The Risk and Reversibility of Osimertinib-related Cardiotoxicity in a Real-World Population.

INTRODUCTION: While osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, as the first-line therapy for metastatic non-small cell lung cancer (NSCLC) has shown significant survival benefits, concerns have arisen regarding its potential cardiotoxicity, particularly in real-world clinical settings. We aimed to investigate the incidence, risk factors, and reversibility of osimertinib-related cardiotoxicity. METHODS: We analyzed 1,126 NSCLC patients treated with osimertinib from May 2016 to April 2023 in two cancer centers. Osimertinib-related cardiotoxicity was defined as a composite of osimertinib-related cardiac dysfunction (ORCD), newly developed arrhythmia, and cardiac death. Total follow-up duration was 20.6 (10.8-35.2) months. RESULTS: The osimertinib was administered for a median of 12.4 months. The incidence of osimertinib-related cardiotoxicity was 4.7%. Advanced age (adjusted hazard ratio with 95% confidence interval; 1.07 [1.04-1.09], P < 0.001), a history of heart failure (HF; 3.35 [1.67-9.64], P = 0.025), atrial fibrillation (AF; 3.42 [1.27-9.22], P = 0.015), and baseline low left ventricle strain (0.87 [0.79-0.96], P = 0.005) were independently associated with development of cardiotoxicity. The recovery rate of ORCD was 82.4%, which did not differ between patients who discontinued medication and those who did not. CONCLUSION: In real-world practice, the incidence of osimertinib-related cardiotoxicity was 4.7%, including 3.4% for ORCD requiring cardiologic intervention, which is higher than previously reported. Given the long-term medication of osimertinib and increased mortality associated with cardiotoxicity, vigilant monitoring is crucial, especially in patients with advanced age, history of HF, AF, or decreased baseline LV strain.

Effect of Evogliptin on the Progression of Aortic Valvular Calcification.

BACKGROUND: Medical therapy for aortic stenosis (AS) remains an elusive goal. OBJECTIVES: This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression. METHODS: A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using 18F-sodium fluoride positron emission tomography (18F-NaF PET). RESULTS: There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (-5.27; 95% CI: -55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (-18.83; 95% CI: -32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm3; 95% CI: 108-163 vs 102 mm3; 95% CI: 75-129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on 18F-NaF PET was significantly lower in both the evogliptin 5 mg (-1,325.6; 95% CI: -2,285.9 to -365.4; P = 0.008) and 10-mg groups (-1,582.2; 95% CI: -2,610.8 to -553.5; P = 0.0038) compared with the placebo group. CONCLUSIONS: This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883).

Survival predictors in patients with pancreatic cancer on liposomal irinotecan plus fluorouracil/leucovorin: a multicenter observational study.

Background: Approximately half of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) receive subsequent lines of chemotherapy. Recently, the liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) regimen is recommended as subsequent lines of chemotherapy. However, little is known about the predictive factors for the nal-IRI + 5-FU/LV regimen, especially in patients with previous irinotecan (IRI) exposure. Objectives: We investigated the predictive factors associated with nal-IRI + 5-FU/LV treatment in patients with PDAC. Design: Multicenter, retrospective cohort study. Methods: This study included patients with advanced PDAC who received the nal-IRI + 5-FU/LV regimen for palliative purposes. Results: Overall, 268 patients were treated with nal-IRI + 5-FU/LV. The median overall survival (OS) was 7.9 months (95% confidence interval (CI): 7.0-8.8), while the median progression-free survival (PFS) was 2.6 months (95% CI: 1.9-3.2). An albumin level of<4.0 g/dL, neutrophil-to-lymphocyte ratio (NLR) of ⩾3.5, liver or peritoneal metastasis, and a history of >3 lines of palliative chemotherapy were associated with worse OS. An NLR of ⩾3.5 and liver metastasis were significant predictive factors for worse PFS. Previous exposure to IRI was not a significant predictor. Patients without prior IRI (no-IRI) treatment showed relatively longer OS and PFS compared to IRI responders and nonresponders, but these differences were not significant when compared specifically to the responders (OS: 8.8 vs 8.1 months, p = 0.388; PFS: 3.6 vs 2.6 months, p = 0.126). Conclusion: An NLR of ⩾3.5 and liver metastasis were associated with worse PFS. Prior IRI exposure was not a significant predictive factor for OS and PFS, especially in IRI responders.

A Single Center Experience of Pulmonary Arterial Hypertension Management in Korea: A 25-Year Comparative Analysis Following the Introduction of Targeted Therapy.

BACKGROUND AND OBJECTIVES: The transformation of pulmonary arterial hypertension (PAH) treatment in Korea, ushered by targeted therapy's advent, prompted our analysis of baseline attributes, treatment trends, and survival shifts within our single-center registry. METHODS: We examined 230 patients (72.6% female, mean age 40.6±17.4 years) diagnosed and/or treated between 1980 and 2021 in our PAH clinic. Given targeted therapy's introduction and active use since 2007, we compared diagnostic classification, demographics, and treatment patterns at that juncture. Survival analysis encompassed PAH types and the overall population. For historical survival comparison, 50 non-registry patients were retrospectively added, and age-sex matching enabled pooled analysis. RESULTS: Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) constituted the largest subset (43.0%), trailed by connective tissue disease-associated PAH (CTD-PAH, 29.6%) and idiopathic PAH (IPAH, 19.1%). Post-2007, CTD-PAH proportions surged, notably with an elevated initiation rate of targeted therapy (95.4%). Overall survival rates at 1, 5, and 10 years stood at 91.3%, 77.4%, and 65.8%, respectively, with CHD-PAH exhibiting superior survival to idiopathic or CTD-PAH. Age-sex matching analysis indicated survival disparities between those starting immediate targeted therapy vs. conservative treatment upon diagnosis, especially driven by IPAH. CONCLUSIONS: In the post-introduction of the targeted therapy era, patients with PAH promptly started treatment right away, and higher survival rates of patients who started initial PAH-targeted therapy were demonstrated. The transition towards early treatment initiation might have likely contributed to the elevated survival rates observed in Korea's PAH patient cohort.

Perioperative Risk of Noncardiac Surgery in Patients With Asymptomatic Significant Aortic Stenosis: A 10-Year Retrospective Study.

BACKGROUND: Aortic stenosis (AS) is a representative geriatric disease, and there is an anticipated rise in the number of patients requiring noncardiac surgeries in patients with AS. However, there is still a lack of research on the primary predictors of noncardiac perioperative complications in patients with asymptomatic significant AS. METHODS AND RESULTS: Among the cohort of noncardiac surgeries under general anesthesia, with an intermediate to high risk of surgery from 2011 to 2019, at Samsung Medical Center, 221 patients were identified to have asymptomatic significant AS. First, to examine the impact of significant AS on perioperative adverse events, the occurrences of major adverse cardiovascular events and perioperative adverse cardiovascular events were compared between patients with asymptomatic significant AS and the control group. Second, to identify the factors influencing the perioperative adverse events in patients with asymptomatic significant AS, a least absolute shrinkage and selection operator regression model was used. There was no significant difference between the control group and the asymptomatic significant AS group in the event rate of major adverse cardiovascular events (4.6% at control group versus 5.5% at asymptomatic significant AS group; P=0.608) and perioperative adverse cardiovascular events (13.8% at control group versus 18.3% at asymptomatic significant AS group; P=0.130). Cardiac damage stage was a significant risk factor of major adverse cardiovascular events and perioperative adverse cardiovascular events. CONCLUSIONS: There was no significant difference in major postoperative cardiovascular events between patients with asymptomatic significant AS and the control group. Advanced cardiac damage stage in significant AS is an important factor in perioperative risk of noncardiac surgery.

Phase Change Heterostructure Memory with Oxygen-Doped Sb2Te3 Layers for Improved Durability and Reliability through Nano crystalline Island Formation.

Phase-change random access memory represents a notable advancement in nonvolatile memory technology; however, it faces challenges in terms of thermal stability and reliability, hindering its broader application. To mitigate these issues, doping and structural modification techniques such as phase-change heterostructures (PCH) are widely studied. Although doping typically enhances thermal stability, it can adversely affect the switching speed. Structural modifications such as PCH have struggled to sustain stable performance under high atmospheric conditions. In this study, these challenges are addressed by synergizing oxygen-doped Sb2Te3 (OST) with PCH technology. This study presents a novel approach in which OST significantly improves the crystallization temperature, power efficiency, and cyclability. Subsequently, the integration of the PCH technology bolsters the switching speed and further amplifies the device's reliability and endurance by refining the grain size (≈7 nm). The resultant OST-PCH devices exhibit exceptional performance metrics, including a drift coefficient of 0.003 in the RESET state, endurance of ≈4 × 108 cycles, an switching speed of 300 ns, and 67.6 pJ of RESET energy. These findings suggest that the OST-PCH devices show promise for integration into embedded systems, such as those found in automotive applications and Internet of Things devices.

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.

Transgelin-2, a novel cancer stem cell-related biomarker, is a diagnostic and therapeutic target for biliary tract cancer.

BACKGROUND: Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC. METHODS: TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application. RESULTS: Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001). CONCLUSION: TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure.

Uncovering the clinicopathological features of early recurrence after surgical resection of pancreatic cancer.

To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age < 60 years, presence of lymph node metastasis, and no adjuvant chemotherapy were significantly associated with early recurrence (all P < 0.05). The proportion of patients with high S100A2 expression (H-score > 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score < 5 (41.5% vs. 63.3%, P = 0.012). The median overall survival of patients with higher S100A2 expression was longer than those with lower S100A2 expression (median 30.1 months vs. 24.2 months, P = 0.003). High-risk factors for early recurrence after surgery for pancreatic cancer include young age, lymph node metastasis, and no adjuvant therapy. Neoadjuvant treatment or intensive adjuvant therapy after surgery may improve the prognosis of patients with high-risk signatures. In patients who receive adjuvant therapy, high S100A2 expression is a good predictor.

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.

Integrative analysis of spatial and single-cell transcriptome data from human pancreatic cancer reveals an intermediate cancer cell population associated with poor prognosis.

BACKGROUND: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. METHODS: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. RESULTS: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. CONCLUSIONS: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets.

First-in-Human Study for Evaluating the Accuracy of Smart Ring Based Cuffless Blood Pressure Measurement.

BACKGROUND: Recently, a ring-type cuffless blood pressure (BP) measuring device has been developed. This study was a prospective, single arm, first-in-human pivotal trial to evaluate accuracy of BP measurement by the new device. METHODS: The ring-type smart wearable monitoring device measures photoplethysmography signals from the proximal phalanx and transmits the data wirelessly to a connected smartphone. For the BP comparison, a cuff was worn on the arm to check the reference BP by auscultatory method, while the test device was worn on the finger of the opposite arm to measure BP simultaneously. Measurements were repeated for up to three sets each on the left and right arms. The primary outcome measure was mean difference and standard deviation of BP differences between the test device and the reference readings. RESULTS: We obtained 526 sets of systolic BP (SBP) and 513 sets of diastolic BP (DBP) from 89 subjects, with ranges of 80 to 175 mmHg and 43 to 122 mmHg for SBP and DBP, respectively. In sample-wise comparison, the mean difference between the test device and the reference was 0.16 ± 5.90 mmHg (95% limits of agreement [LOA], -11.41, 11.72) in SBP and -0.07 ± 4.68 (95% LOA, -9.26, 9.10) in DBP. The test device showed a strong correlation with the reference for SBP (r = 0.94, P < 0.001) and DBP (r = 0.95, P < 0.001). There were consistent results in subject-wise comparison. CONCLUSION: The new ring-type BP measuring device showed a good correlation for SBP and DBP with minimal bias compared with an auscultatory method.

Randomized Trial of Prophylactic Antibiotics for Endoscopic Retrograde Cholangiopancreatography in Patients With Biliary Obstruction.

INTRODUCTION: The incidence of postendoscopic retrograde cholangiopancreatography (ERCP) infections is reported to be up to 18% in patients with biliary obstruction. Antibiotic prophylaxis may reduce the risk of infectious complications after ERCP; however, the clinical value of prophylactic antibiotics in ERCP remains controversial. METHODS: We conducted a double-blind, placebo-controlled, randomized trial to investigate whether the use of prophylactic antibiotics would reduce infectious complications after ERCP in patients with biliary obstruction. We randomly assigned patients in a 1:1 ratio to receive either a single dose of 1 g intravenous cefoxitin or normal saline as a placebo 30 minutes before undergoing ERCP. The primary outcome was the incidence of infectious complications after ERCP. RESULTS: We enrolled 378 patients, and 189 patients were assigned to each group. The risk of infectious complications after ERCP was 2.8% (5 of 176 patients) in the antibiotic prophylaxis group and 9.8% (17 of 173 patients) in the placebo group (risk ratio, 0.29; 95% confidence interval [CI], 0.11-0.74, P = 0.0073). The incidence rates of bacteremia were 2.3% (4 of 176 patients) and 6.4% (11 of 173 patients), respectively (risk ratio, 0.36; 95% CI, 0.12-1.04; P = 0.0599). The incidence rate of cholangitis was 1.7% (3 of 176 patients) in the antibiotic prophylaxis group and 6.4% (11 of 173 patients) in the placebo group (risk ratio, 0.27; 95% CI, 0.08-0.87; P = 0.0267). DISCUSSION: Antibiotic prophylaxis before ERCP in patients with biliary obstruction resulted in a significantly lower risk of infectious complications, especially cholangitis, than placebo ( ClinicalTrials.gov trial number NCT02958059).

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.

Phenotypic characteristics of circulating tumor cells and predictive impact for efficacy of chemotherapy in patients with pancreatic cancer: a prospective study.

Objective: Early chemoresistance and tumor mass progression are associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Circulating tumor cells (CTCs) have been studied as potential predictors of treatment response and prognosis in PDAC; however, this approach has yet to be applied in clinical practice. The aim of our study was to investigate the phenotypic characteristics of CTCs and determine their predictive value for PDAC progression. Methods: We prospectively enrolled 40 patients who were pathologically diagnosed with PDAC and collected blood samples at diagnosis, 2 months after diagnosis, and during disease progression or recurrence. We used a microfabricated filter-based enrichment system to retrieve and analyze CTCs, which were classified using immunofluorescence staining (CD45, EpCAM, and vimentin). Results: Our study included 20 women and 20 men (median age, 66 years). Overall, 45% of the patients (18/40) had disseminated disease, and 77.5% (31/40) received chemotherapy. Multivariate analysis revealed that the total CTC count and carbohydrate antigen 19-9 level at 2 months after diagnosis were associated with disease progression (P<0.05). Linear mixed model analysis revealed that the total CTC count and vimentin-positive CTCs were significantly correlated with treatment response during chemotherapy (P=0.024 and 0.017, respectively). Kaplan-Meier analysis showed that total CTC positivity at 2 months was significantly associated with poor progression-free survival (P=0.038). Conclusion: Our study's findings suggest that CTCs can serve as predictive biomarkers of clinical outcomes in patients with PDAC receiving palliative chemotherapy. In particular, the total CTC count and vimentin-positive CTCs showed changes associated with the chemotherapy response.

Predictors of embolism and death in left-sided infective endocarditis: the European Society of Cardiology EURObservational Research Programme European Infective Endocarditis registry.

BACKGROUND AND AIMS: Even though vegetation size in infective endocarditis (IE) has been associated with embolic events (EEs) and mortality risk, it is unclear whether vegetation size associated with these potential outcomes is different in left-sided IE (LSIE). This study aimed to seek assessing the vegetation cut-off size as predictor of EE or 30-day mortality for LSIE and to determine risk predictors of these outcomes. METHODS: The European Society of Cardiology EURObservational Research Programme European Infective Endocarditis is a prospective, multicentre registry including patients with definite or possible IE throughout 2016-18. Cox multivariable logistic regression analysis was performed to assess variables associated with EE or 30-day mortality. RESULTS: There were 2171 patients with LSIE (women 31.5%). Among these affected patients, 459 (21.1%) had a new EE or died in 30 days. The cut-off value of vegetation size for predicting EEs or 30-day mortality was >10 mm [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.13-1.69, P = .0015]. Other adjusted predictors of risk of EE or death were as follows: EE on admission (HR 1.89, 95% CI 1.54-2.33, P < .0001), history of heart failure (HR 1.53, 95% CI 1.21-1.93, P = .0004), creatinine >2 mg/dL (HR 1.59, 95% CI 1.25-2.03, P = .0002), Staphylococcus aureus (HR 1.36, 95% CI 1.08-1.70, P = .008), congestive heart failure (HR 1.40, 95% CI 1.12-1.75, P = .003), presence of haemorrhagic stroke (HR 4.57, 95% CI 3.08-6.79, P < .0001), alcohol abuse (HR 1.45, 95% CI 1.04-2.03, P = .03), presence of cardiogenic shock (HR 2.07, 95% CI 1.29-3.34, P = .003), and not performing left surgery (HR 1.30 95% CI 1.05-1.61, P = .016) (C-statistic = .68). CONCLUSIONS: Prognosis after LSIE is determined by multiple factors, including vegetation size.

Antiplatelet therapy and long-term mortality in patients with myocardial injury after non-cardiac surgery.

BACKGROUNDS: Myocardial injury after non-cardiac surgery (MINS) has recently been accepted as a common complication associated with increased mortality. However, little is known about the treatment of MINS. The aim of this study was to investigate an association between antiplatelet therapy and long-term mortality after MINS. METHODS: From 2010 to 2019, patients with MINS, defined as having a peak high-sensitivity troponin I higher than 40 ng/L within 30 days after non-cardiac surgery, were screened at a tertiary centre. Patients were excluded if they had a history of coronary revascularisation before or during index hospitalisation. Clinical outcomes at 1 year were compared between patients with and without antiplatelet therapy at hospital discharge. The primary outcome was death, and the secondary outcome was major bleeding. RESULTS: Of the 3818 eligible patients with MINS, 940 (24.6%) received antiplatelet therapy at hospital discharge. Patients with antiplatelet therapy had a significantly lower mortality at 1 year than those without antiplatelet therapy (7.5% vs 15.9%, adjusted HR 0.60, 95% CI 0.45 to 0.79, p<0.001). A risk of major bleeding at 1 year was not significantly different between the patients with and without antiplatelet therapy (6.6% vs 7.6%, adjusted HR 0.85, 95% CI 0.62 to 1.17, p=0.324). In propensity score-matched analysis of 886 pairs, patients with antiplatelet therapy had a significantly lower risk of 1-year mortality (adjusted HR 0.53, 95% CI 0.39 to 0.73, p<0.001) than those without antiplatelet therapy. CONCLUSIONS: In patients with MINS, antiplatelet therapy at discharge was associated with decreased 1-year mortality.

Effect of Transition Metal Dichalcogenide Based Confinement Layers on the Performance of Phase-Change Heterostructure Memory.

Phase-change random-access memory is a promising non-volatile memory technology. However repeated phase-change operations can cause durability issues owing to defects formed by long-distance atom diffusion. To mitigate these issues, phase-change heterostructure (PCH) devices with confinement material (CM) layers based on transition metal dichalcogenides (TMDs) such as TiTe2 have been proposed. This study implements PCH devices with additional TMDs, including NiTe2 and MoTe2 , alongside TiTe2 , and analyzes their characteristics by examining the differences in the CM layers. The results show that the NiTe2 -based PCH device demonstrates a RESET current of 1.4 mA, 38% lower than that of the TiTe2 -based device, enabling low-power operation. Furthermore, the MoTe2 -based PCH device exhibits a cycling endurance exceeding 107 cycles, a five-fold improvement in durability compare with the TiTe2 -based device. The performance differences observe in each PCH device can be attributed to the variation in the material properties, such as the cohesive energy and electrical conductivity, of the TMDs used as the CM layer. These results provide critical clues to improve the performance and reliability of conventional PCH memory devices.

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.

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.