Impact of Guideline-Directed Management Strategies for Low-Density Lipoprotein Cholesterol Control in Patients Who Underwent Percutaneous Coronary Intervention.

There are little direct comparative evidences of strategies between ≥50% and the absolute target goal of low-density lipoprotein cholesterol (LDL-C) level <55 mg/100 ml for the patients who underwent percutaneous coronary intervention (PCI). This study aimed to investigate the clinical impact of different strategies between 2 groups of patients who underwent PCI. A total of 3,104 patients with previous PCI were retrospectively enrolled from 2014 to 2020 at Yeungnam University Medical Center. The study population was stratified into 2 groups based on whether the LDL-C level was <55 mg/100 ml at the 1-year mark or not. Furthermore, the 50% reduction rate of LDL-C was also categorized based on whether it had decreased by ≥50% from the initial LDL-C level at the 1-year mark. The primary end point was 3-year major adverse cardiovascular events (MACEs) which were defined as a composite of cardiovascular death, nonfatal myocardial infarction, target lesion revascularization, hospitalization for heart failure, or nonfatal stroke. There was no significant difference between the LDL <55 mg/100 ml group and the LDL ≥55 mg/100 ml group in the risk of MACEs (hazard ratio 1.06, 95% confidence interval 0.81 to 1.38, p = 0.690) after propensity score matching. However, the group that achieved ≥50% reduction of LDL-C from baseline LDL-C level showed a significant reduction in the occurrence of MACEs in the subgroup of LDL-C level ≥55 mg/100 ml (hazard ratio 0.41, 95% confidence interval 0.19 to 0.89, p = 0.025) compared with the group with <50% reduction of LDL-C. In all patients, the achievement rate of target LDL-C <55 mg/100 ml and more than 50% reduction from baseline was 17.2%. In conclusion, guideline-directed management strategy of ≥50% reduction of LDL-C from the baseline will be needed to reduce the incidence of MACEs in patients with LDL-C ≥55 mg/100 ml who underwent PCI. Additional efforts to increase the target goal achievement rate of LDL-C are warranted.

An enhanced LC-MRM-MS platform for sensitive and simultaneous quantification of cyclic imines in shellfish.

Cyclic imines (CIs) produced by microalgae species and accumulating in the food chain of marine organisms are novel biotoxins that do not belong to the classical group of marine biotoxins. In the past, CIs were found only in limited areas, but in recent years, rapid changes in marine ecosystems have led to widespread CIs, increasing exposure to toxic risks. Monitoring of CIs is therefore required, but still analytically challenging due to the presence of high levels of analogues and interference from other lipophilic substances. Herein, we developed the LC/MRM-MS-based quantitative platform that can selectively enrich for marine-derived CIs and monitor seven CIs simultaneously: pinnatoxin (PnTX E, PnTX F, PnTX G), gymnodimine (GYM A), and spirolide (13-desMe SPX C, 13,19-didesMe SPX C, 20-Me SPX G). In particular, the combination of chromatographic separation by the hydrophobic nature of intrinsic residues of CIs with monitoring of CI structure-specific product ions generated by CID-MS/MS significantly improves the selectivity and sensitivity for quantitative analysis. Indeed, three CIs corresponding to PnTX G, GYM A, and 13-desMe SPX C could be successfully determined at the level of part-per-trillion (ppt) in three species of shellfish collected around the Korean Peninsula. Our analysis revealed that the expression of CIs in the Korean Peninsula was more influenced by the season rather than the species. This analytical platform with high sensitivity can be applied not only to marine biology but also to various other fields requiring CI analysis. Key Contribution: A highly sensitive analytical method for the simultaneous quantitation of cyclic imines based on LC/MRM-MS has been developed.

Panoramic volumetric clinical handheld photoacoustic and ultrasound imaging.

Photoacoustic (PA) imaging has gained much attention, providing structural and functional information in combination with clinical ultrasound (US) imaging systems. 2D PA and US imaging is easily implemented, but its heavy dependence on operator skills makes 3D imaging preferable. In this study, we propose a panoramic volumetric clinical PA and US imaging system equipping a handheld imaging scanner weighing 600 g and measuring 70 × 62 × 110 mm3. Multiple PA/US scans were performed to cover a large field-of-view (FOV), and the acquired PA/US volumes were mosaic-stitched after manually correcting the positions and rotations in a total of 6 degrees of freedom. PA and US maximum amplitude projection images were visualized online, while spectral unmixed data was quantified offline. The performance of the system was tested via tissue-mimicking phantom experiments. The system's potential was confirmed in vivo by panoramically imaging vascular networks in human arms and necks, with FOVs of 331 × 38 and 129 × 120 mm2, respectively. Further, we quantified hemoglobin oxygen saturation levels in the radial artery, brachial artery, carotid artery, and jugular vein. We hope that this system can be applied for various clinical fields such as cardiovascular imaging, dermatology, vascular surgery, internal medicine, and oncology.

Surface ECG-based complexity parameters for predicting outcomes of catheter ablation for nonparoxysmal atrial fibrillation: efficacy of fibrillatory wave amplitude.

Catheter ablation (CA) is a well-established therapy for rhythm control in atrial fibrillation (AF). However, CA outcomes for persistent AF remain unsatisfactory because of the high recurrence rate despite time-consuming efforts and the latest ablation technology. Therefore, the selection of good responders to CA is necessary. Surface electrocardiography (sECG)-based complexity parameters were tested for the predictive ability of procedural termination failure during CA and late recurrence of atrial arrhythmias (AA) after CA. A total of 130 patients with nonparoxysmal AF who underwent CA for the first time were investigated. A 10-second sECG of 4 leads (leads I, II, V1, and V6) was analyzed to compute the fibrillatory wave amplitude (FWA), dominant frequency (DF), spectral entropy (SE), organization index (OI), and sample entropy (SampEn). The study endpoints were procedural termination failure during CA and late (≥1 year) AA recurrence after CA. In the multivariate analysis, FWA in lead V1 and DF in lead I were independent predictors of successful AF termination during CA (P <.05). The optimal cut-off values for FWA in lead V1 and DF in lead I were 60.38 µV (area under the curve [AUC], 0.672; P = .001) and 5.7 Hz (AUC, 0.630; P = .016), respectively. The combination of FWA of lead V1 and DF of lead I had a more powerful odds ratio for predicting procedural termination failure (OR, 8.542; 95% CI, 2.938-28.834; P < .001). FWA in lead V1 was the only independent predictor of late recurrence after CA. The cut-off value is 65.73 µV which was 0.634 of the AUC (P = .009). These sECG parameters, FWA in lead V1 and DF in lead I, predicted AF termination by CA in patients with nonparoxysmal AF. In particular, FWA in lead V1 was an independent predictor of late recurrence of AA after CA.

Chaperon-mediated autophagy can regulate diquat-induced apoptosis by inhibiting α-synuclein accumulation cooperatively with macroautophagy.

α-Synuclein, which is associated with Parkinson's disease, is cleared by the ubiquitin-proteasome system and autophagy lysosome system. Chaperon-mediated autophagy (CMA) and macroautophagy are major subtypes of autophagy and play a critical role in pesticide-induced α-synucleinopathy. In this study, we explored the role of CMA in diquat (DQ)-induced α-synucleinopathy and characterized the relationship between CMA and macroautophagy in the clearance of pathologic α-synuclein for the prevention of DQ neurotoxicity. DQ was cytotoxic to SH-SY5Y cells in a concentration-dependent manner, as shown by decreased cell viability and increased cytotoxicity. DQ treatment was also found to induce autophagy such as CMA and macroautophagy by monitoring the expression of Lamp2A and microtubule-associated protein 1A/1B light chain 3B (LC3-II) respectively. Following DQ treatment, SH-SY5Y cells were found to have induced phosphorylated and detergent-insoluble α-synuclein deposits, and MG132, a proteasome inhibitor, effectively potentiated both CMA and macroautophagy for preventing α-synuclein aggregation. Interestingly, CMA impairment by Lamp2A-knock down decreased the LC3II expression compared to in DQ-treated cells transfected with control siRNA. In Lamp2-knock down cells, pathologic α-synuclein was increased 12 h after DQ treatment, but there was no change observed at 24 h. In DQ-treated cells, macroautophagy by 3-methyladenine and bafilomycin inhibition increased Lamp2A expression, indicating an increase in CMA activity. In addition, CMA modulation affected apoptosis, and inhibiting lysosome activity by NH4Cl increased apoptosis in DQ-treated cells. An increase in autophagy was confirmed to compensate for the decrease in lysosome activity. Pretreatment with z-VAD-fmk, a pan-caspase inhibitor, significantly enhanced the macroautophagy response of DQ-exposed cells without alterations in Lamp2A expression. Our results suggest that CMA can regulate DQ-induced α-synucleinopathy cooperatively with macroautophagy, and crosstalk between macroautophagy and CMA plays an important role in DQ-induced cytotoxicity. Taken together, autophagy modulation may be a useful treatment strategy in pesticide-induced neurodegenerative disorders through preventing α-synucleinopathy.

Identification of new genes of pleomorphic adenoma.

Pleomorphic adenoma is the most common salivary gland neoplasm with a variety of histologic appearances. Due to this diversity, precise preoperative diagnosis through fine needle aspiration cytology is difficult.This study sought to identify the differentially expressed genes in pleomorphic adenoma to aid precise diagnosis and clarify the mechanism of tumorigenesis.Suppressive subtractive hybridization was performed on pleomorphic adenoma tissues and the corresponding normal salivary gland tissues to screen of the differential expression of genes in pleomorphic adenoma.Four known genes (microfibrillar associated protein 4 [MFAP4], dystonin [DST], solute carrier family 35 [SLC35], and potassium channel tetramerization domain containing 15 [KCTD15]) were differentially expressed in the tumors compared with the genes in normal tissues. The expression profiles were further confirmed in 15 pleomorphic adenoma and corresponding normal salivary gland tissues by quantitative real-time reverse transcription-polymerase chain reaction.MFAP4, DST, SLC35, and KCTD15 gene expression could be potential biomarkers of pleomorphic adenoma for precise diagnosis.

Association between salivary secretary function and laryngopharyngeal reflux: a prospective study.

OBJECTIVES: This study aimed to demonstrate the prevalence and risk factors of laryngopharyngeal reflux (LPR) in patients with xerostomia and to investigate the association between salivary function and LPR. STUDY DESIGN: The prevalence of LPR among patients with xerostomia was analyzed and the clinical and salivary gland function were compared between 2 groups; the non-LPR and the LPR groups. RESULTS: The prevalence of LPR was 82.2% in patients with xerostomia. The presence of LPR was correlated with the unstimulated or stimulated salivary flow rate (SFR). LPR did not correlate with scintigraphy findings except time to the minimum count of the parotid gland. Low stimulated SFR and unstimulated SFR were recognized as independent risk factors of LPR. A significant correlation was observed between the Reflux Symptom Index and the xerostomia symptoms score. Furthermore, RFS also correlated with unstimulated and stimulated SFR. CONCLUSIONS: This finding supports that salivary secretory function has an impact on LPR.

Preoperative predictive factors for gallbladder cholesterol polyp diagnosed after laparoscopic cholecystectomy for polypoid lesions of gallbladder.

BACKGROUNDS/AIMS: We investigated patients' clinical and radiological data to determine preoperative factors that predict cholesterol gallbladder (GB) polyps of large size, which can be helpful for decision on further diagnostic tools. METHODS: In this study, we retrospectively analyzed 126 patients who underwent laparoscopic cholecystectomy for GB polyps >10 mm diagnosed preoperatively by abdominal ultrasonography between February 2002 and February 2016 in Department of Surgery, Sanggye Paik Hospital. Patients were divided into non-cholesterol polyps group and cholesterol polyps group, based on the postoperative pathologic diagnosis. Clinical and radiological data, such as gender, age, body weight, height, body mass index (BMI), laboratory findings, size, number and shape of the polypoid lesions, and presence of the concurrent GB stone were compared between the two groups. RESULTS: Of the 126 cases, 73 had cholesterol polyps (57.9%) and 53 cases were non-cholesterol polyps (42.1%). The younger age (<48.5 years), size of polyp <13.25 mm and multiple polyps were independent predictive variables for cholesterol polyps, with odd ratios (OR) of 2.352 (p=0.045), 5.429 (p<0.001) and 0.472 (p<0.001), respectively. CONCLUSIONS: Age, size and polyp number were used to predict cholesterol GB polyp among polypoid lesions of the gallbladder >10 mm. For cases in which these factors are not applicable, it is strongly recommended to evaluate further diagnostic tools, such as computed tomography, endoscopic ultrasonography and tumor markers.

Comparison of compliance of adjuvant chemotherapy between laparoscopic and open surgery in patients with colon cancer.

PURPOSE: Many studies have shown that the completion of adjuvant chemotherapy improves the survival rate. Recently, laparoscopic surgery has been used to treat patients with colon cancer. We analyzed the relationship between the completion of adjuvant chemotherapy and the operation method. METHODS: We retrospectively analyzed the medical records of 147 patients diagnosed with colon cancer from January 1, 2009, to May 31, 2012. The numbers of patients who underwent laparoscopic and open surgery were 91 and 56, respectively. We analyzed the relationship between the operation method and various factors such as the completion rate of chemotherapy, the patient's age, gender, and physical activity, the postoperative hospital stay, the start time of chemotherapy, and the patient's body mass index (BMI), TNM stage, and type of health insurance. RESULTS: In the laparoscopic surgery group, the postoperative hospital stay (13.5 ± 14.82 days vs. 19.6 ± 11.38 days, P = 0.001) and start time of chemotherapy (17.7 ± 17.48 days vs. 23.0 ± 15.00 days, P = 0.044) were shorter, but the percent complete of chemotherapy (71/91 [78.0%] vs. 38/56 [67.8%], P = 0.121), and survival rate (88/91 [96.7%], 47/56 [83.9%], P = 0.007) were higher than they were in the open surgery group. Patients who were elderly, had a low BMI, and a high American Society of Anesthesiologists score were less likely to complete adjuvant chemotherapy than other patients were. CONCLUSION: Laparoscopic surgery shows a shorter postoperative hospital stay, a shorter start time of chemotherapy, and a higher survival rate. Laparoscopic surgery may be expected to increase compliance of chemotherapy and to improve survival rate.

Efficacy and safety of entecavir plus carnitine complex (GODEX®) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study.

BACKGROUND/AIMS: Carnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients. METHODS: 130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months. RESULTS: Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment. CONCLUSIONS: ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.

Comparison of CVF (Cyclophosphamide+Vinorelbine+5-Fluorouracil) and CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil) Adjuvant Chemotherapy in Early Breast Cancer.

PURPOSE: Our study aimed to evaluate the feasibility of adjuvant cyclophosphamide/vinorelbine/5-fluorourail (CVF) chemotherapy as an alternative to cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy for treating early breast cancer. METHODS: One hundred and forty-nine patients were randomly assigned to CMF or CVF adjuvant chemotherapy for treating their early stage breast cancer between September 2000 and December 2007. The disease-free survival (DFS), the overall survival (OS), and the toxicity profiles of both groups were compared. RESULTS: Sixty-seven patients underwent CMF chemotherapy whereas 82 patients underwent CVF chemotherapy. The DFS and OS were 88 months (95% confidence interval [CI], 76-101 months) and 94 months (95% CI, 83-104 months), respectively for the CMF group, and 97 months (95% CI, 93-101 months), and 101 months (95% CI, 98-104 months), respectively for the CVF group. However, those survival gains of the CVF group were not statistically significant (p-value=0.069 for the DFS and 0.99 for the OS). The CVF group showed a favorable toxicity profile in terms of the grade 3/4 hematologic toxicities as compared to that of the CMF group. CONCLUSION: Clinical outcome of CVF chemotherapy was comparable to CMF with a favorable toxicity profiles. However, it is difficult to conclude the feasibility of CVF regimen because of small number of studied patients.

[C-reactive protein level and colorectal adenoma].

BACKGROUND/AIMS: Recent studies implicated inflammation playing an important role in the occurrence and advancement of colorectal cancer. Colorectal adenoma as the representative precursor lesion of colorectal cancer has meaningful association with inflammation. Accordingly, the purpose of this study was to evaluate the association between serum C-reactive protein (CRP) levels and the risk of colorectal adenoma. METHODS: This study was undertaken on 5,487 subjects (3,478 men and 2,009 women) who underwent colonoscopy at the Health Promotion Center in Kangbuk Samsung Hospital and Samsung Medical Center. The subjects were allocated into 3,505 normal control subjects and 1,982 patients with colorectal adenoma. The mean level of CRP was compared between the two groups, and the correlations with other variables were analyzed by multiple regression analysis. Also, the risk of colorectal adenoma according to CRP level and difference of CRP level according to the characteristics of adenomas were analyzed. RESULTS: There was no significant difference in serum CRP level between normal and colorectal adenoma group. After adjusting for the clinically significant variables of colorectal adenoma, multiple logistic regression analysis of the risk of colorectal adenoma according to the CRP level (<1, 1-3, >3) and the CRP level according to characteristics of adenomas showed no significant difference. CONCLUSIONS: An inflammatory marker, CRP is not a risk factor for colorectal adenoma development.

Significance of endoscopy in asymptomatic premenopausal women with iron deficiency anemia.

There is, currently, no consensus with regard to the role of endoscopy in the etiologic investigation of asymptomatic pemenopausal women suffering from iron deficiency anemia (IDA). We conducted a retrospective case-control study to evaluate the contribution of esophagogastroduodenoscopy (EGD) and colonoscopy to the etiologic diagnosis of a group of asymptomatic premenopausal women suffering from IDA. One hundred eight consecutive asymptomatic premenopausal women who fulfilled our entry criteria were included in our patient group between January 1998 and December 2004. One hundred thirty-five age-matched asymptomatic premenopausal women without anemia who had undergone EGD and colonoscopy for medical checkups were included in the control group. Clinically relevant lesions were detected in 7 of 108 (6.5%) of the patients and in 8 of 135 (5.9%) of the controls. There were no differences with regard to the frequency of clinically relevant lesions between the two groups (P > 0.05). Concomitant upper and lower GI lesions were not detected in any patients. In the upper GI tract, the only lesion found to be potentially causative of IDA anemia was a severe erosive gastritis, which was found in both the patient and the control groups. A source consistent with chronic bleeding was detected in the lower GI tract in 6 (5.6%) of the patients and 7 (5.2%) of the controls. Bleeding hemorrhoids represented the most frequently detected lesions in both the patient and control groups. Only one case of colon cancer was detected in the patient group. As IDA in the premenopausal women could not be attributed consistently to GI blood loss in this study, prospective studies should be conducted to validate our findings and to identify which subgroup of asymptomatic premenopausal women would benefit from a diagnostic endoscopic evaluation.