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.

Background: Postpartum depression (PPD) can negatively affect infant well-being and child development. Although the frequency and risk factors of PPD symptoms might vary depending on the country and culture, there is limited research on these risk factors among Korean women. This study aimed to elucidate the potential risk factors of PPD throughout pregnancy to help improve PPD screening and prevention in Korean women. Methods: The pregnant women at 12 gestational weeks (GW) were enrolled from two obstetric specialized hospitals from March 2013 to November 2017. A questionnaire survey was administered at 12 GW, 24 GW, 36 GW, and 4 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale, and PPD was defined as a score of ≥ 10. Results: PPD was prevalent in 16.3% (410/2,512) of the participants. Depressive feeling at 12 GW and postpartum factors of stress, relationship with children, depressive feeling, fear, sadness, and neonatal intensive care unit admission of baby were significantly associated with a higher risk of PPD. Meanwhile, high postpartum quality of life and marital satisfaction at postpartum period were significantly associated with a lower risk of PPD. We developed a model for predicting PPD using factors as mentioned above and it had an area under the curve of 0.871. Conclusion Depressive feeling at 12 GW and postpartum stress, fear, sadness, relationship with children, low quality of life, and low marital satisfaction increased the risk of PPD. A risk model that comprises significant factors can effectively predict PPD and can be helpful for its prevention and appropriate treatment.

Purpose: Tetracycline is not recommended for children under 12 by guideline due to the risk of tooth discoloration. We aimed to assess the incidence of dental discoloration in Korean children prescribed tetracyclines and investigate whether its risk was greater in tetracyclineexposed children than in the general population. Methods: This population-based cohort study using the Health Insurance Review and Assessment service database included children aged 0–12 years exposed to tetracyclines for at least 1 day between January 2008 and December 2020. The primary outcome was the incidence rate of dental discoloration ≥6 months after prescription, and the standardized incidence ratio (SIR) was evaluated as secondary outcome. Results: 56,990 children were included—1,735 and 55,255 aged <8 and 8–12 years, respectively. 61% children were prescribed tetracycline for <14 days with mostly secondgeneration tetracyclines, doxycycline (61%) and minocycline (35%). The 5- and 10-year cumulative incidence rates of dental discoloration were 4.1% (95% confidence interval [CI], 3.0–5.7%) and 5.7% (95% CI, 4.1% to 7.8%), respectively, in the 0–7 years age group and 0.8% (95% CI, 0.7% to 0.9%) and 1.3 (95% CI, 1.1% to 1.4%), respectively, in the 8–12 years age group. Tetracycline exposure did not increase such risk compared to that in the general population (SIR, 1.08; 95% CI, 0.69 to 1.60). Conclusions The incidence of dental discoloration was lower than previously suggested.Relieving the age restriction for prescribing tetracyclines may be considered.

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.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

Background: The global TARGET survey examined real-world management of chronic myeloid leukemia (CML) compared with international guideline recommendations. This report focused on the responses of physicians from South Korea compared with those of physicians from the rest of the world (ROW). Methods: The self-administered, online survey, comprising 23 questions and clinical case scenarios, was completed between April and August 2017. It was designed to gather information on practicing physicians and local practices for CML diagnosis, disease monitoring, treatment, and adverse event (AE) management. Results: While there were similarities in the mutation analysis and treatment efficacy between Korea and the ROW, there were also differences in CML management. Initial diagnostic testing was more comprehensive in Korea than in the ROW, and there was significantly better access to standardized polymerase chain reaction testing. Assessment of BCR-ABL levels during the first 12 months of treatment was excellent in Korea, and there was greater frontline use of second-generation BCR-ABL tyrosine kinase inhibitors. Korean physicians were significantly less likely to switch therapy for hematologic AEs. Treatment-free remission was not an important goal of therapy among Korean or ROW physicians. Conclusion This study identified some differences in the current CML management between Korea and the ROW; CML management in Korean patients was generally in line with the current guidelines.

Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer‒associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type‒specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer‒associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.

Background: Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea. Methods: A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]). Results: Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test). Conclusion The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.

Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer‒associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type‒specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer‒associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.