Purpose: Social distancing and strict visitor restrictions at hospitals have been national policies since the onset of the coronavirus disease 2019 (COVID-19) pandemic. This has challenged the concept of a good death in comfort with the opportunity to say goodbye.Little is known about how these measures have influenced end-of-life (EOL) care among cancer patients who die in acute care hospitals. This study examined changes in the EOL care of cancer patients during the COVID-19 pandemic. Methods: We retrospectively analyzed 1,456 adult cancer patients who died in 2019 (n=752) and 2020 (n=704) at a tertiary hospital. Data on EOL care—symptom control and comfort care in an imminently dying state, preparation for death, place of death, and aggressive care in the last month— were reviewed. Results: The 1,456 patients had a median age of 67 years, and 62.5% were men. Patients who died in 2020 were more likely to experience agitation or delirium before death (17.2% vs. 10.9%), to use inotropes/vasopressors near death (59.2% vs. 52.3%), and to receive cardiopulmonary resuscitation in their last months (16.3% vs. 12.5%) than those who died in 2019. Additionally, the number of deaths in the emergency room doubled in 2020 compared to 2019 (from 7.1% to 14.1%). Conclusion This study suggests that EOL care for cancer patients who died in a tertiary hospital deteriorated during the COVID-19 pandemic. The implementation of medical care at the EOL and the preferred place of death should be discussed carefully in advance for high-quality EOL care.

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

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.

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.

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.

Background: Clinical ethics support is a form of preventive ethics aimed at mediating ethicsrelated conflicts and managing ethical issues arising in the healthcare setting. However, limited evidence exists regarding the specific ethical issues in clinical practice. This study aimed to explore the diverse ethical issues of cases referred to clinical ethics support after the new legislation on hospice palliative care and end-of-life decision-making was implemented in Korea in 2018. Methods: A retrospective study of cases referred to clinical ethics support at a university hospital in Korea from February 2018 to February 2021 was conducted. The ethical issues at the time of referral were analyzed via qualitative content analysis of the ethics consultationrelated documents. Results: A total of 60 cases of 57 patients were included in the study, of whom 52.6% were men and 56.1% were older than 60 years of age. The majority of cases (80%) comprised patients from the intensive care unit. One-third of the patients were judged as being at the end-of-life stage. The most frequent ethical categories were identified as goals of care/ treatment (78.3%), decision-making (75%), relationship (41.7%), and end-of-life issues (31.7%). More specifically, best interests (71.7%), benefits and burdens/harms (61.7%), refusal (53.3%), and surrogate decision-making (33.3%), followed by withholding or withdrawal (28.3%) were the most frequent ethical issues reported, which became diversified by year. In addition, the ethical issues appeared to differ by age group and judgment of the end-of-life stage. Conclusion The findings of this study expand the current understanding of the diverse ethical issues including decision-making and goals of care/treatment that have been referred to clinical ethics support since the enforcement of the new legislation in Korea. This study suggests a need for further research on the longitudinal exploration of ethical issues and implementation of clinical ethics support in multiple healthcare centers.

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.

Vitamin C is a well-known antioxidant with antiviral, anticancer, and anti-inflammatory properties based on its antioxidative function. Aptamin C, a complex of vitamin C with its specific aptamer, has been reported to maintain or even enhance the efficacy of vitamin C while increasing its stability. To investigate in vivo distribution of Aptamin C, Gulo knockout mice, which, like humans, cannot biosynthesize vitamin C, were administered Aptamin C orally for 2 and 4 weeks.The results showed higher vitamin C accumulation in all tissues when administered Aptamin C, especially in the spleen. Next, the activity of natural killer (NK) cells were conducted. CD69, a marker known for activating for NK cells, which had decreased due to vitamin C deficiency, did not recover with vitamin C treatment but showed an increasing with Aptamin C. Furthermore, the expression of CD107a, a cell surface marker that increases during the killing process of target cells, also did not recover with vitamin C but increased with Aptamin C. Based on these results, when cultured with tumor cells to measure the extent of tumor cell death, an increase in tumor cell death was observed. To investigate the signaling mechanisms and related molecules involved in the proliferation and activation of NK cells by Aptamin C showed that Aptamin C treatment led to an increase in intracellular STAT3 activation. In conclusion, Aptamin C has a higher capability to activate NK cells and induce tumor cell death compared to vitamin C and it is mediated through the activation of STAT3.

Vitamin C is a well-known antioxidant with antiviral, anticancer, and anti-inflammatory properties based on its antioxidative function. Aptamin C, a complex of vitamin C with its specific aptamer, has been reported to maintain or even enhance the efficacy of vitamin C while increasing its stability. To investigate in vivo distribution of Aptamin C, Gulo knockout mice, which, like humans, cannot biosynthesize vitamin C, were administered Aptamin C orally for 2 and 4 weeks.The results showed higher vitamin C accumulation in all tissues when administered Aptamin C, especially in the spleen. Next, the activity of natural killer (NK) cells were conducted. CD69, a marker known for activating for NK cells, which had decreased due to vitamin C deficiency, did not recover with vitamin C treatment but showed an increasing with Aptamin C. Furthermore, the expression of CD107a, a cell surface marker that increases during the killing process of target cells, also did not recover with vitamin C but increased with Aptamin C. Based on these results, when cultured with tumor cells to measure the extent of tumor cell death, an increase in tumor cell death was observed. To investigate the signaling mechanisms and related molecules involved in the proliferation and activation of NK cells by Aptamin C showed that Aptamin C treatment led to an increase in intracellular STAT3 activation. In conclusion, Aptamin C has a higher capability to activate NK cells and induce tumor cell death compared to vitamin C and it is mediated through the activation of STAT3.