Effectiveness of Korean Red Ginseng on fatigue in patients with rheumatic diseases: a randomized, double-blind, placebo-controlled study.

Background: To evaluate the effectiveness of Korean Red Ginseng (KRG) in managing fatigue in Korean patients with rheumatic diseases. Methods: Patients were randomly assigned to KRG (2 g/day, n = 60) or placebo (n = 60) groups for 12 weeks of blind phase and then open-label KRG from weeks 12 to 24 (placebo-KRG, continuous-KRG). The primary outcome was the improvement rate in fatigue, defined by an increase in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores at 12 weeks. Secondary outcomes included changes in FACIT-Fatigue and fatigue visual analog scale (VAS) between 0 and 12 weeks and those changes in both indices at 24 weeks. Results: The study enrolled 120 patients (Sjogren syndrome [n = 53], rheumatoid arthritis [n = 43], or both diseases [n = 24]). The mean age was 50.9 ± 11.6 years, with 97.5% being female. Baseline characteristics were similar between the two groups. The improvement rate in FACIT-Fatigue after 12 weeks was higher in the KRG group than in the placebo group, but the difference was statistically insignificant (38.3% vs. 26.7%, p = 0.242). Improvement in fatigue was observed in both groups by increases in FACIT-F (4.6 vs. 4.0) and reductions in fatigue VAS (-16.0 vs. -12.2) scores at 12 weeks. The most frequently reported adverse events during KRG use were pruritus and urticarial, with no significant difference between the two groups. Conclusions: Both KRG and placebo groups showed significant reductions in fatigue. KRG treatment for 24 weeks did not reduce fatigue symptoms more than the placebo in patients with rheumatic diseases.

Self-regulating CAR-T cells modulate cytokine release syndrome in adoptive T-cell therapy.

Cytokine release syndrome (CRS) is a frequently observed side effect of chimeric antigen receptor (CAR)-T cell therapy. Here, we report self-regulating T cells that reduce CRS severity by secreting inhibitors of cytokines associated with CRS. With a humanized NSG-SGM3 mouse model, we show reduced CRS-related toxicity in mice treated with CAR-T cells secreting tocilizumab-derived single-chain variable fragment (Toci), yielding a safety profile superior to that of single-dose systemic tocilizumab administration. Unexpectedly, Toci-secreting CD19 CAR-T cells exhibit superior in vivo antitumor efficacy compared with conventional CD19 CAR-T cells. scRNA-seq analysis of immune cells recovered from tumor-bearing humanized mice revealed treatment with Toci-secreting CD19 CAR-T cells enriches for cytotoxic T cells while retaining memory T-cell phenotype, suggesting Toci secretion not only reduces toxicity but also significantly alters the overall T-cell composition. This approach of engineering T cells to self-regulate inflammatory cytokine production is a clinically compatible strategy with the potential to simultaneously enhance safety and efficacy of CAR-T cell therapy for cancer.

Medication utilisation trends during pregnancy and factors influencing adverse pregnancy outcomes in patients with rheumatoid arthritis.

OBJECTIVES: We aimed to investigate medication utilisation trends during pregnancy and identify factors associated with adverse pregnancy outcomes (APOs) in patients with rheumatoid arthritis (RA). METHODS: Female patients with RA aged 20-50 years were identified from the Korean national health insurance database between 2010 and 2020. Pregnancy episodes were divided into two groups according to pregnancy outcome: the delivery group and the APO group (abortion and stillbirth). The characteristics and medication utilisation patterns were compared between the two groups, and multivariable logistic regression analysis was conducted to identify the factors associated with APOs. RESULTS: A total of 5728 pregnancy episodes were included, comprising 4576 delivery episodes and 1152 APO episodes. The mean maternal age for all pregnancy episodes was 33.7 years; 33.3 years in the delivery group and 33.7 years in the APO group. Hydroxychloroquine was the most commonly used conventional synthetic disease-modifying antirheumatic drug (DMARD) during the preconception period and pregnancy in both groups. The prescription rate of all DMARDs decreased rapidly during pregnancy. In the multivariable analysis, use of methotrexate (adjusted OR (aOR): 2.14, 95% CI 1.57 to 2.92) and leflunomide (aOR: 2.68, 95% CI 1.39 to 5.15) within 3 months before conception was associated with APOs. CONCLUSION: Methotrexate and leflunomide are associated with an increased possibility of APOs, emphasising the importance of appropriate medication adjustment when planning for pregnancy.

Comparative effectiveness of tofacitinib and tumour necrosis factor inhibitors in patients with rheumatoid arthritis in real-world practice: a prospective observational study.

OBJECTIVE: To assess the effectiveness of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in Korean patients with rheumatoid arthritis (RA). METHODS: The study used data from a single academic referral hospital's registries of biologic disease-modifying anti-rheumatic drugs (bDMARDs) and tofacitinib and examined remission rates based on the disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) after 12 months. Multivariable logistic regression analysis was used to estimate the odds ratio (OR) for achieving remission with tofacitinib compared with TNFi, adjusting for potential confounders. RESULTS: This analysis included 665 patients (200 on tofacitinib and 455 on TNFi) who were followed up for at least 12 months. Of these, 96 patients in the tofacitinib group (48.0%) and 409 patients in the TNFi group (89.9%) were treatment-naïve to bDMARDs. Intention-to-treat analysis revealed no significant difference in the remission rates between the two groups (18.0% vs 19.6%, p = 0.640). Multivariable analysis demonstrated comparable remission rates with tofacitinib and TNFi (OR 1.204, 95% confidence interval [CI] 0.720-2.013). In the subpopulation naïve to JAKi and bDMARD, tofacitinib showed better remission rates than TNFi (OR 1.867, 95% CI 1.033-3.377). Tofacitinib had more adverse events (AEs) but similar rates of serious AEs (SAEs) to TNFi. CONCLUSION: In real-world settings, there was no significant difference in remission rates at 12 months between the tofacitinib and TNFi groups. In terms of safety, tofacitinib exhibited a higher incidence of AEs compared with TNFi, while the occurrence of SAEs was comparable between the groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02602704.

Priority analysis of factors affecting family planning practices among Ethiopians using a decision tree analysis.

This study aimed to identify the priorities of the factors affecting family planning practices in Ethiopia, with the ultimate aim of providing evidence to the Ethiopian government and international organizations for establishing family planning policies or family planning-related project plans. Multi-stage, clustered, stratified random sampling was performed on a total of 35,479 men aged above 15 years and women of childbearing age (15-49 years) in two metropolitan cities and five regions of Ethiopia. The survey was conducted by face-to-face interview using Tablet PC, and 25,972 responses, excluding censored data were included in the final analysis. The collected data were first analyzed using the Pearson chi-square test, independent sample t-test, and F-test with the Tukey HSD method as a post-hoc. Second, a decision-making tree analysis was conducted to identify priority factors affecting the decision to implement family planning The primary factor affecting the family planning practice was 'spouse or sexual partner's support for family planning (P <.001)'. 'Region (p <.001)' was the second priority factor for both the group receiving 'support for family planning by spouse or partner' and the group not receiving it. The third priority factors appeared differed by region in both groups. It is necessary to establish family planning policy and program plans targeting both men and women, and participation of religious and community leaders is considered important in the establishment process. In addition, it is considered necessary to enhance the professionalism by dividing the education and evaluation process for HEW to provide high-quality counseling, education, and services on family planning at the community level.

Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

BACKGROUND/AIMS: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. METHODS: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)-28- erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). RESULTS: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. CONCLUSION: Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Increased risk of herpes zoster with tofacitinib treatment in Korean patients with rheumatoid arthritis: a single-center prospective study.

We aimed to determine the risk of herpes zoster (HZ) in Korean rheumatoid arthritis (RA) patients on tofacitinib compared with tumor necrosis factor inhibitor (TNFi) treatment. From the prospective cohorts of RA patients who started tofacitinib or TNFi in an academic referral hospital in Korea, patients who started tofacitinib between March 2017 and May 2021 and those who started TNFi between July 2011 and May 2021 were included. Baseline characteristics of tofacitinib and TNFi users were balanced through inverse probability of treatment weighting (IPTW) using the propensity score including age, disease activity of RA and medication use. The incidence rate of HZ in each group and incidence rate ratio (IRR) were calculated. A total of 912 patients were included: 200 tofacitinib and 712 TNFi users. There were 20 cases of HZ among tofacitinib users and 36 among TNFi users during observation period of 331.4 person-years (PYs) and 1950.7 PYs, respectively. In IPTW analysis with a balanced sample, IRR of HZ was 8.33 (95% confidence interval 3.05-22.76). Tofacitinib use increased the risk of HZ compared with TNFi in Korean patients with RA, but the rate of serious HZ or permanent discontinuation of tofacitinib due to HZ event was low.

Factors associated with selection of targeted therapy in patients with rheumatoid arthritis.

OBJECTIVE: Deciding which drug to choose for targeted therapy is an important step in sequential treatment for rheumatoid arthritis (RA). This study aimed to identify factors for selecting Janus kinase inhibitors (JAKis) rather than biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with RA in real-world practice. METHODS: We selected RA patients starting JAKis or bDMARDs from single-center prospective cohorts in Korea. Patients were divided into JAKi, tumor necrosis factor (TNF) inhibitor, and non-TNF inhibitor groups. We performed multinomial logistic regression analyses to identify factors associated with selecting JAKis. RESULTS: 145, 205, and 89 patients were included in the JAKi, TNF inhibitor, and non-TNF inhibitor groups. In multinomial regression analysis, the JAKi group was older than the TNF inhibitor group (OR 1.03, 95% confidence interval [CI] 1.01-1.05) but younger than the non-TNF inhibitor group (OR 0.97, CI 0.95-1.00). The JAKi group was less likely to have chronic pulmonary diseases compared with the TNF inhibitor group (OR 0.07, CI 0.01-0.56) or the non-TNF inhibitor group (OR 0.06, CI 0.01-0.50). Higher disease activity assessed by physician (OR 1.80, CI 1.51-2.38) and previous tacrolimus use (OR 2.05, CI 1.20-3.51) were factors suggesting selection of JAKis than TNF inhibitors. CONCLUSION: Age, pulmonary comorbidities, previous tacrolimus use, and high disease activity assessed by physician were factors influencing the selection of JAKis for RA patients in Korea.

Validation of the Korean Leeds satisfaction questionnaire in rheumatoid arthritis with Rasch models.

OBJECTIVES: We conducted the cross-cultural adaptation and validation of the Leeds Satisfaction Questionnaire (LSQ) for patients with rheumatoid arthritis (RA) in Korea. METHODS: The adaptation of the LSQ from English into Korean was based on guidelines for cross-cultural adaptation for self-report measures. Patients with RA were recruited from an outpatient clinic of a university hospital in South Korea. Validation of the Korean-LSQ with Rasch models was carried out using WINSTEPS. Model fit was determined by Infit and Outfit statistics (≥0.50 and ≤1.50), including the separation index (≥2.00) and reliability index (≥0.80). RESULTS: The data set comprised 125 patients (82.4% female), with median (interquartile range) age 49.0 (37-57) years, and disease duration of 2.5 (1.2-3.8) years. The total and subscale scores of the Korean-LSQ demonstrated excellent or good test-retest reliability (0.88 for total, 0.71-0.82 for subscales), and items in the scale also revealed a high internal consistency (α = 0.93). The six subscales of the Korean-LSQ were found to have a good fit to the Rasch model and good reliability (Person separation index = 2.63 and reliability index = 0.87; item separation index = 37.03 and reliability index >0.99). In addition, the unidimensionality of the scale was confirmed by the principal component analysis based on the Rasch residuals. CONCLUSION: Fit to the Rasch model confirmed that the construct validity, reliability, and unidimensionality of the LSQ were preserved following the adaptation into Korean. The Korean-LSQ is a valid and reliable tool for measuring satisfaction with care in Korean patients with RA.

Korean LupusPRO: Cross-Cultural validation study for systemic lupus erythematosus.

OBJECTIVE: To establish the reliability and validity of the Korean version of LupusPRO version 1.7 (v1.7) for systemic lupus erythematosus (SLE) patients. METHODS: LupusPRO v1.7 was translated into Korean, followed by pretesting among five native Korean speakers. We administered the LupusPRO v1.7 survey to five SLE patients and made minor changes to clarify the language. Then, 133 SLE patients participated in the validation procedure. In each domain, the internal consistency reliability (ICR) and test-retest reliability (TRR) were assessed using Cronbach's alpha and the intra-class correlation coefficient (ICC), respectively. Criterion validity was evaluated using Spearman's correlation coefficient with the other measures such as SF-36, EQ-5D VAS, and SELENA-SLEDAI PGA. Construct validity was assessed by confirmatory factor analysis (CFA) using the unweighted least square estimation method. RESULTS: The mean age of the 133 patients was 36.14 years, and 97% of them were women. Analysis of 130 returned questionnaires revealed that most ICRs of the Korean LupusPRO v1.7 domains were acceptable, with Cronbach's alphas in the range of 0.579-0.949, and most TRRs were good with ICCs from 0.582 to 0.851. Criterion validities presented significant correlations between the LupusPRO v1.7 and other measures validated. In the analysis of the CFA model, the goodness of fit indices demonstrated an acceptable fit. Factor loadings for most individual items were between 0.548 and 0.985. The average variance extracted (AVE) and composite reliability (CR) of most domains were greater than 0.5 and 0.7, respectively, demonstrating acceptable convergent and discriminant validities. CONCLUSIONS: The Korean version of LupusPRO v.17 had acceptable reliability and validity.

Risk factors for herpes zoster in Korean patients with rheumatoid arthritis treated with JAK inhibitor: a nested case-control study.

OBJECTIVE: To determine the risk of herpes zoster (HZ) in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis). METHODS: We performed a nested case-control study with 1:10 matching for sex and age using single-centre prospective cohorts of patients with RA receiving targeted therapy in Korea. Then we performed conditional logistic regression analyses to determine the risk associated with JAKi use compared with biologic disease-modifying antirheumatic drug (bDMARD) use, with adjusting for various factors. We also used logistic regression analysis to identify other risk factors for the development of HZ in JAKi users. RESULTS: From a total of 1147 patients, 61 cases and 610 matched controls were selected. In conditional logistic regression analysis, JAKi use did not increase the risk of HZ development (OR 1.35, 95% CI 0.70 to 2.61) after adjusting for other factors. Rather, duration of RA less than 10 years (OR 0.54, 95% CI 0.30 to 0.97) and having had three or more previous targeted therapies (OR 5.29, 95% CI 1.45 to 19.31) were risk factors for HZ. Among JAKi users, higher disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) (OR 1.44, 95% CI 1.06 to 1.97) was identified as a risk factor in addition to three or more previous targeted therapies (OR 10.12, 95% CI 1.92 to 53.49). CONCLUSIONS: The number of previous targeted therapies, but not JAKi use, was identified as a risk factor for HZ development in Korean patients with RA in a real-world setting. High disease activity was an additional risk factor for JAKi users.

Effectiveness of bazedoxifene in preventing glucocorticoid-induced bone loss in rheumatoid arthritis patients.

OBJECTIVE: To evaluate the effectiveness of bazedoxifene in preventing bone loss in patients with rheumatoid arthritis (RA) receiving low-dose glucocorticoids (GCs). METHODS: In this randomized, controlled, open-label study, we assigned postmenopausal women with osteopenia who had been receiving low-dose GCs for RA to two groups: a group receiving bazedoxifene (20 mg/day) with elemental calcium 1200 mg and vitamin D 800 IU daily (bazedoxifene group) and a group receiving the same doses of calcium and vitamin D only (control group). As primary outcome, bone mineral density (BMD) change in the lumbar spine (L-spine) from baseline to 48 weeks was assessed. Changes in BMD in the femur, trabecular bone score, bone turnover markers, and development of fracture were assessed as secondary outcomes. For intention-to-treat analysis, 20 completed data sets were created by applying multiple imputations by chained equations. RESULTS: A total of 114 patients (57 patients in each group) were recruited. A significant increase in L-spine BMD (0.015 g/cm2, P = 0.007) was observed in the bazedoxifene group, and the increase was significantly higher than in the control group (0.013, 95% CI 0.0003-0.026, P = 0.047). Reductions in bone turnover markers in the bazedoxifene group were significantly greater than in the control group. Only one fracture was observed in the bazedoxifene group, while four fractures developed in the control group. CONCLUSION: In postmenopausal patients with RA receiving low-dose GCs, bazedoxifene improved BMD and reduced bone turnover markers. However, the change in BMD did not exceed the least significant change. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02602704 .

Mobility restrictions were associated with reductions in COVID-19 incidence early in the pandemic: evidence from a real-time evaluation in 34 countries.

Most countries have implemented restrictions on mobility to prevent the spread of Coronavirus disease-19 (COVID-19), entailing considerable societal costs but, at least initially, based on limited evidence of effectiveness. We asked whether mobility restrictions were associated with changes in the occurrence of COVID-19 in 34 OECD countries plus Singapore and Taiwan. Our data sources were the Google Global Mobility Data Source, which reports different types of mobility, and COVID-19 cases retrieved from the dataset curated by Our World in Data. Beginning at each country's 100th case, and incorporating a 14-day lag to account for the delay between exposure and illness, we examined the association between changes in mobility (with January 3 to February 6, 2020 as baseline) and the ratio of the number of newly confirmed cases on a given day to the total number of cases over the past 14 days from the index day (the potentially infective 'pool' in that population), per million population, using LOESS regression and logit regression. In two-thirds of examined countries, reductions of up to 40% in commuting mobility (to workplaces, transit stations, retailers, and recreation) were associated with decreased cases, especially early in the pandemic. Once both mobility and incidence had been brought down, further restrictions provided little additional benefit. These findings point to the importance of acting early and decisively in a pandemic.

Risk of Tuberculosis Development in Patients with Rheumatoid Arthritis Receiving Targeted Therapy: a Prospective Single Center Cohort Study.

BACKGROUND: Patients with rheumatoid arthritis (RA) undergoing targeted therapy have a higher risk of developing tuberculosis (TB). This requires diagnosis and treatment of latent tuberculosis infection (LTBI). We aimed to evaluate whether diagnosis and treatment of LTBI in RA are effective in Korea, and to estimate the risk of TB development by calculating the incidence rate of active TB among RA patients receiving targeted therapy. METHODS: We analyzed data from two prospective cohort studies of RA patients who received biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase (JAK) inhibitor. We selected new starters of targeted therapy and classified them into three groups receiving tumor necrosis factor (TNF) inhibitor, non-TNF inhibitor, and JAK inhibitor, respectively. We then compared LTBI prevalence, treatments, and active TB incidence during first-line therapy in each group. RESULTS: A total of 765 RA patients (574 TNF inhibitor users, 132 non-TNF inhibitor users, and 59 JAK inhibitor users) were included in this study. Observation periods were 1,255.2 person-years (PYs), 264.7 PYs, and 53.3 PYs, respectively. All 765 patients underwent LTBI screening, and the positivity rate was 26.5% (n = 203). Of the 203 LTBI-positive patients, 189 (93.1%) received treatment. Only one patient, who was in the TNF inhibitor group, and was negative for the interferon gamma release assay (IGRA), did not receive LTBI treatment and developed active TB during follow-up. CONCLUSION: Although the prevalence of LTBI in RA patients who started targeted therapy was slightly elevated, the Korean guidelines specifying LTBI screening and treatment were effective in preventing latent TB from becoming active.

Fall characteristics among elderly populations in urban and rural areas in Korea.

Falling is one of the leading causes of injury among elderly populations. As the population over 65 years old increases, medical costs due to falling will also increase. Urban and rural areas have different fall characteristics, and research into these differences is lacking.A survey was conducted on 2012 people over 60 years old between September 1, 2015, to October 12, 2015. Guro-gu (Seoul), Yeongdeungpo-gu (Seoul), and Jung-gu (Daegu) were classified as urban areas and included 1205 of the study participants. Dalseong-gun (Daegu) and Yangpyeong-gun (Gyeonggi-do) were categorized as rural areas and included 807 participants. The survey included questions about fall history, cause, season and time of recent falls, and external conditions associated with recent falls, like floor or ground materials and shoe types.Rural respondents were older than urban respondents (P < .001) but did not differ significantly in gender proportion (P = .082). Fall history over the past year was not different between the 2 regions (P = .693), but lifetime fall history was greater among rural respondents (P < .001). Only 5.1% of all respondents had undergone fall-prevention education. A slippery floor was the most common cause of falls in both regions, but there was a significant difference in pattern of fall causes (P < .001). Falls were more frequent in the summer, spring, and the afternoon in urban areas, and in the summer, autumn, and the morning in rural areas. Cement and asphalt were the most common ground materials at the time of falls in both regions, but rural respondents had higher fall rates when walking on soil and when wearing slippers.A fall-prevention program that reflects the characteristics and differences of falls in urban and rural areas should be developed and used to effectively prevent falling among elderly people.

Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma.

Chimeric antigen receptor (CAR)-T cell therapy has shown remarkable clinical efficacy against B-cell malignancies, yet marked vulnerability to antigen escape and tumor relapse exists. Here we report the rational design and optimization of bispecific CAR-T cells with robust activity against heterogeneous multiple myeloma (MM) that is resistant to conventional CAR-T cell therapy targeting B-cell maturation antigen (BCMA). We demonstrate that BCMA/CS1 bispecific CAR-T cells exhibit superior CAR expression and function compared to T cells that co-express individual BCMA and CS1 CARs. Combination therapy with anti-PD-1 antibody further accelerates the rate of initial tumor clearance in vivo, while CAR-T cell treatment alone achieves durable tumor-free survival even upon tumor re-challenge. Taken together, the BCMA/CS1 bispecific CAR presents a promising treatment approach to prevent antigen escape in CAR-T cell therapy against MM, and the vertically integrated optimization process can be used to develop robust cell-based therapy against novel disease targets.

Comparative systematic review and meta-analysis of 1- to 5-mm versus 6- to 9-mm adenomas on the risk of metachronous advanced colorectal neoplasia.

BACKGROUND AND AIMS: The current guidelines recommend the same surveillance interval for ≥3 nonadvanced adenomas (NAAs), without discriminating between diminutive (1-5 mm) and small (6-9 mm) adenomas. Additionally, the same surveillance interval is recommended for patients with ≤2 diminutive NAAs and those with ≤2 small NAAs. However, it is questionable whether these recommendations are appropriate. METHODS: We searched all relevant studies published through September 2019 that examined the risk of metachronous advanced colorectal neoplasia (ACRN) according to the size (diminutive vs small) and the number of adenomas found during an index colonoscopy. Low-risk adenomas (LRAs) were subclassified into 2 categories (LRA-1, ≤2 diminutive NAAs; and LRA-2, ≤2 small NAAs), and high-risk adenomas (HRAs) were subclassified into 3 categories (HRA-1, ≥3 diminutive NAAs; HRA-2, ≥3 small NAAs; and HRA-3, advanced adenoma). RESULTS: Eight studies involving 36,142 patients were evaluated. The LRA-2 group had a higher risk of metachronous ACRN than the LRA-1 group (risk ratio, 1.49; 95% confidence interval [CI], 1.23-1.81). Additionally, the HRA-2 and HRA-3 groups had a higher risk of metachronous ACRN than the HRA-1 group (hazard ratios [HRs], 1.51 [95% CI, 1.002-2.28] and 1.92 [95% CI, 1.11-3.33], respectively). However, there was no significant difference between the HRA-1 versus LRA-2 groups (HR, 1.23; 95% CI, .78-1.94). CONCLUSIONS: Among the HRA and LRA groups, those with diminutive NAAs had a lower risk of metachronous ACRN than those with small NAAs. We believe that clinical guidelines should consider extending the surveillance intervals in patients with diminutive NAAs only.

Cryopreserved cord blood mononuclear cells in DMSO are healthy for at least 6 hours after thawing.

PURPOSES: We investigated the impact of time, storage temperature, and dimethyl sulfoxide (DMSO) on the viability of HSCs, as well as on apoptotic changes in thawed CB. MATERIALS & METHODS: Thirteen units of cryopreserved CB were thawed and half of each sample was stored at room temperature (RT) and the other half at 4℃, without removing or diluting DMSO. Flow cytometry was employed to enumerate total nucleated cells (TNCs), total/viable CD34+ cells, and early/late apoptotic cells using anti-CD45, anti-CD34, and annexin V(AnV), 7-amino actinomycin D(AAD) staining, respectively. RESULTS: In CBs stored at 4℃ there were no significant changes in numbers of TNCs, total/viable CD34+ cells, or early/late apoptotic cell up to 48 h. However, the numbers of these cells declined significantly at RT. Total and viable CD34+ cell counts did not change for up to 6 h at RT but viable CD34+ cells decreased significantly after 24 h, and total CD34+ cell after 48 h. Early and late apoptosis tended to increase with time at RT, and numbers of viable CD34+ cells and early apoptotic cells differed significantly between RT and 4℃ after 48 h. CONCLUSIONS: There are no significant changes of viability and apoptosis in CBs stored in DMSO at 4℃ until 48 h after thawing, while at RT, there are no significant changes of total/viable CD34+ cell counts or in the proportion of apoptotic cells for at least 6 h after thawing.

Comparative efficacy of stents in endoscopic ultrasonography-guided peripancreatic fluid collection drainage: A systematic review and network meta-analysis.

BACKGROUND: Although many studies have reported the efficacy of different stents for endoscopic ultrasonography (EUS)-guided peripancreatic fluid collection (PFC) drainage, they have not completely determined which stent is superior. This network meta-analysis comprehensively evaluated the comparative efficacy of stents used in EUS-guided PFC. METHODS: We searched all relevant studies published up to February 2019 that examined the efficacy of double pigtail plastic stent (DPPS), fully covered self-expanding metal stent (FCSEMS), and lumen-apposing metal stent (LAMS) in EUS-guided PFC drainage. We performed a Bayesian network meta-analysis for clinical efficacy and adverse events. RESULTS: Fifteen studies comprising 1746 patients were included in the meta-analysis. In terms of clinical success, no significant differences were noted in LAMS versus DPPS or LAMS versus FCSEMS (risk ratio [RR] 1.04 [95% credible interval (CrI) 0.99-1.11] and RR 0.96 [95% CrI 0.91-1.03]), respectively). FCSEMS was superior in terms of clinical success to DPPS (RR 1.09, 95% CrI 1.02-1.15). There was no significant difference in the recurrence of PFC among groups. Regarding adverse events, LAMS had a higher bleeding risk than FCSEMS (RR 6.70, 95% CrI 1.77-36.27) and tended to have a higher risk of bleeding than DPPS (RR 2.67, 95% CI 0.71-9.28). In terms of stent migration, there was no significant difference between any two groups compared. CONCLUSIONS: FCSEMS had superior efficacy in terms of clinical success compared with DPPS stents. Significant superiority of LAMS to DPPS was not identified. Additionally, LAMS had the higher risk of bleeding than FCSEMS.

Increased mortality in patients with corticosteroid-dependent asthma: a nationwide population-based study.

INTRODUCTION: Chronic systemic corticosteroid (CS) therapy is associated with an increased risk of mortality in patients with many chronic diseases. However, it has not been elucidated whether chronic systemic CS therapy is associated with increased mortality in patients with asthma. The aim of this study was to determine the effects of chronic systemic CS therapy on long-term mortality in adult patients with asthma. METHODS: A population-based matched cohort study of males and females aged ≥18 years with asthma was performed using the Korean National Health Insurance Service database from 2005 to 2015. Hazard ratio (HR) with 95% confidence interval for all-cause mortality among patients in the CS-dependent cohort (CS use ≥6 months during baseline period) relative to those in the CS-independent cohort (CS use <6 months during baseline period) was evaluated. RESULTS: The baseline cohort included 466 941 patients with asthma, of whom 8334 were CS-dependent and 458 607 were CS-independent. After 1:1 matching, 8334 subjects with CS-independent asthma were identified. The HR of mortality associated with CS-dependent asthma relative to CS-independent asthma was 2.17 (95% CI 2.04-2.31). In patients receiving low-dose CS, the HR was 1.84 (95% CI 1.69-2.00); in patients receiving high-dose CS, the HR was 2.56 (95% CI 2.35-2.80). CONCLUSIONS: In this real-world, clinical practice, observational study, chronic use of systemic CS was associated with increased risk of mortality in patients with asthma, with a significant dose-response relationship between systemic CS use and long-term mortality.