Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix GeneChip® Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.
Acetaminophen ; Animals ; Drug-Induced Liver Injury ; Genetic Variation ; Incidence ; Lipoprotein Lipase* ; Lipoproteins* ; Liver ; Methods ; Mice ; Microarray Analysis ; Real-Time Polymerase Chain Reaction ; Receptors, GABA-A* ; Toxicogenetics ; Transcriptome

BACKGROUND: Multiple studies have been reported regarding preeclampsia as a possible risk factor of cerebrovascular disease (CVD). However, the correlation of preeclampsia and CVD, whether it is a cause-effect relationship or they are sharing common predisposing condition, is not well understood. Therefore, the aim of this study was to investigate the association between the preeclampsia during pregnancy and development of postpartum CVD. METHODS: A total of 1,384,550 Korean women who had a delivery between January 1, 2010 and December 31, 2012, were enrolled. Women with the risk of CVD within 1 year prior to pregnancy were excluded based on the Charlson comorbidity index. Primary endpoint was the event of CVD within a year from delivery. After exclusion, 1,075,061 women were analyzed. RESULTS: During the follow-up of 1 year postpartum, there were 25,577 preeclampsia out of 1,072,041 women without postpartum CVD (2.39%), and 121 of 3,020 women with postpartum CVD had preeclampsia before delivery (4.01%). In multivariate logistic regression analysis, women who had preeclampsia during pregnancy showed a higher risk for postpartum CVD (odds ratio, 1.64; 95% confidence interval, 1.37–1.98). CONCLUSION: The incidence of CVD after delivery was higher in women who had preeclampsia during pregnancy.
Cerebrovascular Disorders ; Comorbidity ; Female ; Follow-Up Studies ; Humans ; Incidence ; Insurance Claim Reporting ; Korea ; Logistic Models ; Postpartum Period ; Pre-Eclampsia ; Pregnancy ; Risk Factors

Objective To investigate the therapeutic effects and mechanisms of interleukin-10 (IL-10) gene-modified dendritic cells (DC-IL-10) in mice with liver fibrosis. Methods DC-IL-10 was constructed in vitro, the phenotype and function of which were evaluated by flow cytometry. BALB/c mice were treated with intraperitoneal injection of carbon tetrachloride(CCl4)to establish liver fibrotic model. DC-IL-10 was administrated via tail vein. Animals were divided into 4 groups including normal dendritic cell (DC) control , liver fibrosis only, negative lentiviral transfection DC (DC-mock) and DC-IL-10. Liver function, cytokine secretion, T lymphocyte differentiation and liver histomorphology were tested. Real-time PCR and western blot were used to analyze the effect of DC-IL-10 on Wnt/β-catenin signaling pathway and its role in liver fibrosis. Results When compared with DC control and DC-mock, the expression of DC-IL-10 surface stimulating molecules (major histocompatibity complex-Ⅱ, CD80, CD86) were significantly decreased (F=14.708, 22.503, 12.595, respectively, all P<0.05), and DC-IL-10 significantly inhibited T lymphocyte proliferation (F=50.295, P<0.05). When compared with liver fibrosis group, serum alanine aminotransferase and aspartate transaminase were decreased in DC-IL-10 treated group (all P<0.05), other parameters including inflammatory factors (tumor necrosis factor α, IL-6, IL-1β) reduced (all P<0.05), the proportion of regulatory T cells (Treg) increased (F=6.742, P<0.05), pathological damage improved, the expression of Wnt3a, α-SMA and β-catenin mRNA and protein significantly reduced in DC-IL-10 treatment group(all P<0.001). Conclusions DC-IL-10 induces elevation of Treg for immune tolerance, as well as inhibition of inflammatory response, block of Wnt/β-catenin signaling pathway, which translates into improvement of liver fibrosis.

Purpose: In Korea, since the Act on Hospice and Palliative Care and Decisions on LifeSustaining Treatment for Patients at the End of Life was implemented in February 2018, advance directives (ADs) have become legally effective and should be documented after sufficient explanation by a registered counselor. However, little is known regarding the adequacy of current AD counseling. This qualitative study aimed to explore the barriers to AD counseling based on counselors’ experiences. Methods: We conducted focus group interviews using purposive sampling. Seven counselors working at hospitals, community health institutions, and non-profit organizations participated in this study. They were asked about the challenges and problems they encountered during AD counseling. Results: Three themes emerged from this study; 1) issues regarding consistency in AD counseling, 2) issues regarding AD counselors’ competency and work environment, and 3) issues regarding the adequacy of the service system. The interviewees stated that the lack of a manual for standardized service made AD counseling inconsistent. The limited competency and poor work environment of counselors were pointed out as major barriers. The interviewees also stated that a proper service system considering individual circumstances is absent. Conclusion The goals of AD counseling should be clarified and guidance should be implemented for providing standardized services. Further efforts to enhance the competency of AD counselors and to improve their working conditions are needed. Establishing an integrated framework for an adequate service system is also essential to overcome systematic barriers to AD counseling.

Background: Basiliximab is used as an alternative to tacrolimus in patients with decreased renal function. However, studies on basiliximab as a maintenance immunosuppressant, particularly in patients with lung transplantation, are limited. Therefore, here, we investigated the efficacy and safety of basiliximab in patients with lung transplantation. Methods: Adult patients with acute kidney injury (AKI) who received lung transplantation at a single general hospital between July 1, 2014 and June 30, 2018, were selected and classified in tacrolimus and basiliximab groups. Both groups received a triple-drug regimen (tacrolimus, mycophenolate mofetil, and steroids). However, tacrolimus was discontinued in the basiliximab group when AKI occurred, and two or more repeat basiliximab doses were administered within 3 months after transplantation. The electronic medical records were analyzed retrospectively. Results: Of the 85 patients who met the selection criteria, 61 and 24 were assigned to the tacrolimus and basiliximab groups, respectively. Significant improvement in renal function was observed in the basiliximab group (p <0.001).However, there were no differences in acute and chronic rejection rates in both the groups. No difference was observed in the incidence rate of complications between the groups, except for chronic kidney disease, which showed higher incidence in the basiliximab group (25.0% vs. 4.9%; p =0.013). Conclusions We suggest the use of basiliximab as an immunosuppressant alternative to tacrolimus in patients with acute renal failure after lung transplantation. Basiliximab demonstrated effectiveness as an immunosuppressant and improved renal function. Therefore, basiliximab can be used in patients with decreased renal function.

In the era of coronavirus disease 2019 (COVID-19), social distancing and strict visitation policies at hospitals have made it difficult for medical staff to provide high-quality endof-life (EOL) care to dying patients and their families. There are various issues related to EOL care, including psychological problems of patients and their families, difficulties in EOL decision-making, the complicated grief of the bereaved family, moral distress, and exhaustion of medical staff. In relation to these issues, we aimed to discuss practical considerations in providing high-quality EOL care in the COVID-19 pandemic. First, medical staff should discuss advance care planning as early as possible and use the parallel planning strategy. Second, medical staff should play a role in facilitating patient-family communication. Third, medical staff should actively and proactively evaluate and alleviate dying patients’ symptoms using non-verbal communication. Lastly, medical staff should provide care for family members of the dying patient, who may be particularly vulnerable to postbereavement problems in the COVID-19 era. Establishing a system of screening highrisk individuals for complicated grief and connecting them to bereavement support services might be considered. Despite the challenging and limited environment, providing EOL care is essential for patients to die with dignity in peace and for the remaining family to return to life after the loved one’s death. Efforts considering the practical issues faced by all medical staff and healthcare institutions caring for dying patients should be made.

Purpose: This study aimed to investigate difficulties doctors experience during life-sustaining treatment (LST) discussion with seriously ill patients and their families after enactment of the LST Decisions Act in February 2018. Materials and Methods: A cross-sectional survey was conducted in a tertiary hospital in the Republic of Korea in August 2019. Six hundred eighty-six doctors who care for seriously ill patients were given a structured questionnaire, and difficulties during the discussion were examined. Results: One hundred thirty-two doctors completed the questionnaire. Eighty-five percent answered they treat cancer patients. Most (86.4%) experienced considerable difficulties during LST discussions (mean score, 7.4±1.6/10). The two most common difficulties were communication with patients and family and determining when to discuss LST. Two-thirds of doctors found direct discussions with the patient difficult and said they would initiate LST discussions only with family. LST discussions were actually initiated later than considered appropriate. When medically assessing whether the patient is imminently dying, 56% of doctors experienced disagreements with other doctors, which could affect their decisions. Conclusion This study found that most doctors experienced serious difficulties regarding communication with patients and family and medical assessment of dying process during LST discussions. To alleviate these difficulties, further institutional support is needed to improve the LST discussion between doctors, patients, and family.

Purpose: This study aimed to investigate difficulties doctors experience during life-sustaining treatment (LST) discussion with seriously ill patients and their families after enactment of the LST Decisions Act in February 2018. Materials and Methods: A cross-sectional survey was conducted in a tertiary hospital in the Republic of Korea in August 2019. Six hundred eighty-six doctors who care for seriously ill patients were given a structured questionnaire, and difficulties during the discussion were examined. Results: One hundred thirty-two doctors completed the questionnaire. Eighty-five percent answered they treat cancer patients. Most (86.4%) experienced considerable difficulties during LST discussions (mean score, 7.4±1.6/10). The two most common difficulties were communication with patients and family and determining when to discuss LST. Two-thirds of doctors found direct discussions with the patient difficult and said they would initiate LST discussions only with family. LST discussions were actually initiated later than considered appropriate. When medically assessing whether the patient is imminently dying, 56% of doctors experienced disagreements with other doctors, which could affect their decisions. Conclusion This study found that most doctors experienced serious difficulties regarding communication with patients and family and medical assessment of dying process during LST discussions. To alleviate these difficulties, further institutional support is needed to improve the LST discussion between doctors, patients, and family.

Background: Basiliximab is used as an alternative to tacrolimus in patients with decreased renal function. However, studies on basiliximab as a maintenance immunosuppressant, particularly in patients with lung transplantation, are limited. Therefore, here, we investigated the efficacy and safety of basiliximab in patients with lung transplantation. Methods: Adult patients with acute kidney injury (AKI) who received lung transplantation at a single general hospital between July 1, 2014 and June 30, 2018, were selected and classified in tacrolimus and basiliximab groups. Both groups received a triple-drug regimen (tacrolimus, mycophenolate mofetil, and steroids). However, tacrolimus was discontinued in the basiliximab group when AKI occurred, and two or more repeat basiliximab doses were administered within 3 months after transplantation. The electronic medical records were analyzed retrospectively. Results: Of the 85 patients who met the selection criteria, 61 and 24 were assigned to the tacrolimus and basiliximab groups, respectively. Significant improvement in renal function was observed in the basiliximab group (p <0.001).However, there were no differences in acute and chronic rejection rates in both the groups. No difference was observed in the incidence rate of complications between the groups, except for chronic kidney disease, which showed higher incidence in the basiliximab group (25.0% vs. 4.9%; p =0.013). Conclusions We suggest the use of basiliximab as an immunosuppressant alternative to tacrolimus in patients with acute renal failure after lung transplantation. Basiliximab demonstrated effectiveness as an immunosuppressant and improved renal function. Therefore, basiliximab can be used in patients with decreased renal function.

In the era of coronavirus disease 2019 (COVID-19), social distancing and strict visitation policies at hospitals have made it difficult for medical staff to provide high-quality endof-life (EOL) care to dying patients and their families. There are various issues related to EOL care, including psychological problems of patients and their families, difficulties in EOL decision-making, the complicated grief of the bereaved family, moral distress, and exhaustion of medical staff. In relation to these issues, we aimed to discuss practical considerations in providing high-quality EOL care in the COVID-19 pandemic. First, medical staff should discuss advance care planning as early as possible and use the parallel planning strategy. Second, medical staff should play a role in facilitating patient-family communication. Third, medical staff should actively and proactively evaluate and alleviate dying patients’ symptoms using non-verbal communication. Lastly, medical staff should provide care for family members of the dying patient, who may be particularly vulnerable to postbereavement problems in the COVID-19 era. Establishing a system of screening highrisk individuals for complicated grief and connecting them to bereavement support services might be considered. Despite the challenging and limited environment, providing EOL care is essential for patients to die with dignity in peace and for the remaining family to return to life after the loved one’s death. Efforts considering the practical issues faced by all medical staff and healthcare institutions caring for dying patients should be made.