CD98 axis might be a novel therapeutic strategy for patients with AF and high Gal-3 levels.

The Prediction Model of Medical Expenditure Appling Machine Learning Algorithm in CABG Patients.

Most patients face expensive healthcare management after coronary artery bypass grafting (CABG) surgery, which brings a substantial financial burden to the government. The National Health Insurance Research Database (NHIRD) is a complete database containing over 99% of individuals' medical information in Taiwan. Our research used the latest data that selected patients who accepted their first CABG surgery between January 2014 and December 2017 (n = 12,945) to predict which factors will affect medical expenses, and built the prediction model using different machine learning algorithms. After analysis, our result showed that the surgical expenditure (X4) and 1-year medical expenditure before the CABG operation (X14), and the number of hemodialysis (X15), were the key factors affecting the 1-year medical expenses of CABG patients after discharge. Furthermore, the XGBoost and SVR methods are both the best predictive models. Thus, our research suggests enhancing the healthcare management for patients with kidney-related diseases to avoid costly complications. We provide helpful information for medical management, which may decrease health insurance burdens in the future.

Machine-Learning Techniques for Feature Selection and Prediction of Mortality in Elderly CABG Patients.

Coronary artery bypass surgery grafting (CABG) is a commonly efficient treatment for coronary artery disease patients. Even if we know the underlying disease, and advancing age is related to survival, there is no research using the one year before surgery and operation-associated factors as predicting elements. This research used different machine-learning methods to select the features and predict older adults' survival (more than 65 years old). This nationwide population-based cohort study used the National Health Insurance Research Database (NHIRD), the largest and most complete dataset in Taiwan. We extracted the data of older patients who had received their first CABG surgery criteria between January 2008 and December 2009 (n = 3728), and we used five different machine-learning methods to select the features and predict survival rates. The results show that, without variable selection, XGBoost had the best predictive ability. Upon selecting XGBoost and adding the CHA2DS score, acute pancreatitis, and acute kidney failure for further predictive analysis, MARS had the best prediction performance, and it only needed 10 variables. This study's advantages are that it is innovative and useful for clinical decision making, and machine learning could achieve better prediction with fewer variables. If we could predict patients' survival risk before a CABG operation, early prevention and disease management would be possible.

Evolution of pulmonary valve reconstruction with focused review of expanded polytetrafluoroethylene handmade valves.

OBJECTIVES: Many surgeons develop unique techniques for unmet needs for right ventricular outflow reconstruction to resolve pulmonary regurgitation after corrective surgery for congenital heart diseases. Expanded polytetrafluoroethylene (ePTFE) stands out as a reliable synthetic material, and clinical results with handmade ePTFE valves have been promising. This review focuses on the historical evolution of the use of ePTFE in pulmonary valve replacement and in the techniques for pioneering the translation of the handmade ePTFE trileaflet design for the transcatheter approach. METHODS: We searched for and reviewed publications from 1990 to 2020 in the Pubmed database. Nineteen clinical studies from 2005 to 2019 that focused on ePTFE-based valves were summarized. The evolution of the ePTFE-based valve over 3 decades and recent relevant in vitro studies were investigated. RESULTS: The average freedom from reintervention or surgery in the recorded ePTFE-based valve population was 90.2% at 5 years, and the survival rate was 96.7% at 3 years. CONCLUSIONS: Non-inferior clinical results of this ePTFE handmade valve were revealed compared to allograft or xenograft options for pulmonary valve replacement. Future investigations on transferring ePTFE trileaflet design to transcatheter devices should be considered.

Sugar Fructose Triggers Gut Dysbiosis and Metabolic Inflammation with Cardiac Arrhythmogenesis.

Fructose is a main dietary sugar involved in the excess sugar intake-mediated progression of cardiovascular diseases and cardiac arrhythmias. Chronic intake of fructose has been the focus on the possible contributor to the metabolic diseases and cardiac inflammation. Recently, the small intestine was identified to be a major organ in fructose metabolism. The overconsumption of fructose induces dysbiosis of the gut microbiota, which, in turn, increases intestinal permeability and activates host inflammation. Endotoxins and metabolites of the gut microbiota, such as lipopolysaccharide, trimethylamine N-oxide, and short-chain fatty acids, also influence the host inflammation and cardiac biofunctions. Thus, high-fructose diets cause heart-gut axis disorders that promote cardiac arrhythmia. Understanding how gut microbiota dysbiosis-mediated inflammation influences the pathogenesis of cardiac arrhythmia may provide mechanisms for cardiac arrhythmogenesis. This narrative review updates our current understanding of the roles of excessive intake of fructose on the heart-gut axis and proposes potential strategies for inflammation-associated cardiac vascular diseases.

Hydrogen Sulfide Attenuates Aortic Remodeling in Aortic Dissection Associating with Moderated Inflammation and Oxidative Stress through a NO-Dependent Pathway.

Aortic dissection (AD) is a highly lethal vascular disease characterized by separation of the constituent layers of the aortic wall. An increasing body of research indicates that inflammatory response and oxidative stress are implicated in vascular remodeling, which plays a key role in the development of AD. Hydrogen sulfide (H2S) has been found to protect against various types of cardiovascular disease, including myocardial infarction, arthrosclerosis, and hypertension. However, research on the effect of H2S on AD is insufficient. This study therefore elucidated the effect of H2S on the development and progression of AD, and the potential mechanism involved. Using ß-aminopropionitrile fumarate (BAPN) and angiotensin II (Ang-II)-induced AD animal models, the administration of NaHS (as H2S donor, 56 µmol/kg body weight/day) was found to retard the development of AD. Murine VSMCs (Movas) exposed to interleukin-6 (IL-6) (20 ng/mL) to induce phenotypic switch. Histological analyses indicated that H2S administration inhibited the accumulation of inflammatory cells in the aortic wall and the related expression of inflammatory genes. Additionally, H2S treatment elevated aortic superoxide dismutase (SOD) activity and ablated malonaldehyde (MDA) and nitric oxide (NO) levels. In mechanistic terms, H2S attenuated IL-6 induced a pathological VSMC phenotypical switch through NO modulation by N(G)-monomethyl-L-arginine acetate salt (L-NMMA) stimulation. H2S inhibits AD formation by decreasing the inflammatory response, and oxidative stress, and by positively participating in vascular remodeling. These findings suggest a role for H2S as a novel and promising therapeutic strategy to prevent AD development.

Tetrandrine increased the survival rate of mice with lipopolysaccharide-induced endotoxemia.

BACKGROUND: Endotoxemia usually causes significant morbidity and mortality, and treatment of endotoxemia is often ineffective. The effects of tetrandrine (a bisbenzylisoquinoline alkaloid) on lipopolysaccharide (LPS)-induced endotoxemia were investigated in mice. METHODS: The peritoneal macrophages were stimulated with LPS and treated with or without tetrandrine. The amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 secreted by peritoneal macrophages were measured by enzyme-linked immunosorbent assay. Mice were intraperitoneally injected with LPS to induce endotoxemia and were treated or not treated with oral gavage with 150 mg/kg tetrandrine 1 hour before or after LPS injection. The survival rate of the mice was determined after they were treated with various regiments. The amounts of TNF-alpha, IL-1beta, IL-6, and IL-10 in the serum of the mice were measured by enzyme-linked immunosorbent assay, and the high mobility group box 1 (HMGB1) concentration was studied by Western blot analysis. RESULTS: Tetrandrine suppressed the LPS-induced increase of TNF-alpha, IL-1beta, and HMGB1 secretion by peritoneal macrophages but did not affect the IL-6 and IL-10 concentrations. The animals treated with tetrandrine either 1 hour before or after LPS injection had a 100% survival rate, which was significantly higher than that of the control group (40%) (p = 0.005). The LPS-induced increase in serum TNF-alpha, IL-1beta, and HMGB1 concentrations was reduced by tetrandrine treatment administered either 1 hour before or after LPS injection (p < 0.0001). In contrast, tetrandrine prolonged the LPS-induced elevation in serum IL-10 concentrations only mildly changed the serum IL-6 concentrations. CONCLUSIONS: Tetrandrine treatment either 1 hour before or 1 hour after LPS injection reduced the mortality rate of the mice with LPS-induced endotoxemia. The effects of tetrandrine on LPS-induced endotoxemia might be related to the suppression of TNF-alpha, IL-1beta, and HMGB1 concentrations.

HDAC I inhibitor regulates RUNX2 transactivation through canonical and non-canonical Wnt signaling in aortic valvular interstitial cells.

OBJECTIVES: The cellular mechanisms of calcific aortic valve (AV) disease and optimal medications for its treatment are poorly elucidated. Glycogen synthase kinase (GSK)-3ß and non-canonical wingless-related integration site (Wnt) signaling play crucial roles in regulating the pathogenesis of valvular interstitial cell (VIC) calcification. Histone acetylation was found to regulate VIC calcification. However, whether histone deacetylases (HDACs) modulate the pathophysiology of AV calcification is unclear. Different HDAC isoforms have dissimilar cardiovascular effects. We hypothesized that distinctive HDAC inhibitors modulate runt-related transcription factor 2 (RUNX2) in aortic VICs through the regulation of Wnt signaling. METHODS: Western blotting, real-time polymerase chain reaction, and proliferation assay were used to analyze osteogenesis marker expression, Wnt signaling, bone morphogenetic protein (BMP) signaling, and proliferation in porcine VICs treated with osteogenic (OST) medium alone or in combination with HDAC inhibitors. RESULTS: VICs treated with OST medium for 5 days exhibited higher RUNX2 and GSK-3ß expression levels than did control cells. A class I HDAC inhibitor (MS-275 at 1 µM) reduced the RUNX2 mRNA and protein expression levels and alkaline phosphatase activity and downregulated non-canonical Wnt/GSK-3ß signaling, canonical Wnt/ß-catenin signaling, and BMP signaling. By contrast, a combined class IIa (MC1568) and IIb HDAC (tubacin) inhibitor (0.1 µM) increased RUNX2 expression. MS-275, MC1568, and tubacin reduced VIC proliferation; however, the extent of reduction differed. MS-275 reduced RUNX2 and osteocalcin expression in VICs treated with OST medium for an extended period (14 days). CONCLUSIONS: MS-275 critically regulates RUNX2 transactivation in VICs through both canonical and non-canonical Wnt signaling pathways.

Histone deacetylase inhibition attenuates atrial arrhythmogenesis in sterile pericarditis.

Cardiac surgery is complicated with atrial fibrillation (AF). Histone deacetylase (HDAC) inhibition reduces AF occurrence. In pericarditis, HDAC inhibition may modulate AF trigger and substrate. We recorded electrocardiograms in control and pericardiotomic (op) rabbits without and with an intraperitoneal injection of MPT0E014 (HDAC inhibitor). Conventional microelectrodes recorded action potentials (APs) in pulmonary veins (PVs), the right and left atrium (LA). Masson's trichrome was used to identify collagen fibers in PVs and the LA. Electrocardiograms showed frequent atrial premature contractions in op rabbits, but not in the other 3 groups. The beating rates in PVs and opPVs were decreased by MPT0E014 treatment. Spontaneous burst firings occurred in opPVs (36.4%), but not in control PVs. H2O2 induced greater burst firings in opPVs (72.7%) than in control PVs (11.1%), MPT0E014-treated PVs (16.7%), and MPT0E014-treated opPVs (12.5%). The AP duration at a repolarization extent of 90% (APD90) was shorter in the opLA than that in the control LA. In the presence of isoproterenol (1 µM), rapid atrial pacing (RAP, 20 Hz) induced a higher incidence of burst firings in the opLA (90%) than in the other groups. In contrast, acetylcholine (5 mM) and RAP induced a lower incidence of burst firing in the MPT0E014-treated LA (33.3%) than in the other groups. Fibrosis prevailed in opPVs and the opLA compared to the respective control PVs and LA, which was attenuated in those that received MPT0E014. In conclusion, a pericardiotomy increased fibrosis and arrhythmogenesis in PVs and the LA, which were prevented by HDAC inhibition.

Spiral saphenous vein graft for portal vein reconstruction in pancreatic cancer surgery.

The curative strategy for most pancreatic cancer is surgical resection. Extensive resection with lymph node dissection is the key to providing long-term survival. However, early diagnosis of pancreatic cancer is not always possible (ie, resectability is limited). One reason for such a nonresectable condition is vascular invasion or encasement. Portal vein involvement has been a contraindication for pancreatic cancer surgery for most general surgeons. Combining oncologic and vascular surgeons in the procedure has been a good solution. A multidisciplinary approach that includes general and vascular surgeons is appropriate in selected patients requiring vascular reconstruction at the time of pancreatectomy. The objective of this paper is to report a case in which spiral saphenous vein was used for portal vein reconstruction during pancreatic cancer resection.

Activated p300 acetyltransferase activity modulates aortic valvular calcification with osteogenic transdifferentiation and downregulation of Klotho.

BACKGROUND: The calcific aortic valve (AV) disease is a common disease with the unclear mechanism, and optimal pharmacological treatment remains unavailable. Epigenetic modulation by histone acetyltransferase (HAT) plays a critical role in osteogenic transdifferentiation and atherosclerosis. The purposes of this study were to investigate whether HAT contributes to the pathophysiology of AV calcification and assess the therapeutic potential of HAT inhibition. METHODS: Porcine valvular interstitial cells (VICs) were treated with osteogenic medium (10ng/mL of tumor necrosis factor-α and 4mmol/L of high phosphate) for 7days. We analyzed the RNA and protein expression of myofibroblastic (α-SMA, vimentin, collagen 1A1, collagen 3, Egr-1, MMP2, MMP9) and osteoblastic markers (osteocalcin and alkaline phosphatase) in VICs, and studied the effects of a p300 inhibitor (C646, 10µmol/L) on calcification (Alizarin Red S staining), osteogenesis, HAT activity, the mitogen-activated protein kinase (MAPK) and Akt pathway, and Klotho expression on VICs. RESULTS: Osteogenic medium treated VICs had higher expressions of osteocalcin, alkaline phosphatase and acetylated lysine-9 of histone H3 (ac-H3K9) than control cells. C646 attenuated osteogenesis of VICs with simultaneous inhibition of the HAT activity of p300. There was neither significant increase of p300 protein nor p300 transcript during the osteogenesis process. Additionally, osteogenic medium treated VICs decreased the expression of Klotho, which is attenuated by C646. CONCLUSIONS: Activated HAT activity of p300 modulates AV calcification through osteogenic transdifferentiation of VICs with Klotho modulation. P300 inhibition is a potential therapeutic target for AV calcification.

Surgical resection of primary cardiac lymphoma.

Primary cardiac lymphoma is a rare cardiac malignancy. Surgical resection is rarely performed on this disease entity. We report a case of primary cardiac lymphoma with rapid progression. Debulking surgery was done extensively before final pathology was obtained. Complete remission was exhibited after several courses of chemotherapy.

Less invasive mitral valve surgery via right minithoracotomy.

BACKGROUND/PURPOSE: Current trends in cardiac surgical intervention are moving toward less invasiveness, with smaller wound or sternum-sparing, less pump time or off-pump, and beating rather than arrested heart. Data on the efficacy and safety of these newer less invasive techniques, as well as their cosmetic results, are limited. This study analyzed the results of a sternum-sparing mitral valve operation. METHODS: Thirty patients with mitral valve diseases, including 20 who underwent mitral valve repair and 10 mitral valve replacement, were enrolled. Cardiopulmonary bypass was established via femoral cannulation, and blood cardioplegic arrest was induced by using a percutaneous, transthoracic cross-clamp. The main surgical wound was made over the lateral border of the right breast. Two additional small wounds were required for the transthoracic aortic clamp and the mitral retractor. RESULTS: There was no operative mortality, and all patients had an uneventful recovery. Two patients underwent redo mitral surgery. Nine associated procedures were performed including tricuspid valve annuloplasty in six patients, tricuspid valve replacement in two patients and atrial septal defect repair in one patient. The length of the main wound was between 5.8 and 7.8 cm (mean, 7.1 cm). The mean cardiopulmonary bypass time and cross-clamp time were 91.1 and 43.7 minutes, respectively. Although the length of stay was not significantly reduced compared with traditional median sternotomy, all patients had satisfactory results with good cosmesis. CONCLUSION: Sternum-sparing mitral valve surgery appears to be a safe and effective alternative to conventional mitral valve surgery; it is less invasive and provides superior cosmetic results for patients.

Endoscopic radial artery harvest for coronary artery bypass surgery.

BACKGROUND/PURPOSE: Coronary artery bypass grafting (CABG) provides better long-term patency than percutaneous intervention in patients with significant coronary artery disease. The radial artery is the second most common arterial conduit used for CABG in Western countries. However, radial artery harvesting necessitates a large surgical wound and has gained few patients' acceptance in subtropical areas. This study investigated the use of the minimally invasive approach of endoscopic radial artery harvest for CABG, and the surgical results at the harvest site. METHODS: An endoscopic harvest program for radial arteries was implemented in this hospital in September 2003. During the first 12 months of the program until September 2004, 122 patients underwent the procedure. Preoperative evaluation included Allen's test and the modified palmar arch perfusion test. The age of patients ranged from 32 to 88 years old. Patients were excluded from participation if they had undergone recent transradial catheterization, had end-stage renal disease or documented peripheral artery occlusive disease. The VasoView system was utilized for the procedure. Details of the surgical techniques used were recorded and analyzed. RESULTS: Using the endoscopic technique, 122 radial arteries were harvested successfully. The mean resting length of the harvested radial artery was 15.7 cm. No obvious arterial injury was visually confirmed. All radial arteries were used for CABG, except for two which were noted to have atherosclerotic plaques causing stenoses. Forty-seven patients presented with mild numbness over the dorsum of the thumb base, which improved significantly during the 3-month follow-up. No arterial insufficiency in the forearms or hands was noted. CONCLUSION: Endoscopic harvest of the radial artery is technically demanding, but excellent results can be achieved. The endoscopic approach can provide suitable conduits in a less invasive way than the open harvest technique.