The expression of PD-L1 on tumor-derived exosomes enhances infiltration and anti-tumor activity of αCD3 × αPD-L1 bispecific antibody-armed T cells.

Anti-cluster of differentiation (CD) 3 × α programmed death-ligand 1 (PD-L1) bispecific T-cell engager (BsTE)-bound T-cells (BsTE:T) are a promising new cancer treatment agent. However, the mechanisms of action of bispecific antibody-armed activated T-cells are poorly understood. Therefore, this study aimed to investigate the anti-tumor mechanism and efficacy of BsTE:T. The BsTE:T migration was assessed in vivo and in vitro using syngeneic and xenogeneic tumor models, flow cytometry, immunofluorescence staining, transwell migration assays, microfluidic chips, Exo View R100, western blotting, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. In murine B16 melanoma, MC38 colon cancer, and human multiple myeloma cells, BsTE:T exhibited superior tumor elimination relative to that of T-cells or BsTE alone. Moreover, BsTE:T migration into tumors was significantly enhanced owing to the presence of PD-L1 in tumor cells and secretion of PD-L1-containing exosomes. Furthermore, increased infiltration of CD44highCD62Llow effector memory CD8+ T-cells into tumors was closely associated with the anti-tumor effect of BsTE:T. Therefore, BsTE:T is an innovative potential anti-tumor therapy, and exosomal PD-L1 plays a crucial role both in vitro and in vivo in the anti-tumor activity of BsTE:T.

IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy.

Bispecific T cell engagers (TCEs) show promising clinical efficacy in blood tumors, but their application to solid tumors remains challenging. Here, we show that Fc-fused IL-7 (rhIL-7-hyFc) changes the intratumoral CD8 T cell landscape, enhancing the efficacy of TCE immunotherapy. rhIL-7-hyFc induces a dramatic increase in CD8 tumor-infiltrating lymphocytes (TILs) in various solid tumors, but the majority of these cells are PD-1-negative tumor non-responsive bystander T cells. However, they are non-exhausted and central memory-phenotype CD8 T cells with high T cell receptor (TCR)-recall capacity that can be triggered by tumor antigen-specific TCEs to acquire tumoricidal activity. Single-cell transcriptome analysis reveals that rhIL-7-hyFc-induced bystander CD8 TILs transform into cycling transitional T cells by TCE redirection with decreased memory markers and increased cytotoxic molecules. Notably, TCE treatment has no major effect on tumor-reactive CD8 TILs. Our results suggest that rhIL-7-hyFc treatment promotes the antitumor efficacy of TCE immunotherapy by increasing TCE-sensitive bystander CD8 TILs in solid tumors.

Prognostic impact of the E/e' ratio in patients with chronic severe aortic regurgitation undergoing aortic valve replacement.

OBJECTIVES: The study objective was to evaluate the clinical implication of left ventricular diastolic dysfunction in patients with chronic severe aortic regurgitation undergoing aortic valve replacement. METHODS: We reviewed the medical records of 323 patients (age, 56.3 ± 14.1 years; 111 female) who underwent aortic valve replacement for chronic severe aortic regurgitation between 2005 and 2019. Left ventricular diastolic dysfunction was assessed by the ratio of peak left ventricular inflow velocity over mitral annular velocity (E/e'). The study end point was the composite of death and heart failure requiring hospital admission. RESULTS: The E/e' ratio was significantly correlated with age, left atrial dimension, left ventricular end-diastolic volume, mitral regurgitation grade, and tricuspid regurgitation grade (all P < .001). During follow-up (1748.3 patient-years), death and heart failure occurred in 36 patients (2.06/patient-year) and 9 patients (0.53/patient-year), respectively. In multivariable analysis, E/e' ratio (per 5 increment, hazard ratio, 1.32; 95% confidence interval, 1.02-1.71; P = .03), age (hazard ratio, 1.06; 95% confidence interval, 1.03-1.10; P < .001), and left ventricular ejection fraction (hazard ratio, 0.94; 95% confidence interval, 0.90-0.98; P = .002) were independent predictors of death and heart failure. The 5-year heart failure-free survival was 94.9% ± 1.7% in patients with E/e' less than 15% and 84.2% ± 4.2% in patients with E/e' 15 or greater (P < .001). CONCLUSIONS: The E/e' ratio was significantly associated with adverse outcomes in patients with chronic severe aortic regurgitation undergoing aortic valve replacement and may be useful as a prognostic marker in such patients.

Bovine pericardial versus porcine bioprosthetic aortic valves: A nationwide population-based cohort study in Korea.

OBJECTIVE: To compare the clinical outcomes of aortic valve replacement (AVR) using bovine pericardial and porcine bioprostheses, utilizing a nationwide administrative claims database. METHODS: Adult patients (age ≥40 years) who underwent bioprosthetic AVR, without other valve replacements, between 2003 and 2018 were identified from the Korean National Health Insurance Service database. The outcomes of interest were all-cause mortality, cardiac mortality, and valve-related events, including the incidence of reoperation, endocarditis, systemic thromboembolism, and major bleeding. Baseline adjustment was performed using propensity score matching. Time-related outcomes were evaluated using a competing risk analysis, with death as a competing risk. RESULTS: Among the 7714 patients who underwent bioprosthetic AVR, 5621 (72.9%) received bovine pericardial prostheses and 2093 (27.1%) received porcine bioprostheses. After matching, 1937 pairs were included in the final analysis. During follow-up (median, 4.49 years; interquartile range, 2.83-8.20 years), the use of porcine bioprostheses was associated with a higher risk of aortic valve reoperation (adjusted hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.16 to 3.01); however, no significant differences were observed in cumulative incidences of all-cause mortality, cardiac mortality, thromboembolism, or major bleeding. Subgroup analyses revealed that the use of bovine valves was associated with improved survival in patients with diabetes mellitus, whereas in patients undergoing dialysis, porcine valves exhibited better survival than bovine valves. CONCLUSIONS: In this large nationwide cohort study of patients undergoing bioprosthetic aortic valve replacement, the use of porcine prostheses was significantly associated with an increased risk of reoperation compared with the use of bovine prostheses, supporting previous findings.

Evaluating Reference Ages for Selecting Prosthesis Types for Heart Valve Replacement in Korea.

Importance: Although a patient's age may be the only objective figure that can be used as a reference indicator in selecting the type of prosthesis in heart valve surgery, different clinical guidelines use different age criteria. Objective: To explore the age-associated survival-hazard functions associated with prosthesis type in aortic valve replacement (AVR) and mitral valve replacement (MVR). Design, Setting, and Participants: This cohort study compared the long-term outcomes associated with mechanical and biologic prostheses in AVR and MVR according to recipient's age using a nationwide administrative data from the Korean National Health Insurance Service. To reduce the potential treatment-selection bias between mechanical and biologic prostheses, the inverse-probability-of-treatment-weighting method was used. Participants included patients who underwent AVR or MVR in Korea between 2003 and 2018. Statistical analysis was performed between March 2022 and March 2023. Exposures: AVR, MVR, or both AVR and MVR with mechanical or biologic prosthesis. Main Outcomes and Measures: The primary end point was all-cause mortality after receiving prosthetic valves. The secondary end points were the valve-related events, including the incidence of reoperation, systemic thromboembolism, and major bleeding. Results: Of the total of 24 347 patients (mean [SD] age, 62.5 [7.3] years; 11 947 [49.1%] men) included in this study, 11 993 received AVR, 8911 received MVR, and 3470 received both AVR and MVR simultaneously. Following AVR, bioprosthesis was associated with significantly greater risks of mortality than mechanical prosthesis in patients younger than 55 years (adjusted hazard ratio [aHR], 2.18; 95% CI, 1.32-3.63; P = .002) and in those aged 55 to 64 years (aHR, 1.29; 95% CI, 1.02-1.63; P = .04), but the risk of mortality reversed in patients aged 65 years or older (aHR, 0.77; 95% CI, 0.66-0.90; P = .001). For MVR, the risk of mortality was also greater with bioprosthesis in patients aged 55 to 69 years (aHR, 1.22; 95% CI, 1.04-1.44; P = .02), but there was no difference for patients aged 70 years or older (aHR, 1.06; 95% CI, 0.79-1.42; P = .69). The risk of reoperation was consistently higher with bioprosthesis, regardless of valve position, in all age strata (eg, MVR among patients aged 55-69 years: aHR, 7.75; 95% CI, 5.14-11.69; P < .001); however, the risks of thromboembolism and bleeding were higher in patients aged 65 years and older after mechanical AVR (thromboembolism: aHR, 0.55; 95% CI, 0.41-0.73; P < .001; bleeding: aHR, 0.39; 95% CI, 0.25-0.60; P < .001), with no differences after MVR in any age strata. Conclusions and Relevance: In this nationwide cohort study, the long-term survival benefit associated with mechanical prosthesis vs bioprosthesis persisted until age 65 years in AVR and age 70 years in MVR.

Data-driven mortality risk prediction of severe degenerative mitral regurgitation patients undergoing mitral valve surgery.

AIMS: The outcomes of mitral valve replacement/repair (MVR) in severe degenerative mitral regurgitation (MR) patients depend on various risk factors. We aimed to develop a risk prediction model for post-MVR mortality in severe degenerative MR patients using machine learning. METHODS AND RESULTS: Consecutive severe degenerative MR patients undergoing MVR were analysed (n = 1521; 70% training/30% test sets). A random survival forest (RSF) model was constructed, with 3-year post-MVR all-cause mortality as the outcome. Partial dependency plots were used to define the thresholds of each risk factor. A simple scoring system (MVR-score) was developed to stratify post-MVR mortality risk. At 3 years following MVR, 90 patients (5.9%) died in the entire cohort (59 and 31 deaths in the training and test sets). The most important predictors of mortality in order of importance were age, haemoglobin, valve replacement, glomerular filtration rate, left atrial dimension, and left ventricular (LV) end-systolic diameter. The final RSF model with these six variables demonstrated high predictive performance in the test set (3-year C-index 0.880, 95% confidence interval 0.834-0.925), with mortality risk increased strongly with left atrial dimension >55 mm, and LV end-systolic diameter >45 mm. MVR-score demonstrated effective risk stratification and had significantly higher predictability compared to the modified Mitral Regurgitation International Database score (3-year C-index 0.803 vs. 0.750, P = 0.034). CONCLUSION: A data-driven machine learning model provided accurate post-MVR mortality prediction in severe degenerative MR patients. The outcome following MVR in severe degenerative MR patients is governed by both clinical and echocardiographic factors.

Bovine pericardial versus porcine bioprosthetic mitral valves: results from a Korean Nationwide Cohort Study.

OBJECTIVES: Comparisons of long-term clinical outcomes of mitral valve replacement (MVR) between bovine pericardial and porcine bioprostheses are conflicting, with limited research in large-scale real-world clinical settings. This study examined clinical outcomes in MVR according to bioprosthesis type using a national administrative claims database. METHODS: This study included adult patients undergoing bioprosthetic MVR between 2003 and 2018 using administrative health care data from the Korean National Health Insurance Service database. Propensity score matching with competing risk analysis was used to compare the clinical outcomes according to the type of bioprosthesis. The end points were death, cardiac death, and valve-related events, including the incidence of reoperation, endocarditis, systemic thromboembolism, and major bleeding. RESULTS: A total of 3151 patients underwent bioprosthetic MVR with bovine pericardial (n = 1628, 51.7%) or porcine (n = 1523, 48.3%) bioprostheses. After matching, 1170 pairs were included in the final analysis. During follow-up (median 4.49 years, interquartile range 1.87 -8.75 years), death occurred in 1178 patients (6.8%/patient-year), comprising 730 (4.3%/patient-year) cardiac death. No significant differences were noted between the bovine and porcine groups in the cumulative incidences of death from any cause [adjusted hazard ratio (aHR), 1.00; 95% confidence interval (CI), 0.87-1.14], cardiac mortality (aHR, 0.96; 95% CI, 0.81-1.14), or reoperation (aHR, 1.01; 95% CI, 0.72-1.41). CONCLUSIONS: This study on a nationwide comparison between bovine and porcine bioprostheses in MVR found no significant differences in clinical outcomes including mortality, and valve-related reoperation.

A cross-sectional study of ophthalmologic examination findings in 5385 Koreans presenting with intermittent exotropia.

The Korean Intermittent Exotropia Multicenter Study (KIEMS) was a retrospective, cross-sectional and multicenter study for the investigation of intermittent exotropia involved 65 strabismus specialists from 53 institutions in Korea. Purpose of this study was to present ophthalmologic findings of intermittent exotropia from the KIEMS. Consecutive patients with intermittent exotropia of ≥ 8 prism diopters (PD) at distance or near fixation were included. Best-corrected visual acuity, cycloplegic refraction data, angles of deviation at several cardinal positions, ocular dominance, fusion control, oblique muscle function, and binocular sensory outcomes were collected. A total of 5385 participants (2793 females; age 8.2 years) were included. Non-dominant eye was more myopic than the dominant eye (- 0.60 vs. - 0.47 diopters, P < 0.001). Mean exodeviation angles were 23.5 PD at distance and 25.0 PD at near fixation. Basic type (86.2%) was the most, followed by convergence insufficiency (9.4%) and divergence excess (4.4%) types. Alternating ocular dominance and good fusion control were more common at near than at distance fixation. Good stereopsis at 40 cm was observed in 49.3% in Titmus stereo test (≤ 60 arcsec) and in 71.0% in Randot stereo test (≤ 63 arcsec). Intermittent exotropia was mostly diagnosed in childhood and patients with the condition showed relatively good binocular functions. This study may provide objective findings of intermittent exotropia in a most reliable way, given that the study included a large study population and investigated comprehensive ophthalmology examinations.

Comparison of fiberoptic bronchoscopic intubation using silicone and polyvinyl chloride double-lumen tubes.

BACKGROUND: Direct insertion of a double-lumen tube (DLT) using a flexible fiberoptic bronchoscope (FOB) is an option for DLT intubation. The difficult process of fiberoptic intubation is that the different properties of polyvinyl chloride and silicone DLTs may affect railroading differently. Therefore, we aimed to compare intubation using polyvinyl chloride and silicone DLTs over an FOB. METHODS: Patients aged 19-75 years who required one-lung ventilation under general anesthesia were enrolled in this study. After induction of anesthesia, the anesthesiologist intubated the DLT using FOB. The primary outcome was the difficulty of railroading over the flexible FOB scaled into five grades (I, II-1, II-2, III, and IV). Additionally, the intubation time and mucosal damage were recorded. RESULTS: A total of 46 patients participated in this study, 23 each in the silicone and polyvinyl groups. The difficulty of railroading over the FOB was significantly different between the two groups (P < 0.001). In the silicone group, the grades of difficulty in railroading were limited to I and II-1; 20 patients (87%) presented no difficulty in advancing the tube. In contrast, in the polyvinyl group, 13 patients (57%) had scores of II-2 and III. Both the intubation time and mucosal damage were significantly better in the silicone group than in the polyvinyl group. CONCLUSIONS: Intubation using a silicone DLT over an FOB was easier and faster than that with a polyvinyl chloride DLT with lesser trauma around the glottis.

Long-term outcomes and prognostic factors after aortic valve surgery in patients with Takayasu arteritis.

BACKGROUND: Aortic regurgitation (AR) is a common cardiovascular complication in patients with Takayasu arteritis (TAK), and complication after aortic valve surgery (AVS) is not rare. This study aimed to identify the long-term postoperative outcomes for significant AR in patients with TAK compared with those in patients without TAK. METHODS: We included 35 patients with TAK with moderate-to-severe AR who underwent AVS and compared their postoperative outcomes with those of 105 age- and operation period-matched patients with severe AR but without TAK. The risk factors for poor outcomes [all-cause death and major adverse cardiac and cerebrovascular events (MACCE)] in patients with TAK were analyzed using multivariate Cox regression. RESULTS: The 10-year overall survival rate was 70.5% in patients with TAK and 89.4% in those without TAK (p = 0.048). The MACCE and reoperation rates were significantly higher in patients with TAK (10-year freedom from MACCE, 58.2% vs. 86.4% [p < 0.001]; 10-year freedom from reoperation, 64.5% vs. 98.3% [p < 0.001]). Eighteen of the 35 patients with TAK (51.4%) had poor outcomes, and multivariate analysis revealed that significant coronary artery involvement [hazard ratio (HR), 4.178; 95% confidence interval (CI), 1.222-14.282; p = 0.023] and decreased estimated glomerular filtration rate (HR, 0.968; 95% CI 0.947-0.989; p = 0.003) were associated with poor outcomes. CONCLUSION: The long-term postoperative outcomes for AR were poorer in patients with TAK than in those without TAK. The poor outcomes in patients with TAK were associated with coronary artery involvement and decreased renal function.

Long-term outcomes in distinct phenogroups of patients with primary mitral regurgitation undergoing valve surgery.

OBJECTIVES: Patients with mitral regurgitation (MR) may be heterogeneous with different risk profiles. We aimed to identify distinct phenogroups of patients with severe primary MR and investigate their long-term prognosis after mitral valve (MV) surgery. METHODS: The retrospective cohort of patients with severe primary MR undergoing MV surgery (derivation, n=1629; validation, n=692) was analysed. Latent class analysis was used to classify patients into subgroups using 15 variables. The primary outcome was all-cause mortality after MV surgery. RESULTS: During follow-up (median 6.0 years), 149 patients (9.1%) died in the derivation cohort. In the univariable Cox analysis, age, female, atrial fibrillation, left ventricular (LV) end-systolic dimension/volumes, LV ejection fraction, left atrial dimension and tricuspid regurgitation peak velocity were significant predictors of mortality following MV surgery. Five distinct phenogroups were identified, three younger groups (group 1-3) and two older groups (group 4-5): group 1, least comorbidities; group 2, men with LV enlargement; group 3, predominantly women with rheumatic MR; group 4, low-risk older patients; and group 5, high-risk older patients. Cumulative survival was the lowest in group 5, followed by groups 3 and 4 (5-year survival for groups 1-5: 98.5%, 96.0%, 91.7%, 95.6% and 83.4%; p<0.001). Phenogroups had similar predictive performance compared with the Mitral Regurgitation International Database score in patients with degenerative MR (3-year C-index, 0.763 vs 0.750, p=0.602). These findings were reproduced in the validation cohort. CONCLUSION: Five phenogroups of patients with severe primary MR with different risk profiles and outcomes were identified. This phenogrouping strategy may improve risk stratification when optimising the timing and type of interventions for severe MR.

Impact of valve repair on mild tricuspid insufficiency in rheumatic mitral surgery.

OBJECTIVE: Tricuspid valve repair for mild tricuspid regurgitation during rheumatic mitral valve surgery is controversial. We evaluated the benefit of tricuspid valve repair for mild tricuspid regurgitation in rheumatic mitral valve surgery. METHODS: Among 1208 consecutive patients (52.6 ± 11.9 years) with mild tricuspid regurgitation who underwent rheumatic mitral valve surgery from 2000 to 2018 in 2 referral centers, 419 received concomitant tricuspid valve repair and 789 did not. The primary end point was the development of severe tricuspid regurgitation. Deaths were regarded as competing events. Secondary end points were death and heart failure. Inverse probability of treatment weighting was performed to reduce selection bias. Multivariable competing risk analysis was performed to determine the predictive factors of severe tricuspid regurgitation. RESULTS: There was no significant difference in early mortality rates between patients with and without tricuspid valve repair (P = .26). During a median follow-up of 71.6 (interquartile range: 25.3-124.2) months, the primary end point was detected in 7 of 419 patients (0.25%/patient-years) and 28 of 789 patients (0.57%/patient-years) with and without tricuspid valve repair, respectively (P = .04). There were no significant differences in the secondary end points. After baseline adjustment, the primary end point was not significantly different depending on the addition of tricuspid valve repair (hazard ratio, 0.64; 95% confidence interval, 0.23-1.77; P = .39). In multivariable analysis, only the omission of surgical atrial fibrillation ablation (hazard ratio, 4.52; 95% confidence interval, 2.07-9.87) was significantly associated with the development of severe tricuspid regurgitation. CONCLUSIONS: Tricuspid valve repair for mild tricuspid regurgitation in rheumatic mitral valve surgery provides no overt clinical benefit.

Abdominal core training in table tennis players / Treinamento do centro abdominal em jogadores de tênis de mesa / Entrenamiento del núcleo abdominal en jugadores de tenis de mesa

ABSTRACT Introduction The current teaching mode of table tennis in China is satisfactory, but there are still some problems that are the focus of physical education teachers, such as the low efficiency of sports training. Objective Study the effect of abdominal core training on table tennis teaching. Methods Volunteers trained in table tennis at a physical education college were divided into the experimental and control group. Before and after the beginning of the experiment, table tennis students' physical indices and overall physical scores were obtained under a parameterized protocol. Results The overall score of the experimental group resulted from 7.355 (± 1.827) to 9.072 (± 1.992) before training, and the mean difference was 1.2581 points (P < 0.05), indicating a significant difference. The control group score increased from 7.606 (± 1.937) to 7.989 (± 1.440) before training, and the mean difference was 0.1976, P > 0.05, indicating no significant difference. Conclusion Compared with the current way of teaching table tennis, the scheme proposed in this paper showed better sports efficiency and could help students to improve their physical quality and sports ability. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O atual modo de ensino do tênis de mesa na China é satisfatório, mas ainda existem alguns problemas que são o foco dos professores de educação física, como a baixa eficiência do treinamento esportivo. Objetivo Estudar o efeito do treinamento do centro abdominal no ensino do tênis de mesa. Métodos Voluntários formados em tênis de mesa em uma faculdade de educação física foram divididos em grupo experimental e de controle. Antes e depois do início da experiência, foram obtidos os índices físicos dos alunos de tênis de mesa e a pontuação física geral sob um protocolo parametrizado. Resultados A pontuação geral do grupo experimental resultou em 7,355 (± 1,827) para 9,072 (± 1,992) antes do treinamento, e a diferença média foi de 1,2581 pontos (P < 0,05), indicando uma diferença significativa. A pontuação do grupo de controle aumentou de 7,606 (± 1,937) para 7,989 (± 1,440) antes do treinamento, sendo a diferença média de 0,1976, P > 0,05, indicando que não houve diferença significativa. Conclusão Em comparação com o atual modo de ensino do tênis de mesa, o esquema proposto neste trabalho apresentou melhor eficiência esportiva podendo ajudar os estudantes a melhorar a sua qualidade física e habilidade esportiva. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El modo de enseñanza actual del tenis de mesa en China es satisfactorio, pero todavía hay algunos problemas que son el centro de atención de los profesores de educación física, como la baja eficiencia del entrenamiento deportivo. Objetivo Estudiar el efecto del entrenamiento del núcleo abdominal en la enseñanza del tenis de mesa. Métodos Los voluntarios entrenados en tenis de mesa en una escuela de educación física se dividieron en grupo experimental y grupo de control. Antes y después del inicio del experimento, se obtuvieron los índices físicos de los alumnos de tenis de mesa y la puntuación física global bajo un protocolo parametrizado. Resultados La puntuación global del grupo experimental pasó de 7,355 (± 1,827) a 9,072 (± 1,992) antes del entrenamiento, y la diferencia media fue de 1,2581 puntos (P < 0,05), lo que indica una diferencia significativa. La puntuación del grupo de control aumentó de 7,606 (± 1,937) a 7,989 (± 1,440) antes del entrenamiento, y la diferencia media fue de 0,1976, P > 0,05, lo que indica que no hubo diferencias significativas. Conclusión En comparación con la forma actual de enseñar el tenis de mesa, el esquema propuesto en este trabajo presentaba una mayor eficacia deportiva y podía ayudar a los alumnos a mejorar su calidad física y su capacidad deportiva. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Direct comparison of an automated oscillometric device with an electronic auscultatory device for epidemiologic survey to evaluate the prevalence of hypertension.

Mercury-free sphygmomanometers are gradually replacing the traditional sphygmomanometers in clinical settings and epidemiological surveys for measuring blood pressure (BP) due to mercury toxicity. No direct comparative studies have evaluated BP differences and statistical errors of automated oscillometric devices (ODs) against electronic auscultatory devices (ADs) for epidemiologic surveys. Herein, we evaluated the validity of ODs for the Korea National Health and Nutrition Examination Survey (KNHANES) using the Universal Standard for BP device validation through a direct comparison with ADs as the reference standard. Four trained observers performed validation on 278 volunteers aged ≥ 19 years with a standardized BP measurement protocol. Agreement between the BP measurements recorded with an OD against those recorded with an AD was assessed by Lin's concordance correlation coefficient (CCC) and Bland-Altman's limits of agreement. To evaluate the agreement for BP classification, weighted kappa values were estimated. To explore the factors associated with BP measurement differences between the 2 devices, multiple linear regression analysis was performed. The average BP differences (OD-AD) were 2.6 ±â€…6.2 mm Hg for systolic BP (SBP) and -5.1 ±â€…5.6 mm Hg for diastolic BP (DBP). Lin's CCCs were 0.927 and 0.768 for the overall SBP and DBP, respectively. The cumulative percentage of absolute errors ≤10 mm Hg was 88.1% for SBP and 81.3% for DBP. The weighted kappa value for the Joint National Committee 7 BP classification was 0.75 (95% confidence interval: 0.68-0.81). An OD overestimated the prevalence of SBP (0.3%, P = .0222) and underestimated the prevalence of DBP (1.8%, P < .0001). Multivariate analysis to identify the risk factors for BP difference revealed the arm circumference (AC) to be negatively associated with BP difference. Male sex was positively associated, while age was negatively associated with SBP difference. OD-DBP was positively associated with DBP difference and negatively associated for DBP absolute error. ODs met the accuracy requirements of the Universal Standard criteria against ADs for SBP but not for DBP. Thus, the DBP values may be underestimated by ODs in the KNHANES.

Surgical ablation for atrial fibrillation during aortic and mitral valve surgery: A nationwide population-based cohort study.

OBJECTIVE: There is limited evidence on the effectiveness of surgical atrial fibrillation ablation in reducing mortality or thromboembolic events during aortic/mitral valve surgery. We evaluated the association of surgical ablation versus no ablation with risks of all-cause death and ischemic stroke or systemic embolization among patients with preoperative atrial fibrillation undergoing concomitant aortic valve or mitral valve surgery. METHODS: With the use of administrative healthcare datasets from the Korean National Health Insurance Service database between 2003 and 2018, adult patients with atrial fibrillation undergoing aortic/mitral valve replacement or mitral valve repair were enrolled, and their outcomes were compared according to the performance of concomitant surgical ablation. The primary end points were all-cause death and thromboembolic event of ischemic stroke or systemic embolization. RESULTS: Among 17,247 patients with atrial fibrillation undergoing aortic/mitral valve surgery, 8716 (50.5%) received surgical ablation, whereas 8531 (49.5%) did not. During a median follow-up of 6.7 years (124,842.2 patient-years), death was less in the ablation group than in the no-ablation group (2.7 vs 4.1 patient-years; P < .001). The incidence of ischemic stroke or systemic embolization was also lower in the ablation group (0.9 vs 1.3 patient-years; P < .001). After adjustment with inverse probability of treatment weighting, surgical ablation was associated with decreased risks of all-cause death (hazard ratio, 0.86; 95% confidence interval, 0.80-0.92), ischemic stroke or systemic embolization (hazard ratio, 0.62; 95% confidence interval, 0.55-0.71), and hospitalization from heart failure (hazard ratio, 0.87; 95% confidence interval, 0.79-0.96). CONCLUSIONS: In patients with atrial fibrillation undergoing aortic/mitral valve surgery, concomitant surgical ablation was significantly associated with lower risks of mortality and thromboembolic events.

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Bispecific Antibody-Bound T Cells as a Novel Anticancer Immunotherapy.

Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1+ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8+ T cells having CD8+CD44+CD62Llow phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.

Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody.

In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immuno-oncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb. Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.