Association between Isotretinoin Exposure and Inflammatory Bowel Disease: A Nationwide Case-Control Study in South Korea.

Context: Isotretinoin is commonly prescribed for the treatment of acne. However, its association with inflammatory bowel disease (IBD) could not be confirmed due to inconsistencies in the literature. Furthermore, no related study has been conducted on an Asian population. Aims: The aim of this study was to investigate the association between isotretinoin and inflammatory bowel disease. Methods and Material: A nationwide, population-based, case-control study using the National Health Insurance Service database of South Korea was conducted. The case group comprised 107,434 patients with IBD, while the control group comprised 393,830 patients who were matched using a 1:4 propensity score. Data on isotretinoin exposure within the previous 5 years were extracted, and a multivariable-adjusted, conditional, logistic, regression analysis was performed. Results: After adjusting for age, sex, underlying disease, the Charlson co-morbidity index, and tetracycline use, a significant association between isotretinoin exposure and IBD was found, with an odds ratio of 1.20 (95% confidence interval, 1.10-1.30). Furthermore, the association appeared to become stronger with longer exposure, more of a cumulative dose, and a longer time since the first exposure. When analyzed separately for ulcerative colitis and Crohn's disease, isotretinoin exposure was significantly associated with both diseases. Conclusions: Our study reveals a dose-response relationship between isotretinoin exposure and IBD risk in an Asian population. Healthcare professionals should be aware of the association and consider alternative medications for acne treatment, particularly in patients who are at a higher risk of developing IBD.

Interrupted time series analysis of chronic periodontitis-related procedures before and after the scaling reimbursement policy in Korea.

AIM: To study the use of a quasi-experimental design to assess the effects of scaling reimbursement policies on the incidence of chronic-periodontitis procedures. MATERIALS AND METHODS: Interrupted time series analysis was used to compare the effects before and after policy implementation using data on the number of periodontitis-related procedures from the Korean National Health Insurance Service-National Sample Cohort (n = 740,467) and the Health Screening Cohort (n = 337,904). Periodontitis-related procedures with diagnosis codes were categorized into basic (scaling or root planing), intermediate (subgingival curettage) and advanced (tooth extraction, periodontal flap surgery, bone grafting for alveolar bone defects or guided tissue regeneration). Subjects' demographics and comorbidities were considered. The incidence rate of immediate changes and gradual effects before and after policy implementation was assessed. RESULTS: Following the policy implementation from July 2013, an immediate increase was observed in total and basic procedures. No significant changes were noted in intermediate and advanced procedures initially. A decrease in the slope of intermediate procedures was observed in both databases. Advanced procedures showed varied trends, with no change in the National Sample Cohort but an increase in the Health Screening Cohort, particularly among subjects with comorbidities. CONCLUSIONS: Following the new policy implementation, the number of intermediate procedures decreased while the number of advanced procedures increased, especially among patients with comorbidities. These findings offer valuable insights on policy evaluation.

Association between ursodeoxycholic acid use and COVID-19 in individuals with chronic liver disease: a nationwide case-control study in South Korea.

BACKGROUND: Conflicting evidence exists regarding the effects of ursodeoxycholic acid (UDCA) on coronavirus disease 2019 (COVID-19). This study investigates the association between UDCA administration and COVID-19 infection and its related outcomes in individuals with chronic liver disease (CLD). METHODS: A customized COVID-19 research database (n = 3,485,376) was created by integrating data from the National Health Insurance Service (NHIS) and the Korea Disease Control and Prevention Agency's COVID-19 databases. The study focused on patients diagnosed with COVID-19 in 2021, using the NHIS data from 365 days before diagnosis. To create comparable groups with and without UDCA administration before COVID-19, we used propensity score matching. The primary endpoint was the first confirmed positive result for severe acute respiratory syndrome coronavirus-2. In addition, we identified severe COVID-19-related outcomes. Subgroup analysis were conducted based on the dose of UDCA exposure. RESULTS: Data from 74,074 individuals with CLD was analyzed. The participants' average age was 57.5 years, and 52.1% (19,277) of those in each group were male. Those with prior UDCA exposure had a significantly lower risk of COVID-19 infection (adjusted OR: 0.80, 95% CI [0.76-0.85]) compared to the non-UDCA group. Additionally, the UDCA group had a lower risk of severe COVID-19 outcomes (adjusted OR: 0.67, 95% CI [0.46-0.98]). Subgroup analyses indicated that there was a decrease in COVID-19 infection and its related outcomes with increasing UDCA exposure dose. CONCLUSIONS: Our large observational study highlights the potential use of readily available UDCA as an adjunctive therapy for COVID-19 in individuals with CLD.

Stichoposide C and Rhizochalin as Potential Aquaglyceroporin Modulators.

Aquaporins (AQPs) are a family of integral membrane proteins that selectively transport water and glycerol across the cell membrane. Because AQPs are involved in a wide range of physiological functions and pathophysiological conditions, AQP-based therapeutics may have the broad potential for clinical utility, including for disorders of water and energy balance. However, AQP modulators have not yet been developed as suitable candidates for clinical applications. In this study, to identify potential modulators of AQPs, we screened 31 natural products by measuring the water and glycerol permeability of mouse erythrocyte membranes using a stopped-flow light scattering method. None of the tested natural compounds substantially affected the osmotic water permeability. However, several compounds considerably affected the glycerol permeability. Stichoposide C increased the glycerol permeability of mouse erythrocyte membranes, whereas rhizochalin decreased it at nanomolar concentrations. Immunohistochemistry revealed that AQP7 was the main aquaglyceroporin in mouse erythrocyte membranes. We further verified the effects of stichoposide C and rhizochalin on aquaglyceroporins using human AQP3-expressing keratinocyte cells. Stichoposide C, but not stichoposide D, increased AQP3-mediated transepithelial glycerol transport, whereas the peracetyl aglycon of rhizochalin was the most potent inhibitor of glycerol transport among the tested rhizochalin derivatives. Collectively, stichoposide C and the peracetyl aglycon of rhizochalin might function as modulators of AQP3 and AQP7, and suggests the possibility of these natural products as potential drug candidates for aquaglyceroporin modulators.

Association between nonalcoholic fatty liver disease scores and chronic periodontitis: A retrospective cohort study.

BACKGROUND: Although several studies have demonstrated a bidirectional relationship between nonalcoholic fatty liver disease (NAFLD) and chronic periodontitis, few studies have reported that NAFLD causes chronic periodontitis, especially in the Asian population. METHODS: This study was conducted on 129,087 individuals, and the NAFLD score was assessed using the Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), and Framingham Steatosis Index (FSI). The incidence of chronic periodontitis was defined as a diagnostic code with dental procedures. Multi-variable adjusted Cox proportional hazard regression analysis was performed with hazard ratio (HR) and 95% confidence intervals (CIs). RESULTS: Nine thousand one hundred and twenty-eight chronic periodontitis cases (7.1%) were identified during a mean 7.4 years follow-up period. Each NAFLD score was related to chronic periodontitis. In the FLI score, HR and 95% CIs for the incidence of chronic periodontitis compared with a low FLI group were as follows: indeterminate FLI: 1.19 (1.12-1.26), high FLI: 1.32 (1.18-1.47). In the HSI and FSI scores, HR and 95% CIs for the incidence of chronic periodontitis were 1.13 (1.05-1.22) and 1.23 (1.05-1.31), respectively. CONCLUSIONS: All NAFLD scores were associated with chronic periodontitis in the Korean population. As chronic periodontitis can aggravate the liver status, patients with NAFLD may need regular dental visits.

Dynamics of serum anion gaps with in-hospital mortality: Analysis of the multi-open databases.

BACKGROUND: Few studies have investigated the relationship between the anion gap, including the corrected anion gap, and patient mortality in intensive care units (ICUs) without restricting the analysis to specific diseases or medical specialties. Our primary objective was to investigate the association between the anion gap and ICU mortality using multiple open-access databases. METHODS: We identified 4229 subjects from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, whose entries were from between 2008 and 2019. For each patient, the anion gap and corrected anion gap were calculated, and the study sample was divided into tertile groups (T) according to these levels. The association between the anion gap and in-hospital mortality was assessed using hazard ratios (HRs) and 95% confidence intervals (CIs) derived from a multivariable-adjusted Cox proportional hazards model. Besides MIMIC-IV, we also incorporated study samples from two other databases (MIMIC-III and electronic ICU) to calculate summary HRs using a random-effects meta-analysis. RESULTS: Within MIMIC-IV, 1015 patients (24%) died during an average follow-up period of 15.5 days. The fully adjusted HRs and 95% CIs for T2 and T3, relative to T1, were 1.31 (95% CI 1.08-1.58) and 1.54 (95% CI 1.24-1.90), respectively. When grouped by corrected anion gap, the results remained statistically significant. In the meta-analysis, the summary HRs and 95% CIs for T2 and T3 were 1.24 (95% CI 1.08-1.43) and 1.55 (95% CI 1.33-1.82), respectively. CONCLUSIONS: Both the anion gap and corrected anion gap were associated with in-hospital mortality regardless of specific diseases or medical specialties.

Relationship between METS-IR and thyroid cancer incidence in Korea: a nationwide population-based study.

Background: Several previous studies found a positive relationship between metabolic syndrome (MetS) and thyroid cancer (TC) risk. However, there is no research that has studied the relationship between the metabolic score for insulin resistance (METS-IR), a novel surrogate marker for IR, and TC incidence. Thus, we designed this retrospective cohort study to evaluate the relationship between the incidence of TC and METS-IR. Method: We analyzed a cohort of 314,321 Korean adults aged over 40 years who participated in the National Health Screening Program from 2009 to 2010. The individuals were divided into four groups based on METS-IR quartiles. Follow-up was until the diagnosis of TC or death, or until December 31, 2019, if neither. The relationship between METS-IR and TC incidence was analyzed using the Cox proportional-hazards model with multi-variable adjustments. Results: A total of 4,137 participants (1.3%) were diagnosed with TC during a mean follow-up of 9.5 ± 1.5 years. The population with Q1 METS-IR scores showed higher disease-free probabilities than those with Q4 METS-IR scores (p <0.001). The hazard ratio (95% confidential interval) for TC incidence in Q2, Q3, and Q4 METS-IR value were 1.14 (1.05 to 1.25), 1.21 (1.11 to 1.33), and 1.30 (1.18 to 1.42) compared with Q1 of METS-IR, respectively. The incidence of TC tended to increase with increasing METS-IR values in the total population, especially the male population in the restricted cubic spline. In subgroup analysis, the TC risk was more pronounced in the subgroups under 65 and with a BMI < 25 kg/m2. Conclusion: METS-IR was positively correlated with TC incidence in Korea.

Association between Surrogate Markers of Insulin Resistance and the Incidence of Colorectal Cancer in Korea: A Nationwide Population-Based Study.

Background: Insulin resistance (IR) is assessed using surrogate markers such as the triglyceride-glucose (TyG) index, the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, and the metabolic score for IR (METS-IR). Limited studies investigated their association with colorectal cancer (CRC) incidence, and no research has been conducted on their association with the METS-IR. Method: This study used claims data from the Korean National Health Insurance Service, analyzing a cohort of 314,141 Koreans aged over 40 who participated in the National Health Screening Program from 2009 to 2010. The follow-up period was extended until 31 December 2019. Participants were divided into four groups based on quartiles (Q1-Q4) of the markers. Results: All surrogate markers of IR had sequentially statistically lower disease-free probabilities from Q1 to Q4. The Cox proportional hazard model demonstrated statistically significant positive associations between CRC incidence and Q3 and Q4 of the TyG index, as well as Q3 and Q4 of the TG/HDL-C ratio and Q4 of the METS-IR. The constrained cubic spline method revealed a nonlinear, positive dose-response relationship between the TyG index and the METS-IR in relation to CRC incidence. Conclusions: In conclusion, the TyG index, TG/HDL-C ratio, and METS-IR were positively correlated with CRC incidence in Koreans.

The Impact of Withdrawing or Withholding of Life-Sustaining Treatment: A Nationwide Case-Control Study Based on Medical Cost Analysis.

This study measured the impact of the Decisions on Life-Sustaining Treatment Act by analyzing medical cost data from the National Health Insurance Service-National Sample Cohort. After identifying the patients who died in 2018 and 2019, the case and control groups were set using the presence of codes for managing the implementation of life-sustaining treatment with propensity score matching. Regarding medical costs, the case group had higher medical costs for all periods before death. The subdivided items of medical costs with significant differences were as follows: consultation, admission, injection, laboratory tests, imaging and radiation therapy, nursing hospital bundled payment, and special equipment. This study is the first analysis carried out to measure the impact of the Decision on Life-Sustaining Treatment Act through a cost analysis and to refute the common expectation that patients who decided to withhold or withdraw life-sustaining treatment would go through fewer unnecessary tests or treatments.

Associations of depressive symptoms with lower extremity function and balance in Korean older adults.

OBJECTIVES: The relationship of depressive symptoms to lower extremity function and balance, especially in older adults without a depression diagnosis, remains unclear. Therefore, our study analyzed this relationship using a large sample of Korean older adults. METHODS: We used data from the Korean National Health Insurance Service's Health Screening Program database. Individuals aged 66 years who had undergone the National Screening Program for Transitional Ages in Korea and were without a diagnosis of depressive disorder were included. The lower extremity function and balance were evaluated using 2 physical tests, while depressive symptoms were assessed using a 3-question survey. Multivariable-adjusted logistic regression analysis was used to examine the association between depressive symptoms and lower extremity function and balance. RESULTS: Among 66,041 individuals, those with depressive symptoms showed significantly higher rates of abnormal lower extremity function and abnormal balance. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association of depressive symptoms to abnormal lower extremity function and abnormal balance were (aOR, 1.34; 95% CI, 1.25 to 1.44) and (aOR, 1.38; 95% CI, 1.29 to 1.48), respectively. Assessment of the relationship based on depressive symptom scores revealed that higher scores were associated with higher aORs (p for trend <0.001). Subgroup analyses further confirmed this relationship, especially among patients with cerebrovascular disease or dementia. CONCLUSIONS: This study revealed an association between depressive symptoms and the abnormal lower extremity function and balance of 66-year-old individuals without a diagnosis of depressive disorder.