Late Failure of High-Flow Nasal Cannula May Be Associated with High Mortality in COVID-19 Patients: A Multicenter Retrospective Study in the Republic of Korea

The aim of this study was to determine whether the late failure of high-flow nasal cannula (HFNC) is associated with mortality in patients with coronavirus disease 2019 (COVID-19). This multicenter study included seven university-affiliated hospitals in the Republic of Korea. We collected the data of patients hospitalized with COVID-19 between 10 February 2020 and 28 February 2021. Failure of HFNC was defined as the need for mechanical ventilation despite HFNC application. According to the time of intubation, HFNC failure was divided into early failure (within 48 h) and late failure (after 48 h). During the study period, 157 patients received HFNC and 133 were eligible. Among them, 70 received mechanical ventilation. The median time from HFNC initiation to intubation of the early failure group was 4.1 h (interquartile range [IQR]: 1.1–13.5 h), and that of the late failure group was 70.9 h (IQR: 54.4–145.4 h). Although the ratio of pulse oximetry/fraction of inspired oxygen (ROX index) within 24 h of HFNC initiation tended to be lower in the early failure group than in the late failure group, the ROX index before two hours of intubation was significantly lower in the late failure group (odds ratio [OR], 5.74 [IQR: 4.58–6.98] vs. 4.80 [IQR: 3.67–5.97], p = 0.040). The late failure of HFNC may be associated with high mortality in COVID-19 patients with acute respiratory failure

Comparison of Clinical Characteristics and Outcomes of Younger and Elderly Patients with Severe COVID-19 in Korea: A Retrospective Multicenter Study

Old age is associated with disease severity and poor prognosis among coronavirus disease 2019 (COVID-19) cases; however, characteristics of elderly patients with severe COVID-19 are limited. We aimed to assess the clinical characteristics and outcomes of patients hospitalized with severe COVID-19 at tertiary care centers in South Korea. This retrospective multicenter study included patients with severe COVID-19 who were admitted at seven hospitals in South Korea from 2 February 2020 to 28 February 2021. The Cox regression analyses were performed to assess factors associated with the in-hospital mortality. Of 488 patients with severe COVID-19, 318 (65.2%) were elderly (≥65 years). The older patient group had more underlying diseases and a higher severity score than the younger patient group. The older patient group had a higher in-hospital mortality rate than the younger patient group (25.5% versus 4.7%, p-value < 0.001). The in-hospital mortality risk factors among patients with severe COVID-19 included age, acute physiology and chronic health evaluation II score, presence of diabetes and chronic obstructive lung disease, high white blood cell count, low neutrophil-lymphocyte ratio and platelet count, do-not-resuscitate order, and treatment with invasive mechanical ventilation. In addition to old age, disease severity and examination results must be considered in treatment decision-making

Association between Cardiac Autonomic Neuropathy, Diabetic Retinopathy and Carotid Atherosclerosis in Patients with Type 2 Diabetes

BackgroundIt is not clear whether microangiopathies are associated with subclinical atherosclerosis in type 2 diabetes mellitus (T2DM). We investigated the relation of cardiac autonomic neuropathy (CAN) and other microangiopathies with carotid atherosclerosis in T2DM.MethodsA total of 131 patients with T2DM were stratified by mean carotid intima-media thickness (CIMT) ≥ or <1.0 mm and the number of carotid plaques. CAN was assessed by the five standard cardiovascular reflex tests according to the Ewing's protocol. CAN was defined as the presence of at least two abnormal tests or an autonomic neuropathy points ≥2. Diabetic microangiopathies were assessed.ResultsPatients with CAN comprised 77% of the group with mean CIMT ≥1.0 mm, while they were 29% of the group with CIMT <1.0 mm (P=0.016). Patients with diabetic retinopathy (DR) comprised 68% of the group with CIMT ≥1.0 mm, while they were 28% of the group without CIMT thickening (P=0.003). Patients with CAN comprised 51% of the group with ≥2 carotid plaques, while they were 23% of the group with ≤1 carotid plaque (P=0.014). In multivariable adjusted logistic regression analysis, the patients who presented with CAN showed an odds ratio [OR] of 8.6 (95% confidence interval [CI], 1.6 to 44.8) for CIMT thickening and an OR of 2.9 (95% CI, 1.1 to 7.5) for carotid plaques. Furthermore, patients with DR were 3.8 times (95% CI, 1.4 to 10.2) more likely to have CIMT thickening.ConclusionThese results suggest that CAN is associated with carotid atherosclerosis, represented as CIMT and plaques, independent of the traditional cardiovascular risk factors in T2DM. CAN or DR may be a determinant of subclinical atherosclerosis in T2DM

Corticosteroid outcome may be dependent of duration of use in severe COVID-19

Background/Aims For patients hospitalized with coronavirus disease 2019 (COVID-19) who require supplemental oxygen, the evidence of the optimal duration of corticosteroid is limited. This study aims to identify whether long-term use of corticosteroids is associated with decreased mortality. Methods Between February 10, 2020 and October 31, 2021, we analyzed consecutive hospitalized patients with COVID-19 with severe hypoxemia. The patients were divided into short-term (≤ 14 days) and long-term (> 14 days) corticosteroid users. The primary outcome was 60-day mortality. We performed propensity score (PS) analysis to mitigate the effect of confounders and conducted Kaplan-Meier curve analysis. Results There were 141 (52%) short-term users and 130 (48%) long-term corticosteroid users. The median age was 68 years and the median PaO2/FiO2 at admission was 158. Of the patients, 40.6% required high-flow nasal cannula, 48.3% required mechanical ventilation, and 11.1% required extracorporeal membrane oxygenation. The overall 60-day mortality rate was 23.2%, and that of patients with hospital-acquired pneumonia (HAP) was 22.9%. The Kaplan-Meier curve for 60-day survival in the PS-matched cohort showed that corticosteroid for > 14 days was associated with decreased mortality (p = 0.0033). There were no significant differences in bacteremia and HAP between the groups. An adjusted odds ratio for the risk of 60-day mortality in short-term users was 5.53 (95% confidence interval, 1.90–18.26; p = 0.003). Conclusions For patients with severe COVID-19, long-term use of corticosteroids was associated with decreased mortality, with no increase in nosocomial complications. Corticosteroid use for > 14 days can benefit patients with severe COVID-19

Overexpression of fatty acid synthase attenuates bleomycin induced lung fibrosis by restoring mitochondrial dysfunction in mice

Abstract Proper lipid metabolism is crucial to maintain alveolar epithelial cell (AEC) function, and excessive AEC death plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The mRNA expression of fatty acid synthase (FASN), a key enzyme in the production of palmitate and other fatty acids, is downregulated in the lungs of IPF patients. However, the precise role of FASN in IPF and its mechanism of action remain unclear. In this study, we showed that FASN expression is significantly reduced in the lungs of IPF patients and bleomycin (BLM)-treated mice. Overexpression of FASN significantly inhibited BLM-induced AEC death, which was significantly potentiated by FASN knockdown. Moreover, FASN overexpression reduced BLM-induced loss of mitochondrial membrane potential and the production of mitochondrial reactive oxygen species (ROS). Oleic acid, a fatty acid component increased by FASN overexpression, inhibited BLM-induced cell death in primary murine AECs and rescue BLM induced mouse lung injury/fibrosis. FASN transgenic mice exposed to BLM exhibited attenuated lung inflammation and collagen deposition compared to controls. Our findings suggest that defects in FASN production may be associated with the pathogenesis of IPF, especially mitochondrial dysfunction, and augmentation of FASN in the lung may have therapeutic potential in preventing lung fibrosis

Role of lung ornithine aminotransferase in idiopathic pulmonary fibrosis: regulation of mitochondrial ROS generation and TGF-β1 activity

Abstract Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling and the excessive accumulation of extracellular matrix (ECM) proteins. In a previous study, we found that the levels of ornithine aminotransferase (OAT), a principal enzyme in the proline metabolism pathway, were increased in the lungs of patients with IPF. However, the precise role played by OAT in the pathogenesis of IPF is not yet clear. The mechanism by which OAT affects fibrogenesis was assessed in vitro using OAT-overexpressing and OAT-knockdown lung fibroblasts. The therapeutic effects of OAT inhibition were assessed in the lungs of bleomycin-treated mice. OAT expression was increased in fibrotic areas, principally in interstitial fibroblasts, of lungs affected by IPF. OAT levels in the bronchoalveolar lavage fluid of IPF patients were inversely correlated with lung function. The survival rate was significantly lower in the group with an OAT level >75.659 ng/mL than in the group with an OAT level ≤75.659 ng/mL (HR, 29.53; p = 0.0008). OAT overexpression and knockdown increased and decreased ECM component production by lung fibroblasts, respectively. OAT knockdown also inhibited transforming growth factor-β1 (TGF)-β1 activity and TGF-β1 pathway signaling. OAT overexpression increased the generation of mitochondrial reactive oxygen species (ROS) by activating proline dehydrogenase. The OAT inhibitor L-canaline significantly attenuated bleomycin-induced lung injury and fibrosis. In conclusion, increased OAT levels in lungs affected by IPF contribute to the progression of fibrosis by promoting excessive mitochondrial ROS production, which in turn activates TGF-β1 signaling. OAT may be a useful target for treating patients with fibrotic lung diseases, including IPF

Annexin A1 in plasma from patients with bronchial asthma: its association with lung function

Abstract Background Annexin-A1 (ANXA1) is a glucocorticoid-induced protein with multiple actions in the regulation of inflammatory cell activation. The anti-inflammatory protein ANXA1 and its N-formyl peptide receptor 2 (FPR2) have protective effects on organ fibrosis. However, the exact role of ANXA1 in asthma remains to be determined. The aim of this study was to identify the role of ANXA1 in bronchial asthma. Methods In mice sensitized and challenged with ovalbumin (OVA-OVA mice) and mice sensitized with saline and challenged with air (control mice), we investigated the potential links between ANXA1 levels and bronchial asthma using ELISA, immunoblotting, and immunohistochemical staining. Moreover, we also determined ANXA1 levels in blood from 50 asthmatic patients (stable and exacerbated states). Results ANXA1 protein levels in lung tissue and bronchoalveolar lavage fluid were significantly higher in OVA-OVA mice compared with control mice. FPR2 protein levels in lung tissue were significantly higher in OVA-OVA mice compared with control mice. Plasma ANXA1 levels were increased in asthmatic patients compared with healthy controls. Plasma ANXA1 levels were significantly lower in exacerbated patients compared with stable patients with bronchial asthma (p < 0.05). The plasma ANXA1 levels in controlled asthmatic patients were correlated with forced expiratory volume in 1 s (FEV1) (r = − 0.191, p = 0.033) and FEV1/forced vital capacity (FVC) (r = −0.202, p = 0.024). Conclusion These results suggest that ANXA1 may be a potential marker and therapeutic target for asthma

Comparison of the end-of-life decisions of patients with hospital-acquired pneumonia after the enforcement of the life-sustaining treatment decision act in Korea

Abstract Background Although the Life-Sustaining Treatment (LST) Decision Act was enforced in 2018 in Korea, data on whether it is well established in actual clinical settings are limited. Hospital-acquired pneumonia (HAP) is a common nosocomial infection with high mortality. However, there are limited data on the end-of-life (EOL) decision of patients with HAP. Therefore, we aimed to examine clinical characteristics and outcomes according to the EOL decision for patients with HAP. Methods This multicenter study enrolled patients with HAP at 16 referral hospitals retrospectively from January to December 2019. EOL decisions included do-not-resuscitate (DNR), withholding of LST, and withdrawal of LST. Descriptive and Kaplan–Meier curve analyses for survival were performed. Results Of 1,131 patients with HAP, 283 deceased patients with EOL decisions (105 cases of DNR, 108 cases of withholding of LST, and 70 cases of withdrawal of LST) were analyzed. The median age was 74 (IQR 63–81) years. The prevalence of solid malignant tumors was high (32.4% vs. 46.3% vs. 54.3%, P = 0.011), and the ICU admission rate was lower (42.9% vs. 35.2% vs. 24.3%, P = 0.042) in the withdrawal group. The prevalence of multidrug-resistant pathogens, impaired consciousness, and cough was significantly lower in the withdrawal group. Kaplan–Meier curve analysis revealed that 30-day and 60-day survival rates were higher in the withdrawal group than in the DNR and withholding groups (log-rank P = 0.021 and 0.018). The survival of the withdrawal group was markedly decreased after 40 days; thus, the withdrawal decision was made around this time. Among patients aged below 80 years, the rates of EOL decisions were not different (P = 0.430); however, mong patients aged over 80 years, the rate of withdrawal was significantly lower than that of DNR and withholding (P = 0.001). Conclusions After the LST Decision Act was enforced in Korea, a DNR order was still common in EOL decisions. Baseline characteristics and outcomes were similar between the DNR and withholding groups; however, differences were observed in the withdrawal group. Withdrawal decisions seemed to be made at the late stage of dying. Therefore, advance care planning for patients with HAP is needed