Association Between Antidepressants and Antianxiety Medications and Weight Gain in Korean Adults Aged 19-39 Years.

CONTEXT: The number of young Koreans using antidepressants and antianxiety medications is increasing. OBJECTIVE: Studies evaluating the association between these medications and weight gain are limited. We investigated this association among Korean young adults. METHODS: We included 792,022 participants aged 19-39 years who underwent Korean National Health Insurance Service health examinations more than twice between 2009 and 2019. Multivariate logistic regression analysis was performed to evaluate the association between antidepressants and antianxiety medications and weight gain. RESULTS: The participants' average age and body mass index were 29.4±4.7 years and 23.0±3.6 kg/m2, respectively. The proportions of weight gain ≥10 kg/year were 1.7%; 2.4%; 2.9%; and 4.1% in individuals using neither antidepressants nor antianxiety medications; only antianxiety medications; only antidepressants; and both antidepressants and antianxiety medications, respectively. Compared with individuals using neither antidepressants nor antianxiety medications, the rate ratios (95% confidence intervals) for weight gain ≥10 kg/year were higher in those using only antianxiety medications; only antidepressants; and both antidepressants and antianxiety medications; at 1.77 (1.69-1.85); 2.15 (2.05-2.0); and 3.04 (2.91-3.18), respectively. CONCLUSIONS: Using antidepressants and antianxiety medications may contribute to an increased risk of weight gain among Korean young adults. The potential risk for weight gain should be considered when those medications are used and the prevention of weight gain is needed.

Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry.

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan-Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p < 0.001). Multivariate Cox regression analysis identified older age (HR = 1.057, p = 0.001), male sex (HR = 2.824, p = 0.007), time-averaged DAS28 (HR = 2.241, p < 0.001), and rheumatoid factor titer (HR = 1.009, p = 0.007) as having a significantly increased HR for ILD occurrence. Conclusion: ILD is a rare but critical extra-articular symptom of RA patients. Therefore, RA patients with the above risk factors should be monitored carefully for ILD development.

Erratum: Correction of Text in the Article "Effects of Hormone Replacement Therapy on Bone Mineral Density in Korean Adults With Turner Syndrome".

This corrects the article on p. e9 in vol. 39, PMID: 38193328.

Suppressing anti-citrullinated protein antibody-induced osteoclastogenesis in rheumatoid arthritis using anti-CD64 and PAD-2 inhibitors.

OBJECTIVES: To evaluate the role of Fcγ receptors (FcγR) and peptidyl arginine deiminase (PAD) in anti-citrullinated protein antibody (ACPA)-induced fibroblast-like synoviocytes (FLSs)-mediated osteoclastogenesis in patients with rheumatoid arthritis (RA). METHODS: FLSs and peripheral blood mononuclear cells were collected from patients with RA. We stimulated RA-FLS with ACPA (100 ng/ml) with and without anti-cluster of differentiation (CD)32a/CD64 (FcγRIIA/FcγRI) antibody and PAD-2/4 inhibitors. Flow cytometry and enzyme-linked immunosorbent assay were also performed. CD14+ monocytes were cultured with receptor activator of nuclear factor kappa beta (RANKL) and macrophage colony-stimulating factor, and ACPA-stimulated RA-FLSs were added. These cells were cultured for 14 days, and osteoclastogenesis was quantified using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: ACPA increased RANKL+ and tumour necrotic factor-alpha (TNF-α+) FLS, which decreased dose-dependently by adding 5 and 10 ug/mL anti-CD64 antibody rather than anti-CD32a antibody. In PAD inhibitor experiments, the proportion of RANKL+ and TNF-α+ FLS decreased in 50 µM condition containing PAD-2 inhibitor rather than PAD-4 inhibitor. The co-culture of ACPA-stimulated RA-FLSs and osteoclast precursors increased the TRAP+ multinucleated osteoclast count, which was decreased by anti-CD64 antibody and PAD2 inhibitor. CONCLUSIONS: The present study showed that ACPA increased RANKL and pro-inflammatory cytokine expression in RA-FLSs, and ACPA-activated RA-FLSs could augment osteoclastogenesis. These processes were inhibited by treatment with anti-CD64 antibody and PAD-2 inhibitors. These results show that CD64 and PAD-2-induced pathways may be involved in ACPA-induced FLS activation and osteoclastogenesis in patients with RA. Therefore, regulating the CD64 and PAD-2 pathways may improve RA treatment.

Developing a comprehensive molecular subgrouping model for cervical cancer using machine learning.

This study developed a molecular classification model for cervical cancer using machine learning, integrating prognosis related biomarkers with clinical features. Analyzing 281 specimens, 27 biomarkers were identified, associated with recurrence and treatment response. The model identified four molecular subgroups: group 1 (OALO) with Overexpression of ATP5H and LOw risk; group 2 (LASIM) with low expression of ATP5H and SCP, indicating InterMediate risk; group 3 (LASNIM) characterized by Low expression of ATP5H, SCP, and NANOG, also at InterMediate risk; and group 4 (LASONH), with Low expression of ATP5H, and SCP, Over expression of NANOG, indicating High risk, and potentially aggressive disease. This classification correlated with clinical outcomes such as tumor stage, lymph node metastasis, and response to treatment, demonstrating that combining molecular and clinical factors could significantly enhance the prediction of recurrence and aid in personalized treatment strategies for cervical cancer.

Interleukin-18 binding protein regulates mast cell activation and mast cell induced osteoclastogenesis of rheumatoid arthritis.

OBJECTIVES: Mast cell activation induces pathological responses, including increased osteoclastogenesis in rheumatoid arthritis (RA). Interleukin (IL)-18 binding protein (IL-18BP) has anti-inflammatory effects. In this study, we evaluated the effect of IL-18BP on mast cell activation and mast cell induced osteoclastogenesis. METHODS: Mast cells were activated by IL-33 (100 ng/mL) and cultured with IL-18BP (10, 50, and 100 ng/mL). The proliferation, apoptosis, and necroptosis of mast cells were measured using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of mast cell enzymes, matrix metalloproteinase (MMP), soluble RANKL (sRANKL), and pro-inflammatory cytokines in the culture media. Monocytes from patients with RA patients (n=5) were cultured with activated mast cells with various concentrations of IL-18BP. TRAP+ multinucleated osteoclasts, bone resorption area, and osteoclast differentiation-related genes were measured. RESULTS: Proliferation of tryptase+chymase+c-kit+FcεR1+ mast cells was suppressed following incubation with IL-18BP (10, 50, and 100 ng/mL). RNA expression levels of tryptase and chymase were reduced by 100 ng/mL IL-18BP. Additionally, the levels of MMP-3/9, IL-17A, IL-6, TNF-α, and sRANKL were significantly inhibited by 100 ng/mL IL-18BP. Annexin V+ and annexin V-PI+ mast cells were reduced following incubation with 100 ng/mL IL-18BP. The addition of IL-33 significantly stimulated mast cell and increased TRAP+ multinucleated cells and bone resorption area, and these effects were suppressed by IL-18BP. The osteoclast-related genes (TRAP, ATP6v0d2, RANK, and cathepsin K) expression were suppressed by IL-18BP. CONCLUSIONS: IL-18BP suppressed mast cell activation and mast cell induced osteoclastogenesis. This suggests a potential anti-arthritic role for IL-18BP in patients with RA.

Sex differences in prognosis factors in patients with lung cancer: A nationwide retrospective cohort study in Korea.

Large-scale studies elucidating sex differences in factors impacting prognosis and sex-specific prognossis factors scoring in patients with lung cancer are insufficient. The present study aimed to develop a model to predict sex-specific prognosis factors in Korean patients with lung cancer. This nationwide cohort study included 96,255 patients aged ≥19 years diagnosed with lung cancer and underwent Korean National Health Insurance Service health examinations between January 1, 2005 and December 31, 2015 and followed until 2020. Factors associated with prognosis were estimated using multivariable Cox proportional hazards regression analyses, and separate prognosis scores were calculated for male and female patients. The sex-specific risk scoring models were validated with Kaplan-Meier survival curves and c-statistic. During a mean follow-up of 2.8 years, 60.5% of the patients died. In male patients with lung cancer, age ≥ 65 years (24 points) had the highest mortality risk score, followed by chemotherapy in combination with radiotherapy (16 points), chemotherapy (14 points), and radiotherapy (11 points). In female patients with lung cancer, chemotherapy in combination with radiotherapy (19 points) had the highest mortality risk score, followed by chemotherapy (16 points), age ≥ 65 years (13 points), and radiotherapy (13 points). The analysis of patients categorized into three risk groups based on risk scores revealed that the fatality rates within 5 years were 7%, 54%, and 89% in the low-, intermediate-, and high-risk groups for male patients and 3%, 46%, 85% in the low-, intermediate-, and high-risk groups for female patients, respectively. The c-statistic was 0.86 for male patients and 0.85 for female patients. The strongest fatality risk factors in lung cancer were age ≥ 65 years in male patients and chemotherapy in female patients. The present study developed sex-specific prognosis scoring models to predict fatality risk in patients with lung cancer.

Risk of disease flare in spondyloarthritis patients after tapering tumor necrosis factor inhibitors: A meta-analysis and literature review.

BACKGROUND: Tumor necrosis factor inhibitors (TNFis) have shown dramatic benefit in patients with spondyloarthritis (SpA). Tapering of TNFi medication may be considered in patients with sustained low disease activity because continued use of TNFis at standard doses may increase the risk of side effects including infections and impose an economic burden. However, the optimal TNFi tapering strategy for SpA patients with inactive disease has not been established. In the present study, we investigated whether tapering TNFi doses is associated with similar risk of disease flare to maintaining SpA patients on TNFis at the standard dosage. METHODS: The MEDLINE, Embase, and Cochrane databases were systemically searched to retrieve randomized control trials (RCTs) and observational studies published prior to August 2023, that compared disease flare in SpA (including axial SpA [axSpA], psoriatic arthritis [PsA], and SpA with IBD) patients who received standard TNFi doses and those who received a tapered dose of TNFi. Odds ratios (ORs) and 95% confidence intervals (CIs) were directly retrieved or calculated, and meta-analyses were performed. Bias was assessed using funnel plots with Begg and Mazumdar rank correlation / Egger's regression method. RESULTS: Among 2,237 SpA patients in the 12 studies (9 RCTs and 3 observational studies) retrieved, 1,301 received the standard TNFi dose, while 936 SpA patients underwent TNFi tapering. Of these, 216 (16.6%) standard-dose TNFi and 217 (23.2%) TNF-tapering patients experienced disease flares. The pooled OR for disease flare in TNFi-tapering patients was 1.601 (95% CI 1.276 - 2.008) compared with the standard-dose patients. The funnel plot showed no publication bias. CONCLUSIONS: The strategy of TNFi tapering was associated with a significantly increased risk of disease flare compared to maintaining SpA patients at the standard TNF dose. Further studies are needed to determine which patients can safely undergo tapering of TNFi and to develop safe tapering strategies.

Fever lasting 48 hours as a predictive factor of ESBL-producing bacteria in non-critically ill patients with urinary tract infection.

Urinary tract infection (UTI) is the most prevalent urological condition worldwide. Choosing appropriate antibiotics for patients who have fever before receiving a culture result is challenging. This retrospective study enrolled patients 394 patients hospitalized at Gangneung Asan Hospital for UTI from May 2017 to April 2021. Fever at 48 h of hospitalization was the analysis point, as this is when the response to antibiotic therapy manifest, although the results of antibiogram are not available. Multivariate analysis was performed to assess the correlation between ESBL producing bacteria (EPB) and fever at 48 h. Overall, 36.3% of patients had EPB and 27.9% had fever at 48 h. In multivariate analysis, a significant positive association was found between EPB and fever (odds ratio 1.17, 95% CI 1.05-1.30, P = 0.004) Female had negative association with multivariate model (OR 0.83, 95% CI 0.73-0.94, P = 0.004). Diabetes did not demonstrate a significant association with EPB. (OR 1.10, 95% CI 0.99-1.22, P = 0.072). Fever at 48 h is associated with EPB and could be considered a predictive factor for EPB infection in patients with UTI. Antibiotic escalation may be considered in patients with fever at 48 h.

Association between Daily Dietary Calcium Intake and the Risk of Cardiovascular Disease (CVD) in Postmenopausal Korean Women.

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45-70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: <400 mg, 400-800 mg, and >800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. >10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the >10 postmenopausal years subgroup, daily calcium intake >800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11-0.64), stroke (OR, 0.06; 95% CI, 0.01-0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11-0.64). Our findings suggest that a dietary calcium intake of >800 mg/day decreases the risk of CVD events in women who have been menopausal for >10 years.