BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; mortality ; Extracorporeal Membrane Oxygenation ; Humans ; Lung Transplantation ; methods ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; Pulmonary Fibrosis ; mortality ; surgery ; Respiratory Distress Syndrome, Adult ; mortality ; surgery

Cholangiopathies are rare diseases of the bile duct with high mortality rates. The current treatment for cholangiopathies is liver transplantation, but there are significant obstacles including a shortage of donors and a high risk of complications. Currently, there is only one available medicine on the market targeting cholangiopathies, and the results have been inadequate in clinical therapy. To overcome these obstacles, many researchers have used human induced pluripotent stem cells (hPSC) as a source for cholangiocyte-like cell generation and have incorporated advances in bioprinting to create artificial bile ducts for implantation and transplantation. This has allowed the field to move dramatically forward in studies of biliary regenerative medicine. In this review, the authors provide an overview of cholangiocytes, the organogenesis of the bile duct, cholangiopathies, and the current treatment and advances that have been made that are opening new doors to the study of cholangiopathies.
Bile Ducts ; Bile ; Bioprinting ; Humans ; Induced Pluripotent Stem Cells ; Liver Transplantation ; Mortality ; Organogenesis ; Rare Diseases ; Regenerative Medicine ; Tissue Donors

BACKGROUND: Invasive aspergillosis (IA) is associated with high morbidity and mortality, particularly among immunocompromised patients, such as lung transplant recipients. Voriconazole, the first-line therapy for IA, shows a non-linear pharmacokinetic profile and has a narrow therapeutic range. Careful and appropriate administration is necessary, primarily because it is used for critically ill patients; however, the clinical usefulness of therapeutic drug monitoring (TDM) has not been sufficiently verified. Therefore, in this study, we validated the safety and efficacy of voriconazole TDM in lung transplant recipients receiving only voriconazole for IA treatment. METHODS: The electronic medical records of lung transplant recipients (≥19 years of age) administered only voriconazole for > 7 days for treatment of IA from June 1, 2013 to May 31, 2018 were analyzed retrospectively. RESULTS: Among the 54 patients, 27 each were allocated to TDM and non-TDM groups, respectively. There were no significant differences in patient characteristics between the two groups except for ICU-hospitalization status. Of the TDM group patients, 81.5% needed adjustment of voriconazole dosage because the levels were out of target range. Comparison of two groups showed that treatment response was higher throughout treatment and switching rates of second-line agents were significantly lower in the TDM group, but it was insufficient to confirm safety improvements through voriconazole TDM. CONCLUSION: Considering that the treatment response tended to be higher and the rates of switching to second-line antifungal agents were lower in the TDM group, voriconazole TDM may increase the therapeutic effect on IA in lung transplant patients.
Antifungal Agents ; Aspergillosis ; Critical Illness ; Drug Monitoring ; Electronic Health Records ; Humans ; Immunocompromised Host ; Lung Transplantation ; Lung ; Mortality ; Retrospective Studies ; Transplant Recipients ; Voriconazole

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) patients need parenteral nutrition because of nausea, vomiting, and mucositis caused by conditioning regimens. The demand for glutamine increases during the HSCT period. We evaluated the effects of glutamine-containing parenteral nutrition on the clinical outcomes of HSCT patients. METHODS: In this retrospective analysis, we reviewed HSCT patients from Seoul National University from August 2013 to July 2017. Depending on their glutamine supplementation status, 91 patients were divided into 2 groups: glutamine group (N=44) and non-glutamine group (N=47). We analyzed the rate of weight change, infection (clinically/microbiologically documented), complications (duration of mucositis and neutropenia, acute graft versus host disease), and 100-days mortality in each group. RESULTS: Regarding the clinical characteristics of the patients, there were no significant differences between the 2 groups except that there was a larger proportion of myeloablative conditioning regimen in the glutamine group (P=0.005). In the glutamine group, the average number of days of glutamine use, parenteral nutrition, and mucositis was 7.6±1.4, 14.6±9.9, and 13.3±9.5, respectively. Furthermore, multivariate analysis revealed odds ratios of 0.37 (95% CI, 0.14–0.96; P=0.042) and 0.08 (95% CI, 0.01–0.98; P=0.048) for clinically documented infection and 100-days mortality, respectively, in the glutamine group. CONCLUSION: Results showed that the glutamine group had less clinically documented infection and 100-days mortality than the non-glutamine group, but the other outcomes did not show significant differences. The extended duration of glutamine supplementation according to the period of total parenteral nutrition and mucositis should be considered.
Adult ; Glutamine ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Mortality ; Mucositis ; Multivariate Analysis ; Nausea ; Neutropenia ; Odds Ratio ; Parenteral Nutrition ; Parenteral Nutrition, Total ; Retrospective Studies ; Seoul ; Transplants ; Vomiting

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but near-fatal complication of peritoneal dialysis (PD). Despite the high mortality rate of EPS, the surgical treatment strategy of severe EPS is yet to be established.METHODS: We retrospectively analyzed outcomes of patients with EPS who underwent enterolysis for intractable EPS at Seoul National University Hospital between 2001 and 2018. EPS was diagnosed based on the clinical symptoms and radiological findings of abdominal computed tomography (CT). CT scans were scored according to an EPS scoring system that assessed peritoneal thickening and calcification as well as bowel thickening, tethering, loculation, and dilatation.RESULTS: Thirteen patients (nine males and four females; age, 48 [29–63] years) underwent enterolysis for severe EPS. PD duration (11 [6–21] years) was not associated with survival. Two patients were newly diagnosed with EPS following kidney transplantation. Five patients died of infectious complications immediately after the surgery. Eight patients survived after the first surgery; however, five of them underwent reoperation but died of persistent infection, fistula formation, or adhesive bowel obstruction. Four young (< 60 years) male patients with relatively low CT scan scores (< 13) survived for > 2 years after the first surgery. Median survival duration from EPS diagnosis was 22 (1.3–184) months and that from the first surgery was 9 (0.3–153) months.CONCLUSION: The high mortality rate of EPS suggests the importance of appropriate surgical intervention in young symptomatic male EPS patients with relatively low CT scan scores.
Adhesives ; Diagnosis ; Dilatation ; Female ; Fistula ; Humans ; Kidney Transplantation ; Korea ; Male ; Mortality ; Peritoneal Dialysis ; Peritoneal Fibrosis ; Reoperation ; Retrospective Studies ; Seoul ; Tomography, X-Ray Computed

Disseminated neonatal herpes simplex virus (HSV) infection is a severe disease with a high mortality rate. Here, we report the patient presented with fulminant hepatic failure secondary to HSV infection followed by renal failure without any mucocutaneous symptoms. The patient recovered after treatment with acyclovir and peritoneal dialysis. This is the first known case of a patient in Korea who survived disseminated HSV infection with fulminant liver failure followed by renal failure without undergoing liver transplantation.
Acyclovir ; Hepatitis ; Herpes Simplex ; Humans ; Infant, Newborn ; Korea ; Liver Failure ; Liver Failure, Acute ; Liver Transplantation ; Mortality ; Peritoneal Dialysis ; Renal Insufficiency ; Simplexvirus

Multiple studies have shown that oral antiviral therapies reduced the incidence of hepatocellular carcinoma (HCC) and improved the survival of patients with chronic hepatitis B when compared with that of untreated patients. In particular, entecavir and tenofovir share the qualities of high efficacy in reducing the HBV DNA levels, and they have excellent tolerability and safety. These drugs modified the natural history of liver fibrosis, improve liver function, decrease the incidence of HCC, decrease the need for liver transplantation, and improve survival. Many studies have suggested that long-term antiviral therapy reduces the risk of HCC and liver cirrhosis in patients with chronic hepatitis. The mechanism of these drugs in reducing the risk of HCC is not clear. This article reviews the mechanisms of carcinogenic HBV by conducting a review of the literature on the efficacy of therapy for reducing the risk of HCC. A few recent articles have suggested that tenofovir offers advantages over entecavir in terms of HCC prevention, but these articles have the inherent limitations of observational data. No other head-to-head randomized trials exist. Further randomized studies would help provide stronger evidence of the association between the type of antiviral agent and the HCC outcomes. Only achieving complete viral eradication from the liver will truly decrease the mortality and incidence of HCC.
Antiviral Agents ; Carcinoma, Hepatocellular ; DNA ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Incidence ; Liver ; Liver Cirrhosis ; Liver Transplantation ; Mortality ; Natural History ; Tenofovir

OBJECTIVE: Abnormal body composition is an important modifiable risk factor in lung transplantation. Therefore, precise quantification of different body components, including muscle and fat, may play an important role in optimizing outcomes in lung transplant patients. The purpose of the study was to investigate the prognostic significance of muscle and subcutaneous fat mass measured on chest CT with regard to lung transplantation survival and other post-transplant outcomes. MATERIALS AND METHODS: The study population included 45 consecutive adult lung transplant recipients (mean age of 47.9 ± 12.1 years; 31 males and 14 females) between 2011 and 2017. Preoperative cross-sectional areas of muscle and subcutaneous fat were semi-automatically measured on axial CT images at the level of the 12th thoracic vertebra (T12). Additional normalized indexed parameters, adjusted for either height or weight, were obtained. Associations of quantitative parameters with survival and various other post-transplant outcomes were evaluated. RESULTS: Of the 45 patients included in the present study, 10 mortalities were observed during the follow-up period. Patients with relative sarcopenia (RS) classified based on height-adjusted muscle area with a cut-off value of 28.07 cm²/m² demonstrated worse postoperative survival (log-rank test, p = 0.007; hazard ratio [HR], 6.39:1) despite being adjusted for age, sex, and body mass index (HR, 8.58:1; p = 0.022). Weight-adjusted parameters of muscle area were negatively correlated with duration of ventilator support (R = −0.54, p < 0.001) and intensive care unit (ICU) stay (R = −0.33, p = 0.021). CONCLUSION: Patients with RS demonstrate worse survival after lung transplantation that those without RS. Additionally, quantitative parameters of muscles measured at the T12 level on chest CT were associated with the duration of post-lung transplant ventilator support and duration of stay in the ICU.
Adult ; Body Composition ; Body Mass Index ; Cohort Studies ; Follow-Up Studies ; Humans ; Intensive Care Units ; Lung ; Lung Transplantation ; Male ; Mortality ; Muscles ; Retrospective Studies ; Risk Factors ; Sarcopenia ; Spine ; Subcutaneous Fat ; Thorax ; Tomography, X-Ray Computed ; Transplant Recipients ; Ventilators, Mechanical

BACKGROUND: Kidney transplantation is an effective renal replacement therapy for patients with end-stage renal disease (ESRD). In this study, we assessed the impact of the baseline characteristics and comorbidities of ESRD patients on the probability of deceased donor kidney transplantation (DDKT) and evaluated the morbidity and mortality during the time spent waiting. METHODS: The study population consisted of 544 ESRD patients on the waiting list for DDKT at Chungnam National University Hospital in South Korea between February 2000 and October 2015. The patients were observed from the date of transplantation list registration to the date of transplantation. Baseline characteristics and comorbidities were investigated together with new-onset comorbidities that occurred during the waiting time. RESULTS: Diabetes mellitus (39.0%), hypertension (25.2%), and glomerulonephritis (21.3%) were the three most common causes of ESRD in this study, and coronary artery disease (9.4%) was the most common comorbidity. The 115 patients (19.3%) who underwent DDKT had a mean waiting time of 1,711 days (768–2,654 days or 4.68 years [2.10–7.27]). Blood groups other than type O, peritoneal dialysis, and nondiabetic ESRD were significantly associated with a higher likelihood of DDKT. Infection was the leading cause of death and the most common comorbidity that arose during the waiting time. Patients who experienced cardiovascular events during the waiting time showed a lower transplant rate compared with those who did not. CONCLUSION: The prevalence of comorbidities was high in renal transplantation candidates. During the often-long waiting time, new comorbidities may occur, with long-term sequelae limiting access to kidney transplantation or resulting in death.
Blood Group Antigens ; Cause of Death ; Chungcheongnam-do ; Comorbidity ; Coronary Artery Disease ; Diabetes Mellitus ; Glomerulonephritis ; Humans ; Hypertension ; Kidney Failure, Chronic ; Kidney Transplantation ; Kidney ; Korea ; Mortality ; Peritoneal Dialysis ; Prevalence ; Renal Replacement Therapy ; Tissue Donors ; Waiting Lists

BACKGROUND: Mortality is higher in patients with chronic kidney disease (CKD) than in the general population, but little information is available on CKD-related mortality that is representative of the Korean population. Our objective was to investigate mortality risk in Korean patients with CKD. METHODS: We identified patients with incident CKD who had not undergone dialysis or kidney transplantation between January 1, 2003 and December 31, 2007 in Korea using the database of the Korean National Health Insurance Service-National Sample Cohort, and stratified the population into the following three groups: group 1 (n = 1,473), controls; group 2 (n = 2,212), patients with diabetes or hypertension, but without CKD; and group 3 (n = 2,212), patients with CKD. We then monitored them for all-cause mortality until December 2013. RESULTS: A total of 1,473 patients were included in this analysis. During the follow-up period, 941 patients in group 3 died (134 deaths/1,000 person-years) compared with 550 deaths in the group 2 (34 deaths/1,000 person-years) and 459 deaths in group 1 (30 deaths/1,000 person-years). The rate ratio for mortality rate was 4.5, and the hazard ratio for mortality was 4.88 (95% confidence interval [CI], 4.36–5.47, P < 0.001) in patients in group 3 compared with age- and sex-matched controls (group 1). The rate ratio for mortality rate was 4.0, and the hazard ratio for mortality was 4.36 (95% CI, 3.92–4.85, P < 0.001) in patients in group 3 compared with patients in group 2. CONCLUSION: In this nationally representative sample cohort, excess mortality was observed in Korean patients with incident CKD.
Cohort Studies ; Diabetes Mellitus ; Dialysis ; Follow-Up Studies ; Humans ; Hypertension ; Kidney Transplantation ; Korea ; Mortality ; National Health Programs ; Renal Insufficiency ; Renal Insufficiency, Chronic