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Background and Aim: The clinical impact of perianal Crohn's disease (CD) (pCD), a well‐known poor prognostic factor of CD, has not been fully evaluated in Asian patients. We investigated the outcomes of CD in Korean patients according to the presence of pCD at CD diagnosis. Methods: Using 2010–2014 data from the national health insurance claims database, we evaluated the disease course of CD according to the presence of pCD at CD diagnosis. The results were verified in a hospital‐based cohort of 2923 patients. Results: The cumulative risk of intestinal resection was lower in patients with pCD at diagnosis than in those without, in the population‐based cohort (9.1% vs 14.7% at 5 years after diagnosis, P < 0.001), but it was similar between the two groups in the hospital‐based cohort (36.8% vs 36.8% at 10 years after diagnosis, P = 0.950). Moreover, the cumulative risk of behavioral progression was not significantly different between the two groups in the hospital‐based cohort (43.4% vs 41.6% at 10 years after diagnosis, P = 0.366). On multivariable analysis, pCD at CD diagnosis was not a predictor of intestinal resection, behavioral progression, CD‐related hospital admission, or diverting surgery; however, it was an independent predictor of proctectomy (hazard ratio [HR] 3.210, P < 0.001) and anorectal cancer (HR 3.104, P = 0.047). Conclusions: Although the presence of pCD increased the risk of proctectomy and anorectal cancer in Asian patients, the clinical impact of pCD on the overall outcomes of patients with CD may be less significant in Asian patients compared with Western patients. [ABSTRACT FROM AUTHOR]

Introduction: Immunomodulators remain fundamental for the medical treatment of Crohn's disease (CD). Methotrexate (MTX) is widely used as a second-line immunomodulator; however, there is a lack of recent data on MTX monotherapy among the Asian population with CD. Therefore, in this study, we aimed to investigate the tolerability and clinical outcomes of MTX in Korean patients with CD. Methods: A retrospective chart review was performed for CD patients treated with MTX monotherapy or in combination with 5-aminosalicylic acid (5-ASA), at the Asan Medical Center, Seoul, South Korea. The tolerability of MTX monotherapy within 6 months was assessed and the clinical effectiveness of MTX was evaluated based on the Crohn's disease activity index (CDAI). Results: In total, 85 patients were included, of which 29 (34.1%) discontinued MTX due to intolerability during the follow-up. Adverse events (AEs) were reported in 41 (48.2%) patients. The most common AE was gastrointestinal disorders (17/41) and only one patient experienced a serious AE, a systemic infection that required hospitalization. Among the 56 patients who tolerated MTX within 6 months, 44 (65.9%) showed a clinical response. Moreover, no factor was significantly associated with intolerability. The administration method was the only factor significantly associated with a response to MTX (p = 0.041). The adjusted odds ratio of parenteral injection compared to oral administration was 5.68 (95% confidence interval (CI), 1.07–30.08). Conclusion: In this study, one-third of patients were intolerant to MTX; nonetheless, the response rate was as high as 65.9% among tolerant patients. In addition, no significant factors affected intolerability. In terms of the clinical response, parenteral injection could be better than oral administration. [ABSTRACT FROM AUTHOR]

Background: Little is known about the natural history of perianal fistulas in Asian populations with Crohn's disease (CD).Aims: We investigated the incidence and outcomes of perianal CD (pCD) in Korean CD patients.Methods: A nationwide population-based cohort of 6265 CD patients diagnosed in 2010-2014 was analyzed to investigate the incidence and outcomes of pCD. The results were validated in a hospital-based cohort of 2923 CD patients diagnosed in 1981-2015. Factors associated with pCD development were analyzed. The incidence and outcomes of pCD were compared between the prebiologic and biologic eras.Results: pCD occurred in 39.2% of the population-based cohort and 56.1% of the hospital-based cohort during the median follow-up of 4.2 and 8.5 years, respectively. The cumulative incidence of pCD was 40.0% at 5 years after CD diagnosis in the population-based cohort and 62.5% at 20 years in the hospital-based cohort. In multivariate analysis, pCD development was positively associated with male sex, younger age and colonic involvement at diagnosis, early diagnosis, and CD diagnosis in the prebiologic era. The cumulative probability of proctectomy at 10, 20, and 30 years after pCD diagnosis was 2.9%, 12.2%, and 16.2%, respectively. The cumulative incidence of pCD occurring after CD diagnosis and the cumulative probability of proctectomy were significantly lower in the biologic era than in the prebiologic era (p < 0.001 and p = 0.03, respectively).Conclusions: Compared with Western patients with CD, Korean patients show a high incidence of pCD but have a low probability of proctectomy, suggesting the favorable course of pCD. [ABSTRACT FROM AUTHOR]

Background and Aims: Large-scale studies regarding the long-term outcomes of adalimumab (ADA) treatment in Asian patients with Crohn's disease (CD) are still scarce.Methods: We retrospectively analyzed the long-term outcomes of ADA treatment in Korean CD patients who commenced on scheduled ADA treatment at Asan Medical Center between November 2008 and July 2016. Clinical response was defined as maintaining ADA treatment without dose intensification (DI) and/or major abdominal surgery (MAS).Results: Of the 254 patients who received at least two doses of ADA at 2-week intervals as induction therapy, 250 patients (98.4%) showed an initial favorable response by week 4. Among responders, 243 patients were followed up for longer than 4 weeks and were included for further analysis. The median duration of ADA maintenance therapy was 19.4 months. At the last follow-up, 45 patients (18.5%) required DI after a median of 16.8 months and 31 (12.8%) required MAS after a median of 8.9 months. Finally, 161 patients (66.3%) were still receiving ADA without DI and/or MAS. The cumulative probability of maintaining ADA without DI and/or MAS was 81.1% at 1 year, and 36.5% at 5 years. Secondary loss of response to previous infliximab (P = 0.001) and elevated baseline C-reactive protein at starting ADA treatment (P = 0.008) were identified as independent predictors of a poor response to ADA treatment using multivariate regression analysis.Conclusions: The long-term outcome of ADA treatment in a real-life cohort of Korean patients with CD appears to be comparable to that reported in previously published Western studies. [ABSTRACT FROM AUTHOR]

Background: The mini-mental state examination (MMSE) was adapted by individual countries according to their languages and cultures, though it has not been systematically compared. The objective of this study was to compare the linguistic and cultural variations of the MMSE used in various Asian countries. With this, we can analyze the strengths and weaknesses of the MMSE and consider using a common version in future international clinical studies in Asia.Methods: We collected the MMSEs used in 11 Asian nations. After translating those into English, we compared them to understand the differences in the questionnaires with regard to cultural aspects.Results: Many items may be applicable or comparable with a little modification, for Asian countries. However, attention and calculation and repetition may be incomparable. There were some differences in the contents and the ways to administer.Conclusions: The lack of consideration of the cultural differences and their influences on the interpretation of the same cognitive test makes cross-cultural studies difficult. Some items of MMSE tasks need readjusting for, if any, multi-national studies. This study might serve as a first step in the development of a standardized cross-cultural cognitive instrument, especially in Asia. [ABSTRACT FROM AUTHOR]

Study Question: What is the influence of copy number variation (CNV) in functional RNA binding motif protein Y-linked family 1 (RBMY1) on spermatogenic phenotypes?Summary Answer: The RBMY1 functional copy dosage is positively correlated with sperm motility, and dosage insufficiency is an independent risk factor for asthenozoospermia.What Is Known Already: RBMY1, a multi-copy gene expressed exclusively in the adult testis, is one of the most important candidates for male infertility in the azoospermia factor (AZF) region of the Y-chromosome. RBMY1 encodes an RNA-binding protein that serves as a pre-mRNA splicing regulator during spermatogenesis, and male mice deficient in Rbmy are sterile.Study Design, Size, Duration: A total of 3127 adult males were recruited from 2009 to 2016; of this group, the dosage of RBMY1 functional copy were investigated in 486 fertile males. In the remaining 2641 males with known spermatogenesis status, 1070 Y-chromosome haplogroup (Y-hg) O3* or O3e carriers without chromosomal aberration or known AZF structure mutations responsible for spermatogenic impairment, including 506 men with normozoospermia and 564 men with oligozoospermia or/and asthenozoospermia, were screened, and the RBMY1 functional copy dosage and copy conversion were determined to explore their associations with sperm phenotypes. The correlation between RBMY1 dosage and its mRNA level or RBMY1 protein level and the correlation between sperm RBMY1 level and motility were analysed in 15 testis tissue samples and eight semen samples. Ten additional semen samples were used to confirm the subcellular localization of RBMY1 in individual sperm.Participants/materials, Setting, Methods: All the Han volunteers donating whole blood, semen and testis tissue were from southwest China. RBMY1 copy number, copy conversion, mRNA/protein amount and protein location in sperm were detected using the AccuCopy® assay method, paralog ratio test, quantitative PCR, western blotting and immunofluorescence staining methods, respectively.Main Results and the Role Of Chance: This study identified Y-hg-independent CNV of functional RBMY1 in the enrolled population. A difference in the distribution of RBMY1 copy number was observed between the group with normal sperm motility and the group with asthenozoospermia. A positive correlation between the RBMY1 copy dosage and sperm motility was identified, and the males with fewer than six copies of RBMY1 showed an elevated risk for asthenozoospermia relative to those with six RBMY1 copies, the most common dosage in the population. The RBMY1 copy dosage was positively correlated with its mRNA and protein level in the testis. Sperm with high motility were found to carry more RBMY1 protein than those with relatively low motility. The RBMY1 protein was confirmed to predominantly localize in the neck and mid-piece region of sperm as well as the principal piece of the sperm tail. Our population study completes a chain of evidence suggesting that RBMY1 influences the susceptibility of males to asthenozoospermia by modulating sperm motility.Limitations Reasons For Caution: High sequence similarity between the RBMY1 functional copies and a large number of pseudogenes potentially reduces the accuracy of the copy number detection. The mechanism underlying the CNV in RBMY1 is still unclear, and the effect of the structural variations in the RBMY1 copy cluster on the copy dosage of other protein-coding genes located in the region cannot be excluded, which may potentially bias our observations.Wider Implications Of the Findings: Asthenozoospermia is a multi-factor complex disease with a limited number of proven susceptibility genes. This study identified a novel genomic candidate independently contributing to the condition, enriching our understanding of the role of AZF-linked genes in male reproduction. Our finding provides insight into the physiological and pathological characteristics of RBMY1 in terms of sperm motility, supplies persuasive evidence of the significance of RBMY1 copy number analysis in the clinical counselling of male infertility resulting from asthenozoospermia.Study Funding/competing Interest(s): This work was funded by the National Natural Science Foundation of China (Nos. 81370748 and 30971598). The authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background and Aims: To date, no large-scale studies have evaluated long-term outcomes of infliximab (IFX) treatment in Korean patients with Crohn's disease (CD).Methods: We analyzed long-term clinical responses to IFX in 582 Korean CD patients who received scheduled IFX treatments at Asan Medical Center. Clinical responses were defined as maintaining IFX without major abdominal surgery (MAS) or dose intensification.Results: Between February 2002 and July 2015, a total of 11,990 IFX infusions were administered to 582 Korean patients with CD over a median period of 36 months. At the end of follow-up, 316 (54.3 %) were still receiving IFX without MAS (71 patients, 12.2 %) or dose intensification (86 patients, 14.8 %). IFX was stopped in 109 (18.7 %) patients because of a loss of response (48 patients, 8.2 %), adverse events (30 patients, 5.2 %), or patient preferences or problems with reimbursement (31 patients, 5.3 %). The cumulative survival for maintenance of IFX without MAS or dose intensification was 89.0, 75.9, 68.3, and 50.8 % at 1, 2, 3, and 5 years, respectively. Multivariate regression analysis identified older age at the initiation of IFX (≥40 years, P = 0.006) and a longer disease duration (≥3 years, P = 0.020) as independent positive predictors of a poorer response to IFX.Conclusions: The long-term efficacy of IFX in a large, real-life cohort of Korean patients with CD appears to be similar to that in previously published Western studies. Our findings support the early use of IFX to obtain better clinical outcomes. [ABSTRACT FROM AUTHOR]

Using three experiments, the present study investigates the impact of social exclusion on attention. Specifically, we investigate whether social exclusion promotes attentional bias to social acceptance cues (smiling faces) or social exclusion cues (angry faces) among an Asian population. The Cyberball game was adopted to manipulate social inclusion or exclusion, and a dot-probe task was used to measure individuals' responses to smiling or angry faces. In Experiments 1 and 2, each trial consisted of either a smiling or angry face that was paired with a neutral face. In Experiment 1, when the stimulus onset-asynchronies (SOA) were 500 ms, the inhibition of return emerged, indirectly indicating that social exclusion promotes sensitivity to social acceptance cues. In Experiment 2, after setting the SOA to 200 ms, we found that social exclusion promotes attentional bias to smiling faces compared to neutral faces. In Experiment 3, both smiling and angry faces were shown during each trial, and we found that social exclusion promotes attentional bias to smiling faces compared to angry faces. Therefore, the present study extends our understanding of the relationship between social exclusion and attention. Overall, it appears that after social exclusion, the desire for social reconnection trumps the desire to avoid social exclusion. [ABSTRACT FROM AUTHOR]