Radiofrequency ablation for the treatment of great saphenous venous insufficiency using a newly developed VENISTAR catheter: A preliminary study.

OBJECTIVES: This study was aimed to assess the preliminary outcomes of radiofrequency ablation (RFA) using a newly developed catheter (VENISTAR) for the treatment of incompetent great saphenous veins (GSVs). METHODS: In this prospective observational study, endovenous RFA using a VENISTAR catheter was performed on 16 saphenous veins in 12 patients between August and November 2019. Patients' pre- and post-procedural data were recorded. Doppler ultrasound imaging and clinical evaluation were performed at 1 week and 1, 3, and 6 months to determine the efficacy and safety of the treatment. RESULTS: Technical success and complete closure of the targeted GSVs immediately after the procedure were observed in all 16 limbs (100%). However, one patient (one limb) was found to have partial occlusion without significant reflux after 1 week of follow-up. Kaplan-Meier analysis yielded a complete occlusion rate of 93% at 6 months of follow-up. The Venous Clinical Severity Scores at the time of all follow-up were significantly lower than those at baseline (3.3 ± 1.1 at baseline to 0.6 ± 0.6, 0.3 ± 0.6, 0.1 ± 0.4, and 0.2 ± 0.4 at 1 week and 1, 3, and 6 months, respectively) (p < .001). Mild post-procedural pain was noted in 7 and 4 limbs at 1 week and 1 month, respectively. Grade 1 ecchymosis over the ablated segment was noted in 5 (35.7%) of 14 limbs at 1-week follow-up. CONCLUSIONS: Endovenous treatment of GSV insufficiency using a new VENISTAR radiofrequency catheter has been shown to be feasible, effective, and safe throughout the 6-month follow-up.

Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms.

Porcine heart xenotransplantation is a potential treatment for patients with end-stage heart failure. To understand molecular mechanisms of graft rejection after heart transplantation, we transplanted a 31-day-old alpha-1,3-galactosyltransferase knockout (GTKO) porcine heart to a five-year-old cynomolgus monkey. Histological and transcriptome analyses were conducted on xenografted cardiac tissue at rejection (nine days after transplantation). The recipient monkey's blood parameters were analyzed on days -7, -3, 1, 4, and 7. Validation was conducted by quantitative real-time PCR (qPCR) with selected genes. A non-transplanted GTKO porcine heart from an age-matched litter was used as a control. The recipient monkey showed systemic inflammatory responses, and the rejected cardiac graft indicated myocardial infarction and cardiac fibrosis. The transplanted heart exhibited a total of 3748 differentially expressed genes compared to the non-transplanted heart transcriptome, with 2443 upregulated and 1305 downregulated genes. Key biological pathways involved at the terminal stage of graft rejection were cardiomyopathies, extracellular interactions, and ion channel activities. The results of qPCR evaluation were in agreement with the transcriptome data. Transcriptome analysis of porcine cardiac tissue at graft rejection reveals dysregulation of the key molecules and signaling pathways, which play relevant roles on structural and functional integrities of the heart.

Association between aortic valvular calcification and characteristics of the aortic valve in patients with bicuspid aortic valve stenosis.

BACKGROUND: Aortic valve calcification quantification using cardiac computed tomography (CCT) is a reliable marker for aortic stenosis (AS) in patients with bicuspid aortic valve (BAV) disease. PURPOSE: To determine the association of Agatston aortic valve calcium score (AVCS) with morphological and hemodynamic characteristics of BAV and define cut-off AVCS for optimizing the grade of AS in patients with bicuspid AS. MATERIAL AND METHODS: This study included 161 BAV patients with AS regardless of aortic regurgitation who underwent transthoracic echocardiography and CCT. BAVs were classified according to orientation of cusps and presence of raphe. Associations of AVCS with characteristics of BAV morphology and functional variables were determined by linear regression analysis. Area under the receiver operating characteristic curve (AUC) was used to determine the cut-off AVCS greater than which the diagnosis of severe AS was optimized. RESULTS: AVCS was significantly different according to sex ( P < 0.001), AS severity ( P < 0.001), type of valvular dysfunction ( P = 0.011), and orientation of cusps ( P = 0.028). Multiple linear regression showed that AVCS was significantly associated with sex (estimate = -0.583, P < 0.001) and AS severity (estimate = 0.817, P < 0.001). AVCS was a predictor for severe AS with AUC of 0.80 in both women ( P = 0.002) and men ( P < 0.001). Its cut-off value was 1423 Agatston unit (AU) in women and 2573 AU in men. CONCLUSIONS: In patients with bicuspid AS, AVCS was significantly higher in men and those with severe AS. However, AVCS was not significantly associated with morphological characteristics of BAV or the type of valvular dysfunction.

Molecular immunology profiles of monkeys following xenografting with the islets and heart of α-1,3-galactosyltransferase knockout pigs.

Effective immunosuppression strategies and genetically modified animals have been used to prevent hyperacute and acute xenograft rejection; however, the underlying mechanisms remain unknown. In this study, we evaluated the expression of a comprehensive set of immune system-related genes (89 genes, including five housekeeping genes) in the blood of cynomolgus monkeys (~5 yr old) used as graft recipients, before and after the xenografting of the islets and heart from single and double α-1,3-galactosyltransferase (GalT) knockout (KO) pigs (<6 weeks old). The immunosuppressive regimen included administration of cobra venom factor, anti-thymocyte globulin, rituximab, and anti-CD154 monoclonal antibodies to recipients before and after grafting. Islets were xenografted into the portal vein in type 1 diabetic monkeys, and the heart was xenografted by heterotopic abdominal heart transplantation. Genes from recipient blood were analyzed using RT(2) profiler PCR arrays and the web-based RT(2) profiler PCR array software v.3.5. Recipients treated with immunosuppressive agents without grafting showed significant downregulation of CCL5, CCR4, CCR6, CD4, CD40LG, CXCR3, FASLG, CXCR3, FOXP3, GATA3, IGNG, L10, IL23A, TRAF6, MAPK8, MIF, STAT4, TBX21, TLR3, TLR7, and TYK2 and upregulation of IFNGR1; thus, genes involved in protection against viral and bacterial infection were downregulated, confirming the risk of infection. Notably, C3-level control resulted in xenograft failure within 2 days because of a 7- to 11-fold increase in all xenotransplanted models. Islet grafting using single GalT-KO pigs resulted in upregulation of CXCL10 and MX1, early inflammation, and acute rejection-associated signals at 2 days after xenografting. We observed at least 5-fold upregulation in recipients transplanted with islets grafts from single (MX1) or double (C3, CCR8, IL6, IL13, IRF6, CXCL10, and MX1) GalT-KO pigs after 77 days; single GalT-KO incurred early losses owing to immune attacks. Our results suggest that this novel, simple, non-invasive, and time-efficient procedure (requiring only 1.5 ml blood) for evaluating graft success, minimizing immune rejection, and blocking infection.

Mid-term results for a patch valvuloplasty technique to correct posterior leaflet prolapse.

BACKGROUND AND AIM OF THE STUDY: Most valve repair techniques require resection and multiple sutures. In the present study, a novel technique without resection for correction of posterior leaflet prolapse due to chordal elongation or rupture was employed, the aim being to evaluate the outcomes of a non-resecting valve repair technique in patients with posterior leaflet prolapse that caused significant mitral regurgitation (MR). METHODS: Between May 2008 and December 2010, a total of 90 consecutive patients with posterior leaflet prolapse (55 males, 35 females; mean age 51.5 ± 14.6 years) underwent patch valvuloplasty. The procedure involved suturing the free margin of the prolapsed leaflet, invagination of the folded leaflet tissue into the left ventricular side, coverage of the dimpled portion with a round bovine pericardial patch using a continuous suture technique, and reshaping of the posterior annulus using a 53- to 61-mm strip. All patients underwent postoperative echocardiography after a mean follow up of 41.9 ± 10.4 months. RESULTS: No early death occurred, but there was one late death due to a non-cardiac cause. At the last echocardiographic follow up, 81 patients (90%) showed none or trace MR, seven (7.8%) had mild MR, and two (2.2%) moderate MR. The mean mitral valve area was 2.4 ± 0.5 cm2 and the mean pressure gradient 2.8 ± 1.2 mmHg. No patient required reoperation due to recurrent or aggravated MR. CONCLUSION: In patients with posterior leaflet prolapse, the applied patch valvuloplasty technique was useful and reliable, showing excellent clinical and echocardiographic outcomes. Additional long-term evaluations with close follow up should be performed.

Pathological Substratum for a Case of Fulminant Myocarditis Treated with Extracorporeal Membrane Oxygenation and Subsequent Heart Transplantation.

Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 23-yr-old woman with pathology-proven fulminant lymphocytic myocarditis presenting shock with elevated cardiac troponin I and ST segments in V1-2, following sustained ventricular tachycardia and a complete atrioventricular block. About 55 min of intensive cardio-pulmonary resuscitation, with extracorporeal membrane oxygenation support, bridged the patient to orthotopic heart transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls. Aggressive mechanical circulatory support may be an essential bridge for recovery or even transplantation in patients with fulminant myocarditis with shock.

The 1,470-nm bare-fiber diode laser ablation of the great saphenous vein and small saphenous vein at 1-year follow-up using 8-12 W and a mean linear endovenous energy density of 72 J/cm.

PURPOSE: To demonstrate 1-year outcomes after low-energy endovenous laser ablation (EVLA) of incompetent saphenous veins with linear endovenous energy density (LEED) of 80 J/cm or lower with the use of a 1,470-nm diode laser. MATERIALS AND METHODS: Incompetent saphenous veins in 236 patients (355 limbs; Clinical/Etiology/Anatomy/Pathophysiology classifications of C2-C4) were treated by EVLA with a bare-tipped 1,470-nm laser with LEED no greater than 80 J/cm (mean, 72.4 J/cm) and laser power of 8-12 W. Patients were evaluated clinically and with duplex ultrasonography at 1 week and 1, 3, 6, and 12 months after EVLA to assess the technical and clinical success and complication rates. RESULTS: In the 355 limbs, the technical success rate was 100%. The great saphenous vein (GSV) remained occluded in all 229 limbs (100%) after 1 week, 202 of 203 limbs (99.5%) after 1 month, 157 of 158 limbs after 3 months (99.3%), all 99 limbs after 6 months (100%), and all 41 limbs after 1 year (100%). The small saphenous vein (SSV) remained occluded in all 103 limbs (100%) after 1 week, all 94 limbs (100%) after 1 month, 68 of 69 limbs (98.5%) after 3 months, 40 of 41 limbs (97.5%) after 6 months, and all 14 limbs after 1 year (100%). Two GSVs and two SSVs were recanalized and underwent repeated EVLA. No major complications occurred, although bruising (21% of cases), pain (15%), and paresthesia (4%) were observed. CONCLUSIONS: Low-energy EVLA with the use of a 1,470-nm laser with LEED of 80 J/cm or lower is an effective, safe, and technically successful option for the treatment of incompetent saphenous veins.

Preoperative risk factor analysis of postoperative stroke after Cox-maze procedure with mitral valve repair.

BACKGROUND: Atrial fibrillation (AF) is a life-threatening arrhythmia that carries the high risk of thromboembolic complication. Stroke often develops in patients who undergo successful Cox Maze procedure, despite the fact that the procedure has shown a high rate of success in sinus conversion from AF. This study examined the preoperative risk factors predictive of stroke following Cox Maze procedure in patients with mitral valve disease. METHODS: 240 patients with the mean age of 57 years underwent Cox-Maze IV procedure with mitral valve repair from November 2007 through December 2010. All patients were available during the follow-up period with the mean duration of 23.6 months. This study excluded those patients who had undergone mitral valve replacement because of maintenance of warfarin medication RESULTS: Sixteen patients had an ischemic stroke. Of these sixteen patients, six had a transitional ischemic accident while the remaining ten had cerebral infarction. Twelve of sixteen showed sustained sinus rhythm, three showed AF and one had pacing rhythm. Univariate analysis showed that only preoperative stroke history was associated with postoperative stroke (p = 0.03). High CHA(2)DS(2)-VASc score, rheumatic etiology, large left atrium (LA), preoperative or postoperative LA thrombus, age, sex, hypertension, and concomitant surgery were not associated with predictive risks for stroke. CONCLUSIONS: In the group of patients who underwent the Cox-Maze procedure with mitral valve repair, having a stroke history was the only preoperative risk factor that could lead to a stroke event after surgery. Accordingly, patients with affliction of ischemic stroke, albeit sustained sinus rhythm, may require prophylactic anticoagulation.

Relationship between bicuspid aortic valve phenotype, valvular function, and ascending aortic dimensions.

BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve (BAV) is known to be associated with aortic valve dysfunction and ascending aorta (AA) dilatation. However, the relationship between BAV morphology and AA dimensions remains unclear. Thus, the study aim was to characterize the aortic valve function and AA dimensions according to the presence of raphe and BAV phenotype. METHODS: A total of 164 patients with BAV who underwent aortic valve surgery between October 2007 and November 2012 was investigated. BAV was classified as either type I (anterior-posterior orientation) or type II (right-left orientation), and subdivided as raphe+ (presence of raphe) and raphe-(no raphe). RESULTS: Type I BAV was present in 103 patients (62.8%), and raphe+ in 100 (61.0%). Patients with raphe+ were typically younger than those with raphe-, and male gender was more predominant (88.0% and 53.1%, respectively, p < 0.05). Aortic regurgitation was more common in patients with type I and raphe+ BAV, and aortic stenosis in patients with type II and raphe- BAV. In patients with raphe+, the diameters of aortic annulus related to the body surface area (BSA) were larger, and the diameters of the tubular portion of AA indexed to BSA were smaller than in patients with raphe- (p < 0.05). CONCLUSION: BAV morphology is helpful for predicting the type of aortic valve dysfunction and the location of AA dilatation.

Clinical Outcomes of Arteriovenous Grafts Using the Superficial Vein versus Venae Comitantes as Venous Outflow.

Background: The superficial veins are commonly used in conventional autogenous arteriovenous fistulas and the placement of prosthetic grafts. When they are unsuitable, however, the use of the deep veins (venae comitantes) is generally considered to be a reasonable alternative. This study conducted a comparative analysis of clinical outcomes for arteriovenous grafts between 2 groups based on the type of venous outflow: superficial veins or venae comitantes. Methods: In total, 151 patients who underwent arteriovenous grafts from November 2005 to March 2022 were retrospectively analyzed. The patients were divided into 2 groups: group A (superficial veins, n=89) and group B (venae comitantes, n=62). The primary, secondary patency, and complication rates were analyzed in each group. A propensity score-matched analysis was performed. Results: In total, 55 well-balanced pairs were matched. Kaplan-Meier analysis revealed no significant differences in the primary patency rate between the 2 groups at 1-year, 3-year and 5-year intervals (group A, 54.7%, 35.9%, 25.4% vs. group B, 47.9%, 16.8%, 12.6%; p=0.14), but there was a difference in the secondary patency rate (group A, 98.2%, 95.3%, 86.5% vs. group B, 87.3%, 76.8%, 67.6%; p=0.0095). The rates of complications, simple percutaneous transluminal angioplasty, and stent insertion were comparable between the groups. Conclusion: Although this study demonstrated not particularly favorable secondary patency rates in the venae comitantes group, the venae comitantes may still be a viable option for patients with unsuitable superficial veins because there were no significant differences in the primary patency and complication rates between the 2 groups.

Clinical outcomes of endovascular treatments for critical limb ischemia with chronic total occlusive lesions limited to below-the-knee arteries.

BACKGROUND: Diabetes mellitus tends to have the greatest impact on the smaller vessels and contributes significantly to occlusive disease from the popliteal artery distally. PURPOSE: To evaluate the clinical outcomes after a balloon angioplasty with or without stent placement in diabetic patients with critical limb ischemia (CLI) by chronic total occlusion (CTO) limited to below-the-knee (BTK) arteries. MATERIAL AND METHODS: From August 2005, patients who presented CLI and CTO limited to the BTK arteries, and who underwent endovascular treatment, were included in this study. The primary endpoints evaluated were technical success, limb salvage, and primary patency. The secondary endpoints evaluated were 30-day access site, intervention site, and systemic complications. Patency and limb salvage were evaluated using the Kaplan-Meier method and compared using Fisher's exact test. RESULTS: The BTK endovascular treatment (EVT) was performed on 64 limbs. Technical success rate was 93.8% and limb salvage rate was 90.6%. Three of four limbs with technical failure and three of 60 limbs with technical success underwent BTK amputation and the comparison of these rates were significantly different (75% vs. 5%, P = 0.002). Primary patency rates for the limbs were 75% and 59.1% at 6-month and 12-month follow-up, respectively. Minor complications disappeared through the follow-up periods and there was no 30-day complication or systemic adverse events for the treated vessel. CONCLUSION: Even though EVT for CLI in patients with diabetes and CTO in isolated BTK arteries does not have comparable primary patency, it can lead to a very high rate of limb salvage. This result can accentuate the importance of more blood flow to the foot by means of successful revascularization using EVT rather than long-term patency in CTO of isolated BTK arteries.

Optimal timing of heart transplantation in patients with an implantable left ventricular assist device.

Heart transplantation (HTPL) has been established as the gold-standard surgical treatment for end-stage heart failure. However, the use of a left ventricular assist device (LVAD) as a bridge to HTPL has been increasing due to the limited availability of HTPL donors. Currently, more than half of HTPL patients have a durable LVAD. Advances in LVAD technology have provided many benefits for patients on the waiting list for HTPL. Despite their advantages, LVADs also have limitations such as loss of pulsatility, thromboembolism, bleeding, and infection. In this narrative review, the benefits and shortcomings of LVADs as a bridge to HTPL are summarized, and the available literature evaluating the optimal timing of HTPL after LVAD implantation is reviewed. Because only a few studies have been published on this issue in the current era of third-generation LVADs, future studies are needed to draw a definite conclusion.

Aortic Valve Dysfunction and Aortopathy Based on the Presence of Raphe in Patients with Bicuspid Aortic Valve Disease.

(1) Background: To identify the association between the presence or absence of a raphe and aortic valve dysfunction, as well as the presence of aortopathy in patients with a bicuspid aortic valve (BAV); (2) Methods: This retrospective study enrolled 312 participants (mean (SD) age, 52.7 (14.3) years; 227 men (72.8%)) with BAV. The BAVs were divided into those with the presence (raphe+) or absence (raphe-) of a raphe. Valvular function was classified as normal, aortic regurgitation (AR), or aortic stenosis (AS) using TTE. The pattern of BAV aortopathy was determined by the presence of dilatation at the sinus of Valsalva and the middle ascending aorta using CCT; (3) Results: BAVs with raphe+ had a higher prevalence of AR (148 (79.5%) vs. 48 (37.8%), p < 0.001), but a lower prevalence of AS (90 (48.6%) vs. 99 (78.0%), p < 0.001) compared with those with raphe-. The types of BAV aortopathy were significantly different (p = 0.021) according to those with BAV-raphe+ and BAV-raphe-; (4) Conclusions: The presence of a raphe was significantly associated with a higher prevalence of AR, but a lower prevalence of AS and combined dilatation of the aortic root and middle ascending aorta. The presence of a raphe was an independent determinant of AR.

Historical Review and Future of Cardiac Xenotransplantation.

Along with the development of immunosuppressive drugs, major advances on xenotransplantation were achieved by understanding the immunobiology of xenograft rejection. Most importantly, three predominant carbohydrate antigens on porcine endothelial cells were key elements provoking hyperacute rejection: α1,3-galactose, SDa blood group antigen, and N-glycolylneuraminic acid. Preformed antibodies binding to the porcine major xenoantigen causes complement activation and endothelial cell activation, leading to xenograft injury and intravascular thrombosis. Recent advances in genetic engineering enabled knock-outs of these major xenoantigens, thus producing xenografts with less hyperacute rejection rates. Another milestone in the history of xenotransplantation was the development of co-stimulation blockaded strategy. Unlike allotransplantation, xenotransplantation requires blockade of CD40-CD40L pathway to prevent T-cell dependent B-cell activation and antibody production. In 2010s, advanced genetic engineering of xenograft by inducing the expression of multiple human transgenes became available. So-called 'multi-gene' xenografts expressing human transgenes such as thrombomodulin and endothelial protein C receptor were introduced, which resulted in the reduction of thrombotic events and improvement of xenograft survival. Still, there are many limitations to clinical translation of cardiac xenotransplantation. Along with technical challenges, zoonotic infection and physiological discordances are major obstacles. Social barriers including healthcare costs also need to be addressed. Although there are several remaining obstacles to overcome, xenotransplantation would surely become the novel option for millions of patients with end-stage heart failure who have limited options to traditional therapeutics.

Endovenous radiofrequency ablation using a new bipolar electrode in a canine model: a new endovenous radiofrequency electrode.

Purpose: This study aimed to determine the effectiveness and safety of a newly developed endovenous radiofrequency (RF) catheter compared with that of the existing RF catheter in a canine model. Methods: Seven dogs underwent ablation using 1 control catheter (ClosureFAST, CF; Covidien) and 1 experimental catheter (VENISTAR, VS; STARmed Co., Ltd.) in the femoral and cephalic veins. The ablated vein was evaluated macroscopically (2,3,5-triphenyltetrazolium chloride staining, TTC), microscopically (hematoxylin and eosin staining), and ultrasonographically. Vessel injury score was used to evaluate the ablating effect objectively. Veins from 1 dog were evaluated on the day of ablation, while in the remaining 6 dogs, the ablated veins were evaluated 2 weeks later. Results: A total of 23 veins (CF, 11 veins; VS, 12 veins) were ablated in 7 dogs. Non-TTC-stained vein wall areas were identified in all ablated veins. No significant difference was observed in the mean vessel injury score (2.54 ± 1.16 vs. 2.42 ± 1.13, P = 0.656) and the mean vessel wall thickness (0.32 ± 0.03 mm vs. 0.31 ± 0.05 mm, P = 0.212) between CF and VS. There was no blood flow in all veins ablated with VS, whereas there was remaining blood flow in 1 vein ablated with CF. Perivenous complication was not observed. Conclusion: Endovenous RF ablation using a newly developed VS RF catheter seems to provide comparable occlusion rate and degree of vein wall injury without perivenous adverse events compared to the most commonly used RF catheter (CF).

Comparison of Graft Survival Between Full-Thickness and Lamellar Pig-to-Monkey Corneal Xenotransplantation from the Same Genetically Engineered Pig Model with Minimal Immunosuppression.

BACKGROUND: The graft survival rate of full-thickness corneal xenotransplantation (XTP) with minimal immunosuppression in genetically engineered pigs is unknown, whereas lamellar corneal XTP shows satisfactory results. We compared graft survival between full-thickness and lamellar transplantations in the same genetically engineered pig. METHODS: Six pig-to-monkey corneal transplantations were performed on 3 transgenic pigs. Two corneas harvested from 1 pig were transplanted into 2 monkeys using full-thickness and lamellar corneal xenotransplantation. The transgenic donor pigs used were α1,3-galactosyltransferase gene-knockout + membrane cofactor protein (GTKO+CD46) in one recipient and GTKO+CD46+ thrombomodulin (TBM) in the other. RESULTS: The graft survival time for GTKO+CD46 XTP was 28 days. With the addition of TBM, the survival differences between lamellar and full-thickness XTP were 98 days versus 14 days and >463 days (ongoing) versus 21 days, respectively. An excessive number of inflammatory cells was observed in failed grafts, but none were in the recipient's stromal bed. CONCLUSIONS: Unlike full-thickness corneal XTP, lamellar xenocorneal transplantation does not exhibit surgical complications, such as retrocorneal membrane or anterior synechia. The graft survival of lamellar XTP in this study was not as good as in our previous experiments, although the survival period was superior to that of full-thickness XTP. The difference in graft survival based on transgenic type is not definitive. Further studies using transgenic pigs and minimal immunosuppression need to focus on improving graft survival of lamellar XTP and using a larger sample size to determine the potential of full-thickness corneal XTP.

Current Status of Genetically Engineered Pig to Monkey Kidney Xenotransplantation in Korea.

BACKGROUND: In South Korea, pig-to-nonhuman primate trials of solid organs have only been performed recently, and the results are not sufficiently satisfactory to initiate clinical trials. Since November 2011, we have performed 30 kidney pig-to-nonhuman primate xenotransplantations at Konkuk University Hospital. METHODS: Donor αGal-knockout-based transgenic pigs were obtained from 3 institutes. The knock-in genes were CD39, CD46, CD55, CD73, and thrombomodulin, and 2-4 transgenic modifications with GTKO were done. The recipient animal was the cynomolgus monkey. We used the immunosuppressants anti-CD154, rituximab, anti-thymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The mean survival duration of the recipients was 39 days. Except for a few cases for which survival durations were <2 days because of technical failure, 24 grafts survived for >7 days, with an average survival duration of 50 days. Long-term survival was observed 115 days after the removal of the contralateral kidney, which is currently the longest-recorded graft survival in Korea. We confirmed functioning grafts for the surviving transplanted kidneys after the second-look operation, and no signs of hyperacute rejection were observed. CONCLUSIONS: Although our survival results are relatively poor, they are the best-recorded results in South Korea, and the ongoing results are improving. With the support of government funds and the volunteering activities of clinical experts, we aim to further improve our experiments and contribute to the commencement of clinical trials of kidney xenotransplantation in Korea.

Comparative transcriptome analysis between long- and short-term survival after pig-to-monkey cardiac xenotransplantation reveals differential heart failure development.

Cardiac xenotransplantation is the potential treatment for end-stage heart failure, but the allogenic organ supply needs to catch up to clinical demand. Therefore, genetically-modified porcine heart xenotransplantation could be a potential alternative. So far, pig-to-monkey heart xenografts have been studied using multi-transgenic pigs, indicating various survival periods. However, functional mechanisms based on survival period-related gene expression are unclear. This study aimed to identify the differential mechanisms between pig-to-monkey post-xenotransplantation long- and short-term survivals. Heterotopic abdominal transplantation was performed using a donor CD46-expressing GTKO pig and a recipient cynomolgus monkey. RNA-seq was performed using samples from POD60 XH from monkey and NH from age-matched pigs, D35 and D95. Gene-annotated DEGs for POD60 XH were compared with those for POD9 XH (Park et al. 2021). DEGs were identified by comparing gene expression levels in POD60 XH versus either D35 or D95 NH. 1,804 and 1,655 DEGs were identified in POD60 XH versus D35 NH and POD60 XH versus D95 NH, respectively. Overlapped 1,148 DEGs were annotated and compared with 1,348 DEGs for POD9 XH. Transcriptomic features for heart failure and inhibition of T cell activation were observed in both long (POD60)- and short (POD9)-term survived monkeys. Only short-term survived monkey showed heart remodeling and regeneration features, while long-term survived monkey indicated multi-organ failure by neural and hormonal signaling as well as suppression of B cell activation. Our results reveal differential heart failure development and survival at the transcriptome level and suggest candidate genes for specific signals to control adverse cardiac xenotransplantation effects.

Diagnostic performance of combined noninvasive anatomic and functional assessment with dual-source CT and adenosine-induced stress dual-energy CT for detection of significant coronary stenosis.

OBJECTIVE: The purpose of our study was to prospectively evaluate the incremental diagnostic value of combined dual-source coronary CT angiography (CTA) and CT myocardial perfusion imaging (MPI) for the detection of significant coronary stenoses. SUBJECTS AND METHODS: Forty-five patients with known coronary artery disease detected by dual-source coronary CTA were investigated by adenosine-induced stress dual-source CTA and conventional coronary angiography. Analysis was performed in three steps: classification of coronary stenosis severity using dual-source coronary CTA, identification of myocardial perfusion defects using rest and stress CT MPI, and reclassification of coronary stenosis severity according to combined dual-source coronary CTA and CT MPI. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of dual-source coronary CTA before and after CT MPI were calculated on a per-vessel basis compared with conventional coronary angiography as the standard of reference. RESULTS: Dual-source coronary CTA revealed 87 significantly stenotic vessels in 45 patients. Conventional coronary angiography revealed significant stenoses in 73 vessels in 42 patients. CT MPI showed myocardial perfusion defects in 81 vessel territories in 43 patients. After the CT MPI analysis, dual-source coronary CTA identified significant stenoses in 77 coronary vessels in 42 patients. Sensitivity, specificity, PPV, and NPV of the dual-source coronary CTA on a per-vessel basis before CT MPI were 91.8%, 67.7%, 73.6%, and 87.5%, respectively, and after CT MPI were 93.2%, 85.5%, 88.3%, and 91.4%, respectively. The area under the receiver operating characteristic curve increased significantly from 0.798 to 0.893 (p = 0.004). CONCLUSION: Combined dual-source coronary CTA and CT MPI provides incremental diagnostic value compared with dual-source coronary CTA alone for the detection of significant coronary stenoses.

Randomized clinical trial comparing two methods for endovenous laser ablation of incompetent perforator veins in thigh and great saphenous vein without evidence of saphenofemoral reflux.

BACKGROUND: Percutaneous ablation of incompetent perforators has been introduced as a safe and efficacious alternative. OBJECTIVE: To compare two methods of treating incompetent thigh perforator and great saphenous veins (GSV). MATERIALS AND METHODS: Patients with varicose veins of CEAP C2 and C3 with incompetent perforating veins (IPVs) in the thigh without evidence of saphenofemoral reflux and with obvious venous reflux from IPVs into the GSV distal to IPVs were included. Endovenous laser ablation was done using two methods (IPV ablation (IPVA) versus GSV ablation: GSVA). Their technical success rate, clinical success rate, and complications were compared at 1 week, and 1, 3, 6, and 12 months. RESULTS: Sixty-nine consecutive patients were randomized to IPVA (n = 34) or GSVA (n = 35). Technical success was significantly lower with IPVA than GSVA (p = .002). Clinical success, defined as continued closure of treated veins, was similar with IPVA and GSVA (96.1% vs 100% at 1 week, 100% vs 97.1% at 1 month, and 100% for both at 3, 6, and 12 months, respectively). CONCLUSION: IPVA has clinical results and complications similar to those of GSVA in individuals with C2 and C3 chronic venous disease with IPVs in the thigh combined with incompetent GSV, but its higher technical failure rate makes it difficult to choose it as the primary treatment method.