Serum developmental endothelial locus-1 is associated with severity of sepsis in animals and humans.

Disruption of the endothelial glycocalyx has a prominent role in the pathophysiology of sepsis. Developmental endothelial locus-1 (Del-1) is an endothelial-derived anti-inflammatory factor. We hypothesized that degradation of the endothelial glycocalyx during sepsis may increase serum Del-1. A mouse model of sepsis was created using cecal ligation and puncture. In septic mice, the endothelial glycocalyx was nearly completely degraded, with less formation of Del-1 in the endothelium and extracellular matrix than in control mice. Serum Del-1 levels were significantly increased in the septic mice with increasing severity of sepsis. Serum Del-1 levels were also measured in 84 patients with sepsis and septic shock and in 20 control subjects. The median serum Del-1 level in patients with sepsis was significantly higher than that in healthy controls. The high Del-1 group had higher illness severity scores and contained more patients with organ dysfunction than the low Del-1 group. The 90-day mortality rate was significantly higher in the high Del-1 group than in the low Del-1 group. Multivariate analysis indicated a tendency for a high serum Del-1 level to be associated with a higher mortality risk. Increased serum Del-1 may be a novel diagnostic biomarker of sepsis and an indicator of disease severity.

Characteristics and Clinical Outcomes of Critically Ill Cancer Patients Admitted to Korean Intensive Care Units.

BACKGROUND: The objective of this study was to investigate the characteristics and clinical outcomes of critically ill cancer patients admitted to intensive care units (ICUs) in Korea. METHODS: This was a retrospective cohort study that analyzed prospective collected data from the Validation of Simplified Acute Physiology Score 3 (SAPS3) in Korean ICU (VSKI) study, which is a nationwide, multicenter, and prospective study that considered 5,063 patients from 22 ICUs in Korea over a period of 7 months. Among them, patients older than 18 years of age who were diagnosed with solid or hematologic malignancies prior to admission to the ICU were included in the present study. RESULTS: During the study period, a total of 1,762 cancer patients were admitted to the ICUs and 833 of them were deemed eligible for analysis. Six hundred fifty-eight (79%) had solid tumors and 175 (21%) had hematologic malignancies, respectively. Respiratory problems (30.1%) was the most common reason leading to ICU admission. Patients with hematologic malignancies had higher Sequential Organ Failure Assessment (12 vs. 8, P<0.001) and SAPS3 (71 vs. 69, P<0.001) values and were more likely to be associated with chemotherapy, steroid therapy, and immunocompromised status versus patients with solid tumors. The use of inotropes/vasopressors, mechanical ventilation, and/or continuous renal replacement therapy was more frequently required in hematologic malignancy patients. Mortality rates in the ICU (41.7% vs. 24.6%, P<0.001) and hospital (53.1% vs. 38.6%, P=0.002) were higher in hematologic malignancy patients than in solid tumor patients. CONCLUSIONS: Cancer patients accounted for one-third of all patients admitted to the studied ICUs in Korea. Clinical characteristics were different according to the type of malignancy. Patients with hematologic malignancies had a worse prognosis than did patients with solid tumor.

A case of intravascular large B-cell lymphoma of lung presenting with progressive multiple nodules on chest computed tomography.

A 71-year-old man was admitted to our hospital for dyspnea, which had worsened over a period of more than six months. He was previously diagnosed as having cryptogenic organizing pneumonia, and was treated with steroids in another hospital. He had complained of worsening dyspnea, despite the treatment. We performed video-assisted thoracoscopic surgery because of the high level of lactate dehydrogenase and inconsistency of the usual interstitial pneumonia pattern. Pathologic specimens showed atypical lymphocytes confined to the pulmonary capillaries. On immunohistochemical staining, tumor cells were found positive for CD20, without the T-cell marker. It was consistent with findings of intravascular large B-cell lymphoma. We report this case, which presented with progressive multiple nodules on chest computed tomography.

The Ability of the Acute Physiology and Chronic Health Evaluation (APACHE) IV Score to Predict Mortality in a Single Tertiary Hospital.

BACKGROUND: The Acute Physiology and Chronic Health Evaluation (APACHE) II model has been widely used in Korea. However, there have been few studies on the APACHE IV model in Korean intensive care units (ICUs). The aim of this study was to compare the ability of APACHE IV and APACHE II in predicting hospital mortality, and to investigate the ability of APACHE IV as a critical care triage criterion. METHODS: The study was designed as a prospective cohort study. Measurements of discrimination and calibration were performed using the area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test respectively. We also calculated the standardized mortality ratio (SMR). RESULTS: The APACHE IV score, the Charlson Comorbidity index (CCI) score, acute respiratory distress syndrome, and unplanned ICU admissions were independently associated with hospital mortality. The calibration, discrimination, and SMR of APACHE IV were good (H = 7.67, P = 0.465; C = 3.42, P = 0.905; AUROC = 0.759; SMR = 1.00). However, the explanatory power of an APACHE IV score >93 alone on hospital mortality was low at 44.1%. The explanatory power was increased to 53.8% when the hospital mortality was predicted using a model that considers APACHE IV >93 scores, medical admission, and risk factors for CCI >3 coincidentally. However, the discriminative ability of the prediction model was unsatisfactory (C index <0.70). CONCLUSIONS: The APACHE IV presented good discrimination, calibration, and SMR for hospital mortality.

A case of primary pulmonary NK/T cell lymphoma presenting as pneumonia.

Primary pulmonary lymphoma, particularly non-B cell lymphomas involving lung parenchyma, is very rare. A 46-year-old male was admitted to the hospital with fever and cough. Chest X-ray showed left lower lobe consolidation, which was considered pneumonia. However, because the patient showed no response to empirical antibiotic therapy, bronchoscopic biopsy was performed for proper diagnosis. The biopsied specimen showed infiltrated atypical lymphocytes with angiocentric appearance. On immunohistochemical staining, these atypical cells were positive for CD3, CD30, CD56, MUM-1, and granzyme B, and labeled for Epstein-Barr virus encoded RNA in situ hybridization. These findings were consistent with NK/T cell lymphoma. We report on a case of primary pulmonary NK/T cell lymphoma presenting as pneumonic symptoms and review the literature on the subject.

Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD: results from a national database.

BACKGROUND: Acute exacerbations are major drivers of COPD deterioration. However, limited data are available for the prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD. METHODS: Patients with mild-to-moderate COPD (≥40 years) were extracted from Korean National Health and Nutrition Examination Survey data (2007-2012) and were linked to the national health insurance reimbursement database to obtain medical service utilization records. RESULTS: Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6%) had severe exacerbations over the 6 years (0.012/person-year). Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P<0.001). A multiple logistic regression presented that asthma was an independent risk factor of severe exacerbations in patients with mild-to-moderate COPD regardless of adjustment for all possible confounding factors (adjusted odds ratio, 1.67; 95% confidence interval, 1.002-2.77, P=0.049). In addition, age, female, poor lung function, use of inhalers, and low EuroQoL five dimensions questionnaire index values were independently associated with severe exacerbation in patients with mild-to-moderate COPD. CONCLUSION: In this population-based study, the prevalence of severe exacerbations in patients with mild-to-moderate COPD was relatively low, compared with previous clinical interventional studies. Coexisting asthma significantly impacted the frequency of severe exacerbations in patients with mild-to-moderate COPD, suggesting application of an exacerbation preventive strategy in these patients.

Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study Team Cohort.

The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies.

Massive hemoptysis due to pulmonary vein stenosis following catheter ablation for atrial fibrillation.

Pulmonary vein stenosis, which is one of the rare complications of radiofrequency catheter ablation for atrial fibrillation, has various symptoms. Here, we report a rare case of massive hemoptysis due to pulmonary vein stenosis following radiofrequency catheter ablation, which was successfully managed with pneumonectomy.

Organizing pneumonia associated with M ycobacterium tuberculosis infection.

Organizing pneumonia is an inflammatory lung disease involving the distal bronchioles, respiratory bronchioles, bronchiolar ducts, and alveoli. A number of viral and bacterial organisms have been identified as causative agents of organizing pneumonia. However, M ycobacterium tuberculosis has rarely been reported as a causative agent. Herein, we report our experience with two patients diagnosed with pulmonary tuberculosis, whose biopsies showed patterns associated with organizing pneumonia. Both patients showed positive results for bacteriological tests and presence of acid fast bacilli. Hence, we could successfully treat both patients with anti-tuberculosis medications. Our report suggests that M . tuberculosis infection could be added to the list of infectious conditions associated with organizing pneumonia.

A Case of Segniliparus rugosus Pulmonary Infection in an Immunocompetent Patient with Non-cystic Fibrosis.

Segniliparus species is a novel genus that is reported to be the new emerging respiratory pathogens. Here, we report a very rare case of S. rugosus pulmonary infection in an immunocompetent patient with non-cystic fibrosis. The organism was identified by 16S rRNA gene sequencing. The patient was successfully treated with antibiotics.

Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats.

Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

A case of drug-induced interstitial pneumonia potentially related to quetiapine (seroquel) therapy for behavioral and psychological symptoms.

Quetiapine is regarded as an effective and safe treatment for delirium. An 82-year-old man presented with a 1-week history of violent behavior and dizziness accompanied by weakness on the left side of his body. He was diagnosed with acute cerebral cortical infarction and delirium associated with alcohol abuse. After quetiapine treatment, he complained of fever and coughed up sputum, whereas his aggressive behavior improved. His symptoms persisted despite empirical antibiotic treatment. All diagnostic tests for infectious causes were negative. High-resolution computed tomography revealed bilateral consolidations and ground-glass opacities with predominantly peribronchial and subpleural distributions. The primary differential diagnosis was drug-associated interstitial lung disease, and therefore, we discontinued quetiapine and began methylprednisolone treatment. His symptoms and radiologic findings significantly improved after receiving steroid therapy. We propose that clinicians need to be aware of the possibility that quetiapine is associated with lung injury.

Usefulness of N-terminal pro-B-type natriuretic peptide in patients admitted to the intensive care unit: a multicenter prospective observational study.

BACKGROUND: The role of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) as a prognostic factor in patients admitted to the intensive care unit (ICU) is not yet fully established. We aimed to determine whether NT-pro-BNP is predictive of ICU mortality in a multicenter cohort of critically ill patients. METHODS: A total of 1440 patients admitted to 22 ICUs (medical, 14; surgical, six; multidisciplinary, two) in 15 tertiary or university-affiliated hospitals between July 2010 and January 2011 were assessed. Patient data, including NT-pro-BNP levels and Simplified Acute Physiology Score (SAPS) 3 scores, were recorded prospectively in a web-based database. RESULTS: The median age was 64 years (range, 53-73 years), and 906 (62.9%) patients were male. The median NT-pro-BNP level was 341 pg/mL (104-1,637 pg/mL), and the median SAPS 3 score was 57 (range, 47-69). The ICU mortality rate was 18.9%, and hospital mortality was 24.5%. Hospital survivors showed significantly lower NT-pro-BNP values than nonsurvivors (245 pg/mL [range, 82-1,053 pg/mL] vs. 875 pg/mL [241-5,000 pg/mL], respectively; p < 0.001). In prediction of hospital mortality, the area under the curve (AUC) for NT-pro-BNP was 0.67 (95% confidence interval [CI], 0.64-0.70) and SAPS 3 score was 0.83 (95% CI, 0.81-0.85). AUC increment by adding NT-pro-BNP is minimal and likely no different to SAPS 3 alone. CONCLUSIONS: The NT-pro-BNP level was more elevated in nonsurvivors in a multicenter cohort of critically ill patients. However, there was little additional prognostic power when adding NT-pro-BNP to SAPS 3 score.

Impact of Eastern Cooperative Oncology Group Performance Status on hospital mortality in critically ill patients.

INTRODUCTION: This study evaluates the association between the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and hospital mortality in general critically ill patients. MATERIALS AND METHODS: This is a retrospective cohort study that analyzes prospective collected data from the Validation of Simplified acute physiology score 3 in Korean Intensive care unit study. The study population comprised patients who were consecutively admitted to participating intensive care units from July 1, 2010, to January 31, 2011. Univariate and multivariate logistic regression models were used to evaluate the effect of ECOG-PS on hospital mortality. RESULTS: A total of 3868 patients were included in the analysis. There was a significant trend for increasing hospital mortality as the ECOG-PS grade became higher (P<.001). There was a trend of increasing adjusted odds ratio for hospital mortality, with grade 1 of PS 1.4 (95% confidence intervals [CIs], 1.0-1.8), grade 2 of PS 2.0 (95% CIs, 1.5-2.7), grade 3 of PS 2.9 (95% CIs, 2.1-4.1), and grade 4 of PS 2.5 (95% CIs, 1.6-3.9). Also, there was a significant difference in all grades. Subgroup analysis showed a trend of increasing hospital mortality regardless of the presence of cancer. CONCLUSION: Preadmission PS, assessed with ECOG-PS in critically ill patients, has prognostic value in general critically ill patients.

Mortality after in-hospital cardiopulmonary resuscitation: multicenter analysis in Korea.

PURPOSE: The purpose of this study is to evaluate factors associated with the mortality of patients admitted to intensive care units (ICUs) after in-hospital cardiopulmonary resuscitation (CPR) and the impact of a hospital rapid response system (RRS) on patient mortality in Korea. MATERIALS AND METHODS: A prospective multicenter cohort study was done in 22 ICUs of 15 centers from July 1, 2010, to January 31, 2011. We only enrolled patients admitted to ICUs after in-hospital CPR and divided eligible patients into 2 groups-survivors and nonsurvivors. RESULTS: Among 4617 patients, 150 patients were admitted post-CPR, 76 died, and 74 survived. At 24 hours, the Sequential Organ Failure Assessment score, Simplified Acute Physiology Score II, and the best Glasgow Coma Scale were significantly lower in the nonsurvivors than in the survivors. In multivariate analysis, the Simplified Acute Physiology Score II and presence of lower respiratory infection were both independently associated with mortality. At the first hour after admission, lowest serum potassium and highest heart rate were associated with mortality. At 24 hours after admission, lowest mean arterial pressure, HCO3 level, and venous oxygen saturation level; highest heart rate; and use of vasoactive drugs were associated with mortality. The mortality of patients in hospitals with an RRS was not significantly different from that of hospitals without an RRS. CONCLUSION: Various physiologic and laboratory parameters were associated with the mortality of post-CPR ICU admitted patients, and the presence of an RRS did not reduce mortality of these patients in our study.

Validation of SAPS3 admission score and its customization for use in Korean intensive care unit patients: a prospective multicentre study.

BACKGROUND AND OBJECTIVE: To externally validate the simplified acute physiology score 3 (SAPS3) and to customize it for use in Korean intensive care unit (ICU) patients. METHODS: This is a prospective multicentre cohort study involving 22 ICUs from 15 centres throughout Korea. The study population comprised patients who were consecutively admitted to participating ICUs from 1 July 2010 to 31 January 2011. RESULTS: A total of 4617 patients were enrolled. ICU mortality was 14.3%, and hospital mortality was 20.6%. The patients were randomly assigned into one of two cohorts: a development (n = 2309) or validation (n = 2308) cohort. In the development cohort, the general SAPS3 had good discrimination (area under the receiver operating characteristics curve = 0.829), but poor calibration (Hosmer-Lemeshow goodness-of-fit test H = 123.06, P < 0.001, C = 118.45, P < 0.001). The Australasia SAPS3 did not improve calibration (H = 73.53, P < 0.001, C = 70.52, P < 0.001). Customization was achieved by altering the logit of the original SAPS3 equation. The new equation for Korean ICU patients was validated in the validation cohort, and demonstrated both good discrimination (area under the receiver operating characteristics curve = 0.835) and good calibration (H = 4.61, P = 0.799, C = 5.67, P = 0.684). CONCLUSIONS: General and regional Australasia SAPS3 admission scores showed poor calibration for use in Korean ICU patients, but the prognostic power of the SAPS3 was significantly improved by customization. Prediction models should be customized before being used to predict mortality in different regions of the world.

Clinical outcomes of witnessed and monitored cases of in-hospital cardiac arrest in the general ward of a university hospital in Korea.

BACKGROUND: There are few studies of the epidemiology and clinical outcomes of patients with in-hospital cardiac arrest (IHCA) in a general hospital ward. OBJECTIVE: To investigate the clinical outcomes of IHCA cases that occurred in the general ward of a university hospital and that were witnessed and/or monitored. METHODS: We prospectively gathered data on all IHCAs in the general ward of Asan Medical Center, Seoul, South Korea, that were recorded by the Medical Emergency Team between March 2008 and February 2010. The main outcomes included survival to hospital discharge, incidence of IHCA, and prognostic factors related to hospital mortality. We also investigated preventable cases. RESULTS: We identified 238 index cases of IHCA. The average incidence of IHCA was 0.145 IHCAs per 1,000 patient admissions. Survival to hospital discharge was 19% (46 cases), 66% of which were due to non-cardiac causes, and 77% were due to medical illnesses. The most common first documented rhythm was pulseless electrical activity (38%). Two hundred three cases (85.3%) of IHCA were witnessed at the event; 135 cases (56.7%) were monitored at the event. Non-witnessed cases, monitored cases, night onset, medical illness, metastatic cancer, intubation, and long duration of cardiopulmonary resuscitation were significantly associated with hospital mortality. We identified 91 preventable cases (38%). Respiratory insufficiency (37 cases, 41%) was one of major cause of preventable IHCA. CONCLUSIONS: Witnessed IHCAs in the general ward had a higher rate of survival to hospital discharge; however, monitored cases had a lower rate of survival to hospital discharge. Respiratory insufficiency was a major preventable cause of IHCA. In consideration of the preventable IHCAs, further studies should be performed on monitoring practices in general wards.

Mycobacterium intracellulare Pleurisy Identified on Liquid Cultures of the Pleural Fluid and Pleural Biopsy.

Pleural effusion is a rare complication in non-tuberculous mycobacterial infection. We report a case of Mycobacterium intracellulare pleuritis with idiopathic pulmonary fibrosis in a 69-year-old man presenting with dyspnea. Pleural effusion revealed lymphocyte dominant exudate. M. intracellulare was identified using a polymerase chain reaction-restriction fragment length polymorphism method and liquid cultures of pleural effusion and pleural biopsy. After combination therapy for M. intracellulare pulmonary disease, the patient was clinically well at a 1-month follow-up.

The impact of implementing critical care team on open general intensive care unit.

BACKGROUND: There are a plethora of literatures showing that high-intensity intensive care unit (ICU) physician staffing is associated with reduced ICU mortality. However, it is not widely used in ICUs because of limited budgets and resources. We created a critical care team (CCT) to improve outcomes in an open general ICU and evaluated its effectiveness based on patients' outcomes. METHODS: We conducted this prospective, observational study in an open, general ICU setting, during a period ranging from March of 2009 to February of 2010. The CCT consisted of five teaching staffs. It provided rapid medical services within three hours after calls or consultation. RESULTS: We analyzed the data of 830 patients (157 patients of the CCT group and 673 patients of the non-CCT one). Patients of the CCT group presented more serious conditions than those of the non-CCT group (acute physiologic and chronic health evaluation II [APACHE II] 20.2 vs. 15.8, p<0.001; sequential organ failure assessment [SOFA] 5.5 vs. 4.6, p=0.003). The CCT group also had significantly more patients on mechanical ventilation than those in the non-CCT group (45.9% vs. 23.9%, p<0.001). Success rate of weaning was significantly higher in the CCT group than that of the non-CCT group (61.1% vs. 44.7%, p=0.021). On a multivariate logistic regression analysis, the increased ICU mortality was associated with the older age, non-CCT, higher APACHE II score, higher SOFA score and mechanical ventilation (p<0.05). CONCLUSION: Although the CCT did not provide full-time services in an open general ICU setting, it might be associated with a reduced ICU mortality. This is particularly the case with patients on mechanical ventilation.