Background: Post-transplant diabetes mellitus (PTDM) is one of the most significant complications after transplantation. Patients with end-stage liver diseases requiring transplantation are prone to sarcopenia, but the association between sarcopenia and PTDM remains to be elucidated. We aimed to investigate the effect of postoperative muscle mass loss on PTDM development. Methods: A total of 500 patients who underwent liver transplantation at a tertiary care hospital between 2005 and 2020 were included. Skeletal muscle area at the level of the L3–L5 vertebrae was measured using computed tomography scans performed before and 1 year after the transplantation. The associations between the change in the muscle area after the transplantation and the incidence of PTDM was investigated using a Cox proportional hazard model. Results: During the follow-up period (median, 4.9 years), PTDM occurred in 165 patients (33%). The muscle mass loss was greater in patients who developed PTDM than in those without PTDM. Muscle depletion significantly increased risk of developing PTDM after adjustment for other confounding factors (hazard ratio, 1.50; 95% confidence interval, 1.23 to 1.84; P=0.001). Of the 357 subjects who had muscle mass loss, 124 (34.7%) developed PTDM, whereas of the 143 patients in the muscle mass maintenance group, 41 (28.7%) developed PTDM. The cumulative incidence of PTDM was significantly higher in patients with muscle loss than in patients without muscle loss (P=0.034). Conclusion Muscle depletion after liver transplantation is associated with increased risk of PTDM development.

Objective: To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline. Methods: In all, 20 participants with Alzheimer’s dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer’s dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion The higher the GR, the lower the prevalence of Alzheimer’s dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer’s dementia and cognitive decline.

Background: Although several characteristics of coronavirus disease 2019 (COVID-19), an ongoing pandemic disease, have been identified, data on the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. Methods: This prospective cohort study was conducted to analyze the infectivity of SARSCoV-2 based on data of all patients diagnosed with COVID-19 confirmed using real-time polymerase chain reaction test from January to April 2020 in Gyeonggi-do, the largest province in Korea. Results: Of the 502 patients, 298 consisting of 106 clusters with 5,909 contacts were included. Of these, 277 (93.0%) were symptomatic, and the most common symptoms were cough, fever, sputum, sore throat, and headache. A total of 94 patients (31.5%) had pneumonia, while 8 (2.7%) died during the follow-up period. The secondary attack rate (SAR) in the study population was 3.5% (204/5,909). In exposure settings, the SAR was higher in religious gathering (13.5% [95% confidence interval, 10.7–16.8%]), workplaces (8.49% [95% CI, 6.08–11.74%]), and schools (6.38% [95% CI, 3.39–11.69%]) than in health care facilities (1.92% [95% CI, 1.45–2.55%]). Sore throat at any period, dyspnea at diagnosis or any period, lower cycle threshold value in the lower respiratory tract samples, leukocytosis, and higher bilirubin levels were associated with higher infectivity of COVID-19. The presence of symptoms was not related to the infectivity. Conclusion In establishing the infection control strategies for COVID-19, the variables associated with high infectivity may be considered.

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: Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea. Methods: From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of GAA gene. Results: Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T>A [p.M439K] + c.2015G>A [p.R672Q], c.1857C>G [p.S619R] + c.546G>C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele. Conclusions This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

Background: On March 22, 2020, intense social distancing (SD) was implemented in Korea to prevent the spread of coronavirus disease 19 (COVID-19). This study examined the impact of SD on diabetes control in older adults with diabetes. Methods: Adults aged 60 to 90 years with type 2 diabetes mellitus who were physically and mentally independent were recruited. Participants who had complete blood chemistry data from April to July 2019 (pre-SD era) and April to July 2020 (SD era) were enrolled. Data were obtained about physical activity, nutrition, sarcopenia, and psychological and mental health from questionnaires in April to July 2020. Calf circumference was measured. Results: In total, 246 people (100 men, 146 women; mean age, 73.8±5.7 years) participated in this study. The levels of glycated hemoglobin (HbA1c, 7.4%±1.0% vs. 7.1%±0.8%, P<0.001), fasting glucose (142.2±16.7 mg/dL vs. 132.0±27.7 mg/dL, P<0.001), and body weight (62.6±9.4 kg vs. 61.8±10.1 kg, P<0.01) were higher in the SD era than in the pre-SD era. Total physical activity was lower in the SD era (2,584.6±2,624.1 MET-min/week–1 vs. 1,987.3±2,295.0 MET-min/week–1, P<0.001). A larger increase in HbA1c level was associated with increased body weight and decreased physical activity. Conclusion SD had negative effects on diabetes management in older adults with diabetes. Fasting glucose and HbA1c levels and body weight increased during the SD era. Participants with reduced physical activity gained more weight and had higher blood glucose levels. Given that the COVID-19 pandemic is ongoing, health professionals and diabetes educators should monitor changes in lifestyle factors in older adults with diabetes.

Background: On March 22, 2020, intense social distancing (SD) was implemented in Korea to prevent the spread of coronavirus disease 19 (COVID-19). This study examined the impact of SD on diabetes control in older adults with diabetes. Methods: Adults aged 60 to 90 years with type 2 diabetes mellitus who were physically and mentally independent were recruited. Participants who had complete blood chemistry data from April to July 2019 (pre-SD era) and April to July 2020 (SD era) were enrolled. Data were obtained about physical activity, nutrition, sarcopenia, and psychological and mental health from questionnaires in April to July 2020. Calf circumference was measured. Results: In total, 246 people (100 men, 146 women; mean age, 73.8±5.7 years) participated in this study. The levels of glycated hemoglobin (HbA1c, 7.4%±1.0% vs. 7.1%±0.8%, P<0.001), fasting glucose (142.2±16.7 mg/dL vs. 132.0±27.7 mg/dL, P<0.001), and body weight (62.6±9.4 kg vs. 61.8±10.1 kg, P<0.01) were higher in the SD era than in the pre-SD era. Total physical activity was lower in the SD era (2,584.6±2,624.1 MET-min/week–1 vs. 1,987.3±2,295.0 MET-min/week–1, P<0.001). A larger increase in HbA1c level was associated with increased body weight and decreased physical activity. Conclusion SD had negative effects on diabetes management in older adults with diabetes. Fasting glucose and HbA1c levels and body weight increased during the SD era. Participants with reduced physical activity gained more weight and had higher blood glucose levels. Given that the COVID-19 pandemic is ongoing, health professionals and diabetes educators should monitor changes in lifestyle factors in older adults with diabetes.

Background: Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea. Methods: From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of GAA gene. Results: Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T>A [p.M439K] + c.2015G>A [p.R672Q], c.1857C>G [p.S619R] + c.546G>C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele. Conclusions This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population.METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis.RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence.CONCLUSION: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.
Antiviral Agents ; Carcinoma, Hepatocellular ; Cohort Studies ; DNA ; Follow-Up Studies ; Half-Life ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B ; Hepatitis ; Humans ; Immunoglobulins ; Korea ; Liver Transplantation ; Liver ; Organ Transplantation ; Polymerase Chain Reaction ; Recurrence ; Transplants

Background: The fatality rate of patients with coronavirus disease 2019 (COVID-19) varies among countries owing to demographics, patient comorbidities, surge capacity of healthcare systems, and the quality of medical care. We assessed the clinical outcomes of patients with COVID-19 during the first wave of the epidemic in Korea. Methods: Using a modified World Health Organization clinical record form, we obtained clinical data for 3,060 patients with COVID-19 treated at 55 hospitals in Korea. Disease severity scores were defined as: 1) no limitation of daily activities; 2) limitation of daily activities but no need for supplemental oxygen; 3) supplemental oxygen via nasal cannula; 4) supplemental oxygen via facial mask; 5) non-invasive mechanical ventilation; 6) invasive mechanical ventilation; 7) multi-organ failure or extracorporeal membrane oxygenation therapy; and 8) death. Recovery was defined as a severity score of 1 or 2, or discharge and release from isolation. Results: The median age of the patients was 43 years of age; 43.6% were male. The median time from illness onset to admission was 5 days. Of the patients with a disease severity score of 3–4 on admission, 65 (71.5%) of the 91 patients recovered, and 7 (7.7%) died due to illness by day 28. Of the patients with disease severity scores of 5–7, 7 (19.5%) of the 36 patients recovered, and 8 (22.2%) died due to illness by day 28. None of the 1,324 patients who were < 50 years of age died; in contrast, the fatality rate due to illness by day 28 was 0.5% (2/375), 0.9% (2/215), 5.8% (6/104), and 14.0% (7/50) for the patients aged 50–59, 60–69, 70–79, and ≥ 80 years of age, respectively. Conclusion In Korea, almost all patients of < 50 years of age with COVID-19 recovered without supplemental oxygen. In patients of ≥ 50 years of age, the fatality rate increased with age, reaching 14% in patients of ≥ 80 years of age.