Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.

Lung fluid content during 6MWT in patients with COPD with and without comorbid heart failure.

BACKGROUND: Impact of lung fluid content changing during exercise has not been investigated in chronic obstructive pulmonary disease (COPD). Using a novel point-of-care measurement system (remote dielectric sensing (ReDS) system), we aimed to investigate changes in lung fluid content before and after 6-minute walk test (6MWT); especially, differences between patients with and without comorbid heart failure (HF) were evaluated. METHODS: From June 2021 to July 2022, patients with COPD referred for 6MWT were prospectively enrolled. Measurements of lung fluid content by ReDS were conducted before and after 6MWT. Data on demographics, exacerbation history, spirometry and 6MWT were collected. Patients were also assessed for comorbid HF by cardiovascular evaluation. The main variables of interest were pre-6MWT ReDS, post-6MWT ReDS and post-pre ∆ReDS. RESULTS: In total, 133 patients with COPD were included. Comparisons between patients with COPD with and without HF indicated similar pre-6MWT ReDS (26.9%±5.9% vs 26.5%±4.7%; p=0.751), but a significant difference in post-6MWT ReDS (29.7%±6.3% vs 25.7%±5.3%; p=0.002). Patients with COPD without HF exhibited a significant decrease in post-6MWT ReDS (from 26.5% to 25.7%; paired t-test p=0.001); conversely, those with HF displayed a remarkable increase in post-6MWT ReDS (from 26.9% to 29.7%; paired t-test p<0.001). Receiver operating characteristic curve analysis showed an area under the curve of 0.82 (95% CI 0.71 to 0.93) for post-pre ∆ReDS in differentiating between patients with COPD with and without HF. CONCLUSIONS: Dynamic changes in lung fluid content prior to and following 6MWT significantly differed between patients with COPD with and without HF. Measurements of lung fluid content by ReDS during exercise testing may be of merit to identify patients with COPD with unrecognised HF.

Using cryoprobes of different sizes combined with cone-beam computed tomography-derived augmented fluoroscopy and endobronchial ultrasound to diagnose peripheral pulmonary lesions: a propensity-matched study.

BACKGROUND: Endobronchial ultrasound (EBUS) and cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) are utilized for the diagnosis of peripheral pulmonary lesions (PPLs). Combining them with transbronchial cryobiopsy (TBC) can provide sufficient tissue for genetic analysis. However, cryoprobes of different sizes have varying degrees of flexibility, which can affect their ability to access the target bronchus and potentially impact the accuracy. The aim of this study was to compare the diagnostic efficacy of cryoprobes of varying sizes in CBCT-AF and EBUS for the diagnosis of PPLs. METHODS: Patients who underwent endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) and TBC combined with CBCT-AF for PPLs diagnosis between January 2021 and May 2022 were included. Propensity score matching and competing-risks regression were utilized for data analysis. Primary outcome was the diagnostic accuracy of TBC. RESULTS: A total of 284 patients underwent TBC, with 172 using a 1.7-mm cryoprobe (1.7 group) and 112 using a 1.1-mm cryoprobe (1.1 group). Finally, we included 99 paired patients following propensity score matching. The diagnostic accuracy of TBC was higher in the 1.1 group (80.8% vs. 69.7%, P = 0.050), with a similar rate of complications. Subgroup analysis also revealed that the 1.1 group had better accuracy when PPLs were located in the upper lobe (85.2% vs. 66.1%, P = 0.020), when PPLs were smaller than 20 mm (78.8% vs. 48.8%, P = 0.008), and when intra-procedural CBCT was needed to be used (79.5% vs. 42.3%, P = 0.001). TBC obtained larger specimens than TBB in both groups. There is still a trend of larger sample size obtained in the 1.7 group, but there is no statistically different between our two study groups (40.8 mm2 vs. 22.0 mm2, P = 0.283). CONCLUSIONS: The combination of TBC with CBCT-AF and EBUS is effective in diagnosing PPLs, and a thin cryoprobe is preferred when the PPLs located in difficult areas.

Prognostic Value of Pace Variability, a Novel 6MWT-Derived Feature, in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The 6-minute walk test (6MWT) is often used to evaluate chronic obstructive pulmonary disease (COPD) patients' functional capacity, with 6-minute walk distance (6MWD) and related measures being linked to mortality and hospitalizations. This study investigates the prognostic value of pace variability, a significant indicator in sports medicine, during the 6MWT for COPD patients. Patients and Methods: We retrospectively screened consecutive COPD patients who had been prospectively enrolled in a pay-for-performance program from January 2019 to May 2020 to determine their eligibility. Patient characteristics, including demographics, exacerbation history, and 6MWT data, were analyzed to investigate their potential associations with prognosis. The primary outcome was a composite of adverse events, including overall mortality or hospitalizations due to exacerbations during a 1-year follow-up period. To analyze the 6MWT data, we divided it into three 2-minute epochs and calculated the average walk speed for each epoch. We defined pace variability as the difference between the maximum and minimum average speed in a single 2-minute epoch, divided by the average speed for the entire 6-minute walk test. Results: A total of 163 patients with COPD were included in the study, and 19 of them (12%) experienced the composite adverse outcome. Multivariable logistic regression analyses revealed that two predictors were independently associated with the composite outcome: % predicted 6MWD <72 (adjusted odds ratio [aOR] 7.080; 95% confidence interval [CI] 1.481-33.847) and pace variability ≥0.39 (aOR 9.444; 95% CI 2.689-33.170). Patients with either of these adverse prognostic features had significantly worse composite outcome-free survival, with both log-rank P values less than 0.005. Notably, COPD patients with both adverse features experienced an especially poor outcome after 1 year. Conclusion: Patients with COPD who exhibited greater pace variability during the 6MWT had a significantly higher risk of overall mortality and COPD-related hospitalizations, indicating a worse prognosis.

"Reverse" curtain sign for diagnosis of pneumothorax.

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Impact of ventilator settings during venovenous extracorporeal membrane oxygenation on clinical outcomes in influenza-associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

Background: Patients with influenza-associated acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (vv-ECMO) support have a high mortality rate. Ventilator settings have been known to have a substantial impact on outcomes. However, the optimal settings of mechanical ventilation during vv-ECMO are still unknown. Methods: This multicenter retrospective cohort study was conducted in the intensive care units (ICUs) of three tertiary referral hospitals in Taiwan between July 2009 and December 2019. It aims to describe the effect of ventilator settings during vv-ECMO on patient outcomes. Results: A total of 93 patients with influenza receiving ECMO were screened. Patients were excluded if they: were receiving venoarterial ECMO, died within three days of vv-ECMO initiation, or were transferred to the tertiary referral hospital >24 hours after vv-ECMO initiation. A total of 62 patients were included in the study, and 24 (39%) died within six months. During the first three days of ECMO, there were no differences in tidal volume (5.1 vs. 5.2 mL/kg, p = 0.833), dynamic driving pressure (15 vs. 14 cmH2O, p = 0.146), and mechanical power (11.3 vs. 11.8 J/min, p = 0.352) between survivors and non-survivors. However, respiratory rates were significantly higher in non-survivors compared with survivors (15 vs. 12 breaths/min, p = 0.013). After adjustment for important confounders, a higher mean respiratory rate of >12 breaths/min was still associated with higher mortality (adjusted hazard ratio = 3.31, 95% confidence interval = 1.10-9.97, p = 0.034). Conclusions: In patients with influenza-associated ARDS receiving vv-ECMO support, we found that a higher respiratory rate was associated with higher mortality. Respiratory rate might be a modifiable factor to improve outcomes in this patient population.

Prognostic value of computed tomographic findings in acute respiratory distress syndrome and the response to prone positioning.

BACKGROUND: Prone positioning enables the redistribution of lung weight, leading to the improvement of gas exchange and respiratory mechanics. We aimed to evaluate whether the initial findings of acute respiratory distress syndrome (ARDS) on computed tomography (CT) are associated with the subsequent response to prone positioning in terms of oxygenation and 60-day mortality. METHODS: We retrospectively included patients who underwent prone positioning for moderate to severe ARDS from October 2014 to November 2020 at a medical center in Taiwan. A semiquantitative CT rating scale was used to quantify the extent of consolidation and ground-glass opacification (GGO) in the sternal, central and vertebral regions at three levels (apex, hilum and base) of the lungs. A prone responder was identified by a 20% increase in the ratio of arterial oxygen pressure (PaO2) to the fraction of oxygen (FiO2) or a 20 mmHg increase in PaO2. RESULTS: Ninety-six patients were included, of whom 68 (70.8%) were responders. Compared with nonresponders, responders had a significantly greater median dorsal-ventral difference in CT-consolidation scores (10 vs. 7, p = 0.046) but not in CT-GGO scores (- 1 vs. - 1, p = 0.974). Although dorsal-ventral differences in neither CT-consolidation scores nor CT-GGO scores were associated with 60-day mortality, high total CT-GGO scores (≥ 15) were an independent factor associated with 60-day mortality (odds ratio = 4.07, 95% confidence interval, 1.39-11.89, p = 0.010). CONCLUSIONS: In patients with moderate to severe ARDS, a greater difference in the extent of consolidation along the dependent-independent axis on CT scan is associated with subsequent prone positioning oxygenation response, but not clinical outcome regarding survival. High total CT-GGO scores were independently associated with 60-day mortality.

Prevalence of Vitamin D Deficiency and Associated Factors in Critically Ill Patients: A Multicenter Observational Study.

Background: Vitamin D deficiency is common in the general population worldwide, and the prevalence and severity of vitamin D deficiency increase in critically ill patients. The prevalence of vitamin D deficiency in a community-based cohort in Northern Taiwan was 22.4%. This multicenter cohort study investigated the prevalence of vitamin D deficiency and associated factors in critically ill patients in Northern Taiwan. Methods: Critically ill patients were enrolled and divided into five groups according to their length of stay at intensive care units (ICUs) during enrolment as follows: group 1, <2 days with expected short ICU stay; group 2, <2 days with expected long ICU stay; group 3, 3-7 days; group 4, 8-14 days; and group 5, 15-28 days. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25(OH)D) level < 20 ng/ml, and severe vitamin D deficiency was defined as a 25(OH)D level < 12 ng/ml. The primary analysis was the prevalence of vitamin D deficiency. The exploratory analyses were serial follow-up vitamin D levels in group 2, associated factors for vitamin D deficiency, and the effect of vitamin D deficiency on clinical outcomes in critically ill patients. Results: The prevalence of vitamin D deficiency was 59% [95% confidence interval (CI) 55-62%], and the prevalence of severe vitamin D deficiency was 18% (95% CI 15-21%). The median vitamin D level for all enrolled critically ill patients was 18.3 (13.7-23.9) ng/ml. In group 2, the median vitamin D levels were <20 ng/ml during the serial follow-up. According to the multivariable analysis, young age, female gender, low albumin level, high parathyroid hormone (PTH) level, and high sequential organ failure assessment (SOFA) score were significantly associated risk factors for vitamin D deficiency. Patients with vitamin D deficiency had longer ventilator use duration and length of ICU stay. However, the 28- and 90-day mortality rate were not associated with vitamin D deficiency. Conclusions: This study demonstrated that the prevalence of vitamin D deficiency is high in critically ill patients. Age, gender, albumin level, PTH level, and SOFA score were significantly associated with vitamin D deficiency in these patients.

Endobronchial ultrasound-guided transbronchial biopsy with or without a guide sheath for peripheral pulmonary malignancy.

Endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) is a common procedure used to diagnose peripheral pulmonary lesions (PPLs). However, existing literature did not conclusively show a difference in the ability of EBUS-TBB with and without a guide sheath (GS) to diagnose PPLs. This multicenter cohort study enrolled patients presenting for EBUS-TBB of PPLs that finally proved to be malignant. The diagnostic yield and complication rate were compared between patients undergoing EBUS-TBB with and without a GS (EBUS-TBB+GS versus EBUS-TBB-GS). A propensity score matching method was used to balance differences of pertinent clinical features between the two groups. The original cohort consisted of 975 patients (556 in EBUS-TBB-GS; 419 in EBUS-TBB+GS). GS guidance was more likely to be used with smaller (40 mm versus 44 mm) and middle or lower lobe (60% versus 35%) lesions. After propensity score matching, 720 (360 in each group) patients were included; the diagnostic yields for PPLs were 79% and 78% for EBUS-TBB-GS and EBUS-TBB+GS groups, respectively (p=0.649). The complication rates (5.8% versus 7.2% for bleeding; 0.6% versus 1.9% for pneumothorax) appeared to be lower in the EBUS-TBB+GS group, but the differences did not reach statistical significance. The procedure time was significantly longer in the EBUS-TBB+GS group than in the EBUS-TBB-GS group (29 min versus 24 min; p<0.001). In conclusion, adding a GS to EBUS-TBB did not improve the diagnostic yield for malignant PPLs. GS guidance was seemingly associated with a lower number of complications after TBB but contributed significantly to a longer procedure time.

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described. METHODS: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. RESULTS: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia. CONCLUSION: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

Monitoring levels of vimentin-positive circulating cancer stem cells and tumor cells in patients with advanced EGFR-mutated non-small cell lung cancer.

OBJECTIVES: Circulating tumor cells (CTCs) are associated with tumor spread, whereas cancer stem cells may be related to drug resistance. However, few studies have analyzed the levels of circulating cancer stem cells (CCSCs) and CTCs in patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Treatment-naïve patients with EGFR-mutated NSCLC who received epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy were recruited prospectively. The cell surface vimentin antibody was used for CTC detection and CD133 antibody for CCSC detection. CCSC and CTC levels were measured as cell count per 4 mL of blood, before treatment, after 2 and 12 weeks of treatment, and at disease progression. Data on clinical characteristics and outcomes were also collected. RESULTS: At diagnosis (n = 29), the median CCSC and CTC levels were 0 (interquartile range, 0-2) and 3 (2-9), respectively. After 12 weeks, the CCSC and CTC levels were lower than those at diagnosis (CCSC: 0 (0-0), p = 0.14; CTC: 1 (0-4), p = 0.048). At disease progression, the median CCSC and CTC levels were 0 (0-1) and 1 (0-2), respectively. Patients with higher CCSC and CTC levels at diagnosis had a numerically shorter progression-free survival. CONCLUSION: In patients with EGFR-mutated NSCLC, CCSC and CTC levels became lower after 12 weeks of EGFR-TKI therapy and remained low at disease progression. High pre-treatment CCSC and CTC levels may be associated with a trend towards poor treatment outcomes.

Dynamic Changes in Prognosis with Elapsed Time on Ventilators among Mechanically Ventilated Patients.

Rationale: Previous outcome studies of mechanical ventilation usually adopted a static timeframe to observe the outcome and reported prognosis from the standpoint of the first ventilator day. However, patients and their families may repeatedly inquire about prognosis over time after the initiation of mechanical ventilation.Objectives: We aimed to describe dynamic changes in prognosis according to the elapsed time on a ventilator among mechanically ventilated patients.Methods: For this cohort study we used the entire population dataset of Taiwan's National Health Insurance database. We enrolled adults who newly received invasive mechanical ventilation for at least two consecutive days between March 1, 2010, and August 31, 2011. For every single ventilator day after the initiation of mechanical ventilation, we estimated the cumulative probabilities of weaning success and death in the subsequent 90 days.Results: A total of 162,200 episodes of respiratory failure requiring invasive mechanical ventilation were included. The median age of the subjects was 72 years (interquartile range 57-81 yr) and the median follow-up time was 250 days (interquartile range 30-463 d). The probability curve of weaning success against the time on ventilation showed a unidirectionally decreasing trend, with a relatively sharp slope in the initial 2 months. The probabilities of weaning success in 90 days after the 2nd, 7th, 21st, and 60th ventilator days were 68.3% (95% confidence interval [CI], 68.1-68.5%), 62.6% (95% CI, 62.2-62.9%), 46.3% (95% CI, 45.8-46.8%), and 21.0% (95% CI, 20.3-21.8%), respectively. In contrast, the death curve showed an initial increase and then a decreasing trend after the 19th ventilator day. We also reported tailored prognosis information according to the age, sex, and ventilator day of a mechanically ventilated patient.Conclusions: This study provides ventilator-day-specific prognosis information obtained from a large cohort of unselected patients on invasive mechanical ventilation. The probability of weaning success decreased with the elapsed time on mechanical ventilation, and the decline was particularly remarkable in the first 2 months of ventilatory support.

Pre-extubation functional residual capacity and risk of extubation failure among patients with hypoxemic respiratory failure.

Hypoxemic respiratory failure is usually accompanied with a certain extent of consolidation and alveolar derecruitment, which may still be present even after the patients have achieved the status of readiness to extubate. Functional residual capacity (FRC) is an indicator of lung aeration. This study aimed to evaluate whether pre-extubation FRC is associated with the risk of extubation failure in patients with hypoxemic respiratory failure. We prospectively included 92 patients intubated for hypoxemic respiratory failure. We used a technique based on a nitrogen multiple breath washout method to measure FRC before the planned extubation. The median FRC before extubation was 25 mL/kg (Interquartile range, 20-32 mL/Kg) per predicted body weight (pBW). After extubation, 20 patients (21.7%) were reintubated within 48 hours. The median FRC was higher in the extubation success group than in the extubation failure group (27 versus 21 mL/Kg, p < 0.001). Reduced FRC was associated with higher risk of extubation failure (odds ratio, 1.14 per each decreased of 1 mL/Kg of FRC/pBW, 95% CI, 1.05-1.23, p = 0.002). In conclusion, pre-extubation FRC is associated with the risk of extubation failure. Reduced FRC may be incorporated into the traditional risk factors to identify patients at high risk for extubation failure.

Diagnostic performance of FDG PET/CT in critically ill patients with suspected infection: A systematic review and meta-analysis.

BACKGROUND/PURPOSE: Nuclear imaging, including gallium scintigraphy and fluorodeoxyglucose (FDG) positron emission tomography (PET), has been widely used to identify focus of infection in fever of unknown origin. However, little is known about its role in critically ill patients, who are usually with multiple inflammatory foci and unable to tolerate long image acquisition time. This systematic review aimed to evaluate the diagnostic performance of FDG PET for suspected infection in critically ill patients. METHODS: PubMed and Embase were searched up to July 24th, 2019 to identify studies evaluating the diagnostic performance of FDG PET for finding infection focus in critically ill patients following the PRISMA guidelines. The bivariate mixed-effects model was used to pool the measure for diagnostic performance. Publication bias was evaluated by Deeks' method. RESULTS: A total of 4 studies with 87 patients were included. All the four studies evaluated FDG PET. Majority of the patients were either mechanically ventilated (76%) or shocked requiring vasopressors (61%). Test and transportation related adverse events were rare (2%). The summary sensitivity and specificity were 0.94 (95% CI, 0.79-0.99) and 0.66 (95% CI, 0.45-0.83), respectively. The AUC for summary ROC curve was 0.83. CONCLUSION: FDG PET was a very sensitive tool with acceptable specificity for detecting the origin of infection in critically ill patients. However, current available studies have limitation in evaluating safety issue. Further research should investigate both benefit and risk of doing this test for this group of vulnerable patients.

Performance of a multiplex PCR pneumonia panel for the identification of respiratory pathogens and the main determinants of resistance from the lower respiratory tract specimens of adult patients in intensive care units.

BACKGROUND: Timely diagnostic investigation to establish the microbial etiology of pneumonia is essential to ensure the administration of effective antibiotic therapy to individual patients. METHODS: We evaluated a multiplex PCR assay panel, the FilmArray® pneumonia panel (FilmArray PP, BioFire Diagnostics), for detection of 35 respiratory pathogens and resistance determinants and compared the performance of the standard-of-care test in intensive care unit patients with lower respiratory tract infections. RESULTS: Among the 59 endotracheal aspirates and bronchoalveolar lavage specimens obtained from 51 adult patients, FilmArray PP was effective in detecting respiratory bacterial pathogens with an overall positive percent agreement of 90% (95% confidence interval [CI], 73.5-97.9%) and negative percent agreement of 97.4% (95% CI, 96.0-98.4%). FilmArray PP semi-quantitative reporting demonstrated a concordance rate of 53.6% for the culture-positive specimens and 86.3% for the culture-negative specimens. FilmArray PP detected 16 viral targets, whereas the conventional viral isolation failed, except influenza A, which showed 100% concordance with PCR. Coinfections were detected in 42.3% of the specimens. Substantial discrepancies were observed in identifying antimicrobial resistance gene targets and in the susceptibility testing. However, FilmArray PP may still be useful at the early stage of pneumonia before culture and susceptibility test reports are available. Consequently, the results of FilmArray PP might alter the antibiotic prescription in 40.7% of the patients. CONCLUSIONS: FilmArray PP offers a rapid and sensitive diagnostic method for lower respiratory tract infections. However, clinical correlation is advised to determine its significance in interpreting multiple pathogens and detection of genes involved in antimicrobial resistance.

Prognostic value of the mitogen response in the interferon-γ release assay in patients with culture-confirmed tuberculosis.

BACKGROUND: _The mitogen response in interferon-γ(IFN-γ) release assays(IGRAs) measures IFN-γ after binding to CD2, a surface adhesion marker found on T-cells and NK cells. A lower mitogen response implies either peripheral blood mononuclear cells have fewer adhesion molecules either in absolute numbers or per T-cells, or the pathway from adhesion molecules to IFN-γ production is not functioning well. To date, it remains poorly understood whether the mitogen response is associated with outcomes in tuberculosis patients. METHODS: _From 2012 to 2017, patients with culture-confirmed tuberculosis were tested for QuantiFERON-TB Gold In-Tube(QFT-GIT). The associations between patient outcomes and QFT-GIT as well as IFN-γ responses to the mitogen were investigated. Outcomes of interest included 1-year mortality after tuberculosis diagnosis and 2-month culture conversion. RESULTS: _In total, 466 culture-confirmed tuberculosis patients were enrolled and QFT-GIT was positive in 309(66%). Within 1 year of diagnosis, 20(4%) died and notably, 15(11%) out of 137 patients with a lower mitogen response did so. The multivariate Cox model showed that a lower mitogen response (hazard ratio, 8.789; 95% confidence interval, 3.074-25.129) was independently associated with 1-year mortality. Moreover, among 160 patients with smear-positive culture-confirmed pulmonary tuberculosis, multivariate logistic analysis indicated that a lower mitogen response (odds ratio, 3.966; 95% confidence interval, 1.182-13.303) was significantly associated with 2-month culture persistence. CONCLUSIONS: _This study found that a lower mitogen response was associated with worse 1-year survival in tuberculosis patients and correlated with 2-month culture persistence in patients with sputum smear-positive culture-confirmed tuberculosis. These findings suggest another application of QFT-GIT for prognostication of tuberculosis patients.

Clinical Trajectories and Causes of Death in Septic Patients with a Low APACHE II Score.

Clinical course and mortality in septic patients with low disease severity remain poorly understood and is worth further investigation. We enrolled septic patients admitted to intensive care units (ICUs) between 2010 and 2014 with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ≤15. We sought to determine their clinical trajectories and causes of death, and to analyze risk factors associated with in-hospital mortality. A total of 352 patients were included, of whom 89 (25%) did not survive to hospital discharge, at a rate higher than predicted (<21%) by the APACHE II score. Approximately one third (31/89) of non-survivors succumbed to index sepsis; however, more patients (34/89) died of subsequent sepsis. New-onset ICU sepsis developed in 99 (28%) patients and was an independent risk factor for mortality. In addition, septic patients with comorbid malignancy or index infection acquired in the hospital settings were more likely to have in-hospital mortality than those without. In conclusion, septic patients with low APACHE II scores were at a higher mortality risk than expected, and subsequent sepsis rather than index sepsis was the primary cause of death. This study provides insight into unexpected clinical trajectories and outcomes of septic patients with low disease severity at ICU admission and highlights the need for more research and clinical attention in this patient population.

Clinical characteristics, treatment outcomes, and prognostic factors of Pneumocystis pneumonia in non-HIV-infected patients.

Objectives: The incidence of Pneumocystis pneumonia (PCP) has been increasing among non-HIV-infected patients. Here, we investigated the clinical characteristics, treatment outcomes, and prognostic factors of PCP in non-HIV-infected patients. Patients and methods: Information on clinical characteristics, treatment outcomes, and prognostic factors of PCP patients who were treated at a medical center in northern Taiwan from October 2015 to October 2016 were retrieved from medical records and evaluated. Results: Among the patients with PCP included in the study, 84 were non-HIV-infected and 25 were HIV-infected. Non-HIV-infected patients with PCP had a longer duration between radiographic findings and treatment (P<0.001), and a higher rate of hospital-associated PCP (P<0.001), hypoxia (P=0.015), respiratory failure (P<0.001), and mortality (P=0.006) than HIV-infected patients with PCP. Among non-HIV-infected patients, non-survivors had a higher fungal burden (46.2% vs 22.2%, P=0.039), higher requirement for adjunctive steroid treatment (94.9% vs 71.1%, P=0.011), and higher rate of pneumothorax (17.9% vs 2.2%, P=0.038) than survivors. Multiple logistic regression revealed that lymphopenia (odds ratio [OR] =3.24, 95% confidence interval [CI] =1.07-9.79; P=0.037), adjunctive steroid use (OR =6.23, 95% CI =1.17-33.14; P=0.032), and pneumothorax (OR =10.68, 95% CI =1.00-113.93; P=0.050) were significantly associated with increased 60-day mortality among non-HIV-infected PCP patients. Conclusion: Lymphopenia, adjunctive steroid therapy, and pneumothorax were significantly associated with higher mortality in non-HIV-infected patients with PCP.