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 inter val [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% 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.

Optimal Definition of Oligometastasis Showing Survival Benefits of Local Therapies during Tyrosine Kinase Inhibitor Treatment / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to investigate the feasibility of four criteria on oligometastasis (OM) concerning clear survival benefits of local therapy (LT) during tyrosine kinase inhibitor (TKI) treatment in non–small cell lung cancer (NSCLC). @*Materials and Methods@#This single-center, retrospective study included patients with advanced NSCLC who received LT because of OM during TKI treatment at Asan Medical Center from January 2011 to December 2020. At the application of LT OM was classified according to four criteria: TNM, European Organization for Research and Treatment of Cancer Lung Cancer Group (EORTC-LCG), National Comprehensive Network (NCCN), and ORGAN. We compared survival outcomes between patients with and without OM. @*Results@#The median overall survival of the 117 patients included in the analysis was 70.8 months (95% confidence interval [CI], 56.6 to 85.1). The patients with OM meeting all four criteria (hazard ratio [HR] with 95% CI of TNM criteria 0.24 with 0.10-0.57; p=0.001, EORTC-LCG criteria 0.34 with 0.17-0.67; p=0.002, NCCN criteria 0.41 with 0.20-0.86; p=0.018 and ORGAN criteria 0.33 with 0.18-0.60; p < 0.001) had significantly longer survival compared with patients who did not after adjusting for confounding factors. Furthermore, increasing the number of extra-thoracic metastatic organs to two or more were independent predictive factors for worse survival outcomes (2 organs: HR, 3.51; 95% CI, 1.01 to 12.14; p=0.048; 3 organs: HR, 4.31; 95% CI, 0.94 to 19.73; p=0.060; 4 organs: HR, 24.47; 95% CI, 5.08 to 117.80; p < 0.001). @*Conclusion@#Patients with OM defined by all four criteria showed prognostic benefits from LT during TKI therapy.

Iatrogenic Opioid Withdrawal Syndrome in Critically Ill Patients: a Retrospective Cohort Study

Background@#Opioid withdrawal syndrome (OWS) may occur following the reduction or discontinuation of opioid analgesics. In critically ill pediatric patients, OWS is a common and clinically significant condition. However, OWS in adult patients has not been assessed in detail. Therefore, we aimed to investigate the incidence, risk factors, and clinical features of OWS in mechanically ventilated patients treated in an adult intensive care unit (ICU). @*Methods@#This study was a retrospective evaluation of data from patients treated in the medical ICU for > 3 days and who received only one type of opioid analgesic. OWS was assessed over a 24 hours period from discontinuation or reduction (by > 50%) of continuous opioid infusion. OWS was defined as the presence of ≥ 3 central nervous system or autonomic nervous system symptoms. @*Results@#In 126 patients treated with remifentanil (n = 58), fentanyl (n = 47), or morphine (n = 21), OWS was seen in 31.0%, 36.2%, and 9.5% of patients, respectively (P = 0.078). The most common symptom was a change in respiratory rate (remifentanil, 94.4%; fentanyl, 76.5%; morphine, 100%). Multivariate Cox-proportional hazards model showed that OWS was negatively associated with morphine treatment (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.037–0.743) and duration of opioid infusion (HR, 0.566; 95% CI, 0.451–0.712). @*Conclusion@#OWS is not uncommon in mechanically ventilated adult patients who received continuous infusion of opioids for > 3 days. The use of morphine may be associated with a decreased risk of OWS.

Clinical Phenotypes, Comorbidities, and Exacerbations according to Serum 25-OH Vitamin D and Plasma Fibrinogen Levels in Chronic Obstructive Pulmonary Disease

BACKGROUND: Although vitamin D deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD), the influence of vitamin D deficiency on COPD has not been fully established. Moreover, the inflammation process is associated with vitamin D deficiency in the general population. Therefore, this study aimed to determine whether clinical phenotypes, comorbidities, and exacerbation rates are affected by the level of plasma fibrinogen, well studied by an inflammatory marker in COPD patients, and 25-hydroxy (25-OH) vitamin D. METHODS: This retrospective study analyzed patients with COPD whose inflammatory marker levels, especially plasma fibrinogen and 25-OH vitamin D levels, had been examined. A correlation analysis was conducted for inflammatory markers and 25-OH vitamin D. Clinical characteristics, comorbidities and exacerbation rates were compared among four groups based on plasma fibrinogen concentrations (threshold, 350 mg/dL) and 25-OH vitamin D levels (threshold, 20 ng/mL). RESULTS: Among 611 patients with COPD, 236 were included in the study. The levels of inflammatory markers had no statistical correlation with the serum 25-OH vitamin D levels. The four groups showed no statistically significant differences in age, sex, smoking history, inhaler use, and severity of comorbidities. Patients with high plasma fibrinogen concentrations and low 25-OH vitamin D levels had lower lung function, higher severity index, and higher annual rate of severe exacerbations 12 months before (0.23/year) and after (0.41/year) the measurement of 25-OH vitamin D levels than did the other patients. CONCLUSION: Our findings suggested an interaction between vitamin D deficiency and COPD. The measurement of plasma fibrinogen concentrations could help identify a severe phenotypic group among patients with vitamin D deficiency.

Concurrent, Prolonged Use of Bedaquiline and Delamanid for Multidrug-Resistant Tuberculosis / 대한내과학회지

Bedaquiline and delamanid were recently approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Korea. A treatment duration of 24 weeks was established based on phase 2 clinical trial data, although the combined use of these two drugs is typically not recommended because it may exaggerate QT prolongation. Here, we present a case of prolonged treatment (48 weeks) with a combination of bedaquiline and delamanid for pulmonary MDR-TB. The patient had previously been diagnosed with extensively drug-resistant TB but had been left untreated for the past 9 years due to a shortage of effective drugs. A combination of bedaquiline and delamanid successfully treated MDR-TB, highlighting the potential efficacy of these drugs for patients with drug-resistant TB infections.

Infliximab-Induced Lupus in Crohn's Disease / 대한내과학회지

Infliximab (IFX) is an anti-tumor necrosis factor (TNF) monoclonal antibody used to treat rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. Rarely, anti-TNF-induced lupus (ATIL) may occur. ATIL differs from classical drug-induced lupus. We report a 49-year-old woman who developed polyarthralgia after 2 years of IFX treatment for Crohn's disease. Based on the autoantibody profiles, ATIL was diagnosed and low-dose glucocorticoid, hydroxychloroquine, and celecoxib were prescribed. However, arthralgia and hemolytic anemia developed. Because the anti-dsDNA titers waxed and waned, she was switched to vedolizumab, a monoclonal antibody to the human lymphocyte α4β7 integrin. Six months after switching treatment, the arthralgia had improved and the anti-dsDNA antibody normalized. Here, we report a case of ATIL that resolved after switching from infliximab to vedolizumab.

Concurrent, Prolonged Use of Bedaquiline and Delamanid for Multidrug-Resistant Tuberculosis / 대한내과학회지

Bedaquiline and delamanid were recently approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Korea. A treatment duration of 24 weeks was established based on phase 2 clinical trial data, although the combined use of these two drugs is typically not recommended because it may exaggerate QT prolongation. Here, we present a case of prolonged treatment (48 weeks) with a combination of bedaquiline and delamanid for pulmonary MDR-TB. The patient had previously been diagnosed with extensively drug-resistant TB but had been left untreated for the past 9 years due to a shortage of effective drugs. A combination of bedaquiline and delamanid successfully treated MDR-TB, highlighting the potential efficacy of these drugs for patients with drug-resistant TB infections.

Infliximab-Induced Lupus in Crohn's Disease / 대한내과학회지

Infliximab (IFX) is an anti-tumor necrosis factor (TNF) monoclonal antibody used to treat rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. Rarely, anti-TNF-induced lupus (ATIL) may occur. ATIL differs from classical drug-induced lupus. We report a 49-year-old woman who developed polyarthralgia after 2 years of IFX treatment for Crohn's disease. Based on the autoantibody profiles, ATIL was diagnosed and low-dose glucocorticoid, hydroxychloroquine, and celecoxib were prescribed. However, arthralgia and hemolytic anemia developed. Because the anti-dsDNA titers waxed and waned, she was switched to vedolizumab, a monoclonal antibody to the human lymphocyte α4β7 integrin. Six months after switching treatment, the arthralgia had improved and the anti-dsDNA antibody normalized. Here, we report a case of ATIL that resolved after switching from infliximab to vedolizumab.