Concomitant Pulmonary Tuberculosis in Hospitalized Healthcare-Associated Pneumonia in a Tuberculosis Endemic Area: A Multi-center Retrospective Study

<div><h3>Background</h3><p>In tuberculosis (TB) endemic areas, <em>Mycobacterium tuberculosis</em> is an important but easily misdiagnosed pathogen in community-acquired pneumonia (CAP). However, the occurrence of concomitant pulmonary tuberculosis (PTB) in hospitalized healthcare-associated pneumonia (HCAP) has never been investigated.</p> <h3>Methods and Findings</h3><p>Seven hundred and one hospitalized HCAP and 934 hospitalized CAP patients from six medical centers in Taiwan were included in this nationwide retrospective study. Concomitant PTB was defined as active PTB diagnosed within 60 days of admission due to HCAP or CAP. The predictors for concomitant PTB and the impact of PTB on the outcomes of pneumonia were investigated. Among the enrolled subjects, 21/701 (3%) of the HCAP patients and 25/934 (2.7%) of the CAP patients were documented to have concomitant PTB. In multivariate analysis, a history of previous anti-TB treatment (OR = 5.84, 95% CI: 2.29–20.37 in HCAP; OR = 3.33, 95% CI: 1.09–10.22 in CAP) and escalated pneumonia severity index (PSI) scores (OR = 1.014, 95% CI: 1.002–1.026, in HCAP; OR = 1.013, 95% CI: 1.001–1.026, in CAP) were independent predictors for concomitant PTB in both CAP and HCAP patients. Regarding treatment outcomes, HCAP patients with concomitant PTB were associated with more acute respiratory failure within 48 hours of admission (47.6% vs. 22.6%, p = 0.008), higher intensive care unit admission rate (61.9% vs. 35.7%, p = 0.014), longer hospitalization (39.6±34.1 vs. 23.7±27 days, p = 0.009), and higher in-hospital mortality (47.6% vs. 26.3%, p = 0.03) than those without concomitant PTB. Exposure to certain groups of antibiotics for the treatment of pneumonia was not associated with the occurrence of concomitant PTB.</p> <h3>Conclusions</h3><p>In HCAP patients, the occurrence of concomitant PTB is comparable with that in CAP patients and associated with higher PSI scores, more acute respiratory failure, and higher in-hospital mortality.</p> </div

Univariate and multivariate logistic regression analysis of predictors associated with concomitant pulmonary tuberculosis in hospitalized HCAP and CAP patients^a.

a<p>Univariate and multivariate OR are derived from logistic regression analysis with stepwise selection procedure.</p><p>HCAP, healthcare-associated pneumonia; CAP, community acquired pneumonia; TB, tuberculosis; OR, odds ratio; CI, confidence interval.</p

Relationships between antibiotics exposure and the occurrence of concomitant pulmonary tuberculosis in HCAP and CAP patients^a.

a<p>The data are presented as n (%) unless otherwise stated.</p>b<p>Included levofloxacin and moxifloxacin.</p><p>HCAP, healthcare-associated pneumonia; CAP, community acquired pneumonia; TB, tuberculosis.</p

Demographic profiles between hospitalized HCAP and CAP patients^a.

a<p>The data are presented as n (%) unless otherwise stated.</p><p>HCAP, healthcare-associated pneumonia; CAP, community acquired pneumonia; TB, tuberculosis; SD, standard deviation; COPD, chronic obstructive pulmonary disease; PSI, pneumonia severity index; CURB65, confusion, urea, respiratory rate, blood pressure, age 65.</p

Demographic profiles and clinical characteristics of CAP and HCAP patients with and without concomitant pulmonary tuberculosis^a.

a<p>The data are presented as n (%) unless otherwise stated.</p><p>HCAP, healthcare-associated pneumonia; CAP, community acquired pneumonia; TB, tuberculosis; SD, standard deviation; COPD, chronic obstructive pulmonary disease; PSI, pneumonia severity index; CURB65, confusion, urea, respiratory rate, blood pressure, age 65.</p

Immune profiles and clinical outcomes between sepsis patients with or without active cancer requiring admission to intensive care units

<div><p>Background</p><p>Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis. It would be interesting to see if immune status was different in severe sepsis patients with or without active cancer. The aim of this study was to assess the differences in immune profiles, and clinical outcomes between severe sepsis patients with or without cancer admitted to ICU.</p><p>Methods</p><p>A combined retrospective and prospective observational study from a cohort of adult sepsis patients admitted to three medical ICUs at Kaohsiung Chang Gung Memorial Hospital in Taiwan between August 2013 and June 2016.</p><p>Results</p><p>Of the 2744 patients admitted to the ICU, 532 patients with sepsis were included. Patients were divided into those with or without active cancer according to their medical history. Of the 532 patients, 95 (17.9%) patients had active cancer, and 437 (82.1%) patients had no active cancer history. Patients with active cancer were younger (p = 0.001) and were less likely to have diabetes mellitus (p < 0.001), hypertension (p < 0.001), coronary artery disease (p = 0.004), chronic obstructive pulmonary disease (p = 0.002) or stroke (p = 0.002) compared to patients without active cancer. Patients with active cancer also exhibited higher baseline lactate levels (p = 0.038), and higher baseline plasma interleukin (IL)-10 levels (p = 0.040), higher trend of granulocyte colony-stimulating factor (G-CSF) (p = 0.004) compared to patients without active cancer. The 14-day, 28-day and 90-day mortality rates were higher for patients with active cancer than those without active cancer (P < 0.001 for all intervals).</p><p>Conclusions</p><p>Among patients admitted to the ICU with sepsis, those with underling active cancer had higher baseline levels of plasma IL-10, higher trend of G-CSF and higher mortality rate than those without active cancer.</p></div

MK591 pre-treatment inhibits 5-LO expression in RAW264.7 cells stimulated by LPS and Lipid A.

<p>(A) RAW264.7 cells were pre-treated for 30 minutes with MK591 or vehicle followed by LPS or Lipid A stimulation for 0.5 hr and 4 hr. Expression of 5-LO were evaluated by immunoblotting of RAW264.7 cell lysates. Actin density was quantified as internal control. Representative immunoblots of 5 independent experiments are presented. (B) Quantitative expression is the mean ± S.E.M. of 5 independent experiments. At 0.5 hr, *p<0.05 and ^†p<0.01 compared to LPS-treated cells, ^‡p<0.05 compared to Lipid A-treated cells; as at 4 hr, ^§p<0.05, ^¶p<0.01 and ^||p<0.001 compared to LPS-treated cells, ^@p<0.01 compared to Lipid A-treated cells.</p

MK591 pre-treatment enhanced ERK activation in RAW264.7 cells stimulated by LPS and Lipid A.

<p>(A) RAW264.7 cells were pre-treated for 30 minutes with MK591 or vehicle followed by LPS or Lipid A stimulation for 0.5 hr or 4 hr. Activation of ERK was evaluated by immunoblotting of RAW264.7 cell lysates. Representative immunoblots of 5 independent experiments are presented. Total ERK was quantified as an internal control. (B) Quantitative data are presented as means ± SEM from 5 independent experiments. *p<0.05 compared to LPS-treated cells and ^†p<0.05 compared to Lipid A-treated cells.</p

ICU mortality in patients with or without active malignancy.

<p>ICU mortality in patients with or without active malignancy.</p