Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study.

BACKGROUND: The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. OBJECTIVE: We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. METHODS: We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. RESULTS: Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. CONCLUSIONS: The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.

Incidence and disease burden of autoimmune inflammatory rheumatic diseases after non-pharmaceutical interventions in the COVID-19 era: A nationwide observational study in Korea.

BACKGROUND: Infections are considered risk factors for autoimmune inflammatory rheumatic diseases (AIRDs), the incidence of which is considered to have been impacted by the COVID-19 pandemic. The impact of non-pharmaceutical interventions (NPIs) on the incidence of AIRDs and their associated health care services and medical expenses in Korea was investigated. METHODS: We included all AIRD cases reported between January 2016 and February 2021 based on the National Health Insurance Service data. We evaluated changes in incidence trends for each AIRD before and after NPI implementation (Feb 2020 to Feb 2021) using segmented regression analysis. Changes in health care utilization and medical costs for each AIRD before and after NPI implementation were also investigated. RESULTS: After NPI implementation, monthly incidence rates declined significantly by 0.205 per 1 000 000 (95% confidence interval [CI], -0.308 to -0.101, p < .001) in patients with systemic lupus erythematosus (SLE). No significant changes in the incidence of all AIRDs other than SLE were observed before and after implementation. Further, annual outpatient department visits per patient were lower during implementation for all diseases, except juvenile idiopathic arthritis (JIA). The prescription days per outpatient visit increased significantly during implementation for all diseases, except JIA and ankylosing spondylitis. During implementation, the total annual medical costs per patient tended to decrease for all diseases, except JIA and mixed connective tissue disease. CONCLUSION: Implementation of NPIs to contain the pandemic led to a reduction in the incidence of SLE and changed patterns of medical care utilization and treatment cost for most AIRDs.

Changes in tuberculosis risk after transplantation in the setting of decreased community tuberculosis incidence: a national population-based study, 2008-2020.

BACKGROUND: Transplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population. METHODS: This retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010-2012) and lower-disease burden (2016-2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation. RESULTS: Of 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7-0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P < 0.001). Individuals who underwent allogeneic hematopoietic stem cell transplantation had the highest tuberculosis incidence, followed by those who underwent solid organ transplantation and autologous hematopoietic stem cell transplantation (P < 0.001). The overall standardized incidence ratio was 3.9 (95% CI 3.7-4.2) and was the highest in children aged 0-19 years, at 9.0 (95% CI 5.7-13.5). Male sex, older age, tuberculosis history, liver transplantation, and allogeneic hematopoietic stem cell transplantation were risk factors for tuberculosis. CONCLUSIONS: Transplant recipients are vulnerable to developing tuberculosis, possibly influenced by their immunocompromised status, solid organ transplant type, age, and community prevalence of tuberculosis. Tuberculosis prevalence by country, transplant type, and age should be considered to establish an appropriate tuberculosis prevention strategy for high-risk groups.

Effects of Early Wake-Up Time on Obesity in Adolescents.

Background: Although numerous studies have reported that obesity in adolescents is related to shorter sleep duration, few studies have reported the effect of sleep timing, particularly early wake-up time, on obesity. Objectives: To investigate the association between wake-up time and adolescent obesity. Methods: Using the Korean National Health and Nutrition Examination Survey VII data, 1301 middle school and high school students were selected and grouped according to BMI. Sleep timing and lifestyle factors were evaluated using self-reported questionnaires. Results: The mean bedtime and wake-up time were 00:09 am and 07:06 am, respectively. Despite similar bedtimes, the group with overweight/obesity woke up earlier than the group with underweight/normal weight. The BMI z-score and the overweight/obesity relative risk decreased as the wake-up time was delayed, even after adjustment for covariates. Participants who woke up before 06:50 am had a 1.82-fold higher risk of having overweight/obesity than those who woke up after 07:30 am. Participants who woke up late tended to sleep longer than those who woke up early. Conclusions: Waking up early is significantly associated with an increased BMI z-score in adolescents and may be a risk factor for overweight/obesity.

Incidence and Features of Lymphoid Proliferation and Lymphomas after Solid Organ or Hematopoietic Stem Cell Transplantation in a National Database Cohort.

PURPOSE: Post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic stem transplantation (HCT) or solid organ transplantation (SOT) result in poorer outcomes, including death. There are limited large cohort data on the incidence and natural course of PTLD in Asians. MATERIALS AND METHODS: We investigated PTLD using Korean national health insurance claims data of 47,518 patients who underwent HCT or SOT in 2008-2020. Patient demographics, time and type of PTLD diagnosis, type of PTLD treatment, and death data were collected. We used Fine and Gray subdistribution hazard models to calculate the cumulative incidence and risk factors for PTLD. RESULTS: During median follow-up of 5.32 years, PTLD occurred in 294 of 36,945 SOT patients (0.79%) and 235 of 10,573 HCT patients (2.22%). Cumulative incidence of PTLD were 0.49% at 1 year, 1.02% at 5 years, and 1.50% at 10 years post-transplantation. Age < 20 years (subdistribution hazard ratio [SHR] of 1.67 in age 10-19, SHR 1.51 in age 0-9), HCT (SHR 3.02), heart transplantation (SHR 2.27), and liver transplantation (SHR 1.47) were significant risk factors for PTLD. The presence of PTLD was associated with an increased risk of death (hazard ratio of 2.84). Overall, 5-year survival of PTLD patients was 68.9% (95% confidence interval, 64.9 to 73.2). CONCLUSION: We observed a steady increase in PTLD over 10 years after HCT or SOT in this large cohort study. Pediatric age group, HCT, liver transplantation, and heart transplantation were suggested to be risk factors for PTLD, and PTLD was associated with a higher risk of death.

Harmful effect of repetitive intravenous iodinated contrast media administration on the long-term renal function of patients with early gastric cancer.

This retrospective study investigated whether repetitive exposure to intravenous iodinated contrast media (ICM) affects long-term renal function in patients who undergo curative surgery for early gastric cancer (EGC) collected from the Korean Health Insurance and Review Assessment (HIRA) database. Patients diagnosed with gastric cancer between January 2010 and December 2013 underwent regular computed tomography (CT) scans to monitor for extragastric recurrence. Patients who already had chronic kidney disease (CKD) before cancer diagnosis or had undergone chemotherapy or repeated surgery were excluded. A nested case-control study design was chosen to analyze the effect of repetitive ICM exposure to long-term renal function by comparing patients who developed CKD 2 years after cancer diagnosis and patients who did not. Among 59,971 patients collected according to inclusion and exclusion criteria, 1021 were diagnosed with CKD 2 years after cancer diagnosis. Using 1:5 matching after adjusting for age, sex and date of cancer diagnosis, 5097 control patients were matched to 1021 CKD patients. Conditional logistic regression showed that the number of CTs taken using ICM slightly increased the odds of CKD (odds ratio, 1.080; 95% confidence interval (CI): 1.059, 1.100; P < 0.0001). Thus, the administration of ICM might contribute to chronic renal function impairment.

Risk of depression and anxiety disorders according to long-term glycemic variability.

BACKGROUND: Poor glycemic control has been linked to psychiatric symptoms. However, studies investigating the relationship between glycemic variability (GV) and depression and anxiety disorders are limited. We investigated the association of GV with depression and anxiety disorders. In addition, the relationship between trends in fasting plasma glucose (FPG) levels and these disorders were explored. METHODS: We analyzed the National Health Insurance Service-National Sample Cohort database (2002-2013) with 151,814 participants who had at least three health screenings between 2002 and 2010. Visit-to-visit FPG variability was measured as variability independent of the mean (VIM). Depression and anxiety disorders were diagnosed using ICD-10 codes (F41 for anxiety and F32 or F33 for depression) after index date. We analyzed the association between GV and incidences of these disorders using Kaplan-Meier and Cox proportional hazards methods. Trajectory analysis was conducted to explore the relationship between FPG trends and these disorders. RESULTS: During follow-up, 7166 and 14,149 patients were newly diagnosed with depression and anxiety disorders, respectively. The highest quartile group of FPG-VIM had a greater incidence of depression and anxiety than the lowest quartile group, with adjusted hazard ratios of 1.09 (95 % confidence interval [CI]: 1.02-1.17) and 1.08 (95 % CI: 1.03-1.14). Group with persistent hyperglycemia, identified through trajectory clustering of FPG levels, had a 1.43-fold increased risk of depression compared to those with consistently low FPG levels. LIMITATIONS: Potential selection bias by including participants with at least three health screenings. CONCLUSIONS: High GV and persistent hyperglycemia are associated with increased incidence of depression and anxiety disorders.

The impact of non-pharmaceutical interventions on premature births during the COVID-19 pandemic: a nationwide observational study in Korea.

Background: Non-pharmaceutical interventions (NPIs), such as social distancing and hand washing, have been associated with a decline in the preterm birth rate worldwide. We aimed to evaluate whether the preterm birth rate in Korea during the coronavirus disease 2019 lockdown has changed compared to that in previous years. Method: A birth registry from the Korea Statistical Information Service, which is a nationwide official database, was used to include all births claimed to have occurred between 2011 and 2020. Newborns with gestational age (GA) less than 22 weeks and birth weight less than 220 g were excluded. The pre-NPI period was designated as January 2011 to January 2020, and the NPI period was defined as February 2020 to December 2020. We assessed the effect of NPI on the incidence of prematurity per 100 births using an interrupted time-series quasi-experimental design and implementing an autoregressive integrated moving average (ARIMA) model. Results: From 2011 to 2020, a total of 3,931,974 live births were registered, among which 11,416 were excluded. Consequently, the final study population included 3,920,558 live births (both singleton and multiple births) among which 275,009 (7.0%) were preterm. The preterm birth rate was significantly higher during the NPI period (8.68%) compared to that in the pre-NPI period (6.92%) (P < 0.001). The ARIMA model showed that in all singleton and multiple births, except those in July (observed 9.24, expected 8.54, [95% prediction interval {PI} 8.13-8.96], percent difference 7.81%), September (observed 7.89, expected 8.35, [95% PI 7.93-8.76], percent difference -5.66%), and December (observed 9.90, expected 9.40, [95% PI 8.98-9.82], percent difference 5.2%), most observed values were within the 95% PI of the expected values and showed an increasing trend. Conclusion: In this nationwide observational study, the trend in premature birth rate did not significantly change due to NPI implementation in Korea, as it had been increasing since 2011. The trend of Korea's birth rate appears to be unaffected by the implementation of NPIs; however, further studies with a longer follow-up period are needed.

Does high [18F]FDG uptake always mean poor prognosis? Colon cancer with high-level microsatellite instability is associated with high [18F]FDG uptake on PET/CT.

OBJECTIVES: High-level microsatellite instability (MSI-high) is generally associated with higher F-18 fluorodeoxyglucose ([18F]FDG) uptake than stable microsatellite (MSI-stable) tumors. However, MSI-high tumors have better prognosis, which is in contrast with general understanding that high [18F]FDG uptake correlates with poor prognosis. This study evaluated metastasis incidence with MSI status and [18F]FDG uptake. METHODS: We retrospectively reviewed 108 right-side colon cancer patients who underwent preoperative [18F]FDG PET/CT and postoperative MSI evaluations using a standard polymerase chain reaction at five Bethesda guidelines panel loci. The maximum standard uptake value (SUVmax), SUVmax tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured using SUV 2.5 cut-off threshold. Student's t-test or Mann-Whitney U test was performed for continuous variables, and χ2 test or Fisher's exact test was performed for categorical variables (p value of < 0.05 for statistical significance). Medical records were reviewed for metastasis incidence. RESULTS: Our study population had 66 MSI-stable and 42 MSI-high tumors. [18F]FDG uptake was higher in MSI-high tumors than MSI-stable tumors (TLR, median (Q1, Q3): 7.95 (6.06, 10.54) vs. 6.08 (4.09, 8.82), p = 0.021). Multivariable subgroup analysis demonstrated that higher [18F]FDG uptake was associated with higher risks of distant metastasis in MSI-stable tumors (SUVmax: p = 0.025, MTV: p = 0.008, TLG: p = 0.019) but not in MSI-high tumors. CONCLUSION: MSI-high colon cancer is associated with high [18F]FDG uptake, but unlike MSI-stable tumors, the degree of [18F]FDG uptake does not correlate with the rate of distant metastasis. CLINICAL RELEVANCE STATEMENT: MSI status should be considered during PET/CT assessment of colon cancer patients, as the degree of [18F]FDG uptake might not reflect metastatic potential in MSI-high tumors. KEY POINTS: • High-level microsatellite instability (MSI-high) tumor is a prognostic factor for distant metastasis. • MSI-high colon cancers had a tendency of demonstrating higher [18F]FDG uptake compared to MSI-stable tumors. • Although higher [18F]FDG uptake is known to represent higher risks of distant metastasis, the degree of [18F]FDG uptake in MSI-high tumors did not correlate with the rate at which distant metastasis occurred.

Restless leg syndrome and risk of all-cause dementia: a nationwide retrospective cohort study.

BACKGROUND: Restless leg syndrome (RLS) is associated with poor sleep quality, depression or anxiety, poor dietary patterns, microvasculopathy, and hypoxia, all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia remains unclear. This retrospective cohort study aimed to explore the possibility that RLS could be deemed as a non-cognitive prodromal feature of dementia. METHODS: This was a retrospective cohort study using the Korean National Health Insurance Service-Elderly Cohort (aged ≥ 60). The subjects were observed for 12 years, from 2002 to 2013. Identifying patients with RLS and dementia was based on the 10th revised code of the International Classification of Diseases (ICD-10). We compared the risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in 2501 subjects with newly diagnosed RLS and 9977 matched controls based on age, sex, and index date. The association between RLS and the risk of dementia was assessed using Cox regression hazard regression models. The effect of dopamine agonists on the risk of dementia among RLS patients was also explored. RESULTS: The baseline mean age was 73.4, and the subjects were predominantly females (63.4%). The incidence of all-cause dementia was higher in the RLS group than that in the control group (10.4% vs 6.2%). A baseline diagnosis of RLS was associated with an increased risk of incident all-cause dementia (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.24-1.72). The risk of developing VaD (aHR 1.81, 95% CI 1.30-2.53) was higher than that of AD (aHR 1.38, 95% CI 1.11-1.72). The use of dopamine agonists was not associated with the risk of subsequent dementia among patients with RLS (aHR 1.00, 95% CI 0.76-1.32). CONCLUSIONS: This retrospective cohort study suggests that RLS is associated with an increased risk of incident all-cause dementia in older adults, providing some evidence that requires confirmation through prospective studies in the future. Awareness of cognitive decline in patients with RLS may have clinical implications for the early detection of dementia.

Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding.

BACKGROUND & AIMS: Hemostatic powders have been clinically used in the treatment of gastrointestinal bleeding. We investigated the non-inferiority of a polysaccharide hemostatic powder (PHP), compared with conventional endoscopic treatments, for peptic ulcer bleeding (PUB). METHODS: This study was a prospective multi-center, randomized, open-label, controlled trial at 4 referral institutions. We consecutively enrolled patients who had undergone emergency endoscopy for PUB. The patients were randomly assigned to either a PHP or conventional treatment group. In the PHP group, diluted epinephrine was injected, and the powder was applied as a spray. Conventional endoscopic treatment included the use of electrical coagulation or hemoclipping after injection of diluted epinephrine. RESULTS: Between July 2017 and May 2021, 216 patients were enrolled in this study (PHP group, 105; control group, 111). Initial hemostasis was achieved in 92 of 105 patients (87.6%) in the PHP group and 96 of 111 patients (86.5%) in the conventional treatment group. Re-bleeding did not differ between the 2 groups. In subgroup analysis, the initial hemostasis failure rate in the conventional treatment group was 13.6% for Forrest IIa cases; however, there was no initial hemostasis failure in the PHP group (P = .023). Large ulcer size (≥15 mm) and chronic kidney disease with dialysis were independent risk factors for re-bleeding at 30 days. No adverse events were associated with PHP use. CONCLUSIONS: PHP is not inferior to conventional treatments and could be useful in initial endoscopic treatment for PUB. Further studies are needed to confirm the re-bleeding rate of PHP. CLINICALTRIALS: gov, Number: NCT02717416).

Association Between Proton Pump Inhibitor Exposure and Acute Kidney Injury After Cardiac Surgery.

OBJECTIVE: To evaluate the association of preoperative proton pump inhibitor (PPI) exposure with incident acute kidney injury (AKI) after cardiac surgery. PATIENTS AND METHODS: The Severance cardiac surgery cohort included 9860 cardiac surgery patients aged 18 years or older. The National Health Insurance Service-senior cohort included 2933 patients aged 60 years or older who underwent cardiac surgery. Preoperative PPI exposure was defined as a PPI prescription within 3 weeks prior to cardiac surgery. Primary outcomes were postoperative AKI and AKI requiring dialysis (AKI-dialysis). RESULTS: In the Severance cardiac surgery cohort after propensity score matching for PPI exposure, incident AKI (44.0% [472 of 1073] vs 40.5% [1304 of 3219]) and AKI-dialysis (5.8% [62 of 1073] vs 3.7% [119 of 3219]) were more common in patients exposed to PPI than in those who were not. Hospital and intensive care unit stay durations were longer among PPI-exposed than PPI-nonexposed patients. Multivariable conditional logistic analyses revealed that PPI exposure was significantly associated with incident AKI (adjusted odds ratio [AOR], 1.21; 95% CI, 1.03 to 1.42; P=.02) and AKI-dialysis (AOR, 1.74; 95% CI, 1.15 to 2.63; P=.009). The National Health Insurance Service-Senior cohort had similar results, revealing a significant association between PPI exposure and incident AKI-dialysis (AOR, 1.87; 95% CI, 1.25 to 2.81; P=.003). Discontinuation of PPI prior to operation was associated with a lower odds of AKI development in both cohorts. CONCLUSION: Preoperative PPI exposure may be a modifiable risk factor for AKI among patients undergoing cardiac surgery.

Impact of thyroid cancer on the cancer risk in patients with non-alcoholic fatty liver disease or dyslipidemia.

The raised prevalence of obesity has increased the incidence of obesity-related metabolic diseases such as dyslipidemia (DL) and non-alcoholic fatty liver disease (NAFLD), along with the development and progression of various types of cancer, including thyroid cancer. In this study, we investigated whether thyroid cancer in patients with DL and NAFLD could be a risk factor for other cancers. To achieve our goal, we generated two independent cohorts from our institution and from the National Health Insurance System in South Korea. Based on the ICD-10 code, we conducted exact matching (1:5 matching) and estimated the overall risk of thyroid cancer for other cancers in patients with DL or NAFLD. Univariate and multivariate analyses showed that the hazard ratio (HR) of thyroid cancer was 2.007 (95% Confidence Interval [CI], 1.597-2.522) and 2.092 (95% CI, 1.546-2.829), respectively in the institutional cohort and 1.329 (95% CI, 1.153-1.533) and 1.301 (95% CI, 1.115-1.517), respectively in the nationwide cohort. Risk analysis revealed a significant increase in the HR in lip, tongue, mouth, lung, bone, joint, soft tissue, skin, brain, male cancers and lymphoma after thyroid cancer occurred. Thyroid cancer in patients with DL or NAFLD might be a valuable factor for predicting the development of other cancers.

A decrease in the incidence of encephalitis in South Korea during the COVID-19 pandemic: A nationwide study between 2010 and 2021.

Limited data are available on the impact of the coronavirus disease (COVID-19) pandemic on encephalitis. Therefore, we evaluated trends in encephalitis in South Korea between 2010 and 2021 using data from the National Health Insurance Service. During the pandemic (February 2020 to 2021), the monthly incidence of encephalitis declined by 0.027 per 100 000 population (95% confidence interval [CI]: -0.055 to 0.001, p = 0.062) compared to that before the pandemic. In subgroup analysis, the estimated coefficient for level change during the pandemic in the 0-4 and 5-9 years age groups were -2.050 (95% CI: -2.972 to -1.128, p < 0.001) and -0.813 (95% CI: -1.399 to -0.227, p = 0.008), respectively. The annual incidence of encephalitis during the pandemic period significantly decreased in the 0-4 and 5-9 years age groups (incidence rate ratio: 0.34 [p = 0.007] and 0.28 [p = 0.024], respectively). The intensive care unit admission rate (39.1% vs. 58.9%, p < 0.001) and cases of death (8.9% vs. 11.1%, p < 0.001) decreased significantly during the pandemic compared to the prepandemic. During the pandemic, the incidence of encephalitis decreased markedly in South Korea, particularly in children aged ≤9 years. In addition, there were changes in the clinical outcome of encephalitis during the COVID-19 pandemic.

Comparison of humoral immunogenicity in solid organ transplant recipients after third-dose mRNA vaccine with homologous or heterologous schedules: An observational study.

BACKGROUND: Solid organ transplant recipients (SOTRs) are susceptible to severe coronavirus disease 2019 (COVID-19); however, immunogenicity studies of the Omicron variants per vaccination schedules are still lacking. We examined humoral immunogenicity following third-dose mRNA vaccine administration in Korean SOTRs who received primary COVID-19 vaccine series on homologous or heterologous schedules. METHODS: We recruited SOTRs at Severance Hospital from October 27, 2021, to March 31, 2022. Blood samples were collected between 14 days and 5 months after the second and third mRNA vaccine (BNT162b2 or mRNA-1273) doses. SARS-CoV-2 anti-spike IgG titer was analyzed. The neutralization inhibition rate was analyzed using the surrogate neutralization assay for the wild-type, Delta, and Omicron variants. RESULTS: No significant differences existed in the SARS-CoV-2 anti-spike IgG positivity rate between the homologous BNT162b2/BNT162b2/BNT162b2 (85%) and other heterologous groups (83% of ChAdOx1/ChAdOx1/BNT162b2, 90% of ChAdOx1/ChAdOx1/mRNA-1273, and 78% of ChAdOx1/BNT162b2/BNT162b2). No significant difference existed in the neutralization inhibition rates between the four groups for wild-type, Delta, and Omicron variants. Median neutralization inhibition rates against the Omicron variant (2-5%) were significantly lower than those against the wild-type (87-97%) and Delta (55-89%) variants (P < 0.001). CONCLUSIONS: Regardless of the schedule, the neutralization inhibition rate against the Omicron variant was poor; therefore, additional preventive measures are required in such high-risk populations.

Risk of cancer, tuberculosis and serious infections in patients with ankylosing spondylitis, psoriatic arthritis and psoriasis treated with IL-17 and TNF-α inhibitors: a nationwide nested case-control analysis.

OBJECTIVES: Targeting interleukin (IL)-17 and tumour necrosis factor (TNF)-α is recommended for the management of severe/refractory ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis (PsO); however, safety data comparing these agents, especially in a large Asian population are unavailable. METHODS: Patients with AS, PsA and PsO were searched using the Health Insurance Review and Assessment Service database, defined according to the International Classification of Diseases-10 and unique insurance codes for rare diseases. By including patients newly diagnosed with AS, PsA, and PsO between 2010-2020, the outcomes of cancer, tuberculosis (TB) and serious infections following IL-17 and TNF-α inhibitor usage were evaluated. To investigate the association between treatments and outcomes, nested case-control analyses matching patients to controls (maximum of 1:10 ratio) according to index age, sex, index year, and follow-up duration were performed. RESULTS: Among 40322, 4953, and 5347 patients with AS, PsA, and PsO, respectively, three different datasets were generated to evaluate incidence of outcomes. Conditional logistic regression analysis revealed that cyclosporine use (odds ratio [OR] 2.286, p=0.0176) increased cancer, and a higher Charlson Comorbidity Index (CCI) score (OR 1.085, p=0.0406) and IL-17 inhibitor use only (OR 0.126, p=0.0457) showed a positive and negative association with TB, respectively. Serious infections increased in patients with high CCI scores (OR 1.117, p<0.0001), cyclosporine users (OR 1.445, p=0.0098), and medical-aided individuals (OR 1.667, p<0.0001). CONCLUSIONS: In this nationwide cohort of IL-17 and TNF-α inhibitor users, both treatments conferred comparable risk of cancer and serious infections, while IL-17 inhibitors may be advantageous for TB.

Effects of Emergency Transfer Coordination Center on Length of Stay of Critically Ill Patients in the Emergency Department.

INTRODUCTION: Critically ill patients are frequently transferred from other hospitals to the emergency departments (ED) of tertiary hospitals. Due to the unforeseen transfer, the ED length of stay (LOS) of the patient is likely to be prolonged in addition to other potentially adverse effects. In this study we sought to confirm whether the establishment of an organized unit - the Emergency Transfer Coordination Center (ETCC) - to systematically coordinate emergency transfers would be effective in reducing the ED LOS of transferred, critically ill patients. METHODS: The present study is a retrospective observational study focusing on patients who were transferred from other hospitals and admitted to the intensive care unit (ICU) of the ED in a tertiary hospital located in northwestern Seoul, the capital city of South Korea, from January 2019 - December 2020. The exposure variable of the study was ETCC approval before transfer, and ED LOS was the primary outcome. We used propensity score matching for comparison between the group with ETCC approval and the control group. RESULTS: Included in the study were 1,097 patients admitted to the ICU after being transferred from other hospitals, of whom 306 (27.9%) were transferred with ETCC approval. The median ED LOS in the ETCC-approved group was significantly reduced to 277 minutes compared to 385 minutes in the group without ETCC approval. The ETCC had a greater effect on reducing evaluation time than boarding time, which was the same for populations with different clinical features. CONCLUSION: An ETCC can be effective in systematically reducing the ED LOS of critically ill patients who are transferred from other hospitals to tertiary hospitals that are experiencing severe crowding.

Risk of Dental Discoloration and Enamel Dysplasia in Children Exposed to Tetracycline and Its Derivatives.

PURPOSE: To examine the risk of dental abnormalities after exposure to tetracycline and its derivatives (TCs) in Korean children. MATERIALS AND METHODS: Children aged 0-17 years with a claim for prescriptions of TCs between 2002 and 2015 were identified from the Sample Research Database 2.0 of the National Health Insurance Service. Children not exposed to TCs were selected as the control group by matching sex and age (1:4). Cumulative incidence rate and relative risk of dental abnormalities after TCs exposure were investigated. RESULTS: The 10-year cumulative incidence rate in the 0-12 years group was 3.1% [95% confidence interval (CI), 2.3-3.9]. The 10-year cumulative incidence rates were 7.0%, 1.9%, and 1.6% in the 0-7, 8-12, and 13-17 years age groups (95% CI: 4.7-9.3, 1.2-2.6, and 1.3-1.9, respectively). There was no significant difference in the risk of dental abnormalities according to TC exposure among the age groups of 0-7 years [adjusted hazard ratio (aHR)=1.0], 8-12 years (aHR=1.1), and 13-17 years (aHR=1.2). CONCLUSION: Short-term exposure to TCs does not appear to increase the risk of dental abnormalities in children aged 0-7 and 0-12 years. Restrictions on the use of TCs in children aged 8-12 years, in some countries, may warrant consideration.

Periodontal disease and cancer risk: A nationwide population-based cohort study.

Background: Although emerging evidence suggests that periodontitis might increase the risk of cancer, comorbidity and lifestyle behaviors, such as smoking and body mass index (BMI), may have confounded this reported association. This study aimed to investigate whether chronic periodontitis is associated with cancer risk using a large, nationwide database. Methods: We conducted a population-based, retrospective cohort study using data from the Korean National Health Insurance Cohort Database obtained between January 2003 and December 2015. We included 713,201 individuals without a history of cancer who were followed up to 10 years. Confounding factors included demographic factors (age, sex, income, and residential area), lifestyle behaviors (smoking history and BMI), and comorbidities, such as hypertension, diabetes, heart failure, and pulmonary disease, using the Charlson Comorbidity Index. Multivariable Cox regression analysis was applied to estimate the adjusted hazard ratio (aHR) for cancer risk. Results: Of the 713,201 participants, 53,075 had periodontitis and were placed in the periodontitis group; the remaining 660,126 individuals were included as the control group. Overall, the cumulative incidence of cancer in the periodontitis group was 2.2 times higher than that in the control group. The periodontitis group had an increased risk of total cancer compared to the control group after adjusting for age, sex, comorbidities, BMI, and smoking history (aHR, 1.129; 95% confidence interval [CI], 1.089-1.171; P<0.0001). When examining specific cancer types, significant associations were also observed between periodontitis and stomach cancer (aHR, 1.136; 95% CI, 1.042-1.239; P=0.0037), colon cancer (aHR, 1.129; 95% CI, 1.029-1.239; P=0.0105), lung cancer (aHR, 1.127; 95% CI, 1.008-1.260; P=0.0353), bladder cancer (aHR, 1.307; 95% CI, 1.071-1.595; P=0.0085), thyroid cancer (aHR, 1.191; 95% CI, 1.085-1.308; P=0.0002), and leukemia (aHR, 1.394; 95% CI, 1.039-1.872; P=0.0270). There was no significant association between the development of secondary malignancy and periodontitis in cancer survivors who were alive 5 years after they were diagnosed with the primary malignancy. Conclusions: Periodontal disease, including periodontitis, was associated with increased risk of cancer, which persisted after controlling for confounding factors. Further prospective research is warranted to establish a causal relationship.

Respiratory Syncytial Virus Outbreak Without Influenza in the Second Year of the Coronavirus Disease 2019 Pandemic: A National Sentinel Surveillance in Korea, 2021-2022 Season.

BACKGROUND: This study aimed to investigate whether respiratory syncytial virus (RSV) and influenza virus (IFV) infections would occur in 2021-2022 as domestic nonpharmaceutical interventions (NPIs) are easing. METHODS: Data were collected from the Korean Influenza and Respiratory Virus Monitoring System database. The weekly positivity rates of respiratory viruses and number of hospitalizations for acute respiratory infections were evaluated (January 2016-2022). The period from February 2020 to January 2022 was considered the NPI period. The autoregressive integrated moving average model and Poisson analysis were used for data analysis. Data from 14 countries/regions that reported positivity rates of RSV and IFV were also investigated. RESULTS: Compared with the pre-NPI period, the positivity and hospitalization rates for IFV infection during 2021-2022 significantly decreased to 0.0% and 1.0%, respectively, at 0.0% and 1.2% of the predicted values, respectively. The RSV infection positivity rate in 2021-2022 was 1.8-fold higher than that in the pre-NPI period at 1.5-fold the predicted value. The hospitalization rate for RSV was 20.0% of that in the pre-NPI period at 17.6% of the predicted value. The re-emergence of RSV and IFV infections during 2020-2021 was observed in 13 and 4 countries, respectively. CONCLUSION: During 2021-2022, endemic transmission of the RSV, but not IFV, was observed in Korea.