Validation of TRI-SCORE for Outcome Prediction After Isolated Tricuspid Valve Surgery in Asian Patients.

BACKGROUND: TRI-SCORE was recently developed in Europe as a risk model for predicting in-hospital death after isolated tricuspid valve surgery. We aimed to validate TRI-SCORE in an Asian population and investigate its value for predicting long-term outcomes. METHODS AND RESULTS: The TRI-SCORE was calculated for 202 patients (65±11 years, 61% women, 81% functional tricuspid regurgitation) who underwent isolated tricuspid valve surgery for severe tricuspid regurgitation at 2 Korean centers and was based on 8 parameters: age, New York Heart Association class, right-sided heart failure signs, furosemide daily dose, glomerular filtration rate, bilirubin, left ventricular ejection fraction, and moderate/severe right ventricular dysfunction. The primary outcome was all-cause death during follow-up; the secondary outcome was in-hospital death. During a median follow-up duration of 50 (interquartile range, 21-82) months after isolated tricuspid valve surgery, 23 (11.4%) patients experienced the primary outcome, and 7 (3.5%) patients experienced the secondary outcome. Observed all-cause death and in-hospital death increased by up to 50% in those with higher scores. Patients with the primary outcome had a higher TRI-SCORE (4.5±2.4 versus 2.9±2.1; P=0.001) than those without. The TRI-SCORE showed a significant association with the primary outcome (concordance index, 0.77, cutoff value, 4) and in-hospital death (area under the curve, 0.84; cutoff value, 3). Using the Kaplan-Meier analysis, patients with a high TRI-SCORE exhibited a poor outcome for all-cause death at follow-up (log-rank P<0.001) and in-hospital death (log-rank P=0.004). CONCLUSIONS: TRI-SCORE was validated in an Asian population and helped predict long-term outcomes after isolated tricuspid valve surgery.

Usefulness of cardiopulmonary exercise test combined with exercise stress echocardiography in mild chronic thromboembolic pulmonary disease.

PURPOSE: Chronic thromboembolic pulmonary disease (CTEPD) can lead to exercise limitations even without right ventricular (RV) dysfunction or pulmonary hypertension at rest. Combining exercise stress echocardiography with cardiopulmonary exercise testing (ESE-CPET) for RV function and pressure changes combined measuring overall function may be useful for CTEPD evaluation. This study aims to investigate CPET and ESE results to elucidate the mechanisms of exercise limitation in mild CTEPD cases. METHODS: Among our CTEPD registry, 50 patients who performed both right heart catheterization data of mild disease (less than 30 mm Hg of mean pulmonary arterial pressure (mPAP)) and ESE-CPET were enrolled. Echocardiography and CPET-derived parameters were compared with hemodynamic parameters measured through right heart catheterization. RESULTS: Peak VO2 (maximal oxygen consumption) was decreased in overall population (71.3 ± 16.3% of predictive value). Peak VO2 during exercise was negatively correlate with mPAP and pulmonary vascular resistance at rest. A substantial increase in RV systolic pressure (RVSP) was observed during exercise (RVSP: pre-exercise 37.2 ± 11.8 mm Hg, postexercise 64.3 ± 24.9 mm Hg, p-value < .001). Furthermore, RV function deteriorated during exercise when compared to the baseline (RV fractional area change: 31.5 ± 10.0% to 37.8 ± 7.0%, p-value < .001; RV global longitudinal strain: -17.1 ± 4.2% to -17.7 ± 3.3%, p-value < .001) even though basal RV function was normal. While an excessive increase in RVSP during exercise was noticed in both groups, dilated RV and RV dysfunction during exercise were demonstrated only in the impaired exercise capacity group. CONCLUSION: CTEPD patients with mild PH or without PH exhibited limited exercise capacity alongside an excessive increase in RVSP during exercise. Importantly, RV dysfunction during exercise was significantly associated with exercise capacity. ESE-CPET could aid in comprehending the primary cause of exercise limitation in these patients.

Phf7 has impacts on the body growth and bone remodeling by regulating testicular hormones in male mice.

PHD finger protein 7 (Phf7) is a member of the PHF family proteins, which plays important roles in spermiogenesis. Phf7 is expressed in the adult testes and its deficiency causes male infertility. In this study, we tried to find the causal relationship between Phf7 deficiency and reduced growth retardation which were found in null knock-out (Phf7-/-) mice. Phf7-/- mice were born normally in the Mendelian ratio. However, the Phf7-/- males showed decreased body weight gain, bone mineral density, and bone mineral content compared to those in wild-type (WT) mice. Histological analysis for tibia revealed increased number of osteoclast cells in Phf7-/- mice compared with that in WT mice. When we analyzed the expressions for marker genes for the initial stage of osteoclastogenesis, such as receptor activator of nuclear factor kappa B (Rank) in tibia, there was no difference in the mRNA levels between Phf7-/- and WT mice. However, the expression of tartrate-resistant acid phosphatase (Trap), a mature stage marker gene, was significantly higher in Phf7-/- mice than in WT mice. In addition, the levels of testosterone and dihydrotestosterone (DHT), more potent and active form of testosterone, were significantly reduced in the testes of Phf7-/- mice compared to those in WT mice. Furthermore, testicular mRNA levels for steroidogenesis marker genes, namely Star, Cyp11a1, Cyp17a1 and 17ß-hsd, were significantly lower in Phf7-/- mice than in WT mice. In conclusion, these results suggest that Phf7 deficiency reduces the production of male sex hormones and thereby impairs associated bone remodeling.

Prognostic implication of left atrial strain in patients experiencing early recurrence of atrial fibrillation after totally thoracoscopic ablation.

Background: Although early atrial fibrillation (AF) events during the blanking period after AF ablation are risk factors for late recurrence, data on predictors of late recurrence in patients who experience early AF events are limited. In this study, we investigated the implications of left atrial (LA) strain with respect to long-term outcomes in patients experiencing early AF during the blanking period after totally thoracoscopic ablation (TTA). Methods: A total of 128 patients who underwent TTA between 2012 and 2015 were enrolled from a tertiary center. Peak longitudinal LA strain was measured preoperatively. Early recurrence (ER) was defined as any AF within the 3-month blanking period after TTA. The primary outcome was late recurrence of AF for 5 years, detected on 12-lead electrocardiogram or 24-hour Holter monitoring, excluding the blanking period. Results: Out of 128 patients, 42 (32.8%) experienced ER during the blanking period. Patients who experienced ER had a significantly higher risk of 5-year AF recurrence compared with those who did not [72.7% vs. 29.6%, hazard ratio (HR) =3.69, 95% confidence interval (CI): 2.14-6.36, P<0.001]. Within the group of 42 patients experiencing ER, LA strain with a best cutoff value of 18.6% was the only independent predictor of 5-year AF recurrence (adjusted HR =4.20, 95% CI: 1.08-16.29, P=0.038). Patients with ER and LA strain ≥18.6% had a risk of 5-year AF recurrence, similar to those without ER (35.2% vs. 29.6%, HR =1.21, 95% CI: 0.36-4.04, P=0.755). Patients with ER and LA strain <18.6% had a significantly higher risk of 5-year AF recurrence compared to those without ER (83.0% vs. 29.6%, HR =4.83, 95% CI: 2.75-8.48, P<0.01). Conclusions: Early AF during the blanking period is common in patients undergoing TTA. In patients with ER, LA strain was an independent predictor of long-term AF recurrence.

Deciphering head and neck cancer microenvironment: Single-cell and spatial transcriptomics reveals human papillomavirus-associated differences.

Human papillomavirus (HPV) is a major causative factor of head and neck squamous cell carcinoma (HNSCC), and the incidence of HPV- associated HNSCC is increasing. The role of tumor microenvironment in viral infection and metastasis needs to be explored further. We studied the molecular characteristics of primary tumors (PTs) and lymph node metastatic tumors (LNMTs) by stratifying them based on their HPV status. Eight samples for single-cell RNA profiling and six samples for spatial transcriptomics (ST), composed of matched primary tumors (PT) and lymph node metastases (LNMT), were collected from both HPV- negative (HPV- ) and HPV-positive (HPV+ ) patients. Using the 10x Genomics Visium platform, integrative analyses with single-cell RNA sequencing were performed. Intracellular and intercellular alterations were analyzed, and the findings were confirmed using experimental validation and publicly available data set. The HPV+ tissues were composed of a substantial amount of lymphoid cells regardless of the presence or absence of metastasis, whereas the HPV- tissue exhibited remarkable changes in the number of macrophages and plasma cells, particularly in the LNMT. From both single-cell RNA and ST data set, we discovered a central gene, pyruvate kinase muscle isoform 1/2 (PKM2), which is closely associated with the stemness of cancer stem cell-like populations in LNMT of HPV- tissue. The consistent expression was observed in HPV- HNSCC cell line and the knockdown of PKM2 weakened spheroid formation ability. Furthermore, we found an ectopic lymphoid structure morphology and clinical effects of the structure in ST slide of the HPV+ patients and verified their presence in tumor tissue using immunohistochemistry. Finally, the ephrin-A (EPHA2) pathway was detected as important signals in angiogenesis for HPV- patients from single-cell RNA and ST profiles, and knockdown of EPHA2 declined the cell migration. Our study described the distinct cellular composition and molecular alterations in primary and metastatic sites in HNSCC patients based on their HPV status. These results provide insights into HNSCC biology in the context of HPV infection and its potential clinical implications.

Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA.

DddA-derived cytosine base editors (DdCBEs) and transcription activator-like effector (TALE)-linked deaminases (TALEDs) catalyze targeted base editing of mitochondrial DNA (mtDNA) in eukaryotic cells, a method useful for modeling of mitochondrial genetic disorders and developing novel therapeutic modalities. Here, we report that A-to-G-editing TALEDs but not C-to-T-editing DdCBEs induce tens of thousands of transcriptome-wide off-target edits in human cells. To avoid these unwanted RNA edits, we engineered the substrate-binding site in TadA8e, the deoxy-adenine deaminase in TALEDs, and created TALED variants with fine-tuned deaminase activity. Our engineered TALED variants not only reduced RNA off-target edits by >99% but also minimized off-target mtDNA mutations and bystander edits at a target site. Unlike wild-type versions, our TALED variants were not cytotoxic and did not cause developmental arrest of mouse embryos. As a result, we obtained mice with pathogenic mtDNA mutations, associated with Leigh syndrome, which showed reduced heart rates.

Prognosis of Chronic Kidney Disease and Metabolic Syndrome in Adults With Congenital Heart Disease.

BACKGROUND: Few studies have examined the incidence of chronic kidney disease (CKD) and metabolic syndrome (MS) and their combined prognostic effects in adult congenital heart disease (ACHD). Our aims were to identify the incidence and prognostic implications of CKD and MS in ACHD. METHODS: This is retrospective cohort study. We included 2,462 ACHD ≥ 20 years of age who were treated at a tertiary hospital in Korea from 2006 to 2018. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m². MS was diagnosed based on the presence of abnormal metabolic parameters: blood sugar level, obesity, dyslipidemia, and hypertension. The primary outcome was all-cause mortality from 2006 through 2019 using data from the Ministry of the Interior and Safety in Korea. RESULTS: The incidence of CKD and MS in ACHD was 7.6% and 35.9%, respectively. The coexistence rate of CKD and MS was 4.6%. Although MS was not independently associated with mortality in the multiple analysis (adjusted hazard ratio [aHR], 1.07; 95% confidence interval [CI], 0.79-1.46), it was closely related to the presence of CKD (adjusted odds ratio, 2.62; 95% CI, 1.89-3.63). ACHD patients with CKD had a significantly increased risk of mortality compared with those without CKD (aHR, 2.84; 95% CI, 2.00-4.04). CONCLUSIONS: In patients with ACHD, the distribution of MS is higher, and both MS and its components were associated with CKD. Given the CKD was independently associated with mortality, close monitoring and management of renal dysfunction and metabolic parameters in ACHD patients is needed.

HMBA ameliorates obesity by MYH9- and ACTG1-dependent regulation of hypothalamic neuropeptides.

The global epidemic of obesity remains a daunting problem. Here, we report hexamethylene bisacetamide (HMBA) as a potent anti-obesity compound. Peripheral and central administration of HMBA to diet-induced obese mice regulated the expression of hypothalamic neuropeptides critical for energy balance, leading to beneficial metabolic effects such as anorexia and weight loss. We found that HMBA bound to MYH9 and ACTG1, which were required for the anti-obesity effects of HMBA in both NPY-expressing and POMC-expressing neurons. The binding of HMBA to MYH9 and ACTG1 elevated the expression of HEXIM1 and enhanced its interaction with MDM2, resulting in the dissociation of the HEXIM1-p53 complex in hypothalamic cells. Subsequently, the free HEXIM1 and p53 translocated to the nucleus, where they downregulated the transcription of orexigenic NPY, but p53 and acetylated histone 3 upregulated that of anorexigenic POMC. Our study points to a previously unappreciated efficacy of HMBA and reveals its mechanism of action in metabolic regulation, which may propose HMBA as a potential therapeutic strategy for obesity.

The Development of a Permanent Implantable Spacer with the Function of Size Adjustability for Customized Treatment of Regurgitant Heart Valve Disease.

The Pivot Mandu is an innovative device featuring a leak-tight adjustable 3D balloon spacer, incorporating inner mesh support, an outer e-PTFE layer, and a compliant balloon in the middle layer with a specialized detachable system. To assess its feasibility, proof of concept was rigorously evaluated through bench testing and survival porcine animal experiments. The results demonstrated successful remote inflation of the balloon system, with the balloon spacer exhibiting sustained patent and functional integrity over an extended observation period of up to 6 months. A noteworthy feature of the newly designed 3D balloon spacer is its capability for easy size adjustment during procedures, enhancing its adaptability and practicality in clinical settings. This three-layered 3D balloon spacer, with its established long-term patency, exhibits highly encouraging outcomes that hold promise in overcoming the current limitations of spacer devices for heart valve diseases. Given the compelling results from preclinical investigations, the translation of the Pivot Mandu into human trials is strongly warranted.

Erector spinae plane block in laparoscopic colorectal surgery for reducing opioid requirement and facilitating early ambulation: a double-blind, randomized trial.

Various techniques have been formulated to reduce pain and ensure early recovery after surgery, as these are major concerns among surgeons, anesthesiologists, and patients. Erector spinae plane block (ESPB), the injection of local anesthetic into the fascial plane, is a simple and novel analgesia technique widely used due to its minimal risk of complications. ESPB has been tried in various surgeries; however, no study has reported its use in colorectal surgery. This study investigated whether ESPB could promote early recovery following laparoscopic colorectal surgery (LCS) by reducing opioid consumption and pain intensity. After randomization into the ESPB or control groups, an ultrasound-guided ESPB was performed at the thoracic 10th-11th level with 40 mL of 0.25% bupivacaine or normal saline. The ESPB group used less fentanyl during the initial 24 h after surgery (P = 0.004) and experienced less pain (P < 0.05 at all-time points) than the control group. The time to the first ambulation and the length of hospital stay were shorter in the ESPB group than in the control group (P = 0.015 and P = 0.008, respectively). In conclusion, ESPB could promote early recovery by reducing opioid consumption and pain intensity in patients receiving LCS.

Left atrial strain predicts fibrosis of left atrial appendage in patients with atrial fibrillation undergoing totally thoracoscopic ablation.

Background: Left atrial (LA) fibrosis is related with development and severity of atrial fibrillation (AF). The aim of this study was to investigate the association between LA strain and LA fibrosis in patients undergoing totally thoracoscopic ablation (TTA) for AF. Methods: Between February 2012 and March 2015, a total of 128 patients who underwent TTA were enrolled from a tertiary hospital. Left atrial appendage (LAA) was harvested during surgery to determine the degree of fibrosis. LAA fibrosis was classified as mild (1st quartile), moderate (2nd and 3rd quartile), or severe (4th quartile). Clinical outcome was 5-year recurrence rate of AF detected on electrocardiogram or 24 h Holter monitoring. Results: The mean age was 54.3 ± 8.8 years and 18.8% had paroxysmal AF. Patients with mild LAA fibrosis had a significantly lower rate of recurrent AF (23.3%) at 5 years after TTA compared with those with moderate (51.4%; hazard ratio [HR] 2.69; 95% confidence interval [CI] 1.19-6.12) or severe (53.2%; HR 2.84; 95% CI 1.16-6.97) fibrosis. Among clinical and echocardiographic parameters, peak LA strain was the only predictor of mild LAA fibrosis (coefficient 0.10, p = 0.005) with the best cutoff value of 14.7% (area under the curve 0.732). The prevalence of mild LAA fibrosis was 40.6% in patients with peak LA strain ≥14.7%, but only 6.8% in those with peak LA strain <14.7%. Conclusions: In patients undergoing TTA for AF, mild LAA fibrosis was associated with a lower risk of 5-year AF recurrence. LA strain was the only predictor of mild LAA fibrosis that reflects a lower risk of 5-year AF recurrence.

Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis.

Commensal bacteria are critically involved in the establishment of tolerance against inflammatory challenges, the molecular mechanisms of which are just being uncovered. All kingdoms of life produce aminoacyl-tRNA synthetases (ARSs). Thus far, the non-translational roles of ARSs have largely been reported in eukaryotes. Here, we report that the threonyl-tRNA synthetase (AmTARS) of the gut-associated bacterium Akkermansia muciniphila is secreted and functions to monitor and modulate immune homeostasis. Secreted AmTARS triggers M2 macrophage polarization and orchestrates the production of anti-inflammatory IL-10 via its unique, evolutionary-acquired regions, which mediates specific interactions with TLR2. This interaction activates the MAPK and PI3K/AKT signaling pathways, which converge on CREB, leading to an efficient production of IL-10 and suppression of the central inflammatory mediator NF-κB. AmTARS restores IL-10-positive macrophages, increases IL-10 levels in the serum, and attenuates the pathological effects in colitis mice. Thus, commensal tRNA synthetases can act as intrinsic mediators that maintain homeostasis.

Clinical Implication of Left Atrial Appendage Emptying Velocity in Thoracoscopic Ablation of Atrial Fibrillation.

BACKGROUND: There are limited data about predictors of atrial fibrillation (AF) recurrence after totally thoracoscopic ablation (TTA). This study investigated the clinical implication of left atrial appendage emptying velocity (LAAV) in patients undergoing TTA.Methods and Results: Patients who underwent TTA between 2012 and 2015 at a tertiary hospital were prospectively enrolled in this study. LAAV was measured and averaged over five heart beats from preoperative transesophageal echocardiography. The primary outcome was a freedom from recurrent AF or atrial flutter (AFL) detected on 24-h Holter monitoring or an electrocardiogram over a 3-year period after TTA. In all, 129 patients were eligible for analysis in this study. The mean (±SD) patient age was 54.4±8.8 years, and 95.3% were male. During the 3 years after TTA, the overall event-free survival rate was 65.3%. LAAV was an independent predictor of recurrent AF/AFL during the 3-year period after TTA (per 1-cm/s increase, adjusted hazard ratio [aHR] 0.95; 95% confidence interval [CI] 0.91-0.99; P=0.016). Event-free survival was significantly lower among patients with a low LAAV (<20 cm/s; n=21) compared with those with a normal (≥40 cm/s; n=38; aHR 6.11; 95% CI 1.42-26.15; P=0.015) or intermediate (LAAV ≥20 and <40 cm/s; n=70; aHR 2.74, 95% CI 1.29-5.83; P=0.009) LAAV. CONCLUSIONS: In patients with AF, LAAV was significantly associated with the risk of long-term recurrence of AF after TTA.

Pattern of pericardial calcification determines mid-term postoperative outcomes after pericardiectomy in chronic constrictive pericarditis.

OBJECTIVES: Although pericardiectomy is an effective treatment for constrictive pericarditis (CP), clinical outcomes are not always successful. Pericardial calcification is a unique finding in CP, although the amount and localization of calcification can vary. We investigated how the pattern and amount of pericardial calcification affect mid-term postoperative outcomes after pericardiectomy to treat CP. METHODS: All patients of total pericardiectomy in our hospital from 2010 to 2020 were enrolled. Preoperative Computed tomography (CT) scans of 98 consecutive patients were available and analyzed. Medical records were reviewed retrospectively. Cardiovascular events were defined as cardiovascular death or hospitalization associated with a heart failure symptom, and all-cause events were defined as any event that required admission. CT scans were analyzed, and the volume and localization pattern of peri-calcification were determined. Pericardium calcium scores are presented using Agatston scores. RESULTS: Of the 98 patients, 25 (25.5%) were hospitalized with heart failure symptoms after pericardiectomy. The median follow-up duration for all patients was 172 weeks. The group with a cardiovascular event had a lower calcium score than patients without an event. Multivariate Cox proportional analysis showed that high ln(calcium score+1) before pericardiectomy was a dependent predictor of cardiovascular event (hazard ratio, 0.90; p = 0.04) after pericardiectomy. When we set the cut-off value (ln(calcium score+1) = 7.22), there was a significant difference in cardiovascular events in the multivariate Cox proportional analysis (p = 0.04). CONCLUSION: A low burden of pericardial calcification was associated with a high rate of mid-term clinical events after pericardiectomy to treat CP.

Impact of Atrial Fibrillation on Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI): The K-TAVI Registry.

PURPOSE: The incidence and prognostic implications of atrial fibrillation (AF) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) are controversial, especially for Korean patients. Furthermore, the pattern of antithrombotic therapy for these patients is unknown. The present study sought to identify the impact of AF on Korean patients undergoing TAVI and demonstrate the status of antithrombotic therapy for these patients. MATERIALS AND METHODS: A total of 660 patients who underwent TAVI for severe AS were recruited from the nationwide K-TAVI registry in Korea. The enrolled patients were stratified into sinus rhythm (SR) and AF groups. The primary endpoint was all-cause death at 1-year. RESULTS: AF was recorded in 135 patients [pre-existing AF 108 (16.4%) and new-onset AF 27 (4.1%)]. The rate of all-cause death at 1 year was significantly higher in patients with AF than in those with SR [16.2% vs. 6.4%, adjusted hazard ratio (HR): 2.207, 95% confidence interval (CI): 1.182-4.120, p=0.013], regardless of the onset timing of AF. The rate of new pacemaker insertion at 1 year was also significantly higher in patients with AF than in those with SR (14.0% vs. 5.5%, adjusted HR: 3.137, 95%CI: 1.621-6.071, p=0.001). Among AF patients, substantial number of patients received the combination of multiple antithrombotic agents (77.8%), and the most common combination was that of aspirin and clopidogrel (38.1%). CONCLUSION: AF was an independent predictor of 1-year mortality and new pacemaker insertion in Korean patients undergoing TAVI.

Safety monitoring of COVID-19 vaccines: February 26, 2021, To June 4, 2022, Republic of Korea.

As of June 2022, 5 coronavirus disease 2019 (COVID-19) vaccine brands have been used in Korea's national immunization program. The Korea Disease Control and Prevention Agency has enhanced vaccine safety monitoring through a passive web-based reporting system and active text message-based monitoring. In this study, an enhanced safety monitoring system for COVID-19 vaccines is described and the frequencies and types of adverse events (AEs) associated with the 5 COVID-19 vaccine brands were analyzed. AE reports from the web-based COVID-19 Vaccination Management System and text message-based reports from recipients were analyzed. AEs were classified as nonserious or serious (e.g., death or anaphylaxis). The AE reporting rates were calculated based on the number of COVID-19 vaccine doses administered. A total of 125,107,883 doses were administered in Korea from February 26, 2021, to June 4, 2022. Among them, 471,068 AEs were reported, of which 96.1% were nonserious and 3.9% were serious. Among the 72,609 participants in the text message-based AE monitoring process, a higher AE rate of local and systemic reactions was reported for the 3rd versus 1st doses. A total of 874 cases of anaphylaxis (7.0 per 1,000,000 doses), 4 cases of thrombocytopenia syndrome (TTS), 511 cases of myocarditis (4.1 per 1,000,000 doses), and 210 cases of pericarditis (1.7 per 1,000,000 doses) were confirmed. Six fatalities were causally associated with COVID-19 vaccination (1 of TTS and 5 of myocarditis). Young adult age and female sex were related with a higher AE rate for COVID-19 vaccines. Most reported AEs were nonserious and of mild intensity.

COVID-19 vaccination-related myocarditis: a Korean nationwide study.

AIMS: A comprehensive nationwide study on the incidence and outcomes of COVID-19 vaccination-related myocarditis (VRM) is in need. METHODS AND RESULTS: Among 44 276 704 individuals with at least 1 dose of COVID-19 vaccination, the incidence and clinical courses of VRM cases confirmed by the Expert Adjudication Committee of the Korea Disease Control and Prevention Agency were analyzed. COVID-19 VRM was confirmed in 480 cases (1.08 cases per 100 000 persons). Vaccination-related myocarditis incidence was significantly higher in men than in women (1.35 vs. 0.82 per 100 000 persons, P < 0.001) and in mRNA vaccines than in other vaccines (1.46 vs. 0.14 per 100 000 persons, P < 0.001). Vaccination-related myocarditis incidence was highest in males between the ages of 12 and 17 years (5.29 cases per 100 000 persons) and lowest in females over 70 years (0.16 cases per 100 000 persons). Severe VRM was identified in 95 cases (19.8% of total VRM, 0.22 per 100 000 vaccinated persons), 85 intensive care unit admission (17.7%), 36 fulminant myocarditis (7.5%), 21 extracorporeal membrane oxygenation therapy (4.4%), 21 deaths (4.4%), and 1 heart transplantation (0.2%). Eight out of 21 deaths were sudden cardiac death (SCD) attributable to VRM proved by an autopsy, and all cases of SCD attributable to VRM were aged under 45 years and received mRNA vaccines. CONCLUSION: Although COVID-19 VRM was rare and showed relatively favorable clinical courses, severe VRM was found in 19.8% of all VRM cases. Moreover, SCD should be closely monitored as a potentially fatal complication of COVID-19 vaccination.

Role of cardiovascular magnetic resonance imaging and cardiopulmonary exercise test in predicting composite clinical outcomes in patients with hypertrophic cardiomyopathy.

We aimed to evaluate the additive value of cardiovascular magnetic resonance imaging (CMR) and cardiopulmonary exercise test (CPET) to predict clinical outcomes in patients with HCM. We enrolled 373 patients with HCM and normal left ventricular systolic function who underwent CPET and CMR. The primary outcome was a clinical composite of all-cause death, cardiac transplantation, stroke, heart failure requiring hospitalization and defibrillator implantation. During a follow-up of 70.70 ± 30.74 months, there were 84 composite clinical events. Peak oxygen consumption during CPET was significantly lower (18.51±13.25 vs. 24.59±13.28 mL/kg/min, p < 0.001) and abnormal hemodynamic response to exercise was more frequently detected (41.7 vs. 20.8%, p<0.001) in the group with composite clinical events. The extent of late gadolinium enhancement was larger in the event group (15.39±10.53 vs. 11.97±9.53%LV, p<0.001). Selective parameters were added stepwise to conventional clinical parameters; the final model, where CPET and CMR parameters were added, was verified to have the highest increment value for clinical outcome prediction (p<0.001). This study demonstrated that CPET and CMR findings may be important clinical tools for risk stratification in HCM. Exercise capacity was an independent predictor of composite outcomes in patients with HCM, with incremental value as a risk factor when added to the alleged parameters. These findings could help physicians monitor and manage patients with HCM in the real clinical field.

The incidence and clinical characteristics of myocarditis and pericarditis following mRNA-based COVID-19 vaccination in Republic of Korea adolescents from July 2021 to September 2022.

OBJECTIVES: Age-specific information regarding myocarditis/pericarditis in adolescents following mRNA-based coronavirus disease 2019 (COVID-19) vaccination in Asia remains insufficient. This study investigated the incidence and clinical characteristics of myocarditis/pericarditis in Republic of Korea adolescents after mRNA-based COVID-19 vaccination. METHODS: This retrospective descriptive study utilized patient data from the Korea Immunization Management System. Incidence rates were calculated according to age and sex. Clinical characteristics (symptoms/signs, laboratory values, and imaging results) were compared between mild and severe cases. RESULTS: Between July 19, 2021 and September 30, 2022, 3,728,224 individuals aged 12 to 19 years received 6,484,165 mRNA-based COVID-19 vaccines, and 173 cases met the case definition for myocarditis/pericarditis: 151 mild (87.3%) and 22 severe (12.7%). The incidence was 3.8-fold higher in males than in females. Troponin I/ troponin T was elevated in 96% of myocarditis cases, demonstrating higher sensitivity than creatine kinase-myocardial band (67.6%) or C-reactive protein (75.2%). ST-segment or Twave on electrography abnormalities were found in 60.3% (85/141). Paroxysmal/sustained atrial/ventricular arrhythmias were more common in severe than in mild cases (45.5% vs. 16.8%, p=0.008). Edema on T2-weighted magnetic imaging occurred in 21.6% (8/37) and 62.5% (5/8) of mild and severe cases, respectively (p=0.03). Abnormal pericardial fluid collection or pericardial inflammation was found in 75.4% of pericarditis cases (49/65). CONCLUSION: Myocarditis/pericarditis occurred in rare cases following mRNA-based COVID-19 vaccination. Most cases were mild, but the incidence was higher in adolescent males and after the second dose. As bivalent severe acute respiratory syndrome coronavirus 2 mRNA vaccination started in Republic of Korea in October 2022, the post-vaccination incidence of myocarditis/pericarditis should be closely monitored, considering clinical characteristics.

Rapid Screening and Comparison of Chimeric Lysins for Antibacterial Activity against Staphylococcus aureus Strains.

Chimeric lysins composed of various combinations of cell wall-lysing (enzymatic) and cell-wall-binding (CWB) domains of endolysins, autolysins, and bacteriocins have been developed as alternatives to or adjuvants of conventional antibiotics. The screening of multiple chimeric lysin candidates for activity via E. coli expression is not cost effective, and we previously reported on a simple cell-free expression system as an alternative. In this study, we sufficiently improved upon this cell-free expression system for use in screening activity via a turbidity reduction test, which is more appropriate than a colony reduction test when applied in multiple screening. Using the improved protocol, we screened and compared the antibacterial activity of chimeric lysin candidates and verified the relatively strong activity associated with the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain of secretory antigen SsaA-like protein (ALS2). ALS2 expressed in E. coli showed two major bands, and the smaller one (subprotein) was shown to be expressed by an innate downstream promoter and start codon (ATG). The introduction of synonymous mutations in the promoter resulted in clearly reduced expression of the subprotein, whereas missense mutations in the start codon abolished antibacterial activity as well as subprotein production. Interestingly, most of the S. aureus strains responsible for bovine mastitis were susceptible to ALS2, but those from human and chicken were less susceptible. Thus, the simple and rapid screening method can be applied to select functional chimeric lysins and define mutations affecting antibacterial activity, and ALS2 may be useful in itself and as a lead molecule to control bovine mastitis.