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).

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.

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.

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.

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.

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.

Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis.

BACKGROUND: The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial. METHODS: In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up. RESULTS: In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years. CONCLUSIONS: Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).

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.

Covered versus uncovered double bare self-expandable metal stent for palliation of unresectable extrahepatic malignant biliary obstruction: a randomized controlled multicenter trial.

BACKGROUND AND AIMS: In a recent randomized controlled trial, a double bare metal stent (DBS) showed better stent patency than single-layer metal stents. However, clear evidence comparing the efficacy of uncovered (UCDBS) and partially covered (PCDBS) DBSs for distal malignant biliary obstruction (MBO) is lacking. Therefore, we compared the clinical outcomes including stent patency of UCDBSs versus PCDBSs. METHODS: A multicenter, randomized study was performed in patients with distal MBO. The primary endpoint was stent patency. Secondary endpoints were the proportion of patients with patent stents at 6 months, risk factors for stent dysfunction, overall survival, technical and clinical success rates of stent placement, and other adverse events (AEs). RESULTS: Among 258 included patients, 130 were randomly assigned to the PCDBS group and 128 to the UCDBS group. The mean duration of stent patency of the PCDBS (421.2 days; 95% confidence interval [CI], 346.7-495.7) was longer than that of the UCDBS (377.4 days; 95% CI, 299.7-455.0), although total stent dysfunction and stent dysfunction within 6 months were not different between groups. Multivariate analysis indicated that chemotherapy after stent placement was a significant factor for overall survival (hazard ratio, .570; 95% CI, .408-.796) and had a marginal impact on stent patency (hazard ratio, 1.569; 95% CI, .923-2.667). There were no remarkable differences in AEs, including pancreatitis, cholecystitis, and stent migration, between the 2 groups. CONCLUSIONS: The use of PCDBSs compared with UCDBSs in patients with distal MBO has unclear benefits regarding stent patency and overall survival, although PCDBSs have a lower rate of tumor ingrowth. (Clinical trial registration number: NCT02937246.).

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.

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.

The effects of music intervention on anxiety and stress responses in adults with CHD undergoing cardiac catheterisation.

INTRODUCTION: This study evaluated the effect of music intervention on the anxiety and stress responses of patients who underwent an interventional cardiac catheterisation. METHODS: The study design was a pre- and post-test randomised controlled trial that included 94 patients who underwent a transcatheter atrial septal defect closure. Patients were allocated to receive either music intervention (n = 47) or usual care (n = 47) during the interventional cardiac catheterisation. Music intervention effectiveness was examined in terms of anxiety, salivary cortisol level, and heart rate variability. RESULTS: The average age of participants was 45.40 years (±16.04) in the experimental group and 47.26 years (±13.83) in the control group. Two-thirds (66.0%) of the participants in each group were women. State anxiety (F = 31.42, p < 0.001), anxiety-numerical rating scale (F = 20.08, p < 0.001), salivary cortisol levels (F = 4.98, p = 0.021), and low-frequency component/high-frequency component ratio (F = 17.31, p < 0.001) in the experimental group were significantly reduced compared with those in the control group at the end of the music intervention. CONCLUSION: This study provides practical evidence of a reduction in anxiety and stress response from music intervention preceding an interventional cardiac catheterisation, indicating that this intervention should be considered in clinical management.

A phase I/II study of ivaltinostat combined with gemcitabine and erlotinib in patients with untreated locally advanced or metastatic pancreatic adenocarcinoma.

This phase I/II study evaluated the safety and efficacy of a new histone deacetylase (HDAC) inhibitor, ivaltinostat, in combination with gemcitabine and erlotinib for advanced pancreatic ductal adenocarcinoma (PDAC). Patients diagnosed with unresectable, histologically confirmed PDAC who had not undergone previous therapy were eligible. Phase I had a 3 + 3 dose escalation design to determine the maximum tolerable dose (MTD) of ivaltinostat (intravenously on days 1, 8 and 15) with gemcitabine (1000 mg/m2 intravenously on days 1, 8 and 15) and erlotinib (100 mg/day, orally) for a 28-day cycle. In phase II, patients received a six-cycle treatment with the MTD of ivaltinostat determined in phase I. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), disease control rate (DCR) and progression-free survival (PFS). The MTD of ivaltinostat for the phase II trial was determined to be 250 mg/m2 . In phase II, 24 patients were enrolled. The median OS and PFS were 8.6 (95% confidence interval [CI]: 5.3-11.2) and 5.3 months (95% CI: 3.7-5.8). Of the 16 patients evaluated for response, ORR and DCR were 25.0% and 93.8% with a median OS/PFS of 10.8 (95% CI: 8.3-16.7)/5.8 (95% CI: 4.6-6.7) months. Correlative studies showed that mutation burden detected by cfDNA and specific blood markers such as TIMP1, pro-MMP10, PECAM1, proMMP-2 and IGFBP1 were associated with clinical outcomes. Although the result of a small study, a combination of ivaltinostat, gemcitabine and erlotinib appeared to be a potential treatment option for advanced PDAC.

A Retrospective Population-Based Survival Study of Idiopathic Pulmonary Arterial Hypertension in Korea.

BACKGROUND: Few studies used nationwide data to assess the survival rates (SRs) and death risk for idiopathic pulmonary arterial hypertension (IPAH; ICD-10 I27.0) in Korea. METHODS: IPAH data (N = 9,017; female:male = 6:4) were collected from the National Health Insurance Service in Korea, from 2006 through 2017. The data consisted of primary diagnoses related to IPAH. The Kaplan-Meier method and Cox proportional-hazards analyses were carried out. RESULTS: The mean age was 62.3 (± 19.4) years, 64.2 (± 18.9) years in female and 59.4 (± 19.8) years in male (P < 0.001). The one-, three-, five- and 10-year SRs for IPAH were 89.0%, 79.8%, 72.3% and 57.0%, respectively. The adjusted hazard ratio (HR) of IPAH was 1.81 (95% confidence interval [CI], 1.26-2.59) in 60-69 age group, 3.42 (95% CI, 2.40-4.87) in 70-79, and 7.73 (95% CI, 5.43-11.0) in 80s. Other risk factors were male, low-income status, diabetes, myocardial infarction, atrial fibrillation, ischemic stroke, hemorrhagic stroke, and malignant neoplasm. CONCLUSION: The 10-year SR of IPAH was 57% in Korea. The HR for IPAH was significantly high in patients with older age and other risk factors.

Determinants of Exercise Capacity in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Reduced exercise capacity reflects symptom severity and clinical outcomes in patients with hypertrophic cardiomyopathy (HCM). The present study aimed to identify factors that may affect exercise capacity in patients with HCM. METHODS: In 294 patients with HCM and preserved left ventricular (LV) ejection fraction, we compared peak oxygen consumption (peak VO2) evaluated by cardiopulmonary exercise testing as a representative parameter of exercise tolerance with clinical and laboratory data, including N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP), diastolic parameters on echocardiography, and the grade of myocardial fibrosis on cardiac magnetic resonance imaging (CMR). RESULTS: Median peak VO2, was 29.0 mL/kg/min (interquartile range [IQR], 25.0-34.0). Age (estimated ß = -0.140, P < 0.001), female sex (ß = -5.362, P < 0.001), NT-proBNP (ß = -1.256, P < 0.001), and E/e' ratio on echocardiography (ß = -0.209, P = 0.019) were significantly associated with exercise capacity. Peak VO2 was not associated with the amount of myocardial fibrosis on CMR (mean of late gadolinium enhancement 12.25 ± 9.67%LV). CONCLUSION: Decreased exercise capacity was associated with age, female sex, increased NT-proBNP level, and E/e' ratio on echocardiography. Hemodynamic changes and increased filling pressure on echocardiography should be monitored in this population for improved outcomes.

Discrepancy of Aortic Valve Area Measurements by Doppler vs. Biplane Stroke Volume Measurements and Utility of Combining the Different Areas in Aortic Valve Stenosis　- The Asian Valve Registry.

BACKGROUND: The aortic valve area index (AVAI) in aortic stenosis (AS) is measured by echocardiography with a continuity equation using the stroke volume index by Doppler (SVIDoppler) or biplane Simpson (SVIBiplane) method. AVAIDopplerand AVAIBiplaneoften show discrepancy due to differences between SVIDopplerand SVIBiplane. The degree of discrepancy and utility of combined AVAIs have not been investigated in a large population of AS patients, and the characteristics of subjects with larger discrepancies are unknown.Methods and Results:We studied 820 patients with significant AS (AVADoppler<1.5 cm2) enrolled in the Asian Valve Registry, a prospective multicenter registry at 12 Asian centers. All-cause death and aortic valve replacement were defined as events. SVIDopplerwas significantly larger than SVIBiplane(49±11 vs. 39±11 mL/m2, P<0.01) and AVAIDopplerwas larger than AVAIBiplane(0.51±0.15 vs. 0.41±0.14 cm2/m2, P<0.01). An increase in (AVAIDoppler- AVAIBiplane) correlated with shorter height, lower weight, older age, smaller left ventricular (LV) diameter and increased velocity of ejection flow at the LV outflow tract. Severe AS by AVAIDoppleror AVAIBiplaneenabled prediction of events, and combining these AVAIs improved the predictive value of each. CONCLUSIONS: Discrepancy in AVAI by Doppler vs. biplane method was significantly more pronounced with increased LV outflow tract flow velocity, shorter height, lower weight, older age and smaller LV cavity dimensions. Combining the AVAIs enabled mutual and incremental value in predicting events.

Peripheral natural killer cell activity is associated with poor clinical outcomes in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIM: We aimed to measure the natural killer (NK) cell activity and pro-inflammatory cytokine levels in the peripheral blood of pancreatic cancer patients and investigate the correlation of NK cell activity and cytokines with cancer status and clinical outcomes. METHODS: We prospectively enrolled patients who were pathologically diagnosed with pancreatic ductal adenocarcinoma (PDAC) between 2016 and 2017 at a tertiary hospital in Seoul, South Korea. As a control group, healthy participants were enrolled by mobile application recruitment. RESULTS: A total of 203 patients were enrolled for this study (PDAC, n = 102; healthy participants, n = 101). The peripheral blood NK cell activity of PDAC patients was significantly lower than that of healthy participants (median level, 95 pg/mL vs 2000 pg/mL, P < 0.001), and decreased NK cell activity was correlated to poor clinical outcome in terms of response to chemotherapy, tumor progression, and survival. The pro-inflammatory cytokine interleukin-6 had a strong negative correlation with NK cell activity. CONCLUSIONS: In pancreatic cancer patients, NK cell activity decreased as cancer progressed, and decreased NK cell activity was associated with poor clinical outcomes.

Efficacy and safety of palliative endobiliary radiofrequency ablation using a novel temperature-controlled catheter for malignant biliary stricture: a single-center prospective randomized phase II TRIAL.

BACKGROUND: Endobiliary radiofrequency ablation (EB-RFA) has emerged as a palliative treatment for malignant biliary strictures (MBSs); however, concerns about complications related to thermal injury remain. In this study, we evaluated the efficacy and safety of EB-RFA with a novel catheter for MBS. METHODS: Patients with inoperable cancer causing MBS were randomly assigned to either the radiofrequency ablation (RFA) group or the non-RFA group. The RFA group underwent EB-RFA at the stricture site with a temperature-controlled catheter (ELRA™; STARmed Co., Goyang, Korea) followed by deployment of a self-expanding metal stent (SEMS). For the non-RFA group, only SEMS placement was performed. The duration of stent patency, overall survival (OS), and 30-day complication rate were evaluated. This trial was registered at ClinicalTrials.gov (number NCT02646514). RESULTS: A total of 48 patients were enrolled (24 in each group). During a median follow-up period of 135.0 days (RFA group) and 119.5 days (non-RFA group), the 90-day stent patency rate, median duration of stent patency, and median OS were not different between the groups (58.3% vs. 45.8% [P = 0.386], 132.0 days vs. 116.0 days [P = 0.440], and 244.0 days vs. 180.0 days [P = 0.281], respectively). In the RFA group, procedure-related complications including thermal injury-related complications, such as bile duct perforation or hemobilia, were not reported. The early complication (< 7 days) rates were not different between the groups (4.2% vs. 12.5%, P = 0.609), and there were no late complications (7-30 days) in both groups. CONCLUSION: EB-RFA with a temperature-controlled catheter followed by SEMS placement for patients with inoperable MBS can be safe and feasible with acceptable biliary patency.

Optimal drainage of anastomosis stricture after living donor liver transplantation.

BACKGROUND: Endoscopic biliary stenting (EBS) with a fully covered, self-expandable metallic stent (FC-SEMS) and plastic stent (PS) is safe and efficient for biliary anastomotic strictures (ASs) after a deceased donor liver transplantation. Limited studies have investigated the use of FC-SEMSs for biliary strictures post-living donor liver transplantation (LDLT). We compared the resolution rate of biliary ASs post-LDLT and the 12-month recurrence rates post-stent removal between EBS with an FC-SEMS, PS, and percutaneous transhepatic biliary drainage (PTBD). METHODS: Patients with biliary ASs after an LDLT (mean age: 57.3 years, 76.1% men) hospitalized between 2014 and 2017 were enrolled. Endoscopic retrograde cholangiopancreatography (ERCP) was repeated every 3-4 months. Patients were followed-up for at least 1-year post-stent removal. RESULTS: Of the 75 patients enrolled, 16, 20, and 39 underwent EBS with an FC-SEMS, PS, and PTBD, respectively. Median follow-up period was 39.2 months. Fewer ERCP procedures were needed in the FC-SEMS group than in the PS group (median, 2 vs. 3; P = 0.20). Median stent indwelling periods were 4.7, 9.3, and 5.4 months in the FC-SEMS, PS, and PTBD groups, respectively (P = 0.006). The functional resolution rate was lower in the PS group (16/20) than in the FC-SEMS (16/16) or PTBD (39/39) group (P = 0.005). The radiologic resolution rate was higher in the FC-SEMS group (16/16) than in the PS group (14/20) (P = 0.07). The 12-month recurrence rates showed no significant differences (FC-SEMS, 4/16; PS, 3/16; PTBD, 6/39; P = 0.66). The rates of complications during treatment differed significantly between the groups (P = 0.04). Stent migration occurred in 1 (6.3%) and 5 (25.0%) patients in the FC-SEMS and PS groups, respectively (P = 0.59). CONCLUSIONS: EBS with an FC-SEMS is comparable with EBS with a PS or PTBD in terms of biliary stricture resolution and 12-month recurrence rates. The use of FC-SEMSs is potentially effective and safe for biliary AS resolution after LDLT.

Comparison of high flow nasal oxygen and conventional nasal cannula during gastrointestinal endoscopic sedation in the prone position: a randomized trial.

PURPOSE: Deep sedation for endoscopic retrograde cholangiopancreatography (ERCP) can be challenging in elderly patients in the prone position. This study investigated the effect of a high flow nasal oxygen (HFNO) delivery system on oxygenation in this procedure compared with that of conventional nasal cannula oxygen administration. METHODS: A prospective randomized trial was conducted using HFNO and conventional nasal cannula in patients undergoing ERCP in the prone position. For each patient, the lowest oxygen saturation (SpO2), the incidence of hypoxemia defined as an SpO2 below 90%, and interruptions due to airway interventions were recorded during the procedure. RESULTS: The lowest mean (standard deviation) SpO2 recorded during the procedure was higher in the HFNO group than in the conventional control group [99.8 (0.6)% vs 95.1 (7.3)%; mean difference, 4.7%; 95% confidence interval, 2.3% to 7.1%; P Group x Time < 0.001]. While the lowest SpO2 during the procedure was lower than the baseline SpO2 in the control group, the lowest SpO2 during the procedure was higher than the baseline SpO2 in the HFNO group. Hypoxemia occurred only in the control group (n = 7; 19%; P = 0.01). Procedural interruptions, including discontinuation of sedation, patient stimulation, and jaw thrusting, occurred only in the control group (n = 9 [25%], n = 10 [28%], and n = 10 [28%] cases, respectively; P = 0.001 for each). CONCLUSION: In contrast to conventional nasal cannula, high flow nasal oxygen provided adequate oxygenation without causing procedural interruptions during ERCP, suggesting that HFNO may be used as a standard oxygen delivery method during these procedures. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT03872674); registered 11 March 2019.

RéSUMé: OBJECTIF: La sédation profonde pour cholangiopancréatographie rétrograde endoscopique (CPRE) peut être difficile à réaliser chez des patients âgés en position ventrale. Cette étude a exploré l'effet d'un système d'oxygénothérapie nasale à haut débit (ONHD) sur l'oxygénation pendant cette intervention par rapport à l'administration conventionnelle d'oxygène via une lunette nasale. MéTHODE: Une étude randomisée prospective a été réalisée en utilisant une ONHD ou une lunette nasale conventionnelle chez des patients subissant une CPRE en position ventrale. Pour chaque patient, la saturation en oxygène (SpO2) la plus basse, l'incidence d'hypoxémie définie en tant qu'une SpO2 inférieure à 90 %, et les interruptions provoquées par des interventions au niveau des voies aériennes ont été enregistrées au cours de l'intervention. RéSULTATS: La SpO2 moyenne (écart type) la plus basse enregistrée pendant l'intervention était plus élevée dans le groupe ONHD que dans le groupe témoin conventionnel [99,8 (0,6) % vs 95,1 (7,3) %; différence moyenne, 4,7%; intervalle de confiance 95 %, 2,3 % à 7,1 %; P Groupe x Temps < 0,001]. Alors que la SpO2 la plus basse pendant l'intervention était plus basse que la SpO2 de base dans le groupe témoin, la SpO2 la plus basse pendant l'intervention était plus élevée que la SpO2 de base dans le groupe ONHD. L'hypoxémie n'est survenue que dans le groupe témoin (n = 7; 19 %; P = 0,01). Il n'y a eu d'interruptions de l'intervention, y compris la cessation de la sédation, la stimulation du patient et le déplacement de la mâchoire inférieure vers l'avant, que dans le groupe témoin (n = 9 [25 %], n = 10 [28 %], et n = 10 [28 %] cas, respectivement; P = 0,001 pour chaque intervention). CONCLUSION: Comparativement à une lunette nasale conventionnelle, l'oxygénothérapie nasale à haut débit a procuré une oxygénation adéquate sans provoquer d'interruptions de l'intervention pendant une CPRE, suggérant que cette modalité pourrait être utilisée comme méthode standard d'oxygénothérapie pendant de telles interventions. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03872674); enregistrée le 11 mars 2019.