Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization.However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccineinduced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARSCoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4+ T cells exhibited substantial responses against both ancestral and Omicron spike proteins.Notably, CD4+ T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein.The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants.

Background/Aims: This study aimed to assess the association between local and systemic reactogenicity and humoral immunogenicity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Methods: Adverse events were prospectively evaluated using an electronic diary in 135 healthy adults who received a SARS-CoV-2 vaccine (AZD1222, AstraZeneca/Oxford, n = 42; or BNT162b2, Pfizer/BioNTech, n = 93). We semi-quantitatively measured anti-S1 immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay at baseline, 3 weeks after the first dose of AZD1222 or BNT162b2, and 2 weeks after the second dose of BNT162b2. We evaluated the association between the maximum grade of local or systemic adverse events and the anti-S1 IgG optical density using multivariate linear regression with adjustment for age, sex, and use of antipyretics. Results: The median age of the 135 vaccinees was 30 years (36 years in the AZD1222 group and 29 years in the BNT162b2 group) and 25.9% were male (9.5% in the AZD1222 group and 33.3% in the BNT162b2 group). Local and systemic adverse events were generally comparable after the first dose of AZD1222 and the second dose of BNT162b2. The grades of local and systemic adverse events were not significantly associated with anti-S1 IgG levels in the AZD1222 or BNT162b2 group. Conclusions Local and systemic reactogenicity may not be associated with humoral immunogenicity after SARS-CoV-2 vaccination.

PURPOSE: This study evaluated the oncologic impact of obesity, as determined by body mass index (BMI), in patients who underwent laparoscopic surgery for rectal cancer. METHODS: The records of 483 patients with stage I–III rectal cancer who underwent laparoscopic surgery between June 2003 and December 2011 were reviewed. A matching model based on BMI was constructed to balance obese and nonobese patients. Cox hazard regression models for overall survival (OS) and disease-free survival (DFS) were used for multivariate analyses. Additional analysis using visceral fat area (VFA) measurement was performed for matched patients. The threshold for obesity was BMI ≥ 25 kg/m2 or VFA ≥ 130 cm2. RESULTS: The score matching model yielded 119 patients with a BMI ≥ 25 kg/m2 (the obese group) and 119 patients with a BMI < 25 kg/m2 (the nonobese group). Surgical outcomes including operation time, estimated blood loss, nil per os periods, and length of hospital stay did not differ between the obese and the nonobese group. The retrieved lymph node numbers and pathologic CRM positive rate were also similar in between the 2 groups. After a median follow-up of 48 months (range, 3–126 months), OS and DFS rates were similar between the 2 groups. A tumor location-adjusted model for overall surgical complications showed that a BMI ≥ 25 kg/m2 were not risk factors. Multivariable analyses for OS and DFS showed no significant association with a BMI ≥ 25 kg/m2. CONCLUSION: Obesity was not associated with long-term oncologic outcomes in patients undergoing laparoscopic surgery for rectal cancer in the Asian population.
Asian Continental Ancestry Group ; Body Mass Index ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Intra-Abdominal Fat ; Laparoscopy ; Length of Stay ; Lymph Nodes ; Multivariate Analysis ; Obesity ; Rectal Neoplasms ; Risk Factors

Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of the SUMO modification during myogenesis have not been fully elucidated. Here, we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentiated myoblasts, whereas further sumoylation of HDAC1 contributes to switching its binding partners from MyoD to Rb to induce myocyte differentiation. Differentiation in C2C12 skeletal myoblasts induced new immunoblot bands above HDAC1 that were gradually enhanced during differentiation. Using SUMO inhibitors and sumoylation assays, we showed that the upper band was caused by sumoylation of HDAC1 during differentiation. Basal deacetylase activity was not altered in the SUMO modification-resistant mutant HDAC1 K444/476R (HDAC1 2R). Either differentiation or transfection of SUMO1 increased HDAC1 activity that was attenuated in HDAC1 2R. Furthermore, HDAC1 2R failed to deacetylate MyoD. Binding of HDAC1 to MyoD was attenuated by K444/476R. Binding of HDAC1 to MyoD was gradually reduced after 2 days of differentiation. Transfection of SUMO1 induced dissociation of HDAC1 from MyoD but potentiated its binding to Rb. SUMO1 transfection further attenuated HDAC1-induced inhibition of muscle creatine kinase luciferase activity that was reversed in HDAC1 2R. HDAC1 2R failed to inhibit myogenesis and muscle gene expression. In conclusion, HDAC1 sumoylation plays a dual role in MyoD signaling: enhancement of HDAC1 deacetylation of MyoD in the basally sumoylated state of undifferentiated myoblasts and dissociation of HDAC1 from MyoD during myogenesis.
Creatine Kinase, MM Form ; Gene Expression ; Histone Deacetylase 1 ; Histone Deacetylases ; Histones ; Luciferases ; Muscle Cells ; Muscle Development ; Myoblasts ; Myoblasts, Skeletal ; Sumoylation ; Transfection

OBJECTIVE: To estimate the prevalence of non-adherence to rheumatoid arthritis (RA) medication and identify the associated factors for non-adherence in RA patients. METHODS: Among the KORean Observational study Network for Arthritis 3,523 patients who completed a questionnaire about the adherence to RA medication were analyzed. The patients were divided into two groups: 1) adherent group, patients who skipped medication ≤5 days within the past 2 months; and 2) non-adherent group, patients who skipped ≥6 days of medication. The baseline characteristics were compared, and multivariable regression analysis was performed to identify the associated factors for non-adherence. RESULTS: The non-adherent group had 339 patients (9.6%). The common causes of non-adherence were forgetfulness (45.8%), absence of RA symptoms (24.7%), and discomfort with RA medication (13.1%). Younger age (odds ratio [OR] 1.02, p < 0.01) and higher income (OR 1.70, p < 0.01) were associated with an increased risk of non-adherence. Whereas higher functional disability (OR 0.68, p < 0.01) and oral corticosteroid use (OR 0.73, p=0.02) were associated with a decreased risk of non-adherence. The associated factors differed according to cause of non-adherence. Having adverse events (OR 2.65, p=0.02) was associated with the risk of non-adherence due to discomfort with RA medication while a higher level of education (OR 2.37, p=0.03) was associated with the risk of non-adherence due to an absence of RA symptoms. CONCLUSION: The 9.6% of Korean RA patients were non-adherent to RA medication. The associated factors differed according to the cause of non-adherence. Therefore, an individualized approach will be needed to improve the adherence to RA medication.
Arthritis ; Arthritis, Rheumatoid ; Education ; Humans ; Medication Adherence ; Observational Study ; Prevalence

No abstract available.
Humans ; Surgeons* ; Thyroid Gland* ; Thyroid Neoplasms*

BACKGROUND/AIMS: To determine whether early diagnosis is beneficial for functional status of various disease durations in rheumatoid arthritis (RA) patients. METHODS: A total of 4,540 RA patients were enrolled as part of the Korean Observational Study Network for Arthritis (KORONA). We defined early diagnosis as a lag time between symptom onset and RA diagnosis of ≤ 12 months, whereas patients with a longer lag time comprised the delayed diagnosis group. Demographic characteristics and outcomes were compared between early and delayed diagnosis groups. Logistic regression analyses were performed to identify the impact of early diagnosis on the development of functional disability in RA patients. RESULTS: A total of 2,597 patients (57.2%) were included in the early diagnosis group. The average Health Assessment Questionnaire-Disability Index (HAQ-DI) score was higher in the delayed diagnosis group (0.64 ± 0.63 vs. 0.70 ± 0.66, p < 0.01), and the proportion of patients with no functional disability (HAQ = 0) was higher in the early diagnosis group (22.9% vs. 20.0%, p = 0.02). In multivariable analyses, early diagnosis was independently associated with no functional disability (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40). In a subgroup analysis according to disease duration, early diagnosis was associated with no functional disability in patients with disease duration < 5 years (OR, 1.37; 95% CI, 1.09 to 1.72) but not in patients with longer disease duration (for 5 to 10 years: OR, 1.07; 95% CI, 0.75 to 1.52; for ≥ 10 years: OR, 0.92; 95% CI, 0.65 to 1.28). CONCLUSIONS: Early diagnosis is associated with no functional disability, especially in patients with shorter disease duration.
Arthritis ; Arthritis, Rheumatoid* ; Delayed Diagnosis ; Diagnosis ; Early Diagnosis* ; Humans ; Logistic Models ; Observational Study

The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension. Our findings suggest that posaconazole tablets generate an optimal PPC earlier and in more patients than the oral suspension among Korean patients.
Antifungal Agents ; Biological Availability ; Dosage Forms ; Drug Therapy ; Hematologic Neoplasms* ; Humans ; Plasma* ; Remission Induction ; Tablets

Remission is a primary end point of in clinical practice and trials of treatments for rheumatoid arthritis (RA). The 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were developed to provide a consensus definition of remission. This study aimed to assess the concordance between the new remission criteria and the physician’s clinical judgment of remission and also to identify factors that affect the discordance between these two approaches. A total of 3,209 patients with RA were included from the KORean Observational Study Network for Arthritis (KORONA) database. The frequency of remission was evaluated based on each approach. The agreement between the results was estimated by Cohen's kappa (κ). Patients with remission according to the 2011 ACR/EULAR criteria (i.e. the Boolean criteria) and/or physician judgment (n = 855) were divided into three groups: concordant remission, the Boolean criteria only, and physician judgment only. Multinomial logistic regression analysis was used to identify factors responsible for the assignment of patients with remission to one of the discordant groups rather than the concordant group. The remission rates using the Boolean criteria and physician judgment were 10.5% and 19.9%, respectively. The agreement between two approaches for remission was low (κ = 0.226) and the concordant remission rate was only 5.5% (n = 177). Pain affected classification in both discordant groups, whereas fatigue was associated with remission only by physician clinical judgment. The Boolean criteria were more stringent than clinical judgment. Patient subjective symptoms such as pain and fatigue were associated with discordance between the two approaches.
Arthritis ; Arthritis, Rheumatoid* ; Classification ; Consensus ; Fatigue ; Humans ; Judgment* ; Logistic Models ; Observational Study ; Rheumatic Diseases