Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background/Aims: We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC). Methods: Our study was a multi-center, randomized controlled trial in 11 hospitals. CHC patients were randomly assigned (1:1) to two groups namely, PEGIFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU daily) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR). Results: One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients completed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverseeffects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). Conclusions Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.

Background and Objectives: Severe aortic stenosis (AS) with left ventricular systolic dysfunction (LVSD) is a class I indication for aortic valve replacement (AVR) but this recommendation is not well established in those at the stage of moderate AS. We investigate the clinical impact of AVR among patients with moderate AS and LVSD. Methods: From 2001 to 2017, we consecutively identified patients with moderate AS and LVSD, defined as aortic valve area 1.0–1.5 cm2 and left ventricular ejection fraction <50%. The primary outcome was all-cause death. The outcomes were compared between those who underwent early surgical AVR (within 2 years of index echocardiography) at the stage of moderate AS versus those who were followed medically without AVR at the outpatient clinic. Results: Among 255 patients (70.1±11.3 years, male 62%), 37 patients received early AVR. The early AVR group was younger than the medical observation group (63.1±7.9 vs. 71.3±11.4) with a lower prevalence of hypertension and chronic kidney disease. During a median 1.8-year follow up, 121 patients (47.5%) died, and the early AVR group showed a significantly lower all-cause death rate than the medical observation group (5.03PY vs. 18.80PY, p<0.001). After multivariable Cox-proportional hazard regression adjusting for age, sex, comorbidities, and laboratory data, early AVR at the stage of moderate AS significantly reduced the risk of death (hazard ratio, 0.43; 95% confidence interval 0.20–0.91; p=0.028). Conclusions In patients with moderate AS and LVSD, AVR reduces the risk of all-cause death. A prospective randomized trial is warranted to confirm our findings.

Background: This study was conducted to evaluate the hemodynamic performance and the incidence of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) using bovine pericardial valves (Carpentier-Edwards Perimount Magana and Magna Ease). Methods: In total, 216 patients (mean age, 70.0±10.5 years) who underwent AVR using stented bovine pericardial valves and had follow-up echocardiography between 3 months and 2 years (mean, 12.0±6.6 months) after surgery were enrolled. The implanted valve sizes were 19, 21, 23, and 25 mm in 32, 56, 99, and 29 patients, respectively. Results: On follow-up echocardiography, the mean transvalvular pressure gradients for the 19-mm, 21-mm, 23-mm, and 25-mm valves were 13.3±4.4, 12.6±4.2, 10.5±3.9, and 10.2± 3.7 mm Hg, respectively. The effective orifice area (EOA) was 1.25±0.26, 1.54±0.31, 1.81±0.41, and 1.87±0.33 ㎠ , respectively. These values were smaller than those suggested by the manufacturer for the corresponding sizes. No patients had PPM, when based on the reference EOA. However, moderate (EOA index ≤0.85㎠ /㎡ ) and severe (EOA index ≤0.65 ㎠ /㎡ ) PPM was present in 56 patients (11.8%) and 9 patients (1.9%), respectively, when using the measured values. Conclusion Carpentier-Edwards Perimount Magna and Magna Ease bovine pericardial valves showed satisfactory hemodynamic performance with low rates of PPM, although the reference EOA could overestimate the true EOA for individual patients.

BACKGROUND: This study was conducted to evaluate the prognostic value of the frailty index based on routine laboratory data (FI-L) in elderly patients who underwent surgical aortic valve replacement (SAVR). METHODS: A total of 154 elderly patients (≥ 75 years) (78.7 ± 3.6 years; men:women = 78:76) who underwent aortic valve replacement with stented bioprosthesis between 2001 and 2018 were enrolled. The FI-L was calculated as the proportion of abnormal results out of 32 items based on laboratory tests, pulse rate and blood pressure. The primary outcome was all-cause mortality. Secondary outcomes included operative mortality and aortic valve-related events (AVREs) during follow-up. The predictive values of FI-L for the early and late outcomes were evaluated using logistic regression and Cox proportional hazards models, respectively. The median follow-up duration was 40 months (interquartile, 15–74). RESULTS: The operative mortality rate was 3.9% (n = 6). Late death occurred in 29 patients. The overall survival (OS) rates at 5, 10, and 15 years were 83.3%, 59.0%, and 41.6%, respectively. The AVREs occurred in 28 patients and the freedom rates from AVREs at 5, 10, and 15 years were 79.4%, 72.7%, and 52.9%, respectively. Multivariable analyses demonstrated that FI-L was a significant factor for OS (hazard ratio, 1.075; 95% confidence interval, 1.040–1.111). A minimal P value approach showed that a FI-L of 25% was the best cutoff value to predict OS after SAVR. CONCLUSION: The FI-L is significantly associated with early and long-term outcomes after SAVR in elderly patients. Frailty rather than a patient's age should be considered in the decision-making process for SAVR in elderly patients.
Aged ; Aortic Valve Stenosis ; Aortic Valve ; Bioprosthesis ; Blood Pressure ; Follow-Up Studies ; Freedom ; Heart Rate ; Humans ; Logistic Models ; Mortality ; Proportional Hazards Models ; Stents

BACKGROUND: There has been no study on the time trends of dementia incidence in Korea. We report the 5-year incidence and its correlates of all-cause and Alzheimer's disease (AD) dementia, and compared our results with those of a 12-year-prior cohort study conducted in the same area. METHODS: A total of 751 community-dwelling older adults were followed up for a mean duration of 5.4 years. The age-, gender-, and educational attainment-specific incidence of all-cause and AD dementia were reported as cases per 1,000 person-years. We performed univariate and multivariate cox proportional hazard regression analyses to determine whether baseline sociodemographic, lifestyle, and clinical variables were associated with the risk of all-cause and AD dementia. A 12-year-prior cohort study was used for descriptive comparison to indicate the time trends of dementia incidence. RESULTS: The incidence rates were 16.2 and 13.0 cases per 1,000 person-years for all-cause and AD dementia, respectively. The baseline diagnosis of mild cognitive impairment increased the 5-year incidence of all-cause dementia by more than 4-fold. Old age and low baseline global cognitive function were noted as risk factors for both all-cause and AD dementia. CONCLUSION: Upon comparing the results with those from the earlier cohort study in Yeoncheon, the incidence of all-cause and AD dementia decreased by approximately 40% over 12 years; it has been mainly driven by the increase in the educational level of older adults. The declining time trends of incidence should be taken into account for estimating the future prevalence of dementia in Korea.
Adult ; Alzheimer Disease ; Cognition ; Cohort Studies ; Dementia ; Diagnosis ; Humans ; Incidence ; Korea ; Life Style ; Mild Cognitive Impairment ; Prevalence ; Risk Factors

BACKGROUND/AIMS: Among irritants causing gastric ulcer, Helicobacter pylori (H. pylori) might be pivotal, after which eradication became essential way in either inhibiting ulcerogenesis or preventing ulcer recurrence. Since threonine is essential in either mucus synthesis or cytoprotection, we hypothesized that the dietary threonine from Corynebacterium glutamicum (C. glutamicum) can mitigate the cytotoxicity of H. pylori infection.MATERIALS AND METHODS: RGM-1 cells were challenged with 100 multiplicity of infection H. pylori for 6 hours, during which threonine alone or combination with Corynebacterium sp. was administered and compared for anti-Helicobacter, anti-inflammation, anti-oxidative, and cytoprotective actions.RESULTS: Threonine alone or combination of threonine and C. glutamicum yielded significant bacteriostatic outcomes. The increased expressions of interleukin (IL)-1β, IL-8, Cox-2, and iNOS mRNA after H. pylori infection were significantly decreased with either threonine alone or the combination of threonine and C. glutamicum. The elevated expressions of NF-kB, HIF-1a, and c-jun after H. pylori infection were all significantly decreased with the combination of threonine and broth from C. glutamicum (P < 0.05), leading to significant decreases in 2′,7′-dichlorofluorescein-diacetate (P < 0.01). Tracing further host antioxidative response, the attenuated expression of heme oxygenase-1, Nrf2, and dehydrogenase quinone-1 after H. pylori infection was significantly preserved with combination of threonine and C. glutamicum. H. pylori infection led to significant increases in apoptosis accompanied with Bcl-2 decreases and Bax increases, while the combination of threonine and C. glutamicum significantly attenuated apoptosis, in which attenuated EGF, TGF-β, and VEGF were significantly regulated, while β-catenin did not change.CONCLUSIONS: Threonine synthesized from C. glutamicum significantly alleviated the cytotoxicity of H. pylori in gastric epithelial cells.
Apoptosis ; Corynebacterium glutamicum ; Corynebacterium ; Cytoprotection ; Epidermal Growth Factor ; Epithelial Cells ; Helicobacter pylori ; Heme Oxygenase-1 ; Interleukin-8 ; Interleukins ; Irritants ; Mucus ; NF-kappa B ; Oxidative Stress ; Oxidoreductases ; Recurrence ; RNA, Messenger ; Stomach Ulcer ; Thiram ; Threonine ; Ulcer ; Vascular Endothelial Growth Factor A

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.