Differences of respiratory mechanics in mechanical ventilation of acute respiratory distress syndrome between patients with COVID-19 and Influenza A.

BACKGROUND: Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS. METHODS: This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation. RESULTS: The median age of the 87 participants was 71.0 (62.0-78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p < 0.001, day 1). COVID-19 and influenza A initially showed different directions for peak inspiratory pressure and dynamic compliance; however, after day 3, both groups exhibited similar directions. Dynamic driving pressure exhibited opposite trends between the two groups during mechanical ventilation. CONCLUSIONS: Respiratory mechanics show clear differences between COVID-19-induced ARDS and influenza A induced ARDS. Based on these findings, we can consider future treatment strategies for COVID-19-induced ARDS.

Risk Factors for Unfavorable Outcomes of Tuberculosis in Korea: Implications for Patient-Centered Care in Tuberculosis Treatment.

BACKGROUND: The treatment success rate for tuberculosis (TB) has stagnated at 80-81% in South Korea, indicating unsatisfactory outcomes. Enhancing treatment success rate necessitates the development of individualized treatment approaches for each patient. This study aimed to identify the risk factors associated with unfavorable treatment outcomes to facilitate tailored TB care. METHODS: We retrospectively analyzed the data of patients with active TB between January 2019 and December 2020 at a single tertiary referral center. We classified unfavorable treatment outcomes according to the 2021 World Health Organization guidelines as follows: "lost to follow-up" (LTFU), "not evaluated" (NE), "death," and "treatment failure" (TF). Moreover, we analyzed risk factors for each unfavorable outcome using Cox proportional hazard regression analysis. RESULTS: A total of 659 patients (median age 62 years; male 54.3%) were included in the study. The total unfavorable outcomes were 28.1%: 4.6% LTFU, 9.6% NE, 9.1% deaths, and 4.9% TF. Multivariate analysis showed that a culture-confirmed diagnosis of TB was associated with a lower risk of LTFU (adjusted hazard ratio [aHR], 0.25; 95% confidence interval [CI], 0.10-0.63), whereas the occurrence of adverse drug reactions (ADRs) significantly increased the risk of LTFU (aHR, 6.63; 95% CI, 2.63-16.69). Patients living far from the hospital (aHR, 4.47; 95% CI, 2.50-7.97) and those with chronic kidney disease (aHR, 3.21; 95% CI, 1.33-7.75) were at higher risk of being transferred out to other health institutions (NE). Higher mortality was associated with older age (aHR, 1.06; 95% CI, 1.04-1.09) and comorbidities. The ADRs that occurred during TB treatment were a risk factor for TF (aHR, 6.88; 95% CI, 2.24-21.13). CONCLUSION: Unfavorable outcomes of patients with TB were substantial at a tertiary referral center, and the risk factors for each unfavorable outcome varied. To improve treatment outcomes, close monitoring and the provision of tailored care for patients with TB are necessary.

Clinical Characteristics and Treatment Outcomes of Pulmonary Diseases Caused by Coinfections With Multiple Nontuberculous Mycobacterial Species.

BACKGROUND: Coinfections with multiple nontuberculous mycobacterial (NTM) species have not been widely studied. We aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-pulmonary disease (PD) caused by coinfection with multiple NTM species. METHODS: We retrospectively reviewed patients with NTM-PD at a tertiary referral hospital in Korea between March 2012 and December 2018. Coinfection was defined as two or more species of NTM pathogens isolated from the same respiratory specimen or different specimens within three months. RESULTS: Among 1,009 patients with NTM-PD, 147 (14.6%) NTM coinfections were observed (average age 64.7 years, 69.4% women). NTM species were identified more frequently (median 6 vs. 3 times, P < 0.001) in the coinfection group than in the single species group, and follow-up duration was also longer in the coinfection group (median 44.9 vs. 27.1 months, P < 0.001). Mycobacterium avium complex (MAC) and M. abscessus and M. massiliense (MAB) were the dominant combinations (n = 71, 48.3%). For patients treated for over six months in the MAC plus MAB group (n = 31), sputum culture conversion and microbiological cure were achieved in 67.7% and 41.9% of patients, respectively. We divided the MAC plus MAB coinfection group into three subgroups according to the target mycobacteria; however, no statistical differences were found in the treatment outcomes. CONCLUSION: In NTM-PD cases, a significant number of multiple NTM species coinfections occurred. Proper identification of all cultured NTM species through follow-up is necessary to detect multispecies coinfections. Further research is needed to understand the nature of NTM-PD in such cases.

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.

Risk factors of pneumothorax and pneumomediastinum in COVID-19: a matched case-control study.

BACKGROUND: During the novel coronavirus disease-2019 pandemic, a considerable number of pneumothorax (PNX)/pneumomediastinum (PNM) associated with COVID-19 have been reported, and the incidence is higher in critically ill patients. Despite using a protective ventilation strategy, PNX/PNM still occurs in patients on invasive mechanical ventilation (IMV). This matched case-control study aims to identify the risk factors and clinical characteristics of PNX/PNM in COVID-19. METHODS: This retrospective study enrolled adult patients with COVID-19, admitted to a critical care unit from March 1, 2020, to January 31, 2022. COVID-19 patients with PNX/PNM were compared, in a 1-2 ratio, to COVID-19 patients without PNX/PNM, matched for age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale. Conditional logistic regression analysis was performed to assess the risk factors for PNX/PNM in COVID-19. RESULTS: 427 patients with COVID-19 were admitted during the period, and 24 patients were diagnosed with PNX/PNM. Body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for PNX/PNM in univariate conditional logistic regression analysis [odds ratio (OR), 0.85; confidence interval (CI), 0.72-0.996; P = 0.044]. For patients on IMV support, univariate conditional logistic regression analysis showed the statistical significance of the duration from symptom onset to intubation (OR, 1.14; CI, 1.006-1.293; P = 0.041). CONCLUSIONS: Higher BMI tended to show a protective effect against PNX/PNM due to COVID-19 and delayed application of IMV might be a contributive factor for this complication.

Impact of age on mortality and transfer to long-term care in patients in an intensive care unit.

BACKGROUND: In the global trend of population aging, age is one of the significant factors to be considered in critically ill patients. However, the impact of age on clinical outcomes and long-term prognosis in this population varies across different studies. METHODS: We conducted a retrospective cohort analysis for patients admitted to the medical intensive care unit (ICU) (30 beds) between January 2017 and December 2020 at the tertiary referral hospital in Korea. Patients were classified into three groups according to age: <65 years, old age (65-79 years), and very old age (≥ 80 years). Subsequently, enrolled patients were analyzed for acute mortality and long-term prognosis. RESULTS: Among the 1584 patients, the median age was 67.0 (57.0-76.0) years, and 65.2% were male. Median ICU length of stay (LOS) (8, 9, and 10 days in < 65, 65-79, and ≥ 80 years, respectively; p = 0.006) and the proportion of patients who were transferred to long-term care hospital at the time of discharge (12.9% vs. 28.3% vs. 39.4%, respectively; p < 0.001) increased with age. Multivariable logistic analysis showed no significant difference in the 28-day mortality in the old age (adjusted odds ratio [aOR] 0.88; 95% confidence interval [CI] 0.65-1.17) and very old age (aOR 1.05; 95% CI 0.71-1.55) groups compared to that in patients with age < 65 years. However, the relevance of the proportion of ICU LOS ≥ 7 days and transfers to other hospitals after discharge increased with age. CONCLUSIONS: Age did not affect acute mortality in critical illness patients. However, surviving older age groups required more long-term care facilities compared to patients younger than 65 years after acute management. These results indicate that in an aging society, the importance of not only acute management but also long-term care facilities may increase for critical illness patients.

The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea.

BACKGROUND: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. METHODS: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation-Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. RESULTS: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death (P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.55-0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% CI, 0.56-0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79-1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65-2.17; P = 0.582). CONCLUSION: In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

NADPH oxidase 4 signaling in a ventilator-induced lung injury mouse model.

BACKGROUND: For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model. METHODS: Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV ± DMSO; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 µL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 and EphA2 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined. RESULTS: Cell counts from BALFs were significantly lower in the NOX4 KO with HTV group (p < 0.01) and EphA2 KO with HTV group (p < 0.001) compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p < 0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p < 0.001). In patients with respiratory disease, NOX4 and EphA2 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit. CONCLUSION: In the VILI model with high tidal volume, NOX4 KO, EphA2 KO or monoclonal antibodies attenuated the VILI. NOX4 and EphA2 levels were significantly higher in patients with pneumonia and especially in mechanical ventilated in the ICU. Inhibition of Nox4 is a potential therapeutic target for the prevention and reduction of VILI.

Clinical impact of pneumothorax in patients with Pneumocystis jirovecii pneumonia and respiratory failure in an HIV-negative cohort.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. METHODS: We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. RESULTS: During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). CONCLUSIONS: The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.

Long- and short-term clinical impact of awake extracorporeal membrane oxygenation as bridging therapy for lung transplantation.

BACKGROUND: As lung transplantation (LTx) is becoming a standard treatment for end-stage lung disease, the use of bridging with extracorporeal membrane oxygenation (ECMO) is increasing. We examined the clinical impact of being awake during ECMO as bridging therapy in patients awaiting LTx. METHODS: In this single-center study, we retrospectively reviewed 241 consecutive LTx patients between October 2012 and March 2019; 64 patients received ECMO support while awaiting LTx. We divided into awake and non-awake groups and compared. RESULTS: Twenty-five patients (39.1%) were awake, and 39 (61.0%) were non-awake. The median age of awake patients was 59.0 (interquartile range, 52.5-63.0) years, and 80% of the group was men. The awake group had better post-operative outcomes than the non-awake group: statistically shorter post-operative intensive care unit length of stay [awake vs. non-awake, 6 (4-8.5) vs. 18 (11-36), p < 0.001], longer ventilator free days [awake vs. non-awake, 24 (17-26) vs. 0 (0-15), p < 0.001], and higher gait ability after LTx (awake vs. non-awake, 92% vs. 59%, p = 0.004), leading to higher 6-month and 1-year lung function (forced expiratory volume in 1 s: awake vs. non-awake, 6-month, 77.5% vs. 61%, p = 0.004, 1-year, 75% vs. 57%, p = 0.013). Furthermore, the awake group had significantly lower 6-month and 1-year mortality rates than the non-awake group (6-month 12% vs. 38.5%, p = 0.022, 1-year 24% vs. 53.8%, p = 0.018). CONCLUSIONS: In patients with end-stage lung disease, considering the long-term and short-term impacts, the awake ECMO strategy could be useful compared with the non-awake ECMO strategy.

Comparison of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung adenocarcinoma harboring different epidermal growth factor receptor mutation types.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation types are associated with efficacy of EGFR TKIs. We investigated the clinical outcomes of afatinib, erlotinib, and gefitinib according to EGFR mutation type in patients with lung adenocarcinoma. METHODS: Between May 2010 and December 2018, we investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations who received EGFR TKIs. Efficacies of EGFR TKIs such as response rate, progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated according to exon 19 deletion (E19del), L858R point mutation (L858R) and uncommon mutations. RESULTS: The frequency of E19del was 48.2%, that of L858R was 42.4%, and that of uncommon mutations was 9.4%. E19del and L858R were associated with superior PFS and OS compared with uncommon mutations. Erlotinib showed significantly inferior OS than other TKIs (30.8 ± 3.3 in erlotinib vs. 39.1 ± 4.3 in afatinib vs. 48.4 ± 6.3 in gefitinib; p = 0.031) in patients with L858R. Gefitinib showed significantly inferior PFS (4.6 ± 1.1 in gefitinib vs. 11.6 ± 2.7 in afatinib vs. 10.6 ± 2.7 in erlotinib; p = 0.049) in patients with uncommon mutations. CONCLUSION: Afatinib was significantly associated with a longer PFS, presenting constant effectiveness in all EGFR mutation types. Caution may be needed on the use of erlotinib for L858R and the use of gefitinib for uncommon EGFR mutations.

The ratio of plasma angiopoietin-2 to angiopoietin-1 as a prognostic biomarker in patients with sepsis.

BACKGROUND: We aimed to investigate the role of angiopoietin (Angpt) as a predictive biomarker for sepsis by evaluating associations between plasma Angpt and various inflammatory cytokines and mortality in critically ill patients with sepsis. METHODS: This study was a retrospective cohort study of the prospectively collected samples and clinical data of 145 patients with sepsis who were admitted to the medical intensive care unit (ICU) of a 2000-bed university tertiary referral hospital in South Korea. We collected plasma within 24 h of medical ICU admission, and several biomarkers (Angpt-1 and -2, Tie2, vascular endothelial growth factor, interleukin (IL)-1ß, IL-10, IL-18, IL-6, interferon gamma-induced protein-10, and tumor necrosis factor-α) were measured using a Human Magnetic Luminex Screening Assay kit. RESULTS: Plasma Angpt-2 was correlated with IL-6 (rs = 0.555) and tumor necrosis factor-α (rs = 0.559). Plasma Angpt-2 (rs = 0.530) and Angpt-2/1 (rs = 0.562) were correlated with the Sequential Organ Failure Assessment (SOFA) score. The area under the curve (AUC) for the 28-day mortality prediction for the plasma Angpt-2/1 ratio was 0.736; AUCs for the Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 0.659 and 0.745, respectively. Using multivariate Cox proportional hazard regression analysis for 28-day mortality, we found that acute respiratory distress syndrome (hazard ratio (HR) = 2.235, 95% CI = 1.163-4.296,p = 0.016), APACHE II score (HR = 1.127, 95% CI = 1.037-1.224,p = 0.005), and Angpt-2/1 > 3.2 (HR = 2.522, 95% CI = 1.205-5.278,p = 0.014) were risk factors for 28-day mortality. CONCLUSIONS: Plasma Angpt-2 was related to cytokines, but Angpt-2/1 ratio was a good predictor of 28-day mortality in patients with sepsis.

Risk Factors for Cytomegalovirus Reactivation in Lung Transplant Recipients.

PURPOSE: We examined risk factors that may have contributed to Cytomegalovirus (CMV) reactivation among patients who underwent lung transplantation (LTx). METHODS: We reviewed medical records of patients who underwent LTx at a tertiary healthcare hospital in South Korea between January 2013 and May 2017. We excluded patients who died within the first year after LTx and those lost to follow-up. CMV reactivation was defined as the detection of CMV titers above 3000 copies/ml regardless of specific symptoms after prophylaxis cessation. RESULTS: Of 89 patients included, 39 (43.8%) developed CMV reactivation. Of those 39 patients, 16 (41.0%) experienced additional CMV reactivation. Multivariate analysis identified lymphocyte counts below 1.0 × 103/µl (hazard ratio [HR] 49.33, p < 0.001) and use of steroids at more than twice the standard dose (HR 8.07, p < 0.001) as risk factors for CMV reactivation. The multivariate model also identified chronic kidney disease (CKD; HR 5.19, p = 0.016) and pneumonia (HR 17.22, p = 0.013) as risk factors for repetitive CMV reactivation. CONCLUSION: This study suggests that lymphopenia and high doses of steroids may be important risk factors for CMV reactivation in LTx patients. Our results also suggest that repetitive CMV reactivation may be associated with CKD and pneumonia.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.

Hemoptysis requiring bronchial artery embolization in patients with nontuberculous mycobacterial lung disease.

BACKGROUND: Although infections caused by nontuberculous mycobacteria (NTM) are increasing in prevalence, there are few data about hemoptysis in patients with NTM lung disease. This study investigated the characteristics and prognosis of hemoptysis secondary to NTM infection. METHODS: Following a retrospective review of cases managed between 2006 and 2016, 183 patients with NTM lung disease were enrolled and analyzed. RESULTS: Among 183 patients with NTM lung disease, Mycobacterium intracellulare (n = 64, 35%) was the major cause of NTM infection, followed by M. avium (n = 59, 32.2%) and M. abscessus complex (n = 40, 21.9%). Hemoptysis developed in 78 patients (42.6%), among whom 33 (42.3%) required bronchial artery embolization (BAE). Between patients with and without hemoptysis, there were no significant differences with respect to sex, radiographic manifestations, distribution over 3 lobes on chest computed tomography, history of pulmonary tuberculosis, antiplatelet or anticoagulation therapy, and species of NTM. However, mean age at diagnosis was significantly lower in the hemoptysis group in univariate and multivariate analyses (65.7 ± 12.8 vs. 59.7 ± 11.8, P = 0.002, odds ratio: 0.969, 95% confidence interval: 0.944-0.996). Among patients with hemoptysis, those requiring medical therapy and those requiring BAE were not significantly different in terms of demographic characteristics, radiographic manifestations, and distribution over 3 lobes. All patients who received BAE showed immediate clinical improvement, no procedure-related complications, and none of them died during the period under review. CONCLUSIONS: NTM lung disease patients commonly experienced hemoptysis without specific risk factors except for relatively young age. Although some patients with hemoptysis needed BAE, the success rate of BAE was high, and there were no serious complications associated with BAE.

Clinical characteristics of patients with newly developed acute cholecystitis after admission to the intensive care unit.

INTRODUCTION: Critical care patients have many risk factors for acute cholecystitis (AC). However, less data are available regarding newly developed AC in critically ill patients. OBJECTIVES: To investigate the clinical features of AC occurring in critically ill patients after admission to an intensive care unit (ICU). METHODS: We performed a retrospective cohort study from January 2006 to August 2016 at a tertiary care university hospital. We included patients diagnosed with AC with or without gallstones after ICU admission. All cases of AC were confirmed by gastroenterologists or general surgeons. We excluded patients with AC diagnosed before or at the time of ICU admission. RESULTS: A total of 38 patients were diagnosed with AC after ICU admission between January 2006 and August 2016. Seventeen (44.7%) had acute acalculous cholecystitis, while 21 (55.3%) had acute calculous cholecystitis. The median age was 73 years (interquartile range = 63-81 years), and 22 (57.9%) patients were male. The most common reason for ICU admission was pneumonia or sepsis. The median interval from ICU admission to diagnosis of AC was 11 days (interquartile range = 4.8-22.8 days). Before AC diagnosis, almost 90% of patients used total parenteral nutrition, 68% used opioids, 76% were mechanically ventilated, and 42% received vasoactive drugs. More than half of patients underwent cholecystectomy, and all surgically resected gallbladders had pathology results for cholecystitis. Gangrenous cholecystitis was observed in five patients with acute calculous cholecystitis. The overall mortality was 42.1%, and 1/3 of these deaths were directly associated with AC. The average length of stay in the ICU and hospital was 26.5 and 44.5 days, respectively. CONCLUSION: The development of AC in the ICU should be carefully monitored, especially in patients who have been infected and admitted to the ICU for more than 10 days. Proper diagnosis and treatment at a critical time could be lifesaving.

Inhibition of insulin-like growth factor receptor-1 reduces necroptosis-related markers and attenuates LPS-induced lung injury in mice.

Insulin-like growth factor-1 (IGF-1) levels are known to increase in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome. Herein, we investigated the role of IGF-1 in lipopolysaccharide (LPS)-induced lung injury. In LPS-treated cells, expressions of receptor-interacting protein 3 (RIP3) and phosphorylated mixed lineage kinase domain-like protein (MLKL) were decreased in IGF-1 receptor small interfering RNA (siRNA)-treated cells compared to control cells. The levels of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, IL-10, tumour necrosis factor-α, and macrophage inflammatory protein 2/C-X-C motif chemokine ligand 2 in the supernatant were significantly reduced in IGF-1 receptor siRNA-treated cells compared to control cells. In LPS-induced murine lung injury model, total cell counts, polymorphonuclear leukocytes counts, and pro-inflammatory cytokine levels in the BALF were significantly lower and histologically detected lung injury was less common in the group treated with IGF-1 receptor monoclonal antibody compared to the non-treated group. On western blotting, RIP3 and phosphorylated MLKL expressions were relatively decreased in the IGF-1 receptor monoclonal antibody group compared to the non-treated group. IGF-1 may be associated with RIP3-mediated necroptosis in vitro, while blocking of the IGF-1 pathway may reduce LPS-induced lung injuries in vivo.

Clinical outcomes and prognostic factors in patients directly transferred to the intensive care unit from long-term care beds in institutions and hospitals: a retrospective clinical study.

BACKGROUND: There has been a steady increase in the aging population and an increase in the need for long-term care beds in institutions and hospitals (LTCHs) in Korea. The aim of this study was to investigate prognosis and to identify factors contributing to mortality of critically ill patients with respiratory problems who were directly transferred to intensive care units (ICU) from LTCHs. METHODS: Following a retrospective review of clinical data and radiographic findings between July 2009 and September 2016, we included 111 patients with respiratory problems who had visited the emergency room (ER) transferred from LTCHs due to respiratory symptoms and who were then admitted to the ICU. RESULTS: The mean age of the 111 patients was 79 years, and 71 patients (64%) were male. Pneumonia developed in 98 patients (88.3%), pulmonary thromboembolism in 4 (3.6%) and pulmonary tuberculosis in 3 (2.7%). Overall mortality was 19.8% (22/111). Multiple-drug-resistant (MDR) pathogens (odds ratio [OR], 17.43; 95% confidence interval [CI], 1.96-155.40) and serum albumin levels < 2.15 g/dL, which were derived through ROC (sensitivity, 72.7%; specificity, 85.4%) (OR, 28.05; 95% CI, 5.47-143.75), were independent predictors for mortality. The need for invasive ventilation (OR, 2.74; 95% CI, 1.02-7.32) and history of antibiotic use within the 3 months (OR, 3.23; 95% CI, 1.32-7.90) were risk factors for harboring MDR pathogens. CONCLUSIONS: The presence of MDR pathogens and having low serum albumin levels may be poor prognostic factors in patients with respiratory problems who are admitted to the ICU from LTCHs. A history of antibiotic use within the 3 months and the need for invasive ventilation can be helpful in choosing the appropriate antibiotics to combat MDR pathogens at the time of admission.

The Risk Factors and Characteristics of COPD Among Nonsmokers in Korea: An Analysis of KNHANES IV and V.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is increasing in prevalence and mortality. This study evaluated the prevalence, risk factors, characteristics, and health-related quality of life (HRQoL) of COPD among nonsmokers in Korea. METHODS: This was a population-based cross-sectional study using data obtained from the Fourth and Fifth Korean National Health and Nutrition Examination Survey, which was conducted from 2007 to 2011. RESULTS: A total of 15,063 participants completely answered the questionnaire and performed the spirometry. Among them, 59.6 % were nonsmokers and 40.4 % were smokers. The prevalence of nonsmoker COPD was 7.1 %. On multivariate analysis, age ≥65 years (OR, 2.93; 95 % CI, 2.44-3.51), male sex (OR, 2.98; 95 % CI, 2.40-3.71), living in rural area (OR, 1.26; 95 % CI, 1.05-1.51), lower body mass index (BMI) (<18.5 kg/m(2)) (OR, 3.00; 95 % CI, 1.78-5.01), self-reported asthma (OR, 2.72; 95 % CI, 2.05-3.60), and self-reported tuberculosis (OR, 4.73; 95 % CI, 3.63-6.17) showed a significantly higher risk of nonsmoker COPD. Analysis of nonsmoker and smoker COPD revealed that there are more females in nonsmoker COPD patients (73.9 vs. 6.9 %, P < 0.001). Nonsmoker COPD patients presented with impaired mobility, pain/discomfort, and anxiety/depression functions as well as a lower mean EuroQol Five-Dimension Questionnaire utility score, which showed HRQoL. CONCLUSIONS: The burden of nonsmoker COPD was considerable. Older age, male sex, lower BMI, self-reported asthma, and self-reported tuberculosis were risk factors for nonsmoker COPD and there were differences between nonsmoker and smoker COPD in terms of sex, comorbidities, and HRQoL.

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.