Background and Objectives: Early diastolic mitral annular tissue (e’) velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e’ velocity in patients with mitral regurgitation (MR). Methods: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively.According to the current guidelines, the cut-off value of e’ velocity was defined as 7 cm/s. Results: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e’ velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634–0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477–0.998;p=0.049). Abnormal e’ velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170–5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189–21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e’ velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308– 0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680–1.356; p<0.001). Conclusions In patients aged <65 years with primary MR, e’ velocity served as an independent predictor of all-cause and cardiovascular deaths.

Background and Objectives: The prognostic or safety implication of renin-angiotensinaldosterone system inhibitors (RASi) in hypertrophic cardiomyopathy (HCM) are not well established, mainly due to concerns regarding left ventricular outflow tract (LVOT) obstruction aggravation. We investigated the implications of RASi in a sizable number of HCM patients. Methods: We enrolled 2,104 consecutive patients diagnosed with HCM in 2 tertiary university hospitals and followed up for five years. RASi use was defined as the administration of RASi after diagnostic confirmation of HCM. The primary and secondary outcomes were all-cause mortality and hospitalization for heart failure (HHF). Results: RASi were prescribed to 762 patients (36.2%). During a median follow-up of 48.1months, 112 patients (5.3%) died, and 94 patients (4.5%) experienced HHF. Patients using RASi had less favorable baseline characteristics than those not using RASi, such as older age, more frequent history of comorbidities, and lower ejection fraction. Nonetheless, there was no difference in clinical outcomes between patients with and without RASi use (log-rank p=0.368 for all-cause mortality and log-rank p=0.443 for HHF). In multivariable analysis, patients taking RASi showed a comparable risk of all-cause mortality (hazard ratio [HR], 0.70, 95% confidence interval [CI], 0.43–1.14, p=0.150) and HHF (HR, 1.03, 95% CI, 0.63–1.70, p=0.900). In the subgroup analysis, there was no significant interaction of RASi use between subgroups stratified by LVOT obstruction, left ventricular (LV) ejection fraction, or maximal LV wall thickness. Conclusions RASi use was not associated with worse clinical outcomes. It might be safely administered in patients with HCM if clinically indicated.

Background and Objectives: Recent studies have described direct reprogramming of mouse and human somatic cells into induced neural stem cells (iNSCs) using various combinations of transcription factors. Although iNSC technology holds a great potential for clinical applications, the low conversion efficiency and limited reproducibility of iNSC generation hinder its further translation into the clinic, strongly suggesting the necessity of highly reproducible method for human iNSCs (hiNSCs). Thus, in orderto develop a highly efficient and reproducible protocol for hiNSC generation, we revisited the reprogramming potentials of previously reported hiNSC reprogramming cocktails by comparing the reprogramming efficiency of distinct factor combinations including ours. Methods: We introduced distinct factor combinations, OSKM (OCT4+SOX2+KLF4+C-MYC), OCT4 alone, SOX2 alone, SOX2+HMGA2, BRN4+SKM+SV40LT (BSKMLT), SKLT, SMLT, and SKMLT and performed comparative analysis of reprogramming potentials of distinct factor combinations in hiNSC generation. Results: Here we show that ectopic expression of five reprogramming factors, BSKMLT leads the robust hiNSC generation (>80 folds enhanced efficiency) from human somatic cells compared with previously described factor combinations. With our combination, we were able to observe hiNSC conversion within 7 days of transduction. Throughout further optimization steps, we found that both BRN4 and KLF4 are not essential for hiNSC conversion. Conclusions Our factor combination could robustly and reproducibly generate hiNSCs from human somatic cells with distinct origins. Therefore, our novel reprogramming strategy might serve as a useful tool for hiNSC-based clinical application.

BACKGROUND/AIMS: In the ABC classification system, group A consists of seronegative subjects without gastric corpus atrophy. This study aimed to determine the prevalence and characteristics of pseudo group A subjects. METHODS: Group A subjects were identified among consecutive Korean adults who underwent a serum anti-Helicobacter pylori immunoglobulin G (IgG) test and pepsinogen (PG) assay on the day of endoscopy. Past infection was defined as the presence of either eradication history or endoscopic findings suggesting past infection (i.e., gastric xanthoma, metaplastic gastritis, or advanced atrophy >closed-type 1). RESULTS: Among 2,620 group A subjects, 448 (17.1%) had eradication history, and 133 (5.1%) showed endoscopic findings suggesting past infection. Older age (odds ratio [OR], 1.148; 95% confidence interval [CI], 1.067 to 1.236) and earlier year of birth (OR, 1.086; 95% CI, 1.009 to 1.168) were independent risk factors for classification into pseudo group A, with cutoff points at 50.5 years and birth year of 1959.5, respectively. Positive H. pylori test findings were found in 22 subjects (3.1%) among the 715 subjects who underwent the urea breath test or Giemsa staining on the same day. Current infection was positively correlated with PG I and PG II levels (p<0.001) but not with age, anti-H. pylori IgG titer, or classification into pseudo group A. CONCLUSIONS: Among the group A subjects, 22.2% had past infection. The risk was higher in subjects older than 50 years, especially those born before 1960. Furthermore, current infection was found in 3.1% of the subjects and was correlated with increased gastric secretory ability.
Adult ; Atrophy ; Azure Stains ; Breath Tests ; Classification ; Endoscopy ; Gastritis ; Helicobacter pylori ; Humans ; Immunoglobulin G ; Parturition ; Pepsinogen A ; Prevalence ; Risk Factors ; Urea ; Xanthomatosis

BACKGROUND: Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker whose level is elevated in many types of cancers and other benign conditions. CA 19-9 levels are frequently found to be elevated in individuals during general health examinations. This study aimed to investigate the clinical characteristics of such individuals and to determine the need for medical follow-up. METHODS: We investigated individuals who underwent a health inspection, including a serum CA 19-9 test, at our center. Their CA 19-9 levels, age, sex, body mass index (BMI), and personal and past histories were investigated. Additionally, subgroup analyses were performed for those who underwent follow-up study for the elevated CA 19-9 levels. RESULTS: Of 58,498 subjects, 581 (1.0%) had elevated CA 19-9 levels. Multivariate analyses revealed that older age, female sex, lower BMI, and diabetes were independent predisposing factors for elevated CA 19-9 level. A subgroup analysis revealed that the causative conditions were identified in 129 of 351 subjects (36.8%). Among them, the causative conditions in 31 subjects (8.8%, including four cases of cancer and 15 of benign tumors) were not detected at the initial check-up and were found during the follow-up period. CONCLUSION: The use of CA 19-9 as a marker for cancer in healthy individuals is inappropriate. However, medical follow-up in individuals with elevated CA 19-9 levels may be useful because some causative diseases may be detected during follow-up.
Biomarkers, Tumor ; Body Mass Index ; CA-19-9 Antigen ; Causality ; Female ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Reagent Kits, Diagnostic

BACKGROUND/AIMS: Nodular gastritis (NG) is a well-known endoscopic finding observed in patients with a Helicobacter pylori infection, which may lead to invasive gastric cancer. Lymphofollicular gastritis consists of lymphoid follicles or lymphoid cell aggregates, and is common in children. The aim of this study was to identify patients with NG from those in whom gastric biopsied specimens showed lymphoid follicles and lymphoid cell aggregates. METHODS: Subjects, whose gastric biopsy specimens showed lymphoid follicles or lymphoid cell aggregates, were included in this study. The inclusion criterion was that they underwent a serum pepsinogen assay on the day of upper gastrointestinal endoscopy. NG was diagnosed if the endoscopy findings revealed regular-sized, multiple, colorless subepithelial nodules. RESULTS: Among 108 subjects who showed lymphoid follicles or lymphoid cell aggregates, 13 (12.0%) revealed NG on endoscopy, and all these subjects showed positive Giemsa staining. Patients diagnosed with NG were younger (p=0.012) and showed a female predominance (p=0.001) compared to those without NG. The mean serum pepsinogen levels were higher (p=0.001) and lymphoid follicle-dominant subjects were more common (p<0.001) in the NG subjects than in those without NG. Logistic regression analysis revealed a younger age (p=0.041) and female gender (p=0.002) to be significant independent risk factors for NG. CONCLUSIONS: NG should be distinguished from lymphofollicular gastritis because only 12% of patients showing gastric biopsy findings of lymphoid follicles and lymphoid cell aggregates demonstrated NG on endoscopy. NG is an endoscopic finding that is more common in women and in the younger population, irrespective of the biopsy findings and gastric secretory ability.
Azure Stains ; Biopsy ; Child ; Endoscopy ; Endoscopy, Gastrointestinal ; Female ; Gastritis* ; Helicobacter pylori ; Humans ; Logistic Models ; Lymphocytes ; Lymphoid Tissue ; Pepsinogen A ; Risk Factors ; Stomach Neoplasms

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) seroconversion may develop in seronegative adults. Although a positive correlation has been reported between alcohol consumption and seroconversion in Korea, an inverse correlation has been reported in other countries. The aim of this study was to investigate the risk factors for seroconversion in Korea. METHODS: We included Korean adults who were H. pylori-negative negative in their annual serum immunoglobulin G and pepsinogen assays, and in upper gastrointestinal endoscopy. Subjects with a history of H. pylori eradication or gastrectomy were excluded. The criteria for heavy alcohol consumption were ≥ 15 drinks/week for males and ≥ 8 drinks/week for females. RESULTS: Of 267 H. pylori-seronegative subjects, 26 (9.7%) exhibited seroconversion at a mean follow-up time of 39.0 ± 19.1 months. Seroconversion was positively correlated with alcohol consumption (p = 0.001), nonsteroidal anti-inflammatory drug use (p = 0.015), a higher body mass index (p = 0.033), a longer follow-up period (p = 0.038), and a greater number of follow-up tests (p = 0.004). Heavy drinking (odds ratio 6.754, 95% confidence interval 1.892–24.102, p = 0.003) and social drinking (odds ratio 4.360, 95% confidence interval 1.130–16.826, p = 0.033) were independent risk factors for seroconversion. During follow-up, subjects with seroconversion had higher serum levels of pepsinogen II (12.0 ± 7.8 ng/mL) than others (9.1 ± 5.3 ng/mL) (p = 0.038). CONCLUSIONS: Alcohol consumption is related to seroconversion in Koreans. H. pylori transmission might be prevented by reducing alcohol consumption and controlling drinking habits.
Adult ; Alcohol Drinking* ; Body Mass Index ; Drinking ; Endoscopy, Gastrointestinal ; Female ; Follow-Up Studies ; Gastrectomy ; Helicobacter pylori ; Helicobacter* ; Humans ; Immunoglobulin G ; Korea ; Male ; Pepsinogen A ; Pepsinogen C ; Risk Factors ; Seroconversion*

BACKGROUND/AIMS: The serum anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG) and serum pepsinogen (PG) assays are widely used to screen for gastric cancer. An equivocal serology test finding indicates IgG titer between the positive and negative test findings. This study aims to evaluate the long-term follow-up result after an equivocal test finding on the serum anti-H. pylori IgG assay. METHODS: Koreans aged 18 years or older with an equivocal serum anti-H. pylori IgG assay finding were included. Subjects were excluded if they did not undergo H. pylori serology test, serum PG assay, and upper gastrointestinal (UGI) endoscopy on the same day at our center. The annual test findings were followed-up using the same methods. RESULTS: Of the 7,178 subjects who underwent the serum assays and UGI endoscopy on the same day, 274 (3.8%) subjects showed an equivocal H. pylori serology test finding. Of the 98 subjects who were followed-up, 58 (59.2%) showed seropositive finding at the mean follow-up period of 30.6±12.4 months. Subjects with seroconversion showed a higher initial serum PG I (p=0.023) and PG II (p=0.036) levels than those without seroconversion. CONCLUSIONS: An equivocal H. pylori serology test finding was not rare (3.8%) in Korean adults, and 60% of equivocal subjects showed seroconversion within 3 years. Higher seroconversion rates in subjects with high PG I and PG II levels suggest that intact gastric secreting ability plays a role in the survival of H. pylori. Therefore, equivocal subjects with increased serum PG levels should be considered as potential seropositive subjects.
Adult ; Endoscopy ; Follow-Up Studies ; Helicobacter pylori ; Helicobacter* ; Humans ; Immunoglobulin G ; Pepsinogen A ; Seroconversion ; Stomach Neoplasms

BACKGROUND/AIMS: The presence of invasion is a diagnostic criterion of early gastric cancer (EGC) in Korea, whereas diagnosis in Japan is based on enlarged nuclei and prominent nucleoli. Moreover, the depth of invasion is the location of cancer cell infiltration in Korea, whereas it is the location of lymphovascular invasion (LVI) or cancer cell infiltration in Japan. We evaluated the characteristics of EGC with LVI to uncover the effects of different diagnostic criteria. METHODS: Consecutive T1-stage EGC patients who underwent complete resection were included after endoscopic or surgical resection. The presence of LVI was evaluated. RESULTS: LVI was present in 112 of 1,089 T1-stage EGC patients. LVI was associated with depth of invasion (p<0.001) and age (p=0.017). The prevalence of LVI in mucosal cancer was significantly higher in Korea (p<0.001), whereas that of submucosal cancer was higher in Japan (p=0.024). For mucosal EGC types, LVI was positively correlated with diagnostic criteria applied in Korea (p=0.017). For submucosal EGC types, LVI was positively correlated with Japanese criteria (p=0.001) and old age (p=0.045). CONCLUSIONS: The higher prevalence of LVI for mucosal EGC in Korea and for submucosal EGC in Japan indicates that different diagnostic criteria should be considered when reading publications from other countries.
Asian Continental Ancestry Group ; Diagnosis ; Humans ; Japan* ; Korea* ; Prevalence* ; Stomach Neoplasms*

The serum pepsinogen (PG) assay findings are correlated with the status of Helicobacter pylori infection, but there are controversies on the link with upper gastrointestinal (UGI) endoscopic findings. The aim of this study was to determine the significance of a serum PG assay for correlating with endoscopic findings in H. pylori-seroprevalent adult population. Korean adults who visited for a health check-up were included consecutively. Subjects after gastrectomy or H. pylori eradication were excluded. After completing the serum PG assay and anti-H. pylori immunoglobulin G (IgG) titer on the same day of UGI endoscopy, subjects with equivocal serology test finding or gastric neoplasm were excluded. Of the 4,830 included subjects, 3,116 (64.5%) were seropositive for H. pylori. Seropositive finding was related to high serum PG I (P < 0.001) and PG II (P < 0.001) concentrations, low PG I/II ratio (P < 0.001), old age (P < 0.001), and male gender (P = 0.006). After adjusting age and gender, the serum PG I and II concentrations were positively correlated with the presence of nodular gastritis (NG) (all P = 0.003). The serum PG I was positively correlated with gastric ulcer (P = 0.003), and it was correlated with duodenal ulcer in seropositive subjects (P = 0.008). The PG I/II ratio was positively correlated with erosive esophagitis, while it was inversely related to chronic atrophic gastritis and metaplastic gastritis (all P < 0.001). Our findings suggest that the serum PG assay finding correlates well with the UGI endoscopic finding. A higher serum PG concentration in subjects with NG and peptic ulcer disease suggests that endoscopic findings reflect gastric secreting ability.
Adult ; Duodenal Ulcer ; Endoscopy ; Esophagitis ; Gastrectomy ; Gastritis ; Gastritis, Atrophic ; Helicobacter pylori ; Humans ; Immunoglobulin G ; Male ; Pepsinogen A* ; Peptic Ulcer ; Stomach Neoplasms ; Stomach Ulcer