Search

Background: The aim of this randomized and controlled trial was to investigate the effect of a glucose-insulin-potassium (GIK) solution on myocardial protection in acute coronary syndrome (ACS) patients undergoing urgent multivessel off-pump coronary artery bypass (OPCAB) surgery.Methods: Sixty-six patients were randomly allocated either to receive 0.3 ml kg(-1) h(-2) GIK solution (potassium 80 mEq and regular insulin 325 IU in 500 ml of 50% glucose) or equivalent volume of normal saline (control) upon anaesthetic induction until 6 h after reperfusion. The primary endpoints were to compare the concentrations of creatine kinase-MB (CK-MB) and troponin-T between the groups after reperfusion. The secondary endpoints were to compare the incidences of postoperative troponin-T >0.8 ng ml(-1) and myocardial infarction (MI) between the groups.Results: Highest CK-MB [8.7 (4.4) vs 13.1 (7.9) ng ml(-1), P=0.006] and troponin-T [0.20 (0.13-0.49) vs 0.48 (0.18-0.91) ng ml(-1), P<0.0001] values after reperfusion were significantly lower in the GIK group compared with the control group. The area under the curve of serially measured troponin-T was also significantly smaller in the GIK group compared with the control group [0.83 (0.43-1.81) vs 0.46 (0.31-1.00), P=0.036]. Significantly fewer patients in the GIK group showed troponin-T >0.8 ng ml(-1) after reperfusion compared with the control group (3 vs 11, P=0.033). The incidence of postoperative MI was similar between the groups.Conclusions: GIK administration in ACS patients undergoing urgent multivessel OPCAB significantly attenuated the degree of ensuing myocardial injury without complications related to glycaemic control. Clinical Trial Registry. URL: http://clinicaltrials.gov/ct2/show/NCT01384656?term=GIK+AND+OPCAB&rank=1. Unique identification number NCT01384656. [ABSTRACT FROM AUTHOR]

Introduction: Acute myocardial infarction (AMI) is a major global health concern. However, the optimum timing of coronary artery bypass grafting (CABG) in AMI patients remains controversial. This study investigated the optimal timing of CABG and its impact on postoperative outcomes. We hypothesized that determining the optimal timing of CABG could positively impact postoperative outcomes., Methods: We conducted a nationwide retrospective analysis of the National Health Insurance Service of Korea database, focusing on 1 705 843 adult AMI patients diagnosed between 2007 and 2018 who underwent CABG within 1 year of diagnosis. Patients were categorized based on CABG timing. Primary endpoints included cohort identification and the time interval from AMI diagnosis to CABG. Secondary endpoints encompassed major adverse cardiac and cerebrovascular events (MACCEs) and the impact of postoperative medications., Results: Of the patients, 20 172 underwent CABG. Surgery within 24 h of AMI diagnosis demonstrated the most favorable outcomes, reducing cardiac death, myocardial infarction recurrence, and target vessel revascularization. Delayed CABG within 3 days also outperformed surgery within 1-2 days post-AMI. Additionally, postoperative aspirin use was associated with improved MACCE outcomes., Conclusion: CABG within 24 h of AMI diagnosis was associated with significantly minimized myocardial injury, emphasizing the critical role of rapid revascularization. Delayed CABG within 3 days related to better outcomes compared with that of surgery within 1-2 days. These findings provide evidence-based recommendations for optimizing CABG timing in AMI patients, consequentially reducing morbidity and mortality., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: While human papillomavirus (HPV) vaccines have been available since 2006, the coverage has varied among countries. Our aim is to analyse the equity impact of HPV vaccination on the lifetime projections of cervical cancer burden among vaccinated cohorts of 2010-22 in 84 countries., Methods: We used WHO and UNICEF estimates of national immunisation coverage for HPV vaccination in 84 countries during 2010-22. We used PRIME (Papillomavirus Rapid Interface for Modelling and Economics) to estimate the lifetime health impact of HPV vaccination on cervical cancer burden in terms of deaths, cases, and disability-adjusted life years (DALYs) averted by vaccination in their respective countries. We generated concentration indices and curves to assess the equity impact of HPV vaccination across 84 countries., Findings: The health impact of HPV vaccination varied across the 84 countries and ranged from Switzerland to Tanzania at 2 to 34 deaths, 4 to 47 cases, and 40 to 735 DALYs averted per 1000 vaccinated adolescent girls over the lifetime of the vaccinated cohorts of 2010-22. The concentration index for the distribution of average coverage during 2010-22 among the 84 countries ranked by vaccine impact was 0.33 (95% CI: 0.27-0.40) and highlights the wide inequities in HPV vaccination coverage., Interpretation: Our findings suggested that countries with a relatively higher cervical cancer burden and thereby a relatively higher need for HPV vaccination had relatively lower coverage during 2010-22. Further, there were significant inequities in HPV vaccination coverage within the Americas, Europe, and Western Pacific regions, and in high- and low-income countries with a pro-advantaged and regressive distribution favouring countries with lower vaccine impact., Funding: Gavi, the Vaccine Alliance; Bill & Melinda Gates Foundation., Competing Interests: We declare no competing interests., (© 2024 The Author(s).)

Objectives: In this cohort study, we aimed to assess the 1-year clinical outcomes of using the E-vita Open NEO™ hybrid prosthesis for total arch replacement with frozen elephant trunk (FET) to repair extensive aortic pathologies., Methods: We reviewed individuals who underwent thoracic aortic surgery between April 2021 and March 2023 from the Gangnam Severance Aortic Registry. Exclusion criteria included ascending aortic replacement, 1 or 2 partial arch replacement, descending aortic replacement and total arch replacement without an FET. Finally, all consecutive patients who underwent total arch replacement and FET with E-vita Open NEO for aortic arch pathologies between April 2021 and March 2023 were included in this cohort study. The patients were divided into 3 groups based on their pathology: acute aortic dissection, chronic aortic dissection and thoracic aortic aneurysm. The primary end point was in-hospital mortality. The secondary end points during the postoperative period comprised stroke, spinal cord injury and redo sternotomy for bleeding. Additionally, the secondary end points during the follow-up period included the 1-year survival rate, 1-year freedom from all aortic procedures and 1-year freedom from unplanned aortic interventions., Results: The study included 167 patients in total: 92 patients (55.1%) with acute aortic dissection, 20 patients (12.0%) with chronic aortic dissection and 55 patients (32.9%) with thoracic aortic aneurysm. The in-hospital mortality was 1.8% (n = 3). Strokes occurred in 1.8% (n = 3) of the patients, spinal cord injury in 1.8% (n = 3) and redo sternotomy for bleeding was performed in 3.0% (n = 5). There were no significant differences between the pathological groups. The median follow-up period (quartile 1-quartile 3) was 198 (37-373) days, with 1-year survival rates of 95.9%. At 1 year, the freedom from all aortic procedures and unplanned aortic interventions were 90.3% and 92.0%, respectively., Conclusions: The 1-year clinical outcomes of total arch replacement with FET using the E-vita Open NEO were favourable. Long-term follow-up is required to evaluate the durability of the FET., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance may inform therapeutic strategies to effectively reprogram and reverse acquired resistance., Competing Interests: Declaration of interests A.J.S. reports consulting/advising role to J&J, KSQ therapeutics, BMS, Merck, Enara Bio, Perceptive Advisors, Oppenheimer and Co, Umoja Biopharma, Legend Biotech, Iovance Biotherapeutics, Prelude Therapeutics, Immunocore, Lyell Immunopharma, Amgen and Heat Biologics. Research funding: GSK (Inst), PACT pharma (Inst), Iovance Biotherapeutics (Inst), Achilles therapeutics (Inst), Merck (Inst), BMS (Inst), Harpoon Therapeutics (Inst) and Amgen (Inst). MDH reports research grant from BMS; personal fees from Achilles; Arcus; AstraZeneca; Blueprint; BMS; Genentech/Roche; Genzyme/Sanofi, Immunai; Instil Bio; Janssen; Merck; Mirati; Natera; Nektar; Pact Pharma; Regeneron; Shattuck Labs; Syndax; as well as equity options from Arcus, Factorial, Immunai, and Shattuck Labs. A patent filed by Memorial Sloan Kettering related to the use of tumor mutational burden to predict response to immunotherapy (PCT/US2015/062208) is pending and licensed by PGDx. J.L. has received honoraria from Targeted Oncology and Physicians’ Education Resource. D.M. is an employee of M:M Bio Limited. D.M. reports consulting role to Shattuck Labs and Corbus Pharma. T.M. is a consultant for Daiichi Sankyo Co, Leap Therapeutics, Immunos Therapeutics, and Pfizer, and co-founder of Imvaq Therapeutics. T.M. has equity in Imvaq therapeutics. T.M. reports grants from Bristol Myers Squibb, Surface Oncology, Kyn Therapeutics, Infinity Pharmaceuticals, Peregrine Pharmaceuticals, Adaptive Biotechnologies, Leap Therapeutics, and Aprea. T.M. is an inventor on patent applications related to work on oncolytic viral therapy, alphavirus-based vaccines, neo-antigen modeling, CD40, GITR, OX40, PD-1, and CTLA-4. B.D.G. has received honoraria for speaking engagements from Merck, Bristol Meyers Squibb, and Chugai Pharmaceuticals; has received research funding from Bristol Meyers Squibb and Merck; and has been a compensated consultant for Darwin Health, Merck, PMV Pharma, Shennon Biotechnologies, and Rome Therapeutics of which he is a co-founder. B.D.G. is part of a patent related to neoantigen prediction (WO2018136664A1, PCT/US2023/011643). G.F. and T.H.S. are employees and stockholders of Shattuck Labs, Inc. M.L.M. has received honorarium from GSK. H.R., X.Z., M.R.K., I.A., R.S., J.C.B., M.L.M., and M.D.H. are current employees and stockholders of AstraZeneca., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Reports on the residual descending aortic dissection (AD) after acute type A AD (TAAD) repair has been limited. Therefore, we evaluated the fate of descending aorta in patients who underwent acute TAAD repair., Methods: We reviewed 299 patients (mean: 60.4 years, 51.5% male) patients who received acute TAAD repair between 2009 and 2018, except genetic aortopathy and concomitant surgeries for the descending aorta. Subjects are categorized into classic TAAD (Classic, n=226), retrograde extension of TAAD from the intimal tear in the descending aorta (Retro, n=31), and intramural hematoma (IMH, n=42) types of AD. Interested outcome was expansion rate of descending aorta. Secondary outcome was descending aorta events including surgical repair, interventions, and aortic rupture. To reduce selection bias, baseline variables were adjusted. Multivariable risk analyses were performed to find risk factors of the study outcomes., Results: In crude analysis, descending aorta in Retro [beta, 2.260; standard error (SE), 0.559] and Classic (beta, 1.542; SE, 0.233) groups expanded faster than IMH (beta, 0.443; SE, 0.491) group. Unadjusted risk of aortic event was significantly higher in the Retro group compared with the IMH [hazard ratio (HR) =4.80; 95% confidence interval (CI): 1.56-14.7] and Classic (HR =2.36; 95% CI: 1.24-4.49) groups. Baseline adjustment did not alter these findings. In multivariable analyses, the presence of intimal tear in the upper thoracic descending aorta (above 7th thoracic vertebra) was significantly associated with the aortic expansion (beta, 2.06; SE, 0.61) and events (HR =8.74; 95% CI: 4.34-17.6)., Conclusions: The descending aorta growth was faster in Retro and Classic than IMH and related with the tear location. Careful assessment on the descending is warranted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-920/coif). S.W.S. serves as an unpaid editorial board member of Journal of Thoracic Disease from February 2023 to January 2025. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Objectives: Intramural hematoma may be generated by a minimal intimal tear. Most surgeries for acute type A intramural hematoma are performed on the proximal aorta alone regardless of the intimal tear site. Under the assumption that major adverse aortic events (MAAEs) would be related to the location of primary intimal tear, we reviewed preoperative computed tomography scan findings., Methods: Sixty patients with acute type A intramural hematoma who underwent surgery from January 2008 to December 2019 were retrospectively analyzed. The maximal diameter, maximal thickness of the intramural hematoma, and hematoma thickness ratio of the ascending and descending aortae were measured. MAAEs were defined as newly developed aortic dissection, rupture, newly developed penetrating aortic ulcer (PAU), enlargement of the PAU, and aortic death., Results: The number of patients with PAU in the descending aorta (dPAU) was significantly higher in the MAAE (+) group. The MAAE (+) group showed lower measurements of the ascending aorta and higher measurements of the descending aorta than the MAAE (-) group. In the univariate analysis, dPAU, hematoma thickness ratio of the ascending and descending aortae, and descending aorta hematoma thickness >8.58 mm were risk factors of MAAE. Intimal tear noted intraoperatively and ascending aorta hematoma thickness >10.25 mm were protective factors of MAAE., Conclusions: Aortopathies (ie, PAU, ulcer-like projections, and the hematoma thickness ratio) are important clues to determine the location of intimal tear. Occurrence of MAAEs seems to be highly related to the pathology of the descending aorta. The modalities of treatment for stable acute type A intramural hematoma that do not meet the existing guidelines should be tailored to the location of the intimal tear., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic substantially disrupted healthcare utilization patterns, globally. South Korea had been praised widely in its efforts to contain the spread of the pandemic, which may have contributed to a significantly smaller reduction in healthcare utilization compared to neighboring countries. However, it remains unknown how the COVID-19 pandemic impacted utilization patterns across population sub-groups, particularly vulnerable patient groups in South Korea. This paper quantifies the changes in healthcare utilization attributable to COVID-19 and the COVID-19 vaccination by sub-groups., Methods: An interrupted time series analysis was conducted to examine the impact of COVID-19 on healthcare utilization in South Korea from January 2016 to December 2022 using aggregated patient-level data from the national health insurance system that accounts for 99% of all healthcare services in South Korea. We applied negative binomial models adjusting for seasonality and serial correlation. Falsification tests were conducted to test the validity of breakpoints. Stratified analyses by type of healthcare services, age, sex, income level, health facility type, and avoidable/non-avoidable hospitalizations was performed, and we assessed differences in utilization trends between population groups across three phases of the pandemic., Findings: In early 2020, the COVID-19 pandemic caused a reduction in monthly volume of outpatient utilization by 15.7% [95% CI 13.3%-18.1%, p < 0.001] and inpatient utilization by 11.6% [10.1%-13.0%, p < 0.001]. Most utilization recovered and rebounded to pre-COVID-19 levels as of December 2022 although variations existed. We observed heterogeneity in the magnitude of relative changes in utilization across types of services, varying from a 42.7% [36.8%-48.0%, p < 0.001] decrease for pediatrics, a 23.4% [20.1%-26.5%%, p < 0.001] reduction in utilization of public health centers, and a 24.2% [21.2%-27.0%, p < 0.001] reduction in avoidable hospitalizations compared to the pre-pandemic period. Contrary to global trends, health utilization among the elderly population (65 and older) in South Korea saw only marginal reductions compared to other age groups. Similarly, Medicaid patients and lower income groups experienced a smaller reduction compared to higher income groups., Interpretation: The impact of the COVID-19 pandemic on healthcare utilization in South Korea was less pronounced compared to the global average. Utilization of vulnerable populations, including adults over 65 years old and lowest-income groups reduced less than other type of patients., Funding: No funding., Competing Interests: The authors whose names are listed immediately above certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2023 The Author(s).)

Off-pump coronary surgery requires mechanical cardiac displacement, which results in bi-ventricular systolic and diastolic dysfunction. Although transient, subsequent hemodynamic deterioration can be associated with poor prognosis and, in extreme cases, emergency conversion to on-pump surgery, which is associated with high morbidity and mortality. Thus, appropriate decision-making regarding whether the surgery can be proceeded based on objective hemodynamic targets is essential before coronary arteriotomy. For adequate hemodynamic management, avoiding myocardial oxygen supply-demand imbalance, which includes maintaining mean arterial pressure above 70 mmHg and preventing an increase in oxygen demand beyond the patient's coronary reserve, must be prioritized. Maintaining mixed venous oxygen saturation above 60%, which reflects the lower limit of adequate global oxygen supply-demand balance, is also essential. Above all, severe mechanical cardiac displacement incurring compressive syndromes, which cannot be overcome by adjusting major determinants of cardiac output, should be avoided. An uncompromising form of cardiac constraint can be ruled out as long as the central venous pressure is not equal to or greater than the pulmonary artery diastolic (or occlusion) pressure, as this would reflect tamponade physiology. In addition, transesophageal echocardiography should be conducted to rule out mechanical cardiac displacement-induced ventricular interdependence, dyskinesia, severe mitral regurgitation, and left ventricular outflow tract obstruction with or without systolic motion of the anterior leaflet of the mitral valve, which cannot be tolerated during grafting. Finally, the ascending aorta should be carefully inspected for gas bubbles to prevent hemodynamic collapse caused by a massive gas embolism obstructing the right coronary ostium.

Purpose: It is unclear if a second or third arterial graft can improve clinical outcomes in coronary artery bypass graft surgery. We compared the outcomes of bilateral internal thoracic artery (BITA) plus radial artery (RA) grafting versus left internal thoracic artery (LITA) plus RA grafting after off-pump coronary artery bypass grafting., Materials and Methods: Between January 2009 and December 2020, a total of 3007 patients with three-vessel coronary artery disease who underwent off-pump coronary artery bypass were analyzed. Among them, 971 patients received total arterial grafting using LITA. We divided the patients into two groups [group A, BITA+RA grafting (n=227) and group B, LITA+RA grafting (n=744)], and compared the survival and major adverse cardiac and cerebrovascular event (MACCE) rates between the two groups at 10 years., Results: After risk adjustment with inverse probability treatment weighting methods, the freedom from all-cause mortality was 93.1% and 88.3% in groups A and B, respectively ( p =0.140). The freedom from MACCE rates were 68.3% and 89.0%, respectively ( p <0.0001). LITA plus RA grafting [hazard ratio (HR): 1.3, 95% confidence interval (CI): 1.05-2.37, p =0.025] and incomplete revascularization (HR 1.2, 95% CI: 0.70-2.15, p =0.046) were significant risk factors for MACCEs in multivariable Cox regression analysis., Conclusion: The rates of MACCEs were lower with LITA plus RA grafting than with BITA plus RA grafting in total arterial revascularization. Furthermore, complete revascularization improved long-term outcomes following total arterial grafting., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Transit-time flowmetry (TTFM) is commonly used during coronary artery bypass grafting for intraoperative graft assessment. This study aimed to investigate whether TTFM values were predictive of graft failure and major adverse cardiac and cerebrovascular events (MACCEs). Between 2011 and 2018, 1933 patients with 3-vessel coronary artery disease who underwent off-pump coronary artery bypass were retrospectively analyzed. Among them, 1288 sequential venous grafts in 538 consecutive patients were measured using TTFM's 2 parameters, pulsatility index (PI) and flow (mL/min). The anastomoses were divided in the 3 groups depending on the anastomotic site: group A, first side-to-side anastomoses (n = 538), group B; second side-to-side (n = 212), group C; end-to-side (n = 538). MACCEs were related to TTFM. The mean clinical follow-up time was 64.8 ± 21.2 months. Postoperative graft patency was confirmed with multi-slice computed tomography or coronary angiography (follow-up interval: 64.8 ± 50.4 and 27.8 ± 20.5 months based on the date of examination). The 5-year survival rate was 93.7%. The mean graft flow was 59.1 ± 31.3, 41.0 ± 25.2, and 38.9 ± 22.8 mL/minute, and the PI was 2.2 ± 1.3, 2.5 ± 3.4, and 2.4 ± 2.5, in groups A, B, and C, respectively. Graft failure occurred in 23/1055 (2.2%) anastomoses. The 5-year MACCE rate was 6.9% (37/538 patients). Kaplan-Meier analysis revealed that graft patency was significantly lower in low MGF (p = 0.044) and high PI (p < 0.001). Multivariable logistic analysis showed that high PI (>5; HR 2.276; 95%CI 2.188-2.406, p < 0.001) was an independent risk factor for MACCEs. The cutoff values for PI of sequential grafts were 3.65, 3.55, and 3.17 in groups A, B, and C, respectively for the prediction of MACCE. A high PI predicts more predictive poor outcomes of sequential venous grafts after surgery than the low mean graft blood flow., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to compare the outcomes of aspirin in combination with either ticagrelor or clopidogrel after off-pump coronary artery bypass (OPCAB) in patients with clopidogrel resistance., Methods: Between November 2014 and November 2020, 1739 patients underwent OPCAB. Aspirin and clopidogrel treatment was initiated the day after surgery. On postoperative days 7 to 9, clopidogrel resistance was evaluated using a point-of-care assay. A total of 278 (18.9%) patients had clopidogrel resistance ( platelet reaction unit >208) and were enrolled in the study. The study investigators excluded patients with coresistance to aspirin (n = 74) and divided the remaining patients (mean age, 67.4 ± 8.5 years) into 2 groups (an aspirin and ticagrelor group [AT group; n = 102] and an aspirin and clopidogrel group [AC group; n = 102]), randomly assigned using a 1:1 ratio block table. The primary end point was graft patency and major adverse cardiovascular events (MACEs; defined as the composite of cardiovascular mortality, myocardial infarction, and repeat revascularization at 1 year after OPCAB), and the coprimary end point was the graft patency rate. The data were analyzed using the intent-to-treat method., Results: The graft occlusion rates in the AT and AC groups were 3.9% and 5.9%, respectively (P = .52). Neither death from cardiovascular causes (1.0% vs 2.9%; P = .32) nor myocardial infarction showed significant differences (1.0% vs 3.9%; P = .18). No significant difference in the rates of major bleeding were found between the 2 groups (P = .75). However, the AT group was associated with a lower rate of MACEs after OPCAB (hazard ratio, 0.77; 95% CI, 0.684-0.891; P = .01)., Conclusions: These results suggest that ticagrelor may be associated with reducing MACEs in patients with clopidogrel resistance after OPCAB., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: This study evaluated the effect of residual arch tears on late reinterventions and arch dilatation after hemiarch replacement for patients with acute DeBakey type I aortic dissection., Methods: Between January 1995 and October 2018, 160 consecutive patients who underwent hemiarch replacement for DeBakey type I dissection were retrospectively enrolled. They were divided into patients with (n = 73) and without (n = 87) residual arch tears. The arch tears group was subdivided into the proximal/middle arch (n = 26) and distal arch (n = 47) groups to evaluate arch growth rates according to the locations of residual arch tears. The endpoints were arch growth rate and late arch and composite events., Results: The arch diameter increased significantly over time in patients with residual arch tears (1.620 mm/y, P < .001). The increase occurred more rapidly when residual tears occurred at the distal arch than at the proximal/middle arch level (2.101 vs 1.001 mm/y). In the adjusted linear mixed model, residual arch tears or luminal communications at the distal arch level were significant factors associated with increases in the arch diameter over time. The 10-year freedom from late arch and composite event rate was significantly lower for patients with residual arch tears than for those without (82.4% vs 95.5%, P = .001; and 68.0% vs 89.3%, P = .002, respectively)., Conclusions: Residual arch tears are significant factors associated with late arch dilatation and reinterventions, especially for patients with distal arch tears. Extensive arch replacement during the initial surgery to avoid residual arch tears may improve long-term outcomes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients scheduled for cardiac surgery often have anemia and iron deficiency. We investigated the effect of the preoperative administration of intravenous ferric carboxymaltose (IVFC) in patients with iron deficiency anemia (IDA) who were due to undergo off-pump coronary artery bypass grafting (OPCAB). Patients who were due to undergo elective OPCAB between February 2019 and March 2022 who had IDA ( n = 86) were included in this single center, randomized, parallel-group controlled study. The participants were randomly assigned (1:1) to receive either IVFC or placebo treatment. Postoperative hematologic parameters [hemoglobin (Hb), hematocrit, serum iron concentration, total iron-binding capacity, transferrin saturation, transferrin concentration, and ferritin concentration] and the changes in these parameters during the follow-up period were the primary and secondary outcomes, respectively. The tertiary endpoints were early clinical outcomes, such as the volume of mediastinal drainage and the need for blood transfusions. IVFC treatment significantly reduced the need for red blood cell (RBC) and platelet transfusions. Despite receiving fewer RBC transfusions, patients in the treatment group had higher levels of Hb, hematocrit, and serum iron and ferritin concentrations during weeks 1 and 12 after surgery. No serious adverse events occurred during the study period. Preoperative IVFC treatment in patients with IDA undergoing OPCAB improved the values of the hematologic parameters and iron bioavailability. Therefore, is a useful strategy for stabilizing patients prior to OPCAB.

Background: The aim of this study was to investigate whether distal aortic maximum false lumen area (MFLA) ratio predicts late aortic dilation and reintervention after open repair of acute type I aortic dissection., Methods: We analyzed 309 nonsyndromic acute type I aortic dissection patients who were treated with a repair to the proximal aorta between 1994 and 2017. In 230 patients who did not show completely thrombosed false lumen on postoperative computed tomography, the MFLA ratio (MFLA/aortic area) on the descending thoracic aorta (DTA) was measured with postoperative computed tomography. Patients were divided into 3 groups according to the quartile range of MFLA ratio: low MFLA, <0.62 (n = 57); intermediate MFLA, 0.62 to 0.81 (n = 116); and high MFLA, ≥0.82 (n = 57)., Results: The aortic expansion rate was significantly higher in the high MFLA group (11.1 ± 21.2 mm/y) compared with intermediate (3.0 ± 7.4 mm/y; P < .01) and low (0.6 ± 6.6 mm/y; P < .01) MFLA groups. High MFLA was found to be an independent risk factor for significant aortic expansion (adjusted hazard ratio, 5.26; 95% CI, 1.53-18.12; P < .01) and aorta-related reintervention (hazard ratio, 4.99; 95% CI, 2.23-11.13; P < .01), and the MFLA ratio was significantly related to proximal DTA reentry tears (adjusted odds ratio, 12974.3; P < .001; area under curve, 0.807)., Conclusions: A high MFLA ratio on the DTA after acute type I aortic dissection repair is associated with increased risk of late aortic reintervention and distal aortic dilation. A high MFLA ratio is strongly associated with proximal DTA reentry tears., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Infective endocarditis is a life-threatening condition and is associated with embolic events. We aimed to evaluate the association of vegetation size, multiplicity, and position with cerebral embolism and late mortality in patients with infective endocarditis., Methods: We retrospectively reviewed patients with infective endocarditis who were admitted to a single institution between November 2005 and August 2017. A total of 419 patients with infective endocarditis were included in the study, 273 of whom had undergone surgery. The primary endpoint was all-cause mortality, and the secondary endpoint was cerebral embolism. Multivariate Cox regression and logistic regression analyses were performed to identify independent risk factors for 30-day mortality, late mortality, and cerebral embolism., Results: Age (hazard ratio [HR] 1.02; 95% confidence interval [CI], 1.00 to 1.04), renal failure (HR 4.21; 95% CI, 2.67 to 6.65), surgery (HR 0.31; 95% CI, 0.21 to 0.46), and Acute Physiology and Chronic Health Evaluation II score (HR 1.08; 95% CI, 1.01 to 1.15) were associated with late mortality. Vegetation size, multiplicity, and position were not significantly associated with late mortality, but a mitral vegetation size of greater than 10 mm (odds ratio 2.25; 95% CI, 1.32 to 3.84) was an independent risk factor for cerebral embolism., Conclusions: A vegetation size of greater than 10 mm and the mitral position were found to be significant risk factors for cerebral embolism, and for this group, early surgery might be considered to prevent cerebral embolism., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Vγ9Vδ2 + T cell-targeted immunotherapy is of interest to harness its MHC-independent cytotoxic potential against a variety of cancers. Recent studies have identified heterodimeric butyrophilin (BTN) 2A1 and BTN3A1 as the molecular entity providing "signal 1" to the Vγ9Vδ2 TCR, but "signal 2" costimulatory requirements remain unclear. Using a tumor cell-free assay, we demonstrated that a BTN2A1/3A1 heterodimeric fusion protein activated human Vγ9Vδ2 + T cells, but only in the presence of costimulatory signal via CD28 or NK group 2 member D. Nonetheless, addition of a bispecific γδ T cell engager BTN2A1/3A1-Fc-CD19scFv alone enhanced granzyme B-mediated killing of human CD19 + lymphoma cells when cocultured with Vγ9Vδ2 + T cells, suggesting expression of costimulatory ligand(s) on tumor cells is sufficient to satisfy the "signal 2" requirement. These results highlight the parallels of signal 1 and signal 2 requirements in αβ and γδ T cell activation and demonstrate the utility of heterodimeric BTNs to promote targeted activation of γδ T cells., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Background: Atrial fibrillation (Afib) is a marker of increased cardiovascular morbidity and mortality. Owing to the increased prevalence of Afib in patients undergoing cardiac surgery, assessing the effect of Afib on postsurgical outcomes is important. We aimed to analyze the effect of preoperative Afib on clinical outcomes in patients undergoing cardiac surgery using a large surgical database., Methods: This retrospective cohort study was based on the national health claims database established by the National Health Insurance Service of the Republic of Korea from 2009 to 2015. Diagnosis and procedure codes were used to identify diseases according to the International Statistical Classification of Diseases, 10th revision., Results: We included 1,037 patients (0.1%) who had undergone cardiac surgery from a randomized 1,000,000-patient cohort, and 15 patients (1.5%) treated with isolated surgical Afib ablation were excluded. Of these 1,022 patients, 412 (39.7%), 303 (29.2%), and 92 (9.0%) underwent coronary artery bypass, heart valve surgery, and Cox-maze surgery, respectively. Preoperative Afib was associated with higher patient mortality (p=0.028), regardless of the surgical procedure. Patients with preoperative Afib (n=190, 18.6%) experienced a higher cumulative risk of overall mortality (hazard ratio [HR], 1.435; 95% confidence interval [CI], 1.263-2.107; p=0.034). Subgroup analysis revealed a reduced risk of overall mortality with Cox-maze surgery in Afib patients (HR, 0.500; 95% CI, 0.266-0.938; p=0.031). Postoperative cerebral ischemia or hemorrhage events were not related to Afib., Conclusion: Preoperative Afib was independently associated with worse long-term postoperative outcomes after cardiac surgery. Concomitant Cox-maze surgery may improve the survival rate.

Objective: The study objective was to examine the long-term fate of aortic diameter expansion at 4 cardiac regions (annulus, sinus, ascending aorta, and proximal arch) after wrapping or replacement during aortic valve surgery of the moderately dilated ascending aorta., Methods: From January 1995 to December 2018, 964 consecutive patients who underwent aortic valve replacement at our institution were reviewed. Of them, 204 (mean age, 60.7 ± 7.4 years) underwent ascending aorta wrapping (n = 96) or replacement (n = 108) for a moderately dilated ascending aorta (40 to 55 mm). The overall fate of the aortic diameter was analyzed with a linear mixed-effect model. The median follow-up duration was 7.1 years., Results: After propensity score matching, the baseline maximal ascending aortic diameter median value was 47.3 ± 3.1 mm and 49.4 ± 13.5 mm in the wrapping and replacement groups, respectively. The annulus, sinus, and ascending aorta did not redilate in either group. The proximal aortic arch diameter significantly increased over time (0.343 mm/year; P = .006) in the wrapping group but not in the replacement group (0.066 mm/year; P = .649). Multivariable competing risk analysis identified the initial ascending aorta diameter at the wrapping procedure as an independent risk factor of proximal arch redilation (0.071 ± 0.037, P < .001). The cutoff value was an initial ascending aorta diameter of 47.2 mm for the prediction proximal arch redilation (area under the curve, 0.703; P = .014)., Conclusions: Aortic wrapping and replacement may be long-term durable treatment options in patients with a moderately enlarged ascending aorta. We suggest careful evaluation of redilation in the proximal arch after an aorta wrapping procedure., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Coinhibition of TIGIT (T cell immunoreceptor with Ig and ITIM domains) and PD-1/PD-L1 (PD-1/L1) may improve response rates compared with monotherapy PD-1/L1 blockade in checkpoint naive non-small cell lung cancer with PD-L1 expression >50%. TIGIT mAbs with an effector-competent Fc can induce myeloid cell activation, and some have demonstrated effector T cell depletion, which carries a clinical liability of unknown significance. TIGIT Ab blockade translates to antitumor activity by enabling PVR signaling through CD226 (DNAM-1), which can be directly inhibited by PD-1. Furthermore, DNAM-1 is downregulated on tumor-infiltrating lymphocytes (TILs) in advanced and checkpoint inhibition-resistant cancers. Therefore, broadening clinical responses from TIGIT blockade into PD-L1 low or checkpoint inhibition-resistant tumors, may be induced by immune costimulation that operates independently from PD-1/L1 inhibition. TNFSF14 (LIGHT) was identified through genomic screens, in vitro functional analysis, and immune profiling of TILs as a TNF ligand that could provide broad immune activation. Accordingly, murine and human bifunctional fusion proteins were engineered linking the extracellular domain of TIGIT to the extracellular domain of LIGHT, yielding TIGIT-Fc-LIGHT. TIGIT competitively inhibited binding to all PVR ligands. LIGHT directly activated myeloid cells through interactions with LTβR (lymphotoxin β receptor), without the requirement for a competent Fc domain to engage Fcγ receptors. LIGHT costimulated CD8 + T and NK cells through HVEM (herpes virus entry mediator A). Importantly, HVEM was more widely expressed than DNAM-1 on T memory stem cells and TILs across a range of tumor types. Taken together, the mechanisms of TIGIT-Fc-LIGHT promoted strong antitumor activity in preclinical tumor models of primary and acquired resistance to PD-1 blockade, suggesting that immune costimulation mediated by LIGHT may broaden the clinical utility of TIGIT blockade., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Objectives: We aimed to simulate blood flow at an aortic dissection in an in vitro vascular model and assess the impact of the cannulation method on visceral perfusion., Methods: An aortic-dissection model with an acrylic aortic wall and silicone intimal flap was developed to study visceral perfusion under various cannulation conditions. The primary tear was placed in the proximal descending aorta and the re-entry site in the left common iliac artery. A cardiovascular pump was used to reproduce a normal pulsatile aortic flow and a steady cannulation flow. Axillary and axillary plus femoral cannulation were compared at flow rates of 3-7 l/min. Haemodynamics were analysed by using four-dimensional flow magnetic resonance imaging., Results: Axillary cannulation (AC) was found to collapse the true lumen at the coeliac and superior mesentery arteries, while combined axillary and femoral cannulation did not change the size of the true lumen. Combined axillary and femoral cannulation resulted in a larger visceral flow than did AC alone. When axillary plus femoral cannulation was used, the visceral flow increased by 125% at 3 l/min, by 89% at 4 l/min, by 67% at 5 L/min, by 98% at 6 l/min and by 101% at 7 l/min, respectively, compared to those with the AC only., Conclusions: Our model was useful to understanding the haemodynamics in aortic dissection. In this specific condition, we confirmed that the intimal flap motion can partially block blood flow to the coeliac and superior mesenteric arteries and that additional femoral cannulation can increase visceral perfusion., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: To evaluate equity in the allocation and distribution of vaccines for coronavirus disease 2019 (COVID-19) to countries and territories participating in the COVID-19 Vaccines Global Access (COVAX) Facility., Methods: We used publicly available data on the numbers of COVAX vaccine doses allocated and distributed to 88 countries and territories qualifying for COVAX-sponsored vaccine doses and 60 countries self-financing their vaccine doses facilitated by COVAX. We conducted a benefit-incident analysis to examine the allocation and distribution of vaccines based on countries' gross domestic product (GDP) per capita. We plotted cumulative country-level per capita allocation and distribution of COVID-19 vaccines from COVAX against the ranked per capita GDP of the countries and territories to generate a measure of the equity of COVAX benefits., Findings: By 23 January 2022 the COVAX Facility had allocated a total of 1 678 517 990 COVID-19 vaccine doses, of which 1 028 291 430 (61%) doses were distributed to 148 countries and territories. Taking account of COVAX subsidies, we found that countries and territories with low per capita GDP benefited more than higher-income countries in the numbers of vaccines. The benefits increased further when the analysis was adjusted by population age group (aged 65 years and older)., Conclusion: The COVAX Facility is helping to balance global inequities in the allocation and distribution of COVID-19 vaccines. However, COVAX alone has not been enough to reverse the inequality of total COVID-19 vaccine distribution. Future studies could examine the equity of all COVID-19 vaccine allocation and distribution beyond the COVAX-facilitated vaccines., ((c) 2022 The authors; licensee World Health Organization.)

Opioid abuse has become a public health concern among many developed countries, with policymakers searching for strategies to mitigate adverse effects on population health and the wider economy. The United Kingdom has seen dramatic increases in opioid-related mortality following the financial crises in 2008. We examine the impact of spending cuts resulting from government prescribed austerity measures on opioid-related hospitalisations and mortality, thereby expanding on existing evidence suggesting a countercyclical relationship with macroeconomic performance. We take advantage of the variation in spending cuts passed down from central government to local authorities since 2010, with reductions in budgets of up to fifty percent in some areas resulting in the rescaling of vital public services. Longitudinal panel data methods are used to analyse a comprehensive, linked dataset that combines information from spending records, official death registry data and large administrative health care data for 152 local authorities (i.e., unitary authorities and county councils) in England between April 2010 and March 2017. A total of 280,827 people experienced a hospital admission in the English National Health Service because of an opioid overdose and 14,700 people died from opioids across the study period. Local authorities that experienced largest spending cuts also saw largest increases in opioid abuse. Interactions between changes in unemployment and spending items for welfare programmes show evidence about the importance for governments to protect populations from social-risk effects at times of deteriorating macroeconomic performance. Our study carries important lessons for countries aiming to address high rates of opioid abuse, including the United States, Canada and Sweden., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cardiac adipose tissue is a well-known risk factor for the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation, but its correlation with maze surgery remains unknown. The aim of this study was to investigate the correlation between the recurrence of AF and the adipose component of the left atrium (LA) in patients who underwent a modified Cox maze (CM) III procedure. We reviewed the pathology data of resected LA tissues from 115 patients, including the adipose tissue from CM-III procedures. The mean follow-up duration was 30.05 ± 23.96 months. The mean adipose tissue component in the AF recurrence group was 16.17% ± 14.32%, while in the non-recurrence group, it was 9.48% ± 10.79% ( p = 0.021), and the cut-off value for the adipose component for AF recurrence was 10% ( p = 0.010). The rates of freedom from AF recurrence at 1, 3, and 5 years were 84.8%, 68.8%, and 38.6%, respectively, in the high-adipose group (≥10%), and 96.3%, 89.7%, and 80.3%, respectively, in the low-adipose group (<10%; p = 0.002). A high adipose component (≥10%) in the LA is a significant risk factor for AF recurrence after CM-III procedures. Thus, it may be necessary to attempt to reduce the perioperative adipose portion of the cardiac tissue using a statin in a randomized study.

Background: Intramural hematomas (IMHs) may originate from small intimal tears. Although most surgeries for acute type A IMH are conventionally performed solely at the proximal aorta, regardless of the primary intimal tear site, the remnant aortic remodeling stays important during the follow-up period after surgery., Methods: Forty-seven patients with "pure" acute type A IMHs who underwent surgery from January 2008 to December 2019 were retrospectively analyzed. Acute type A IMH in the entire region without penetrating aortic ulcer (PAU) and aortic dissection (AD), which upon initial computed tomography (CT), can be considered as an intimal tear site, was defined as "pure" type. The maximal diameter of the aorta, maximal thickness of the IMH, and hematoma thickness ratio (HTR) of the ascending and descending aortae were measured from the preoperative computed tomographic scan. The hematoma thickness index was defined as the HTR of the descending aorta divided by that of the ascending aorta. Major adverse aortic events (MAAEs) were defined as AD, rupture, or newly developed PAU and aortic death. Predictors for postoperative MAAEs were analyzed using preoperative computed tomographic findings., Results: The measurements of the descending aorta were larger and those of the ascending aorta were smaller in the MAAEs group, than in the corresponding other. The hematoma thickness index was significantly higher in the group with MAAEs, than in the group without; this variable was an independent predictor of MAAEs. During surgery, intimal tears were found in 16/47 (34%) patients. The hematoma thickness index was significantly smaller in the group with intimal tears than in the group without the tears. The aortic measurement appears to reflect the tear site., Conclusions: Hematoma thickness index was an independent predictor of MAAE after acute type A IMH surgery. Long-term periodical follow-up with early reintervention may, therefore, be necessary to improve outcome in these patients. As the optimal treatment method is still controversial, inferring the location of the primary tear through the hematoma thickness index can be helpful in determining the treatment method., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-21-674). Suk-Won Song serves as an unpaid editorial board member of Journal of Thoracic Disease from Feb 2021 to Jan 2023. The other authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Effects of bioaugmentation of the composite microbial culture CES-1 on a full scale textile dye wastewater treatment process were investigated in terms of water quality, sludge reduction, dynamics of microbial community structures and their functional genes responsible for degradation of azo dye, and other chemicals. The removal efficiencies for Chemical Oxygen Demand (COD), Total Nitrogen (T-N), Total Phosphorus (T-P), Suspended Solids (SS), and color intensity (96.4%, 78.4, 83.1, 84.4, and 92.0, respectively) 300-531 days after the augmentation were generally improved after bioaugmentation. The denitrification linked to T-N removal appeared to contribute to the concomitant COD removal that triggered a reduction of sludge (up to 22%) in the same period of augmentation. Azo dye and aromatic compound degradation and other downstream pathways were highly metabolically interrelated. Augmentation of CES-1 increased microbial diversity in the later stages of augmentation when a strong microbial community selection of Acinetobacter parvus , Acinetobacter johnsonii , Marinobacter manganoxydans , Verminephrobacter sp., and Arcobacter sp. occurred. Herein, there might be a possibility that the CES-1 augmentation could facilitate the indigenous microbial community successions so that the selected communities made the augmentation successful. The metagenomic analysis turned out to be a reasonable and powerful tool to provide with new insights and useful biomarkers for the complex environmental conditions, such as the full scale dye wastewater treatment system undergoing bioaugmentation.

Background: This study aimed to evaluate the early outcomes of Perceval sutureless valves in the Korean population and to introduce a modified technique of guiding suture placement during valve deployment.Methods and Results:From December 2014 to April 2019, 121 patients (mean age: 74.7±6.2 years; 53.7% female) received a Perceval sutureless aortic valve replacement. To prevent conduction system injury, the depth of guiding suture placement (1 mm below the nadir of the annulus) was modified. All patients underwent echocardiographic evaluation at discharge and 6-12 months postoperatively, with a mean follow up of 13.7±11.2 months. Concomitant surgeries, such as coronary artery bypass grafting, and other valvular surgeries, were performed in 45.5% of cases. The mean aortic cross-clamp times for isolated and minimal procedures were 32.8±7.9, and 41.2±8.0 min, respectively. The overall transvalvular mean gradients were 13.1±3.8 mmHg at discharge and 11.5±4.7 mmHg at the last follow up. After modifying the guiding suture placement, permanent pacemaker implantation risk decreased from 9.9% to 2.5%. Cardiac-related mortality was 0.8%, with no patient developing valvular or paravalvular aortic regurgitation, valve thrombosis, or endocarditis., Conclusions: Perceval valve implantation provided a significant cardiac-related survival benefit with excellent early hemodynamic and clinical outcomes. Further research is needed to determine whether adjusting the implantation depth, such as modification of the guiding suture technique, can reduce the risk of permanent pacemaker implantation.

South Korea's COVID-19 control strategy has been widely emulated. Korea's ability to rapidly achieve disease control in early 2020 without a "Great Lockdown" despite its proximity to China and high population density make its achievement particularly intriguing. This paper helps explain Korea's pre-existing capabilities which enabled the rapid and effective implementation of its COVID-19 control strategies. A systematic assessment across multiple domains demonstrates that South Korea's advantages in controlling its epidemic are owed tremendously to legal and organizational reforms enacted after the MERS outbreak in 2015. Successful implementation of the Korean strategy required more than just a set of actions, measures and policies. It relied on a pre-existing legal framework, financing arrangements, governance and a workforce experienced in outbreak management., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The relationship between functional mitral stenosis (MS) after mitral valve (MV) repair and long-term clinical outcomes is not fully understood. Therefore, we reviewed an institutional series to identify the determinants of functional MS and its effect on long-term clinical outcomes after MV repair for degenerative mitral regurgitation., Methods: Between January 1990 and December 2015, 792 patients who underwent MV repair for degenerative mitral regurgitation were retrospectively enrolled and divided into 2 groups: functional MS (n = 192) (≥5 mm Hg mean diastolic pressure gradient across the MV) and nonfunctional MS (n = 600) (<5 mm Hg mean diastolic pressure gradient). Mean follow-up was 11.6 ± 5.8 years., Results: After propensity-score matching, patients' characteristics were comparable between groups (n = 192/group). At 20 years, the functional MS group had significantly lower rates of freedom from new-onset atrial fibrillation (73.0% ± 5.6% versus 93.2% ± 2.3%; P = .003), overall survival (72.1% ± 4.6% versus 85.6% ± 4.3%; P = .010), and freedom from MV reoperation (82.8% ± 4.1% versus 92.5% ± 4.2%; P = .019) than the nonfunctional group. The functional MS group also had a significantly greater postoperative left atrial volume index and tricuspid regurgitation grade. A small left ventricular end-diastolic dimension (hazard ratio = 0.975; 95% confidence interval, 0.955-0.996; P = .022) and annuloplasty ring (hazard ratio = 0.757; 95% confidence interval, 0.685-0.837; P < .001) were independent risk factors for functional MS., Conclusions: A small left ventricle and annuloplasty ring increased the risk for functional MS after MV repair and was associated with progressive left atrial enlargement and tricuspid regurgitation exacerbation. As a result, functional MS increased the risk for new-onset atrial fibrillation, MV reoperation, and decreased long-term survival., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The Trifecta valve has externally mounted leaflets; it differs from classic internally mounted valves (e.g., Carpentier-Edwards [C-E]). We evaluated post-implantation hemodynamics and clinical outcomes of these bioprostheses in small aortic annuli. From January 2015 to April 2019, 490 patients who underwent aortic valve replacement (AVR) were reviewed retrospectively. Altogether, 183 patients received 19 or 21 mm diameter C-E ( n = 121) or Trifecta ( n = 62) prostheses. To minimize confounding variables, we performed propensity-score matching analysis. The mean transvalvular pressure gradient (TVPG) was significantly lower in the Trifecta than in the C-E group at discharge (12.9 ± 4.8 vs. 15.0 ± 5.3 mmHg, p = 0.044). TVPG change over time was not significantly different between groups ( p = 0.357). Left ventricular mass index decreased postoperatively (reduction: C-E, 28.1%; Trifecta, 30.1%, p = 0.879). No late mortality, severe patient-prosthesis mismatch, moderate-to-severe paravalvular leakage, structural valve degeneration, or valve thromboses were observed. Freedom from valve-related events at 3 years were similar for C-E (97.9% ± 2.1%) and Trifecta (97.7% ± 2.2%) patients (log-rank p = 0.993). Bioprosthesis design for small annuli significantly affected TVPG immediately after AVR. However, hemodynamics over time and clinical outcomes did not differ between the two designs.

Hexokinase 2 (HK2) is a metabolic sensor that couples glycolysis and oxidative phosphorylation of mitochondria by binding to the outer mitochondrial membrane (OMM), and it also has been implicated in induction of apoptotic process by regulating the integrity of OMM. When HK2 detaches from the mitochondria, it triggers permeability increase of the OMM and subsequently facilitates the cytosolic release of cytochrome c, a major apoptosis-inducing factor. According to previous studies, a harsh microenvironment created by ischemic heart disease such as low tissue oxygen and nutrients, and increased reactive oxygen species (ROS) can cause cardiomyocyte apoptosis. Under these conditions, the expression of HK2 in heart significantly decrease and such down-regulation of HK2 was correlated to the increased apoptosis of cardiomyocytes. Therefore, prevention of HK2 down-regulation may salvage cardiomyocytes from apoptosis. MicroRNAs are short, non-coding RNAs that either inhibit transcription of target mRNAs or degrade the targeted mRNAs via complementary binding to the 3'UTR (untranslated region) of the targeted mRNAs. Since miRNAs are known to be involved in virtually every biological processes, it is reasonable to assume that the expression of HK2 is also regulated by miRNAs. Currently, to my best knowledge, there is no previous study examined the miRNA-mediated regulation of HK2 in cardiomyocytes. Thus, in the present study, miRNA-mediated modulation of HK2 during ROS (H2O2)-induced cardiomyocyte apoptosis was investigated. First, the expression of HK2 in cardiomyocytes exposed to H2O2 was evaluated. H2O2 (500 μM) induced cardiomyocyte apoptosis and it also decreased the mitochondrial expression of HK2. Based on miRNA-target prediction databases and empirical data, miR-181a was identified as a HK2-targeting miRNA. To further examine the effect of negative regulation of the selected HK2-targeting miRNA on cardiomyocyte apoptosis, anti-miR-181a, which neutralizes endogenous miR-181a, was utilized. Delivery of anti-miR-181a significantly abrogated the H2O2-induced suppression of HK2 expression and subsequent disruption of mitochondrial membrane potential, improving the survival of cardiomyocytes exposed to H2O2. These findings suggest that miR-181a-mediated down-regulation of HK2 contributes to the apoptosis of cardiomyocytes exposed to ROS. Neutralizing miR-181a can be a viable and effective means to prevent cardiomyocyte from apoptosis in ischemic heart disease.

Objective: This study aimed to evaluate the changes in postoperative aortic regurgitation (AR) and determine the predictors of significant AR and root reoperation after ascending aortic replacement (AAR) in patients with acute type A aortic dissection., Methods: From January 1995 to December 2017, 271 consecutive patients underwent valve/root-preserving AAR (n = 225) and root replacement (n = 46). AR grade trend over time was analyzed by the ordinal mixed-effects model. Significant AR was defined as AR grade ≥3+ during the follow-up period. Predischarge and follow-up echocardiograms were obtained in 95.6% and 88.8% of enrolled patients, respectively., Results: At predischarge, postoperative ≥2+ AR was present in 20 (9.3%) and 1 (2.3%) patients in the AAR and root replacement groups, respectively. With increasing time after surgery, the grade of AR increased. At 10 years, 4.6% of patients had developed 3+ or 4+ AR. Considering death as the competing risk, the 10-year cumulative incidence of significant AR was significantly higher in the AAR than in the root replacement group (12.3% vs 2.2%; P = .047). The risk of root reoperation at 10 years was not different between the groups (P = .118). On Cox analysis, preoperative ≥3+ AR (P = .002), postoperative ≥2+ AR (P = .040), and false to true lumen ratio (P = .005) were associated predictors of significant AR., Conclusions: Although valve/root-preserving AAR demonstrated reasonable long-term outcomes when compared with root replacement, preoperative ≥3+ AR, postoperative ≥2+ AR, and high false to true lumen ratio significantly increased the risk of significant AR. Therefore, careful echocardiographic surveillance may be warranted in patients with postoperative ≥2+ AR and small true lumen., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

We compared the long-term outcomes and difference in dilatation rates of the ascending aorta after aortic valve (AV) replacement (AVR) between bicuspid and tricuspid AV patients, and evaluated risk factors associated with ascending aorta dilatation and aortic events during the follow-up. Of 1,127 patients who underwent AVR from 1995 to 2015, 259 patients with a dilated ascending aorta (≥40 mm in diameter) were included. The patients were divided into those with bicuspid (group bicuspid aortic valve [BAV], n = 105) and with tricuspid (group tricuspid aortic valve [TAV], n = 154) AV, and a propensity score-matched analysis was performed to match 98 patients in each group. The differences in the dilation rate of the ascending aorta and long-term outcomes were analyzed. Risk factors for ascending aorta dilatation, mortality, and aortic events were identified. Follow-up was completed in 100% of patients with a median follow-up duration of 106.1 [68.8, 163.0] months. The early clinical outcomes and dilation rate of the ascending aorta were similar between the groups. Overall survivals up to 15 years postoperatively were similar between groups BAV and TAV (p = 0.223). Aortic events occurred in 6 patients (groups BAV vs TAV, 2 vs 4;p = 0.678). Preoperative ascending aorta diameter showed a linear relationship with the dilatation rate of ascending aorta (p <0.001) and was related to progressive aortic dilatation and aortic events (odds ratio: 1.25, p <0.001 and hazard ratio = 1.56, p <0.001, respectively). In conclusion, the long-term outcomes and ascending aorta dilatation rate were similar between the BAV and TAV patients up to 15 years after AVR. Bicuspid AV was not a risk factor of mortality or aortic events., Competing Interests: Conflict of Interests None., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Endovascular treatment has emerged as a safe procedure for treating chronic DeBakey IIIb dissection. The objective of this study was to investigate the mid-term outcome and temporal pattern of aortic remodelling after endovascular treatment for DeBakey IIIb dissection., Methods: From 2012 to 2017, 85 patients who underwent endovascular aortic repair for DeBakey IIIb dissection were enrolled. The temporal pattern of aortic remodelling in terms of false lumen (FL) thrombosis [level 1 (∼T7), level 2 (T7 ∼ coeliac axis) and level 3 (coeliac trunk ∼ aortic bifurcation)] and aortic diameter [mid-thoracic level (T7), coeliac axis and the largest infrarenal abdominal aorta] was investigated on serial follow-up computed tomography scan., Results: Eighty-five patients underwent endovascular treatment during the study period. Male sex was a significant risk factor for repetitive reintervention and segments 2 and 3 FL thrombosis. The preoperative FL diameter at T7 was significantly associated with FL diameter regression. The number of visceral vessels from the FL and residual DeBakey IIIb dissection after type A repair were significant factors for FL growth at the coeliac trunk and at the largest infrarenal abdominal aorta. The overall mortality was 3 (3.6%)., Conclusions: Endovascular treatment is a safe strategy in the management of DeBakey IIIb dissection. However, unfavourable aortic remodelling and repetitive reintervention were expected in male patients with a large number of visceral vessels from the FL and residual DeBakey IIIb dissection after type A repair. Endovascular treatment should be cautiously considered, and close follow-up is required for these patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The role of a reentry tear in the descending thoracic aorta (DTA) after repair of acute aortic dissection is not well known. We therefore investigated the impact of reentry tear location on late aorta reintervention and the aortic expansion rate after open repair of acute type I aortic dissection., Methods: We analyzed 309 nonsyndromic acute type I aortic dissection patients who were treated with a repair to the proximal aorta between 1994 and 2017. The locations of reentry tears, identified with predischarge computed tomography, were the proximal DTA in 119 patients (38.5%), distal DTA in 78 (25.2%), and abdominal aorta in 129 (41.7%). Patients who had a proximal DTA reentry tear were defined as the PDR group (119 [38.5%]), and the others were defined as the non-PDR group (190 [61.5%])., Results: The 15-year freedom from aorta reintervention was significantly lower in the PDR group (51.5% ± 0.7% vs 90.4% ± 4.4%, P < .001). The aortic expansion rates of the proximal DTA (7.6 ± 16.1 mm/y vs 0.1 ± 2.5 mm/y, P < .001) and distal DTA (6.8 ± 15.5 mm/y vs 0.3 ± 3.1 mm/y, P < .001) were significantly higher in the PDR group. The 15-year freedom from significant aortic expansion was significantly lower in the PDR group (34.6% ± 6.9% vs 83.6% ± 7.9%, P < .001). Multivariate analysis showed that a proximal DTA reentry tear was an independent risk factor for aorta reintervention (hazard ratio, 4.955; 95% confidence interval, 1.691-14.523; P = .004) and significant aortic expansion (HR, 4.214; 95% CI, 1.691-10.498; P = .002)., Conclusions: A proximally located DTA reentry tear was associated with an increased risk of late aorta reintervention and distal aortic dilatation., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Importance: Observational studies have suggested that the use of radial artery grafts for coronary artery bypass grafting may improve clinical outcomes compared with the use of saphenous vein grafts, but this has not been confirmed in randomized trials., Objective: To compare clinical outcomes between patients receiving radial artery vs saphenous vein grafts for coronary artery bypass grafting after long-term follow-up., Design, Setting, and Participants: Patient-level pooled analysis comparing radial artery vs saphenous vein graft in adult patients undergoing isolated coronary artery bypass grafting from 5 countries (Australia, Italy, Serbia, South Korea, and the United Kingdom), with enrollment from 1997 to 2009 and follow-up completed in 2019., Interventions: Patients were randomized to undergo either radial artery (n = 534) or saphenous vein (n = 502) grafts for coronary artery bypass grafting., Main Outcomes and Measures: The primary outcome was a composite of death, myocardial infarction, or repeat revascularization and the secondary outcome was a composite of death or myocardial infarction., Results: A total of 1036 patients were randomized (mean age, 66.6 years in the radial artery group vs 67.1 years in the saphenous vein group; 376 [70.4%] men in the radial artery group vs 351 [69.9%] in the saphenous vein group); 942 (90.9%) of the originally randomized patients completed 10 years of follow-up (510 in the radial artery group). At a median (interquartile range) follow-up of 10 (10-11) years, the use of the radial artery, compared with the saphenous vein, in coronary artery bypass grafting was associated with a statistically significant reduction in the incidence of the composite outcome of death, myocardial infarction, or repeat revascularization (220 vs 237 total events; 41 vs 47 events per 1000 patient-years; hazard ratio, 0.73 [95% CI, 0.61-0.88]; P < .001) and of the composite of death or myocardial infarction (188 vs 193 total events; 35 vs 38 events per 1000 patient-years; hazard ratio, 0.77 [95% CI, 0.63-0.94]; P = .01)., Conclusions and Relevance: In this individual participant data meta-analysis with a median follow-up of 10 years, among patients undergoing coronary artery bypass grafting, the use of the radial artery compared with the saphenous vein was associated with a lower risk of a composite of cardiovascular outcomes.

Background: This study evaluated the impact of the intimal tear location on aortic dilation and reintervention after nontotal arch replacement (non-TAR) for acute type I aortic dissection., Methods: Between 2009 and 2017, 92 patients who underwent non-TAR for acute type I aortic dissection were enrolled. Intimal tears were analyzed at the supraaortic (SA) segment; segment 1, proximal descending thoracic aorta (DTA); segment 2, distal DTA; and segment 3, abdominal aorta. Aortic diameter was measured at the pulmonary artery bifurcation, celiac axis, maximal abdominal aorta, and maximal thoracoabdominal aorta using serial follow-up computed tomographic scans. The Fisher exact or χ 2 test, independent t or Mann-Whitney U test, and log-rank test were used in the statistical analyses., Results: The significant factors for increasing aortic diameter were the first location of intimal tear in the SA segment and segments 1 and 2. In the adjusted analysis, the first location of intimal tear in the SA segment and segment 1 was statistically significant. In the additional adjusted analysis, a segment 1 tear without SA tear was the only significant factor for increasing aortic diameter. The 5-year freedom from reintervention rate was significantly higher in patients with no intimal tear than in those with a segment 1 intimal tear with/without SA tear., Conclusions: We confirmed that SA and proximal DTA intimal tears are associated with subsequent aortic dilation and reintervention. These proximal aortic intimal tears might warrant aggressive surgical treatment at the initial operation or close postoperative follow-up., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Many variables may affect the hemodynamic performance of the aortic valve prosthesis, and suture technique remains an important factor for determining maximum valve performance. The objective of this study was to determine the suture technique that produces better hemodynamic performance for aortic valve replacement (AVR)., Methods: Patients who underwent AVR between January 2015 and September 2018 in our institution were analyzed. We compared the preoperative clinical information and 1-year postoperative hemodynamic data of interrupted pledget mattress sutures (pledgeted group), interrupted nonpledget mattress sutures (nonpledgeted group), and figure-of-8 nonpledget sutures (figure-of-eight group). We compared the incidence of prosthesis-patient mismatch (PPM) and cardiac adverse events among the groups and subanalyzed the PPM rate in a small aortic annulus (18 to 21 mm)., Results: A total of 439 patients underwent AVR (pledgeted, n = 212; nonpledgeted, n = 122; figure-of-eight, n = 105). The groups were similar in age (P = .359), sex (P = .055), underlying disease, and valve pathology. There was no difference in inhospital mortality or cardiac adverse events in each suture group (P = .282). The nonpledgeted suture had significantly lower moderate (P < .01) and severe PPM rates (P = .01) in patients with a small aortic annulus (18 to 21 mm)., Conclusions: The interrupted nonpledget mattress suture offers complete supraannular implantation, which reduces the incidence of PPM and results in better hemodynamic improvement after small-size AVR., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We used a large patient-level data set including 6 angiographic randomized controlled trials (RCTs) on coronary artery bypass conduits to explore incidence and determinants of coronary graft failure., Methods: Patient-level angiographic data of 6 RCTs comparing long-term outcomes of the radial artery and other conduits were joined. Primary outcome was graft occlusion at maximum follow-up. The analysis was divided as (1) left anterior descending coronary (LAD) distribution and (2) non-LAD distribution (circumflex and right coronary artery). Mixed-model multivariable Cox regression including all baseline characteristics with stratification by individual trials was used to identify predictors of graft occlusion., Results: Included were 1091 patients and 2281 grafts, consisting of 921 left internal mammary arteries, 74 right internal mammary arteries, 710 radial arteries, and 576 saphenous veins. All left internal mammary arteries were used on the LAD, the other conduits were used on the non-LAD distribution. Mean angiographic follow up was 65 ± 29 months. Occlusion rates were 2.3% for the left internal mammary arteries, 13.5% for the left internal mammary arteries, 9.4% for the right internal mammary arteries, and 17.5% for the saphenous veins. At multivariable analysis, type of conduit used, age, female sex, left ventricular ejection fraction of less than 0.50, and use of the Y graft were significantly associated with graft occlusion in the non-LAD distribution., Conclusions: Our analyses showed that failure of the left internal mammary arteries-to-LAD bypass is a very uncommon event. For the non-LAD distribution, the nonuse of radial artery, age, female sex, left ventricular ejection fraction of less than 0.50, and use of the Y graft configuration were significantly associated with midterm graft failure., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of axillary artery cannulation for early embolic stroke and operative mortality, we retrospectively compared the outcomes between patients with or without axillary artery cannulation during open aortic arch repair with circulatory arrest., Methods: Between January 2004 and December 2017, 468 patients underwent open aortic arch repair with circulatory arrest using antegrade cerebral perfusion and were divided into 2 groups according to the site of arterial cannulation: the axillary artery (axillary group, n = 352) or another site (nonaxillary group, n = 116) groups. Embolic stroke was defined as a physician-diagnosed new postoperative neurologic deficit lasting more than 72 hours, generally confirmed by computed tomography or magnetic resonance imaging., Results: After propensity score matching, the patients' characteristics were comparable between the groups (n = 116 in each). The incidences of acute type A dissection, aortic rupture, shock, or emergency operation were similar between groups. The incidence of early embolic stroke was significantly lower in axillary group (n = 3 [2.6%] vs n = 10 [8.6%]; P = .046). Also, 30-day mortality (n = 3 [2.6%] vs n = 10 [8.6%]; P = .046) and in-hospital mortality (n = 3 [2.6%] vs n = 11 [9.5%]; P = .027) occurred significantly lower in the axillary group., Conclusions: Axillary artery cannulation reduced the early embolic stroke and early mortality after open arch repair with circulatory arrest. Axillary artery cannulation as the arterial cannulation site during open arch repair with circulatory arrest may be helpful in preventing embolic stroke and reducing early mortality., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Long-term outcomes of mitral valve replacement (MVR) recipients with pulmonary hypertension (PH) remain unclear. We determined the effect of concomitant PH on the clinical outcomes and late-onset progression of tricuspid regurgitation (TR) after MVR for rheumatic mitral stenosis., Methods: We retrospectively reviewed 394 patients who underwent MVR between January 2000 and December 2013. PH was defined as systolic pulmonary arterial pressure (sPAP) >50 mm Hg. Changes in echocardiographic parameters (preoperative to postoperative), TR progression (grade ≥ II), and long-term survival were evaluated according to the presence of PH at MVR (non-PH, n = 322; PH, n = 72)., Results: The 10-year overall survival rate was significantly lower in the PH group (79.7% vs 90.7%, P = .04), whereas the rate of freedom from TR progression was similar between groups (76.9% vs 80.5%, P = .373). High preoperative sPAP and right ventricular systolic pressure (RVSP) did not affect TR progression. However, substantial postoperative reductions in sPAP and RVSP protected against TR progression (hazard ratio [95% confidence interval], 0.966 [0.942-0.991], P = .008, and 0.973 [0.960-0.986], P < .001, respectively). The 10-year rate of freedom from TR progression was significantly higher in patients with substantial sPAP and RVSP reductions (sPAP, 84.2% vs 70.6%, P = .003; RVSP, 84.9% vs 71.0%, P < .001)., Conclusions: Although concomitant PH at MVR is associated with poor long-term survival, adequate sPAP and RVSP reduction can prevent TR progression even in patients with severe PH preoperatively. Therefore, we suggest careful monitoring of PAP and RVSP after MVR and should make an effort to reduce postoperative PAP., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Disrupting the binding of CD47 to SIRPα has emerged as a promising immunotherapeutic strategy for advanced cancers by potentiating antibody-dependent cellular phagocytosis (ADCP) of targeted antibodies. Preclinically, CD47/SIRPα blockade induces antitumor activity by increasing the phagocytosis of tumor cells by macrophages and enhancing the cross-presentation of tumor antigens to CD8 + T cells by dendritic cells; both of these processes are potentiated by CD40 signaling. Here we generated a novel, two-sided fusion protein incorporating the extracellular domains of SIRPα and CD40L, adjoined by a central Fc domain, termed SIRPα-Fc-CD40L. SIRPα-Fc-CD40L bound CD47 and CD40 with high affinity and activated CD40 signaling in the absence of Fc receptor cross-linking. No evidence of hemolysis, hemagglutination, or thrombocytopenia was observed in vitro or in cynomolgus macaques. Murine SIRPα-Fc-CD40L outperformed CD47 blocking and CD40 agonist antibodies in murine CT26 tumor models and synergized with immune checkpoint blockade of PD-1 and CTLA4. SIRPα-Fc-CD40L activated a type I interferon response in macrophages and potentiated the activity of ADCP-competent targeted antibodies both in vitro and in vivo These data illustrated that whereas CD47/SIRPα inhibition could potentiate tumor cell phagocytosis, CD40-mediated activation of a type I interferon response provided a bridge between macrophage- and T-cell-mediated immunity that significantly enhanced durable tumor control and rejection., (©2019 American Association for Cancer Research.)

Purpose: The long-term outcomes of aortic wrapping in patients with ascending aortic aneurysms, which are rare, but can be fatal, remain poorly understood. This retrospective study analyzed the outcomes of aortic diameter, including aortic root, ascending aorta, and proximal arch diameters, after aortic wrapping during aortic valve replacement surgery., Materials and Methods: Ninety-six patients with ascending aortic dilation of 40-55 mm who underwent aortic wrapping during aortic valve replacement were selected for this study. Aortic diameter was measured at three levels perioperatively and at follow-up (median time of 9.1±4.2 years). A linear mixed-effects model was used to analyze aortic diameter expansion., Results: Freedom from adverse aortic events (aortic dissection or rupture, reoperation, or sudden death) at 10 years was 97.9%. No significant dilation at the level of the sinuses of Valsalva (0.069 mm/year, p =0.524) or ascending aorta (0.152 mm/year, p =0.124) was observed. Significant dilation occurred at the proximal aortic arch (0.343 mm/year, p =0.006). Subgroup analysis with a multivariable linear mixed model identified initial ascending aortic diameter to be a significant predictor of proximal arch dilation ( p =0.032). Receiver operating characteristic curve analysis revealed that the cut-off for the prediction of proximal arch redilation was an initial mid-ascending aortic diameter of 47.0 mm (area under the curve 0.747, 90% confidence interval 0.613-0.881, p =0.023)., Conclusion: Aortic wrapping could be considered as a safe and long-term therapeutic option. Redilation of the proximal arch should be carefully observed during long-term follow-up., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

It is generally accepted that radial artery (RA) grafts have better mid-term patency rate compared to saphenous vein grafts. However, the clinical correlates of the improved patency rate are still debated. Observational studies have suggested increased survival and event-free survival for patients who receive an RA rather than a saphenous vein, but they are open to bias and confounders. The only evidence based on randomized data is a pooled meta-analysis of 6 randomized controlled trial comparing the RA and the saphenous vein published by the RADial artery International Alliance (RADIAL). In the RADIAL database, improved freedom from follow-up cardiac events (death, myocardial infarction and repeat revascularization) was found at 5-year follow-up in the RA arm. The most important limitation of the RADIAL analysis is that most of the included trials had an angiographic follow-up in the first 5 years and it is unclear whether the rate of repeat revascularization (the main driver of the composite outcome) was clinically indicated due to per-protocol angiographies. Here, we present the protocol for the long-term analysis of the RADIAL database. By extending the follow-up beyond the 5th postoperative year (all trials except 1 did not have angiographic follow-up beyond 5 years), we aim to provide data on the role of RA in coronary artery bypass surgery with respect to long-term outcomes., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)