Background: Whether the combination of antimicrobial therapy is a factor in mortality in Pseudomonas aeruginosa bacteremia remains to be elucidated. This study investigated the risk factors for mortality in P. aeruginosa bacteremia patients and the influence of adequate antimicrobial therapy and combination therapy on clinical outcomes. Methods: This retrospective study analyzed data of 234 patients with P. aeruginosa bacteremia at a 1,200-bed tertiary teaching university hospital in South Korea between January 2010 and December 2012. Factors associated with mortality were determined. Mortality was compared in patients with adequate empirical and targeted combination therapy, and monotherapy, and inappropriate therapy. Results: A total of 141 (60.3%) patients were given appropriate empirical antibiotic treatment (combination therapy in 38 and monotherapy in 103). Among 183 patients (78.2%) who finally received appropriate targeted treatment, 42 had combination therapy and 141 had monotherapy. The percentage of patients receiving empirical combination therapy was slightly, but not significantly higher, in the survivor group than in the nonsurvivor group (17.0% [31/182] vs. 13.5% [7/52], p = 0.74). A similar tendency was demonstrated for targeted combination therapy (19.8% [36/182] vs. 11.5% [6/52], respectively; p = 0.31). However, in a subgroup analysis of data from patients (n = 54) with an absolute neutrophil count less than 500/mm³, the patients who had appropriate empirical or targeted combination therapy showed better outcomes than those who underwent monotherapy or inappropriate therapy (p < 0.05). Mechanical ventilation (odds ratio [OR], 6.93; 95% confidence interval [CI], 2.64–18.11; p = 0.0001), the use of a central venous catheter (OR, 2.95; 95% CI, 1.35–6.43; p = 0.007), a high Acute Physiology and Chronic Health Evaluation II score (OR, 4.65; 95% CI, 1.95–11.04; p = 0.0001), and presence of septic shock (OR, 2.91; 95% CI, 1.33–6.38; p = 0.007) were independent risk factors for 14-day mortality. Conclusions: Disease severity was a critical factor for mortality in our patients with P. aeruginosa bacteremia. Overall, combination therapy had no significant effect on 14-day mortality compared with monotherapy. However, appropriate combination therapy showed a favorable effect on survival in patients with febrile neutropenia.

Extrapulmonary tuberculosis (EPTB) is a heterogeneous disease, and diagnosis is sometimes difficult. We investigated the diagnostic performance of the QuantiFERON-TB Gold assay (QFT-GIT) according to sites of EPTB and predictors for false-negative QFT-GIT results. A total of 2176 patients were registered with active TB from January 2012 to December 2016 in Seoul St. Mary’s Hospital, a 1200-bed tertiary teaching hospital in Seoul, Korea. We retrospectively reviewed the medical records of 163 EPTB patients who underwent QFT-GIT. False negative QFT-GIT results were found in 28.8% (95% CI 0.22–0.36) of patients with EPTB. In the proven TB group, negative QFT-GIT results were found in 28.6% (95% CI 0.04–0.71) of pleural, 8.3% 0.002–0.38of lymph node, 8.3% (95% CI 0.002–0.38) of skeletal and 5.8% (95% CI 0.001–0.28) of gastrointestinal TB cases. Among probable TB cases, QFT-GIT negative results were identified in 46.2% (95% CI 0.19–0.75) of skeletal, 33.3% (95% CI 10–0.65) of pericardial, 30.8% (95% CI 0.09–0.61) of pleural and 17.2% (95% CI 0.10–0.56) of gastrointestinal TB cases. In the possible TB cases, central nervous system TB (n = 21) was most frequent, and 66.7% (95% CI 0.43–0.85) of those showed QFT-GIT negative results. By multivariate analysis, possible TB was independently associated with false-negative QFT-GIT results (OR 4.92, 95% CI 1.51–16.06, p = 0.008). Prudent interpretation of QFT-GIT results might be needed according to anatomic site of involvement and diagnostic criteria in patients with high suspicion of EPTB.

Introduction: Neutropenia recovery may be associated with deterioration in oxygenation and exacerbation of pre-existing pulmonary disease. However, risk factors for acute respiratory distress syndrome (ARDS) during neutropenia recovery in patients with hematologic malignancies have not been studied. Methods: We studied critically ill patients with hematologic malignancies with the dual objectives of describing patients with ARDS during neutropenia recovery and identifying risk factors for ARDS during neutropenia recovery. A cohort of consecutive neutropenic patients with hematologic malignancies who were admitted to the intensive care unit (ICU) was studied. During a 6-year period, 71 patients recovered from neutropenia, of whom 38 (53.5%) developed ARDS during recovery. Results: Compared with non-ARDS patients, patients who experienced ARDS during neutropenia recovery were more likely to have pneumonia, be admitted to the ICU for respiratory failure, and receive mechanical ventilator therapy. The in-ICU mortality was significantly different between the two groups (86.8% versus 51.5%, respectively, for patients who developed ARDS during neutropenia recovery versus those who did not during neutropenia recovery). In multivariate analysis, only occurrence of pneumonia during the neutropenic episode was associated with a marked increase in the risk of ARDS (odds ratio, 4.76). Conclusions: Patients with hematologic malignancies complicated by pneumonia during neutropenia are at increased risk for ARDS during neutropenia recovery.

Aim of the Study: MicroRNA-21 (miR-21) is up-regulated during allergic airway inflammation, reflecting a Th2 immune response. We investigated the effects of an miR-21 antagomir and its mechanism of action in a mouse model of acute bronchial asthma. Materials and Methods: BALB/c mice were sensitized and challenged with ovalbumin (OVA). The anti-miR-21 antagomir was administered by intranasal inhalation from the day of sensitization. Changes in cell counts, Th2 cytokine levels in bronchoalveolar (BAL) fluid, and airway hyper-responsiveness (AHR) were examined. Histopathological changes and expression levels of miR-21 in lung tissues were analyzed. The mechanism of action of the antagomir was investigated by counting CD4⁺/CD8⁻ T cells in splenocytes and by measuring the expression levels of transcription factors associated with T cell polarization. Results: MiR-21 expression was selectively down-regulated in the lung tissues of mice treated with anti-miR-21. The antagomir suppressed AHR compared with that of the OVA-challenged and scrambled RNA-treated groups. It also reduced the total cell and eosinophil counts in BAL fluid and the levels of Th2 cytokines, including IL-4, IL-5, and IL-13. The direct target of miR-21, IL-12p35, was induced in the antagomir-treated group, decreasing the CD4⁺/CD8⁻ T cell proportions in splenocytes. The levels of transcription factors involved in the Th2-signaling pathway were reduced in lung tissues on treatment with the antagomir. Conclusions: The miR-21 antagomir suppresses the development of allergic airway inflammation in a mouse model of acute bronchial asthma, inhibiting Th2 activation. These results suggest that this antagomir might be useful for treating bronchial asthma.

Lee HY, et al. Allergy Asthma Immunol Res. 2021 Mar;13(2):312-329. https://doi.org/10.4168/aair.2021.13.2.312