Circulating eNAMPT as a biomarker in the critically ill: acute pancreatitis, sepsis, trauma, and acute respiratory distress syndrome.

BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) exhibits dual functionality - as an intracellular enzyme regulating nicotinamide adenine dinucleotide metabolism and as an extracellular secreted protein (eNAMPT) to function as a cytokine regulator of innate immunity via binding to Toll-Like receptor 4 and NF-κB activation. In limited preclinical and clinical studies, eNAMPT was implicated in the pathobiology of acute respiratory distress syndrome (ARDS) suggesting that eNAMPT could potentially serve as a diagnostic and prognostic biomarker. We investigated the feasibility of circulating eNAMPT levels to serve as a biomarker in an expanded cohort of patients with ARDS and ARDS-predisposing conditions that included acute pancreatitis, sepsis, and trauma with comparisons to controls. METHODS: A total of 671 patients and 179 healthy controls were included in two independent cohorts. Plasma and serum eNAMPT levels were quantified using one of two complementary Enzyme-linked Immunosorbent Assays. After log base 2 variance stabilizing transformation of plasma/serum eNAMPT measurements, differences between healthy controls and each disease cohort were compared using linear regression or a generalized estimating equation (GEE) model where applicable. Complementary analyses included sensitivity, specificity, positive predictive values, negative predictive values, and the area under the receiver operating curve. RESULTS: Compared to controls, circulating eNAMPT levels were significantly elevated in subjects with acute pancreatitis, sepsis, trauma, and ARDS (all p < 0.01). In the acute pancreatitis cohort, circulating eNAMPT levels positively correlated with disease severity (p < 0.01). CONCLUSIONS: Circulating eNAMPT levels are novel biomarker in the critically ill with acute pancreatitis, sepsis, trauma, and/or ARDS with the potential to reflect disease severity.

Lung transplantation for severe COVID-19-related ARDS.

BACKGROUND: Lung transplantation (LT) is the gold standard for various end-stage chronic lung diseases and could be a salvage therapeutic option in acute respiratory distress syndrome (ARDS). However, LT is uncertain in patients with coronavirus disease 2019 (COVID-19)-related ARDS who failed to recover despite optimal management including extracorporeal membrane oxygenation (ECMO). This study aims to describe the pooled experience of LT for patients with severe COVID-19-related ARDS in Korea. METHODS: A nationwide multicenter retrospective observational study was performed with consecutive LT for severe COVID-19-related ARDS in South Korea (June 2020-June 2021). Data were collected and compared with other LTs after bridging with ECMO from the Korean Organ Transplantation Registry. RESULTS: Eleven patients with COVID-19-related ARDS underwent LT. The median age was 60.0 years [interquartile range (IQR), 57.5-62.5; six males]. All patients were supported with venovenous ECMO at LT listing and received rehabilitation before LT. Patients were transplanted at a median of 49 (IQR, 32-66) days after ECMO cannulation. Primary graft dysfunction within 72 h of LT developed in two (18.2%). One patient expired 4 days after LT due to sepsis and one patient underwent retransplantation for graft failure. After a median follow-up of 322 (IQR, 299-397) days, 10 patients are alive and recovering well. Compared with other LTs after bridging with ECMO (n = 27), post-transplant outcomes were similar between the two groups. CONCLUSIONS: LT in patients with unresolving COVID-19-related ARDS were effective with reasonable short-term outcome.

Experience of International Air Transportation and Subsequent Lung Transplant in a Patient with COVID-19-associated Acute Respiratory Distress Syndrome: a Case Report.

We report an inspiring case of a 55-year-old Korean female diagnosed with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) in Mexico. The patient was assessed for lung transplant as a salvage therapy for treatment-refractory ARDS following no signs of clinical improvement for > 7 weeks, despite best treatment. The patient was transported from Mexico to Korea by air ambulance under venovenous extracorporeal membrane oxygenation (ECMO) support. She was successfully bridged to lung transplant on day 88, 49 days after the initiation of ECMO support. ECMO was successfully weaned at the end of operation, and no bleeding or primary graft dysfunction was observed within the first 72 hours. The patient was liberated from mechanical ventilation on postoperative day 9 and transferred to the general ward 5 days later. Despite the high doses of immunosuppressants, there was no evidence of viral reactivation after transplant. At 3 months post-transplantation, she was discharged to home without complication. Our experience suggests that successful lung transplant for COVID-19-associated ARDS is feasible even in a patient with prolonged pre-transplant ECMO support. Lung transplant may be considered a salvage therapy for COVID-19-associated ARDS that does not respond to conventional treatments.