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.

Decreased annual risk of tuberculosis infection in South Korean healthcare workers using interferon-gamma release assay between 1986 and 2005.

BACKGROUND: Tuberculosis (TB) has been a major public health problem in South Korea. Although TB notification rate in Korea is gradually decreasing, still highest among the member countries of the Organization for Economic Cooperation and Development. To effectively control TB, understanding the TB epidemiology such as prevalence of latent tuberculosis infection (LTBI) and annual risk of TB infection (ARI) are important. This study aimed to identify the prevalence of LTBI and ARI among South Korean health care workers (HCWs) based on their interferon-gamma release assays (IGRA). METHODS: This was single center, cross-sectional retrospective study in a tertiary hospital in South Korea. We performed IGRA in HCWs between May 2017 and March 2018. We estimated ARI based on IGRA results. Logistic regression model was used to identify factors affecting IGRA positivity. RESULTS: A total of 3233 HCWs were analyzed. Median age of participants was 38.0 and female was predominant (72.6%). Overall positive rate of IGRA was 24.1% and IGRA positive rates age-group wise were 6.6%, 14.4%, 34.3%, and around 50% in the age groups 20s, 30s, 40s, and 50s and 60s, respectively. The ARIs was 0.26-1.35% between 1986 and 2005; rate of TB infection has gradually decreased in the last two decades. Multivariable analysis indicated that older age, healed TB lesion in x-ray, and male gender were risk factors for IGRA positivity, whereas working in high-risk TB departments was not. CONCLUSIONS: Results showed that ARI in South Korean HCWs gradually decreased over two decades, although LTBI remained prevalent. Our results suggest that the LTBI test result of HCWs might be greatly affected by age, rather than occupational exposure, in intermediate TB burden countries. Thus, careful interpretation considering the age structure is required.

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.

Usefulness of Impulse Oscillometry in Predicting the Severity of Bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic respiratory disease that leads to airway inflammation, destruction, and airflow limitation, which reflects its severity. Impulse oscillometry (IOS) is a non-invasive method that uses sound waves to estimate lung function and airway resistance. The aim of this study was to assess the usefulness of IOS in predicting the severity of bronchiectasis. METHODS: We retrospectively reviewed the IOS parameters and clinical characteristics in 145 patients diagnosed with bronchiectasis between March 2020 and May 2021. Disease severity was evaluated using the FACED score, and patients were divided into mild and moderate/severe groups. RESULTS: Forty-four patients (30.3%) were in the moderate/severe group, and 101 (69.7%) were in the mild group. Patients with moderate/severe bronchiectasis had a higher airway resistance at 5 Hz (R5), a higher difference between the resistance at 5 and 20 Hz (R5-R20), a higher resonant frequency (Fres), and a higher area of reactance (AX) than patients with mild bronchiectasis. R5 ≥0.43, resistance at 20 Hz (R20) ≥0.234, R5-R20 ≥28.3, AX ≥1.02, reactance at 5 Hz (X5) ≤-0.238, and Fres ≥20.88 revealed significant univariable relationships with bronchiectasis severity (p<0.05). Among these, only X5 ≤-0.238 exhibited a significant multivariable relationship with bronchiectasis severity (p=0.039). The receiver operating characteristic curve for predicting moderate- to-severe bronchiectasis of FACED score based on IOS parameters exhibited an area under the curve of 0.809. CONCLUSION: The IOS assessed by the disease severity of FACED score can effectively reflect airway resistance and elasticity in bronchiectasis patients and serve as valuable tools for predicting bronchiectasis severity.

Development of a Simple Scoring System for Predicting Discharge Safety from the Medical ICU to Low-Acuity Wards: The Role of the Sequential Organ Failure Assessment Score, Albumin, and Red Blood Cell Distribution Width.

Despite advancements in artificial intelligence-based decision-making, transitioning patients from intensive care units (ICUs) to low-acuity wards is challenging, especially in resource-limited settings. This study aimed to develop a simple scoring system to predict ICU discharge safety. We retrospectively analyzed patients admitted to a tertiary hospital's medical ICU (MICU) between July 2016 and December 2021. This period was divided into two phases for model development and validation. We identified risk factors associated with unexpected death within 14 days of MICU discharge and developed a predictive scoring system that incorporated these factors. We verified the system's performance using validation data. In the development cohort, 522 patients were discharged from the MICU, and 42 (8.04%) died unexpectedly. In multivariate analysis, the Sequential Organ Failure Assessment (SOFA) score (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.13-1.41), red blood cell distribution width (RDW) (OR 1.20, 95% CI 1.07-1.36), and albumin (OR 0.37, 95% CI 0.16-0.84) were predictors of unexpected death. Each variable was assigned a weighted point in the scoring system, and the area under the curve (AUC) was 0.788 (95% CI 0.714-0.855). The scoring system was performed using an AUC of 0.738 (95% CI 0.653-0.822) in the validation cohort of 343 patients with 9.62% of unexpected deaths. When a cut-off of 0.032 was applied, a sensitivity and a specificity of 81.8% and 55.2%, respectively, were achieved. This simple bedside predictive score for ICU discharge uses the SOFA score, albumin level, and RDW to aid in timely decision-making and optimize critical care facility allocation in resource-limited settings.

Biomarker-Based Assessment Model for Detecting Sepsis: A Retrospective Cohort Study.

The concept of the quick sequential organ failure assessment (qSOFA) simplifies sepsis detection, and the next SOFA should be analyzed subsequently to diagnose sepsis. However, it does not include the concept of suspected infection. Thus, we simply developed a biomarker-based assessment model for detecting sepsis (BADS). We retrospectively reviewed the electronic health records of patients admitted to the intensive care unit (ICU) of a 2000-bed university tertiary referral hospital in South Korea. A total of 989 patients were enrolled, with 77.4% (n = 765) of them having sepsis. The patients were divided into a ratio of 8:2 and assigned to a training and a validation set. We used logistic regression analysis and the Hosmer-Lemeshow test to derive the BADS and assess the model. BADS was developed by analyzing the variables and then assigning weights to the selected variables: mean arterial pressure, shock index, lactate, and procalcitonin. The area under the curve was 0.754, 0.615, 0.763, and 0.668 for BADS, qSOFA, SOFA, and acute physiology and chronic health evaluation (APACHE) II, respectively, showing that BADS is not inferior in sepsis prediction compared with SOFA. BADS could be a simple scoring method to detect sepsis in critically ill patients quickly at the bedside.

The prognosis of patients with lung cancer admitted to the medical intensive care unit.

AIMS: Lung cancer remains the leading cause of cancer mortality worldwide. Despite their poor prognosis, patients with lung cancer are increasingly being admitted to the medical intensive care unit (MICU) for treatment of critical illnesses. The aim of this study was to assess the outcome of patients with lung cancer who are admitted to an MICU and to identify the measurable predictors of their MICU outcome. METHODS: We conducted retrospective analysis on 97 patients with lung cancer admitted to the MICU between 2007 and 2011. RESULTS: The mean age ± standard deviation was 71.8 ± 6.8 years. Of the 97 patients (82 male), 73 patients (75%) had non-small cell lung cancer stage IIIB, IV and 24 patients (25%) had small cell lung cancer. The intensive care unit mortality and in-hospital mortality rates were 53.6 and 61.8%. The main reasons for MICU admission were pneumonia (n = 51) and complication of cancer management (n = 45). The predictors of poor MICU outcome were history of diabetes mellitus (P = 0.028), Acute Physiology and Chronic Health Evaluation II score (P = 0.018), need for mechanical ventilation (P = 0.014), use of vasoactive agents (P < 0.0001), the presence of acute renal failure (P < 0.0001) and presence of multiorgan failure (P < 0.0001). CONCLUSIONS: We found that in-hospital mortality was not influenced by age, sex or performance status score of patients with lung cancer but increased with the severity of organ failure at MICU admission.

Synergistic Effect of Sulindac and Simvastatin on Apoptosis in Lung Cancer A549 Cells through AKT-Dependent Downregulation of Survivin.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) and statins are potential chemopreventive or chemotherapeutic agents. The mechanism underlying the deregulation of survivin by NSAIDs and statins in human non-small cell lung cancer cells has not been elucidated. In this study, we investigated the synergistic interaction of sulindac and simvastatin in lung cancer A549 cells. MATERIALS AND METHODS: Cell viability was measured by an MTT assay, while the expression of apoptotic markers, AKT, and survivin in response to sulindac and simvastatin was examined by Western blotting. DNA fragmentation by apoptosis was analyzed by flow cytometry in A549 cells. Reactive oxygen species (ROS) generation was measured by flow cytometry using H2DCFDA and MitoSOX Red, and the effects of pretreatment with N-acetylcysteine were tested. The effects of AKT on survivin expression in sulindac- and simvastatin-treated cells were assessed. Survivin was knocked down or overexpressed to determine its role in apoptosis induced by sulindac and simvastatin. RESULTS: Sulindac and simvastatin synergistically augmented apoptotic activity and intracellular ROS production in A549 cells. Inhibition of AKT by siRNA or LY294002 inhibited survivin, while AKT overexpression markedly increased survivin expression, even in the presence of sulindac and simvastatin. Moreover, survivin siRNA enhanced sulindac- and simvastatininduced apoptosis. In contrast, survivin upregulation protected against sulindac- and simvastatin-induced apoptosis. CONCLUSION: Combined treatment with sulindac and simvastatin augmented their apoptotic potential in lung cancer cells through AKT signaling-dependent downregulation of survivin. These results indicate that sulindac and simvastatin may be clinically promising therapies for the prevention of lung cancer.

Diagnostic value and prognostic significance of pleural C-reactive protein in lung cancer patients with malignant pleural effusions.

PURPOSE: C-reactive protein (CRP) has been implicated in various inflammatory and advanced malignant states. Increased serum CRP (s-CRP) levels have been shown to be associated with independent prognostic factors for survival in patients with advanced lung cancer. However, only few studies have focused on the role of CRP in pleural effusions. This study aimed to evaluate the diagnostic and prognostic value of pleural CRP (p-CRP) in lung cancer patients with malignant pleural effusion (MPE). MATERIALS AND METHODS: Pleural effusion (PE) samples were collected from patients with MPE (68 lung cancers; 12 extrathoracic tumors), and from 68 patients with various benign conditions (31 with pneumonia; 37 with tuberculosis). Concentrations of p- and s-CRP were measured by enzyme-linked immunosorbent assay. CRP level in pleural fluid and its association with survival were examined. RESULTS: p-CRP levels correlated with s-CRP levels (r=0.82, p<0.0001). For the differential diagnosis of MPE and benign PE, the area under the receiver operating characteristic curve was greater for p-CRP (0.86) than for s-CRP (0.77). High p-CRP expression significantly correlated with shorter overall survival (p=0.006). P-CRP was independent prognostic factor significantly associated with overall survival on multivariated analysis (p=0.0001). The relative risk of death for lung cancer patients with high p-CRP levels was 3.909 (95% confidence interval, 2.000-7.639). CONCLUSION: P-CRP is superior to s-CRP in determining pleural fluid etiology. Quantitative measurement of p-CRP might be a useful complementary diagnostic and prognostic test for lung cancer patients with MPE.

Clostridium difficile Infection in lung cancer patients.

Clostridium difficile infection (CDI) is a common nosocomial infection. Lung cancer patients have a high risk of developing CDI because of continuous antibiotic treatment or chemotherapy, prolonged hospitalization, and general weakness. This study aimed to analyze predisposing or associated risk factors for CDI in lung cancer patients receiving chemotherapy. This study was a retrospective review of 188 lung cancer patients who were admitted to the Wonkwang University Hospital between 2008 and 2009. Of the 188 patients, 44 were diagnosed with CDI. The albumin levels were significantly lower and the performance status (PS) score was significantly higher in lung cancer patients with CDI than in those without CDI (P < 0.05). In conclusion, clinicians should consider the possibility of CDI occurrence in lung cancer patients receiving chemotherapy, particularly in those with low albumin levels and high PS scores, because most lung cancer patients have a high risk of developing CDI.

Primary malignant fibrous histiocytoma of the pleura.

Malignant fibrous histiocytoma, a type of sarcoma, is a malignant neoplasm with uncertain origin that arises in both the soft tissues and the bone. The occurrence of primary malignant fibrous histiocytoma of the pleura is extremely rare. We report a case of a 65-year-old Korean man who is being diagnosed with primary malignant fibrous histiocytoma of the pleura.

Elevated prx1 provides resistance to docetaxel, but is not associated with predictive significance in lung cancer.

BACKGROUND: This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. METHODS: Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. RESULTS: Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). CONCLUSION: Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.