Analysis of the waitlist performance and post-transplant outcomes of lung transplant in elderly recipients in Korea: A nationwide cohort study.

BACKGROUND: There is a lack of information on the waitlist performance and post-transplant outcomes of lung transplants in elderly recipients in Korea. METHODS: We retrospectively reviewed and analyzed data from the Korean Network for Organ Sharing database between March 2010 and August 2023. RESULTS: In total, 2574 patients were listed for lung transplantation during the study period, with 511 (19.9%) of them being over 65 years of age. Among these, 188 patients (36.8%) underwent transplantation, while 184 patients (36%) passed away without undergoing transplantation at the time of data extraction. The most prevalent underlying disease on the waitlist was idiopathic pulmonary fibrosis, accounting for 68.1%. The 1-year survival rate was significantly lower in the elderly compared to that in the nonelderly (65.4 vs. 75.4%; p = .004). In the multivariate Cox analysis, elderly (hazard ratio [HR], 1.49; 95% CI, 1.14-1.97; p = .004) and a high urgent status at registration (HR, 1.83; 95% CI, 1.40-2.40; p < .001) were significantly associated with post-transplant 1-year mortality. Kaplan-Meier curves demonstrated a significant difference in post-transplant mortality based on the urgency status at enrollment (χ2 = 8.302, p = .016). Even with the same highly urgent condition at the time of transplantation, different prognoses were observed depending on the condition at listing (χ2 = 9.056, p = .029). CONCLUSION: The elderly exhibited worse transplant outcomes than nonelderly adults, with a highly urgent status at registration identified as a significant risk factor. Unprepared, highly urgent transplantation was associated with poor outcomes.

Risk Factors for the Mortality of Patients With Coronavirus Disease 2019 Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study.

BACKGROUND: Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. METHODS: We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan-Meier (KM) method. RESULTS: Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010-1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312-7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). CONCLUSION: Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.

Navigating the Modern Landscape of Sepsis: Advances in Diagnosis and Treatment.

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.

Obesity Paradox and Functional Outcomes in Sepsis: A Multicenter Prospective Study.

OBJECTIVES: In Asian populations, the correlation between sepsis outcomes and body mass is unclear. A multicenter, prospective, observational study conducted between September 2019 and December 2020 evaluated obesity's effects on sepsis outcomes in a national cohort. SETTING: Nineteen tertiary referral hospitals or university-affiliated hospitals in South Korea. PATIENTS: Adult patients with sepsis ( n = 6,424) were classified into obese ( n = 1,335) and nonobese groups ( n = 5,089). MEASUREMENTS AND RESULTS: Obese and nonobese patients were propensity score-matched in a ratio of 1:1. Inhospital mortality was the primary outcome. After propensity score matching, the nonobese group had higher hospital mortality than the obese group (25.3% vs 36.7%; p < 0.001). The obese group had a higher home discharge rate (70.3% vs 65.2%; p < 0.001) and lower median Clinical Frailty Scale (CFS) (4 vs 5; p = 0.007) at discharge than the nonobese group, whereas the proportion of frail patients at discharge (CFS ≥ 5) was significantly higher in the nonobese group (48.7% vs 54.7%; p = 0.011). Patients were divided into four groups according to the World Health Organization body mass index (BMI) classification and performed additional analyses. The adjusted odds ratio of hospital mortality and frailty at discharge for underweight, overweight, and obese patients relative to normal BMI was 1.25 ( p = 0.004), 0.58 ( p < 0.001), and 0.70 ( p = 0.047) and 1.53 ( p < 0.001), 0.80 ( p = 0.095), and 0.60 ( p = 0.022), respectively. CONCLUSIONS: Obesity is associated with higher hospital survival and functional outcomes at discharge in Asian patients with sepsis.

Vasopressor Initiation Within 1 Hour of Fluid Loading Is Associated With Increased Mortality in Septic Shock Patients: Analysis of National Registry Data.

OBJECTIVES: To investigate whether administration of a vasopressor within 1 hour of first fluid loading affected mortality and organ dysfunction in septic shock patients. DESIGN: Prospective, multicenter, observational study. SETTING: Sixteen tertiary or university hospitals in the Republic of Korea. PATIENTS: Patients with septic shock (n = 415) were classified into early and late groups according to whether the vasopressor was initiated within 1 hour of the first resuscitative fluid load. Early (n = 149) patients were 1:1 propensity matched to late (n = 149) patients. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The median time from the initial fluid bolus to vasopressor was shorter in the early group (0.3 vs 2.3 hr). There was no significant difference in the fluid bolus volume within 6 hours (33.2 vs 35.9 mL/kg) between the groups. The Sequential Organ Failure Assessment score and lactate level on day 3 in the ICU were significantly higher in the early group than that in the late group (Sequential Organ Failure Assessment, 9.2 vs 7.7; lactate level, 2.8 vs 1.7 mmol/L). In multivariate Cox regression analyses, early vasopressor use was associated with a significant increase in the risk of 28-day mortality (hazard ratio, 1.83; 95% CI, 1.26-2.65). CONCLUSIONS: Vasopressor initiation within 1 hour of fluid loading was associated with higher 28-day mortality in patients with septic shock.

Novel (1E,3E,5E)-1,6-bis(Substituted phenyl)hexa-1,3,5-triene Analogs Inhibit Melanogenesis in B16F10 Cells and Zebrafish.

The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1E,3E,5E)-1,6-bis(substituted phenyl)hexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively analyzed using three-dimensional quantitative structure-activity relationship approach. Inhibitory activities of these synthetic compounds against melanin synthesis were determined by evaluating melanin content and melanogenic regulatory enzyme expression in B16F10 cells. The anti-melanogenic activity was verified by observing body pigmentation in zebrafishes treated with these compounds. Compound #2, #4, and #6 effectively decreased melanogenesis induced by α-melanocyte-stimulating hormone. In particular, compound #2 remarkably lowered the mRNA and protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and TYRP2 in B16F10 cells and substantially reduced skin pigmentation in the developed larvae of zebrafish. These findings suggest that compound #2 may be used as an anti-melanogenic agent for cosmetic purpose.

Vascular Complications Arising from Hemostasis with Manual Compression Following Extracorporeal Membrane Oxygenation Decannulation.

BACKGROUND: We evaluated the vascular complications and success rate of manual compression in achieving hemostasis and access site closure after transfemoral arterial extracorporeal membrane oxygenation (ECMO) decannulation. METHODS: Between February 2010 and July 2014, 63 patients who underwent veno-arterial ECMO were retrospectively studied. Patients who developed postprocedural vascular complications after manual compression were identified, and the hemostasis success rate was evaluated. RESULTS: The overall manual compression success rate was 95.2%. Eleven patients (17.5%) developed vascular complications: hematoma (more than 5 cm) occurred in six patients (9.5%) who were treated with repeat manual compression. Retroperitoneal bleeding occurred in one patient, requiring abdominal hematoma evacuation surgery. One patient (1.6%) developed access site bleeding, requiring suturing. One patient (1.6%) developed an arteriovenous fistula (AVF). Two patients (3.2%) had a pseudoaneurysm, of whom one was treated with sclerotherapy in the femoral artery; the other patient and the AVF patient were treated with repeat manual compression. The hematoma rate was significantly higher in patients with an activated partial thromboplastin time (aPTT) >56, and in whom dual antiplatelet drugs were used (OR: 11.55, 95% CI: 1.32-100.92, p = 0.027; OR: 8.17, CI: 1.61-41.46, p = 0.011, respectively). CONCLUSION: The use of dual antiplatelet drugs and a higher aPTT can lead to an increased risk of post-procedural vascular complications. Therefore, manual compression should be applied cautiously after the correction of coagulopathy factors such as activated clotting time (ACT), aPTT, and platelets.

Functional Aspects of the Obesity Paradox in Patients with Severe Coronavirus Disease-2019: A Retrospective, Multicenter Study.

BACKGROUND: Results of studies investigating the association between body mass index (BMI) and mortality in patients with coronavirus disease-2019 (COVID-19) have been conflicting. METHODS: This multicenter, retrospective observational study, conducted between January 2020 and August 2021, evaluated the impact of obesity on outcomes in patients with severe COVID-19 in a Korean national cohort. A total of 1,114 patients were enrolled from 22 tertiary referral hospitals or university-affiliated hospitals, of whom 1,099 were included in the analysis, excluding 15 with unavailable height and weight information. The effect(s) of BMI on patients with severe COVID-19 were analyzed. RESULTS: According to the World Health Organization BMI classification, 59 patients were underweight, 541 were normal, 389 were overweight, and 110 were obese. The overall 28-day mortality rate was 15.3%, and there was no significant difference according to BMI. Univariate Cox analysis revealed that BMI was associated with 28-day mortality (hazard ratio, 0.96; p=0.045), but not in the multivariate analysis. Additionally, patients were divided into two groups based on BMI ≥25 kg/m2 and underwent propensity score matching analysis, in which the two groups exhibited no significant difference in mortality at 28 days. The median (interquartile range) clinical frailty scale score at discharge was higher in nonobese patients (3 [3 to 5] vs. 4 [3 to 6], p<0.001). The proportion of frail patients at discharge was significantly higher in the nonobese group (28.1% vs. 46.8%, p<0.001). CONCLUSION: The obesity paradox was not evident in this cohort of patients with severe COVID-19. However, functional outcomes at discharge were better in the obese group.

Clinical Characteristics and Prognosis of Older Patients with Coronavirus Disease 2019 Requiring Mechanical Ventilation.

An older age is associated with severe progression and poor prognosis in coronavirus disease 2019 (COVID-19), and mechanical ventilation is often required. The specific characteristics of older patients undergoing mechanical ventilation and their prognostic factors are largely unknown. We aimed to identify potential prognostic factors in this group to inform treatment decisions. This retrospective cohort study collected data from patients with COVID-19 at 22 medical centers. Univariate and multivariate Cox regression analyses were performed to assess factors that influence mortality. We allocated 434 patients in geriatric (≥80 years) and elderly (65-79 years) groups. The former group scored significantly higher than the elderly group in the clinical frailty scale and sequential organ failure assessment, indicating more severe organ dysfunction. Significantly lower administration rates of tocilizumab and extracorporeal membrane oxygenation and higher intensive care unit (ICU) and in-hospital mortality were noted in the geriatric group. The factors associated with ICU and in-hospital mortality included high creatinine levels, the use of continuous renal replacement therapy, prone positioning, and the administration of life-sustaining treatments. These results highlight significant age-related differences in the management and prognosis of critically ill older patients with COVID-19. Increased mortality rates and organ dysfunction in geriatric patients undergoing mechanical ventilation necessitate age-appropriate treatment strategies to improve their prognoses.

Association between Age-Adjusted Endothelial Activation and Stress Index and Intensive Care Unit Mortality in Patients with Severe COVID-19.

BACKGROUND: Endothelial activation and stress index (EASIX) reflects endothelial dysfunction or damage. Because endothelial dysfunction is one of the key mechanisms, a few studies have shown the clinical usefulness of original and age-adjusted EASIX (age-EASIX) in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical utility of age-EASIX in predicting intensive care unit (ICU) mortality in critically ill patients with COVID-19 in South Korea. METHODS: Secondary analysis was performed using clinical data retrospectively collected from 22 nationwide hospitals in South Korea between January 1, 2020, and August 31, 2021. Patients were at least 19 years old and admitted to the ICU for severe COVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactate dehydrogenase (U/L)×creatinine (mg/dL)/platelet count (109 cells/L)] and age-EASIX (EASIX×age) were calculated and log2-transformed. RESULTS: The mean age of 908 critically ill patients with COVID-19 was 67.4 years with 59.7% male sex. The mean log2 age-EASIX was 7.38±1.45. Non-survivors (n=222, 24.4%) in the ICU had a significantly higher log2 age-EASIX than of survivors (8.2±1.52 vs. 7.1±1.32, p<0.001). log2 age-EASIX was significantly associated with ICU mortality (odds ratio, 1.541; 95% confidence interval, 1.322 to 1.796; p<0.001) and had a better area under the receiver operating characteristic curve than of the sequential organ failure assessment (SOFA) score in predicting ICU mortality (0.730 vs. 0.660, p=0.001). CONCLUSION: Age-EASIX is significantly associated with ICU mortality and has better discriminatory ability than the SOFA score in predicting ICU mortality.