Comparing underwater endoscopic submucosal dissection and conventional endoscopic submucosal dissection for large laterally spreading tumor: a randomized controlled trial.

BACKGROUND AND AIMS: Colorectal endoscopic submucosal dissection (ESD) is challenging despite its usefulness. Underwater ESD (UESD) provides better traction and a clearer view of the submucosal layer than conventional ESD (CESD). This study compared the efficiency of UESD and CESD for large (20-50 mm) laterally spreading tumor (LST). METHODS: Preplanned sample size was calculated from our previous experience. As a results, 28 patients were required to UESD group or CESD group, respectively. The primary outcome was total procedure time while the secondary outcome was dissection speed. RESULTS: Fifty-six patients were enrolled and a total of 28 patients were assigned to each group. The mean size of LST was 31.6 mm and 31.3 mm in the UESD and CESD group, respectively. Fibrosis was observed in 67.9% and 60.7% patients in the UESD and CESD group. Total procedure time (mean [SD]) for the UESD group was significantly shorter than that for the CESD group, respectively (49.5 minutes [20.3] vs 75.7 minutes [36.1]; mean difference, -26.2 minutes; 95% CI, -42.0 to -10.5). Dissection speed of the UESD group was significantly faster than that of the CESD group (21.9 mm2/min [6.9] vs 15.2 mm2/min [7.3]; mean difference, 6.7 mm2/minutes; 95% CI, 2.8-10.4). There was no difference between groups in the R0 resection rate or en bloc resection rate. No perforations were observed in either group. CONCLUSIONS: UESD was superior to CESD in total procedure time and dissection speed. UESD can be recommended as the preferred method for the resection of large LST.

Efficacy comparison of 7- and 14-day P-CAB based bismuth-containing quadruple regimen with PPI based bismuth-containing quadruple regimen for Helicobacter pylori infection: rationale and design of an open-label, multicenter, randomized controlled trial.

BACKGROUND: Owing to its strong acid inhibition, potassium-competitive acid blocker (P-CAB) based regimens for Helicobacter pylori (H. pylori) eradication are expected to offer clinical advantages over proton pump inhibitor (PPI) based regimens. This study aims to compare the efficacy and adverse effects of a 7-day and a 14-day P-CAB-based bismuth-containing quadruple regimen (PC-BMT) with those of a 14-day PPI-based bismuth-containing quadruple regimen (P-BMT) in patients with high clarithromycin resistance. METHODS: This randomized multicenter controlled clinical trial will be performed at five teaching hospitals in Korea. Patients with H. pylori infection who are naive to treatment will be randomized into one of three regimens: 7-day or 14-day PC-BMT (tegoprazan 50 mg BID, bismuth subcitrate 300 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or 14-day P-BMT. The eradication rate, treatment-related adverse events, and drug compliance will be evaluated and compared among the three groups. Antibiotic resistance testing by culture will be conducted during the trial, and these data will be used to interpret the results. A total of 366 patients will be randomized to receive 7-day PC-BMT (n = 122), 14-day PC-BMT (n = 122), or 14-day P-BMT (n = 122). The H. pylori eradication rates in the PC-BMT and P-BMT groups will be compared using intention-to-treat and per-protocol analyses. DISCUSSION: This study will demonstrate that the 7-day or 14-day PC-BMT is well tolerated and achieve similar eradication rates to those of 14-day P-BMT. Additionally, the 7-day PC-BMT will show fewer treatment-related adverse effects and higher drug compliance, owing to its reduced treatment duration. TRIAL REGISTRATION: Korean Clinical Research Information Service registry, KCT0007444. Registered on 28 June 2022, https://cris.nih.go.kr/cris/index/index.do .

Prevalence and prognosis of acute pancreatitis in critically ill patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic issue. In addition to the well-known respiratory and fever symptoms, gastrointestinal symptoms have also been reported. This study aimed to evaluate the prevalence and prognosis of patients with COVID-19 infection complicated with acute pancreatitis in intensive care unit (ICU). METHODS: This was a retrospective observational cohort study, and patients aged 18 years or older, admitted into the ICU in a single tertiary center from January 1, 2020, to April 30, 2022 were enrolled. Patients were identified by electronic medical records and reviewed manually. The primary outcome was the prevalence of acute pancreatitis among ICU patients with COVID-19. The secondary outcomes were the length of hospital stay, need for mechanical ventilation (MV), need for continuous renal replacement therapy (CRRT), and in-hospital mortality. RESULTS: A total of 4133 patients, admitted into the ICU, were screened. Among these patients, 389 were infected by COVID-19, and 86 were diagnosed with acute pancreatitis. COVID-19 positive patients were more likely to present with acute pancreatitis than COVID-19 negative patients (odds ratio = 5.42, 95% confidence interval: 2.35-6.58, P < 0.01). However, the length of hospital stay, need for MV, need for CRRT, and in-hospital mortality were not significantly different between acute pancreatitis patients with and without COVID-19 infection. CONCLUSIONS: Severe COVID-19 infections may cause acute pancreas damage in critically ill patients. However, the prognosis may not differ between acute pancreatitis patients with and without COVID-19 infection.

Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Effect of alcohol consumption on the risk of adverse events in atrial fibrillation: from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry.

AIMS: The aim of this study is to determine the relationship between alcohol consumption and atrial fibrillation (AF)-related adverse events in the AF population. METHODS AND RESULTS: A total of 9411 patients with nonvalvular AF in a prospective observational registry were categorized into four groups according to the amount of alcohol consumption-abstainer-rare, light (<100 g/week), moderate (100-200 g/week), and heavy (≥200 g/week). Data on adverse events (ischaemic stroke, transient ischaemic attack, systemic embolic event, or AF hospitalization including for AF rate or rhythm control and heart failure management) were collected for 17.4 ± 7.3 months. A Cox proportional hazard models was performed to calculate hazard ratios (HRs), and propensity score matching was conducted to validate the results. The heavy alcohol consumption group showed an increased risk of composite adverse outcomes [adjusted hazard ratio (aHR) 1.32, 95% confidence interval (CI) 1.06-1.66] compared with the reference group (abstainer-rare group). However, no significant increased risk for adverse outcomes was observed in the light (aHR 0.88, 95% CI 0.68-1.13) and moderate (aHR 0.91, 95% CI 0.63-1.33) groups. In subgroup analyses, adverse effect of heavy alcohol consumption was significant, especially among patients with low CHA2DS2-VASc score, without hypertension, and in whom ß-blocker were not prescribed. CONCLUSION: Our findings suggest that heavy alcohol consumption increases the risk of adverse events in patients with AF, whereas light or moderate alcohol consumption does not.

Effects of Acupuncture on Cardiac Remodeling in Patients with Persistent Atrial Fibrillation: Results of a Randomized, Placebo-Controlled, Patient- and Assessor-Blinded Pilot Trial and Its Implications for Future Research.

Background and Objectives: In this study, we attempted to determine the effects of acupuncture on cardiac remodeling and atrial fibrillation (AF) recurrence rates in patients with AF after electrical cardioversion (EC). Materials and Methods: We randomly assigned 44 patients with persistent AF to an acupuncture group or a sham acupuncture group. An electroacupuncture treatment session was administered once weekly for 12 weeks at four acupuncture points (left PC5, PC6, ST36, and ST37). Results: Among the 44 recruited participants, 16 (treatment group) and 15 (control group) completed the trial. The three-month AF recurrence rate (primary outcome) was not significantly different between the two groups. Following the completion of treatment, patients who had been treated with acupuncture had a significant reduction in left atrial volume index (42.2 ± 13.9 to 36.1 ± 9.7 mL/m2; p = 0.028), whereas no change in atrial size was observed in the sham acupuncture group. No serious adverse events were observed. The AF recurrence rate and cardiac function did not differ significantly between the two groups. At three months, the acupuncture treatment group showed more favorable atrial structural remodeling compared to the sham acupuncture group. Conclusion: In future research on acupuncture in AF management, it is recommended that the inclusion criteria be amended to include only symptomatic AF, that an appropriate control group is designed, and that the acupuncture treatment frequency is increased to several times per week.

Usefulness of an Implantable Loop Recorder in Diagnosing Unexplained Syncope and Predictors for Pacemaker Implantation.

BACKGROUND: An implantable loop recorder (ILR) is an effective tool for diagnosing unexplained syncope (US). We examined the diagnostic utility of an ILR in detecting arrhythmic causes of US and determining which clinical factors are associated with pacemaker (PM) implantation. METHODS: This retrospective, multicenter, observational study was conducted from February 2006 to April 2018 at 11 hospitals in Korea. Eligible patients with recurrent US received an ILR to diagnose recurrent syncope and document arrhythmia. RESULTS: A total of 173 US patients (mean age, 67.6 ± 16.5 years; 107 men [61.8%]) who received an ILR after a negative conventional workup were enrolled. During a mean follow-up of 9.4 ± 11.1 months, 52 patients (30.1%) had recurrent syncope, and syncope-correlated arrhythmia was confirmed in 34 patients (19.7%). The ILR analysis showed sinus node dysfunction in 24 patients (70.6%), supraventricular tachyarrhythmia in 4 (11.8%), ventricular arrhythmia in 4 (11.8%), and sudden atrioventricular block in 2 (5.9%). Overall, ILR detected significant arrhythmia in 99 patients (57.2%) irrespective of syncope. Among patients with clinically relevant arrhythmia detected by ILR, PM implantation was performed in 60 (34.7%), an intra-cardiac defibrillator in 5 (2.9%), and catheter ablation in 4 (2.3%). In a Cox regression analysis, history of paroxysmal atrial fibrillation (PAF) (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.33-4.12; P < 0.01) and any bundle branch block (BBB) (HR, 2.52; 95% CI, 1.09-5.85; P = 0.03) were significantly associated with PM implantation. CONCLUSION: ILR is useful for detecting syncope-correlated arrhythmia in patients with US. The risk of PM is high in US patients with a history of PAF and any BBB.

GAREM1 regulates the PR interval on electrocardiograms.

PR interval is the period from the onset of P wave to the start of the QRS complex on electrocardiograms. A recent genomewide association study (GWAS) suggested that GAREM1 was linked to the PR interval on electrocardiograms. This study was designed to validate this correlation using additional subjects and examined the function of Garem1 in a mouse model. We analyzed the association of rs17744182, a variant in the GAREM1 locus, with the PR interval in 5646 subjects who were recruited from 2 Korean replication sets, Yangpyeong (n = 2471) and Yonsei (n = 3175), and noted a significant genomewide association by meta-analysis (P = 2.39 × 10-8). To confirm the function of Garem1 in mice, Garem1 siRNA was injected into mouse tail veins to reduce the expression of Garem1. Garem1 transcript levels declined by 53% in the atrium of the heart (P = 0.029), and Garem1-siRNA injected mice experienced a significant decrease in PR interval (43.27 ms vs. 44.89 ms in control, P = 0.007). We analyzed the expression pattern of Garem1 in the heart by immunohistology and observed specific expression of Garem1 in intracardiac ganglia. Garem1 was expressed in most neurons of the ganglion, including cholinergic and adrenergic cells. We have provided evidence that GAREM1 is involved in the PR interval of ECGs. These findings increase our understanding of the regulatory signals of heart rhythm through intracardiac ganglia of the autonomic nervous system and can be used to guide the development of a therapeutic target for heart conditions, such as atrial fibrillation.

Quality of Anticoagulation and Treatment Satisfaction in Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonist: Result from the KORean Atrial Fibrillation Investigation II.

BACKGROUND: Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction. METHODS: We conducted a multicenter, prospective, non-interventional study. Patients with CHADS2 ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up. RESULTS: A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS2 ≥ 2 and 83.6% had CHA2DS2-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain. CONCLUSION: INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.

Platelet reactivity after receiving clopidogrel compared with ticagrelor in patients with kidney failure treated with hemodialysis: a randomized crossover study.

BACKGROUND: Patients with kidney failure treated with maintenance hemodialysis (HD) are poor responders to clopidogrel. More beneficial platelet-inhibiting strategies in HD patients therefore are required. STUDY DESIGN: Single-center, prospective, randomized, crossover study. SETTING & PARTICIPANTS: 25 HD patients in Seoul, Korea. INTERVENTION: Patients were randomly assigned to receive clopidogrel (300mg loading, 75mg once daily for maintenance dose) or ticagrelor (180mg loading, 90mg twice daily for maintenance dose) for 14 days, and after a 14-day washout period, crossover treatment for another 14 days. All patients received aspirin (100mg/d). OUTCOMES & MEASUREMENTS: Platelet function was evaluated predosing and at 1, 5, and 48 hours and 14 days after the first loading dose. During the offset phase, platelet function was assessed at 1 hour and 2, 4, and 14 days after the last dose by light transmittance aggregometry and the VerifyNow P2Y12 assay, and patients were genotyped for the CYP2C19*2 allele. Maximal extent of aggregation, inhibition of platelet aggregation (IPA), P2Y12 reaction units (PRUs), and percentage of inhibition were evaluated. We performed per-protocol analysis, excluding patients who did not complete the protocol. RESULTS: 9 patients did not complete the protocol (7 patients due to adverse events; 2, nonadherence). Higher IPA occurred with ticagrelor than with clopidogrel at 1, 5, and 48 hours and 14 days after loading. By 5 hours after loading, a greater proportion of patients in the ticagrelor group than in the clopidogrel group achieved IPA>50% (75% vs 12%, respectively; P<0.05) and IPA>70% (44% vs 0%, respectively; P<0.05). Rates (slope) of onset and offset of the antiplatelet effect were faster in patients receiving ticagrelor than for those receiving clopidogrel (P<0.05). Regardless of CYP2C19*2 allele, the ticagrelor group had significantly lower PRUs at all times than the clopidogrel group. LIMITATIONS: Single-center study with a small number of patients, not a double-blind study, and not intention-to-treat analysis. CONCLUSIONS: Ticagrelor may result in more rapid and greater platelet inhibition than clopidogrel in patients with kidney failure receiving HD.

Transenteral bowel preparation for colonoscopy is more comfortable than the traditional method with no inferiority in efficacy.

BACKGROUND: Transenteral (TE) administration of a bowel cleanser prior to colonoscopy avoids the discomfort associated with drinking a large volume of unpalatable cleanser. AIM: To explore patient comfort, preference for future colonoscopy, the efficacy and adverse events associated with TE bowel preparation. METHODS: Bowel preparation is traditionally practised using polyethylene glycol (PEG) + ascorbic acid (ASC), which was the treatment used in the control group (peroral group; PO group). In the study group (TE group), PEG + ASC were administered directly to the third portion of the duodenum through a scope immediately after completing upper gastrointestinal endoscopy. RESULTS: A higher proportion of subjects in the TE group graded their degree of comfort as very or rather comfortable (28.4 % in the PO group, 65.1 % in the TE group; p = 0.000) and had greater preference for future colonoscopy (69.6 % in the PO group, 82.5 % in the TE group; p = 0.030), compared with the PO group. The TE group had non-inferiority in efficacy compared with the PO group (non-inferiority margin -15 %; lower limit of 95 % confidence interval for difference between success rates -6.4 %, when using the Aronchick Scale, and -7.1 % when using the Ottawa Scale). Nausea or vomiting were more prevalent during preparation in the PO group (46.1 vs. 17.5 %; p = 0.000), and dizziness was more common in the TE group (0 vs. 12.6 %; p = 0.000). CONCLUSIONS: TE preparation was found to be more comfortable than the traditional peroral method and not inferior in efficacy. The adverse events rate was acceptable.

Impact of lysophosphatidylcholine on survival and function of UEA-1(+)acLDL (+) endothelial progenitor cells in patients with coronary artery disease.

Lysophosphatidylcholine (LPC) generated from oxidized low-density lipoprotein by lipoprotein-associated phospholipase A2 plays a key role in plaque inflammation and vulnerability. Endothelial progenitor cells (EPCs) can repair injured endothelium and exert anti-inflammatory effects of vulnerable plaque. We study the impact and mechanisms of LPC on UEA-1 and acLDL binding EPCs (UEA-1(+)acLDL(+) EPCs). UEA-1(+)acLDL(+) EPCs from coronary artery disease (CAD) patients were cultured and exposed to LPC at different concentrations and different timepoints. We determined the significant concentration (40 µM). UEA-1(+)acLDL(+) EPCs were preincubated for 30 min with pravastatin (20 µM) with LY249002, a specific inhibitor of the Akt signaling pathway, and exposed for 24 h to LPC 40 µM. The survival, migration, adhesion, and proliferation of UEA-1(+)acLDL(+) EPCs were assessed. To examine the mechanisms of LPC toxicity and pravastatin effects, phosphorylated Akt and endothelial nitric oxide synthase (eNOS) levels and the ratio of Bcl-2/Bax protein expression were assessed. LPC induced apoptosis and impaired migration and adhesion of UEA-1(+)acLDL(+) EPCs significantly. The detrimental effects of LPC were attenuated by pravastatin. However, when UEA-1(+)acLDL(+) EPCs were pretreated with pravastatin and LY249002, a specific inhibitor of the Akt signaling pathway, simultaneously, the beneficial effects of pravastatin were abolished. Furthermore, LPC suppressed Akt and eNOS phosphorylation and increased Bcl-2/Bax expression. The effects of LPC on Akt/eNOS and Bcl-2/Bax activity were reversed by pravastatin. In conclusion, LPC inhibited UEA-1(+)acLDL(+) EPCs survival and impaired its functions, and these were attributable to inhibition of the Akt/eNOS and Bcl-2/Bax pathway. Pravastatin reversed the detrimental action of LPC. These findings suggest that LPC inhibition can be a possible strategy for CAD through EPC revitalization.

Effects of electroacupuncture on endothelial function and circulating endothelial progenitor cells in patients with cerebral infarction.

This study evaluated the effects of electroacupuncture (EA) on endothelial function and endothelial progenitor cells (EPC) in patients with cerebral infarction. In a randomized, placebo-controlled, crossover study, 20 patients with cerebral infarction were randomized into two treatment groups: EA or placebo. Before and after each intervention, pulse amplitude tonometry (PAT) was used to assess endothelial function and peripheral blood was analyzed for the number of EPCs. Circulating EPCs were quantified by flow cytometry as CD45(low) CD34(+) KDR2(+) cells. Plasma vascular endothelial growth factor (VEGF) and interleukin (IL)-10 levels were measured. Seven days later, crossover was performed on each group, with each group receiving the other treatment using the same protocol. The PAT hyperemia ratio ranged from 1.57 ± 0.41 to 2.04 ± 0.51 after EA, representing a significant improvement (P = 0.002); however, there was no improvement in the placebo group (P = 0.48). Circulating EPCs, as measured by flow cytometry, increased to 110.6 ± 74.3/100 µL in the EA group (P = 0.001) but did not change in the placebo group (45.9 ± 35.3/100 µL, P = 0.08). The increases in the number of EPCs and the PAT ratio after treatment were correlated (r = 0.78, P < 0.001). Plasma VEGF levels increased with EA compared to baseline (261.2 ± 34.0 vs 334.9 ± 80.5 pg/mL, P = 0.003). The number of circulating EPCs was positively correlated with plasma levels of VEGF (r = 0.50, P = 0.02). In conclusion, EA induced improvement of EPC levels and the PAT ratio in patients with cerebral infarction.

Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study.

OBJECTIVE: Experimental evidence suggests that exenatide, a glucagon-like peptide 1 receptor analogue, has significant cardiovascular protective effects in various conditions. We examined whether routine use of exenatide at the time of primary percutaneous coronary intervention would reduce infarct size in patients with ST-segment-elevation myocardial infarction. APPROACH AND RESULTS: Fifty-eight patients with ST-segment-elevation myocardial infarction and thrombolysis in myocardial infarction flow 0 were enrolled in the study and randomly assigned to receive either exenatide or placebo (saline) subcutaneously. Infarct size was assessed by measuring the release of creatine kinase-MB and troponin I during 72 hours and by performing cardiac magnetic resonance imaging at 1 month after infarction. Routine and speckle tracking echocardiography was performed at initial presentation and at 3 days and 6 months after primary percutaneous coronary intervention. The exenatide and control groups had similar results with respect to ischemia time, demographic characteristics, and ejection fraction before primary percutaneous coronary intervention. The releases of creatine kinase-MB and troponin I were significantly reduced in the exenatide group. In 58 patients evaluated with cardiac magnetic resonance, the absolute mass of delayed hyperenhancement was significantly reduced in the exenatide group as compared with the control group (12.8±11.7 versus 26.4±11.6 g; P<0.01). At 6 months, the exenatide group showed a significantly lower value of E/E' with improved strain parameters. No significant adverse effects of exenatide administration were detected. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, adjunctive exenatide therapy with primary percutaneous coronary intervention was associated with reduction of infarct size and improvement of subclinical left ventricular function.

Is annual endoscopic surveillance necessary for the early detection of gastric remnant cancer in Korea? A retrospective multi-center study.

BACKGROUND/AIMS: This study investigated the clinical characteristics, survival outcomes of the patients with gastric remnant cancers (GRC) diagnosed after gastric cancer surgery and the need of annual endoscopic surveillance after gastric resection for early detection of GRC. METHODOLOGY: We reviewed the medical records of 30 patients who underwent endoscopy and diagnosed with GRC between 1999 and 2009. We analyzed the clinical features, tumor characteristics, regular endoscopic surveillance, treatment, and survival outcomes. RESULTS: The median time interval between first operation and diagnosis of GRC was 36 months. Fifteen patients (50%) had GRC at non-anastomotic sites. Seventeen patients (56.7%) underwent annual endoscopic surveillance and nine patients (30%) had no symptom at the time of diagnosis of GRC. GRC were detected earlier in patients with annual endoscopic surveillance than those without surveillance (p=0.0014). The median overall survival (OS) after the diagnosis of GRC for all patients was 35.9 months. The median OS of patients with curative resection including endoscopic resection for early gastric cancer was longer than those without resectability (46.3 vs. 13.6 months, p=0.0026). CONCLUSIONS: These results suggest that annual endoscopic surveillance program after gastric partial resection would be helpful to detect early cancer of remnant stomach for curative resection.

Association Between Atrial Fibrillation Symptoms and Clinical Outcomes: A Prospective Multicenter Registry Study.

The presence of symptoms plays an important role in determining whether to focus on rhythm control or rate control when treating atrial fibrillation (AF). Previous comparative studies on the clinical outcomes of symptomatic and asymptomatic AF have yielded inconsistent results, and a link between AF symptoms and left atrial (LA) remodeling is not established. Patients selected from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, which is a prospective, multicenter study consisting of patients with non-valvular AF, were grouped into 2 groups: symptomatic and asymptomatic. The primary outcome was a composite of the following cardiovascular outcomes: all-cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and heart failure hospitalization. Of 10,210 patients with AF, 4,327 (42%) had symptomatic AF. The asymptomatic group had an older mean age, more men, and more patients with hypertension and diabetes mellitus than the symptomatic group. The asymptomatic group had a larger left atrium (LA) diameter (43.6 vs 42.2 mm, p <0.001) than the symptomatic group. During a median follow-up of 32.9 (29.5 to 36.4) months, the asymptomatic and symptomatic groups showed similar incidences of the primary outcome (1.44 vs 1.45 per 100 person-years; log-rank, p = 0.8). In conclusion, the absence of AF symptoms is associated with increased LA. However, symptomatic and asymptomatic patients with AF have a similar risk of cardiovascular outcomes. This suggests that beneficial treatment for AF may be considered regardless of whether patients have symptomatic or asymptomatic AF.

Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

Alpha B-crystallin prevents the arrhythmogenic effects of particulate matter isolated from ambient air by attenuating oxidative stress.

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated by particulate matter (PM) isolated from ambient air and linked to prolonged repolarization and cardiac arrhythmia. We evaluated whether alpha B-crystallin (CryAB), a heat shock protein, could prevent the arrhythmogenic effects of PM by preventing CaMKII activation. CryAB was delivered into cardiac cells using a TAT-protein transduction domain (TAT-CryAB). ECGs were measured before and after tracheal exposure of diesel exhaust particles (DEP) and each intervention in adult Sprague-Dawley rats. After endotracheal exposure of DEP (200 µg/mL for 30 minutes, n=11), QT intervals were prolonged from 115±14 ms to 144±20 ms (p=0.03), and premature ventricular contractions were observed more frequently (0% vs. 44%) than control (n=5) and TAT-Cry (n=5). However, DEP-induced arrhythmia was not observed in TAT-CryAB (1 mg/kg) pretreated rats (n=5). In optical mapping of Langendorff-perfused rat heats, compared with baseline, DEP infusion of 12.5 µg/mL (n=12) increased apicobasal action potential duration (APD) differences from 2±6 ms to 36±15 ms (p<0.001), APD restitution slope from 0.26±0.07 to 1.19±0.11 (p<0.001) and ventricular tachycardia (VT) from 0% to 75% (p<0.001). DEP infusion easily induced spatially discordant alternans. However, the effects of DEP were prevented by TAT-CryAB (1mg/kg, n=9). In rat myocytes, while DEP increased reactive oxygen species (ROS) generation and phosphated CaMKII, TAT-CryAB prevented these effects. In conclusion, CryAB, a small heat shock protein, might prevent the arrhythmogenic effects of PM by attenuating ROS generation and CaMKII activation.

Preventive effects of exenatide on endothelial dysfunction induced by ischemia-reperfusion injury via KATP channels.

OBJECTIVE: The purpose of this study was to evaluate whether exenatide administration can prevent impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) injury and whether this effect is mediated by K(ATP) channel opening. METHODS AND RESULTS: In a double-blind, placebo-controlled, crossover design, 20 volunteers were randomly assigned to 2 groups: subcutaneous exenatide (10 µg) or placebo administration. At 30 minutes after the study drug administration, endothelium-dependent flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion) injury. Seven days later, both groups were crossed over and received the other treatment (ie, placebo or exenatide) and underwent the same protocol. Pre-IR radial artery diameter, FMD, and baseline radial artery diameter after IR injury were similar between 2 groups (P=no significant difference). After placebo administration, IR significantly blunted FMD (before IR: 12.0±6.23%; after IR: 4.6±3.57%, P=0.02). Exenatide prevented this impairment (FMD before IR: 15.0±7.14%; FMD after IR: 15.0±5.96%, P=no significant difference; P<0.001 compared with placebo). In a separate protocol, this protective effect was completely abolished by pretreatment with glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 12.0±2.2%; after IR: 3.2±2.1%, P<0.001). CONCLUSIONS: The present study demonstrates that subcutaneous exenatide protects IR-induced endothelial dysfunction through opening of K(ATP) channels in human IR injury model.

Effect of endogenous substance P on visceral afferent signal integration in the nucleus tractus solitaries of rat brainstem slices.

In the first synapse of the blood-pressure-regulating pathway, a neurokinin (NK) family peptide substance P (SP) is release with an excitatory neurotransmitter, glutamate, to enhance the sensitivity of the baroreflex responses. However, the underlying mechanisms of action are not yet well understood. The effects of NK receptor antagonists and agonists on solitary tract stimulation-evoked excitatory postsynaptic responses were recorded using whole-cell patch-clamp recordings of neurons in the medial portion of the nucleus tractus solitarius (mNTS) in the brainstem. SP reduced the amplitude of the evoked excitatory postsynaptic currents (eEPSCs) and shifted the holding current inward, in a dose-dependent manner. The concentrations of SP needed to induce such responses were different between capsaicin-sensitive unmyelinated (C-type) and capsaicin-resistant myelinated (A-type) neurons. The perfusion of a NK1 receptor antagonist, sendide, reduced the amplitude of eEPSCs in all tested neurons but did not affect the levels of the holding current. A Neurokinin type 1 receptor (NK1 receptor) agonist, [Sar9, Met(O2)11]-SP, reduced the amplitude of the eEPSCs and shifted the holding current inward in capsaicin-resistant neurons; however, it failed to induce any significant changes in the capsaicin-sensitive neurons. Furthermore, a selective Neurokinin type 3 receptor (NK3 receptor) antagonist, SB223412, failed to induce any changes in any tested neuron. In current-clamp experiments, sendide reduced solitary tract (ST)-stimulation evoked firing of action potentials in both A- and C-type neurons. [Sar9, Met(O2)11]-SP suppressed the firing of the action potentials in C-type but not A-type neurons. In spontaneous synaptic recordings, SP reduced frequency of the sEPSCs in CAP sensitive neuron but NK1 agonist reduced at capsaicin resistant neurons. Taken together, the findings show that ST activation leads to the co-transmission of SP and glutamate and enhances baroreflex sensitivity by potentiating the amplitude of eEPSC in an NK1 receptor activity-dependent manner.