Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010-2019.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

Prognosis of mechanically ventilated patients with COVID-19 after failure of high-flow nasal cannula: a retrospective cohort study.

BACKGROUND: There is an argument whether the delayed intubation aggravate the respiratory failure in Acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). We aimed to investigate the effect of high-flow nasal cannula (HFNC) failure before mechanical ventilation on clinical outcomes in mechanically ventilated patients with COVID-19. METHODS: This retrospective cohort study included mechanically ventilated patients who were diagnosed with COVID-19 and admitted to the intensive care unit (ICU) between February 2020 and December 2021 at Asan Medical Center. The patients were divided into HFNC failure (HFNC-F) and mechanical ventilation (MV) groups according to the use of HFNC before MV. The primary outcome of this study was to compare the worst values of ventilator parameters from day 1 to day 3 after mechanical ventilation between the two groups. RESULTS: Overall, 158 mechanically ventilated patients with COVID-19 were included in this study: 107 patients (67.7%) in the HFNC-F group and 51 (32.3%) in the MV group. The two groups had similar profiles of ventilator parameter from day 1 to day 3 after mechanical ventilation, except of dynamic compliance on day 3 (28.38 mL/cmH2O in MV vs. 30.67 mL/H2O in HFNC-F, p = 0.032). In addition, the HFNC-F group (5.6%) had a lower rate of ECMO at 28 days than the MV group (17.6%), even after adjustment (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11-0.83; p = 0.045). CONCLUSIONS: Among mechanically ventilated COVID-19 patients, HFNC failure before mechanical ventilation was not associated with deterioration of respiratory failure.

The association of arterial partial oxygen pressure with mortality in critically ill sepsis patients: a nationwide observational cohort study.

BACKGROUND: Although several trials were conducted to optimize the oxygenation range in intensive care unit (ICU) patients, no studies have yet reached a universal recommendation on the optimal a partial pressure of oxygen in arterial blood (PaO2) range in patients with sepsis. Our aim was to evaluate whether a relatively high arterial oxygen tension is associated with longer survival in sepsis patients compared with conservative arterial oxygen tension. METHODS: From the Korean Sepsis Alliance nationwide registry, patients treated with liberal PaO2 (PaO2 ≥ 80 mm Hg) were 1:1 matched with those treated with conservative PaO2 (PaO2 < 80 mm Hg) over the first three days after ICU admission according to the propensity score. The primary outcome was 28-day mortality. RESULTS: The median values of PaO2 over the first three ICU days in 1211 liberal and 1211 conservative PaO2 groups were, respectively, 107.2 (92.0-134.0) and 84.4 (71.2-112.0) in day 1110.0 (93.4-132.0) and 80.0 (71.0-100.0) in day 2, and 106.0 (91.9-127.4) and 78.0 (69.0-94.5) in day 3 (all p-values < 0.001). The liberal PaO2 group showed a lower likelihood of death at day 28 (14.9%; hazard ratio [HR], 0.79; 95% confidence interval [CI] 0.65-0.96; p-value = 0.017). ICU (HR, 0.80; 95% CI 0.67-0.96; p-value = 0.019) and hospital mortalities (HR, 0.84; 95% CI 0.73-0.97; p-value = 0.020) were lower in the liberal PaO2 group. On ICU days 2 (p-value = 0.007) and 3 (p-value < 0.001), but not ICU day 1, hyperoxia was associated with better prognosis compared with conservative oxygenation., with the lowest 28-day mortality, especially at PaO2 of around 100 mm Hg. CONCLUSIONS: In critically ill patients with sepsis, higher PaO2 (≥ 80 mm Hg) during the first three ICU days was associated with a lower 28-day mortality compared with conservative PaO2.

Risk Factors for the Mortality of Patients With Coronavirus Disease 2019 Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study.

BACKGROUND: Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. METHODS: We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan-Meier (KM) method. RESULTS: Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010-1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312-7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). CONCLUSION: Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.

Automatic adjustment of oxygen concentration during high-flow nasal cannula treatment using a targeted SpO2 feedback system.

AIM: To test whether targeted SpO2 feedback (TSF), an automatic control system for fraction of inspired oxygen (FiO2), achieves more time in the optimal SpO2 range and/or reduces the frequency of manual adjustments to administered FiO2 compared with conventional manual titration in patients with hypoxia on high-flow nasal cannula (HFNC) therapy. STUDY DESIGN: Twenty-two patients were recruited from two hospitals. For each, two sessions of manual mode and two sessions of TSF were applied in a random order, each session lasting 2 h. The target SpO2 on TSF was 95%. Oxygen monitoring levels were classified into four SpO2 ranges: hypoxia (≤ 89%), borderline (90%-93%), optimal (94%-96%) and hyperoxia (≥ 97%). The two modes were compared based on the proportion of time spent in each SpO2 range and the number of manual FiO2 adjustments. RESULTS: The proportion of time in the optimal SpO2 range was 20.5% under manual titration mode and 65.4% under TSF (p < .01). The proportions of time in the hypoxia range were 1.1% and 0.4%, respectively (p = .31), in the borderline range 4.7% and 3.5%, respectively (p = .54), and in the hyperoxia range 73.7% and 30.7%, respectively (p < .01). There were statistical differences only in the optimal and hyperoxia SpO2 ranges. During the 8 h, the frequency of manual FiO2 adjustment was 0.7 times for the manual mode and 0.2 times for TSF, showing no statistically significant difference (p = 0.076). CONCLUSION: Compared with manual titration, TSF achieved greater time of the optimal SpO2 and less time of hyperoxia during HFNC. The frequency of manual adjustments on TSF tended to be less than on manual titration mode. RELEVANCE TO CLINICAL PRACTICE: Automatic closed-loop algorithm FiO2 monitoring systems can achieve better oxygen treatments than conventional monitoring and may reduce nurse workloads. In the era of pandemic respiratory diseases, this system can also facilitate contactless SpO2 monitoring during HFNC therapy.

Role of extracorporeal membrane oxygenation as a salvage therapy for liver transplantation recipients in a high-volume transplant center.

Extracorporeal membrane oxygenation (ECMO) has been used sporadically in adult orthotopic liver transplantation (OLT) recipients for the treatment of acute cardiopulmonary failure. This retrospective study aimed to identify OLT patients who would benefit from ECMO support. We reviewed 109 OLT patients who received ECMO support for more than 24 h from January 2007 to December 2020. Among the enrolled patients, 15 (13.8%) experienced 18 ECMO-related complications and 12 (11.0%) experienced ECMO reapplication after weaning during the same hospitalization period. The successful weaning rates were 50.98% in patients who received ECMO support during the peritransplantation period (0-30 days from transplantation) and 51.72% in patients who received ECMO support in the post-OLT period (more than 30 days after OLT); 24 (47.1%) and 23 (39.7%) patients survived until hospital discharge, respectively. The 109 enrolled OLT recipients who received ECMO support during the perioperative period had a 1-year survival rate of 42.6%. Multivariate analyses identified the following as significant and independent risk factors for in-hospital mortality: ECMO treatment prior to 2011 ( p = 0.04), septic shock as the indication for ECMO treatment ( p = 0.001), and a total bilirubin level of ≥5.0 mg/dl ( p = 0.02). The outcomes of adult OLT recipients with ECMO treatment were acceptable in terms of weaning success and survival until hospital discharge. This study confirmed that ECMO treatment for OLT recipients with septic shock and elevated bilirubin levels might be associated with a higher in-hospital mortality and demonstrated the importance of a multidisciplinary ECMO team approach.

Clinical impact of pre-existing acute exacerbation in patients with interstitial lung disease who underwent lung transplantation.

BACKGROUND: Acute exacerbation of interstitial lung disease (AE-ILD) significantly impacts prognosis, leading to high mortality rates. Although lung transplantation is a life-saving treatment for selected patients with ILD, its outcomes in those presenting with AE-ILD have yielded conflicting results compared with those with stable ILD. This study aims to investigate the impact of pre-existing AE on the prognosis of ILD patients who underwent lung transplantation. METHOD: We conducted a single-center retrospective study by reviewing the medical records of 108 patients who underwent lung transplantation for predisposing ILD at Asan Medical Center, Seoul, South Korea, between 2008 and 2022. The primary objective was to compare the survival of patients with AE-ILD at the time of transplantation with those without AE-ILD. RESULTS: Among the 108 patients, 52 (48.1%) experienced AE-ILD at the time of lung transplantation, and 81 (75.0%) required pre-transplant mechanical ventilation. Although the type of ILD (IPF vs. non-IPF ILD) did not affect clinical outcomes after transplantation, AE-ILD was associated with worse survival outcomes. The survival probabilities at 90 days, 1 year, and 3 years post-transplant for patients with AE-ILD were 86.5%, 73.1%, and 60.1%, respectively, while those for patients without AE-ILD were higher, at 92.9%, 83.9%, and 79.6% (p = 0.032). In the multivariable analysis, pre-existing AE was an independent prognostic factor for mortality in ILD patients who underwent lung transplantation. CONCLUSIONS: Although lung transplantation remains an effective treatment option for ILD patients with pre-existing AE, careful consideration is needed, especially in patients requiring pre-transplant mechanical respiratory support.

False positive Aspergillus galactomannan assay results caused by specific parenteral nutrition.

In September 2022, the proportion of clinically false positive results with high index values for the galactomannan (GM) assay increased dramatically in our hospital and remained high until November 2022. We aimed to identify the possible causative agent that led to the dramatic increase in false positivity in GM assay. A case-control-control study was conducted, and patients admitted to two intensive care units between September and November 2022 were included. We defined each time point at which the GM assay was conducted in a patient as an episode and classified episodes into strong-positive (≥10.0 index; case), positive (control), and negative (<0.5 index; control) groups. We compared the medications administered in three groups and measured GM levels in relevant medications, including parenteral nutrition (PN). In total, 118 episodes in 33 patients were classified into three groups. There were 46 negative, 23 positive, and 49 strong-positive episodes, and there was a significant difference in the use of Winuf® PNs (P < .001) between the three groups. Forty episodes (82%) in the strong-positive group received Winuf®, compared with three (6.5%) in the negative group and one (4.3%) in the positive group (P < .001). All samples of Winuf® PNs used in the five patients whose GM results were repeatedly strong-positive were strongly positive for GM. False positivity in GM assay can be caused by the administration of specific PNs. A thorough investigation of prescribed medications should be considered when there is an abrupt increase in the proportion of strong-positive or positive GM results.

A targeted metabolomics approach for sepsis-induced ARDS and its subphenotypes.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is etiologically and clinically a heterogeneous disease. Its diagnostic characteristics and subtype classification, and the application of these features to treatment, have been of considerable interest. Metabolomics is becoming important for identifying ARDS biology and distinguishing its subtypes. This study aimed to identify metabolites that could distinguish sepsis-induced ARDS patients from non-ARDS controls, using a targeted metabolomics approach, and to identify whether sepsis-induced direct and sepsis-induced indirect ARDS are metabolically distinct groups, and if so, confirm their metabolites and associated pathways. METHODS: This study retrospectively analyzed 54 samples of ARDS patients from a sepsis registry that was prospectively collected from March 2011 to February 2018, along with 30 non-ARDS controls. The cohort was divided into direct and indirect ARDS. Metabolite concentrations of five analyte classes (energy metabolism, free fatty acids, amino acids, phospholipids, sphingolipids) were measured using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry by targeted metabolomics. RESULTS: In total, 186 metabolites were detected. Among them, 102 metabolites could differentiate sepsis-induced ARDS patients from the non-ARDS controls, while 14 metabolites could discriminate sepsis-induced ARDS subphenotypes. Using partial least-squares discriminant analysis, we showed that sepsis-induced ARDS patients were metabolically distinct from the non-ARDS controls. The main distinguishing metabolites were lysophosphatidylethanolamine (lysoPE) plasmalogen, PE plasmalogens, and phosphatidylcholines (PCs). Sepsis-induced direct and indirect ARDS were also metabolically distinct subgroups, with differences in lysoPCs. Glycerophospholipid and sphingolipid metabolism were the most significant metabolic pathways involved in sepsis-induced ARDS biology and in sepsis-induced direct/indirect ARDS, respectively. CONCLUSION: Our study demonstrated a marked difference in metabolic patterns between sepsis-induced ARDS patients and non-ARDS controls, and between sepsis-induced direct and indirect ARDS subpheonotypes. The identified metabolites and pathways can provide clues relevant to the diagnosis and treatment of individuals with ARDS.

Contributed Session II: Immune cell speed changes over 5 orders of magnitude in response to inflammation in the retina.

Inflammation in vascularized tissues is mediated by circulating immune cells that are recruited to damaged tissue. Immune cells undergo dramatic changes in speed and motility indicating the severity and staging of inflammation. Here, we characterize the spectrum of retinal leukocyte kinetics in response to an acute inflammatory stimulus using adaptive optics scanning light ophthalmoscopy (AOSLO) in living mice. C57BL/6J male mice were injected intravitreally with 1 µL lipopolysaccharide (LPS) and imaged at 6, 24 and 72 hours after LPS injection using phase contrast and fluorescence AOSLO. Speed of circulating leukocytes (n= 286 cells, 2 mice) was measured with 15kHz point-scan imaging using automated approach (Joseph et al. 2019). Rolling leukocytes (n=300 cells, 5 mice, 6 hrs after LPS) and extravasated cells (n=92 cells, 8 mice) were visualized with time-lapse imaging and manually tracked using ImageJ. Using our custom AOSLO, we observed leukocyte speeds spanning 5 orders of magnitude in the living retina. The fastest speeds were the circulating leukocytes (13,257.37 ± 7,086.41 µm/s). After LPS, leukocytes roll along the venular wall, where cell speed was 1000x slower (11.45 ± 7.45 µm/s.) When immune cells extravasated into the tissue, cell speed dropped further by 100x (0.3 ± 0.15 µm/s). Observed leukocyte speeds cluster around three distinct velocity bands that stratify the unique and purposeful behavior of these cells as they progress through the inflammatory cascade.

Pseudomonas aeruginosa-Derived DnaJ Induces the Expression of IL-1ß by Engaging the Interplay of p38 and ERK Signaling Pathways in Macrophages.

As members of pathogen-associated molecular patterns, bacterial heat shock proteins (HSPs) are widely recognized for their role in initiating innate immune responses. This study aimed to examine the impact of DnaJ, a homolog of HSP40 derived from Pseudomonas aeruginosa (P. aeruginosa), on the regulation of IL-1ß expression in macrophages. We demonstrated that DnaJ modulates macrophages to secrete IL-1ß by activating NF-κB and MAPK signaling pathways. Specifically, ERK was identified as a positive mediator for IL-1ß expression, while p38 acted as a negative mediator. These results suggest that the reciprocal actions of these two crucial MAPKs play a vital role in controlling IL-1ß expression. Additionally, the reciprocal actions of MAPKs were found to regulate the activation of inflammasome-related molecules, including vimentin, NLRP3, caspase-1, and GSDMD. Furthermore, our investigation explored the involvement of CD91/CD40 in ERK signaling-mediated IL-1ß production from DnaJ-treated macrophages. These findings emphasize the importance of understanding the signaling mechanisms underlying IL-1ß induction and suggest the potential utility of DnaJ as an adjuvant for stimulating inflammasome activation.

Severe Pneumonia Caused by Corynebacterium striatum in Adults, Seoul, South Korea, 2014-2019.

We investigated the proportion and characteristics of severe Corynebacterium striatum pneumonia in South Korea during 2014-2019. As part of an ongoing observational study of severe pneumonia among adult patients, we identified 27 severe C. striatum pneumonia cases. Most (70.4%) cases were hospital-acquired, and 51.9% of patients were immunocompromised. C. striatum cases among patients with severe hospital-acquired pneumonia (HAP) increased from 1.0% (2/200) during 2014-2015 to 5.4% (10/185) during 2018-2019, but methicillin-resistant Staphylococcus aureus (MRSA) infections among severe HAP cases decreased from 12.0% to 2.7% during the same timeframe. During 2018-2019, C. striatum was responsible for 13.3% of severe HAP cases from which bacterial pathogens were identified. The 90-day mortality rates were similarly high in the C. striatum and MRSA groups. C. striatum was a major cause of severe HAP and had high mortality rates. This pathogen is emerging as a possible cause for severe pneumonia, especially among immunocompromised patients.

DnaJ-induced TLR7 mediates an increase in interferons through the TLR4-engaged AKT/NF-κB and JNK signaling pathways in macrophages.

Toll-like receptor 7 (TLR7) signaling plays pivotal roles in innate immunity by sensing viral single-stranded RNA thereby triggering inflammatory signaling cascades and eliciting protective antiviral responses. In this study, we found that TLR7 expression is highly induced in response to Pseudomonas aeruginosa (P. aeruginosa) infection in a dose- and time-dependent manner. P. aeruginosa-derived DnaJ, a homolog of HSP40, was identified as a related inducing agent for TLR7 expression, and expression of DnaJ was stimulated when host cells were infected with P. aeruginosa. Interestingly, DnaJ was not involved in mediating an increase in the expression levels of TLR3 and TLR8, other well-known antiviral receptors. The induction of TLR7 in response to DnaJ was mediated by the activation of the AKT (Thr308 and Ser473)/NF-κB and p38/JNK MAPKs signaling pathways, consequently transmitting related signals for the expression of interferons (IFNs). Of note, these antiviral responses were regulated, at least in part, by TLR4, which senses the presence of DnaJ and then promotes downstream activation of the AKT (Ser473)/NF-κB and JNK signaling cascades. Taken together, these results suggest that P. aeruginosa-derived DnaJ is sufficient to promote an increase in TLR7 expression in the TLR4-engaged AKT/NF-κB and JNK signaling pathways, thereby promoting an increased antiviral response through the elevated expression of IFNs.

Mortality of patients with hospital-onset sepsis in hospitals with all-day and non-all-day rapid response teams: a prospective nationwide multicenter cohort study.

BACKGROUND: Hospital-onset sepsis is associated with a higher in-hospital mortality rate than community-onset sepsis. Many hospitals have implemented rapid response teams (RRTs) for early detection and timely management of at-risk hospitalized patients. However, the effectiveness of an all-day RRT over a non-all-day RRT in reducing the risk of in-hospital mortality in patient with hospital-onset sepsis is unclear. We aimed to determine the effect of the RRT's operating hours on in-hospital mortality in inpatient patients with sepsis. METHODS: We conducted a nationwide cohort study of adult patients with hospital-onset sepsis prospectively collected from the Korean Sepsis Alliance (KSA) Database from 16 tertiary referral or university-affiliated hospitals in South Korea between September of 2019 and February of 2020. RRT was implemented in 11 hospitals, of which 5 (45.5%) operated 24-h RRT (all-day RRT) and the remaining 6 (54.5%) had part-day RRT (non-all-day RRT). The primary outcome was in-hospital mortality between the two groups. RESULTS: Of the 405 patients with hospital-onset sepsis, 206 (50.9%) were admitted to hospitals operating all-day RRT, whereas 199 (49.1%) were hospitalized in hospitals with non-all-day RRT. A total of 73 of the 206 patients in the all-day group (35.4%) and 85 of the 199 patients in the non-all-day group (42.7%) died in the hospital (P = 0.133). After adjustments for co-variables, the implementation of all-day RRT was associated with a significant reduction in in-hospital mortality (adjusted odds ratio 0.57; 95% confidence interval 0.35-0.93; P = 0.024). CONCLUSIONS: In comparison with non-all-day RRTs, the availability of all-day RRTs was associated with reduced in-hospital mortality among patients with hospital-onset sepsis.

Factors and Outcomes of Intensive Care Unit Readmission in Elderly Patients.

INTRODUCTION: An increase in age has been observed among patients admitted to the intensive care unit (ICU). Age is a well-known risk factor for ICU readmission and mortality. However, clinical characteristics and risk factors of ICU readmission of elderly patients (≥65 years) have not been studied. METHODS: This retrospective single-center cohort study was conducted in a total of 122-bed ICU of a tertiary care hospital in Seoul, Korea. A total of 85,413 patients were enrolled in this hospital between January 1, 2007, and December 31, 2017. The odds ratio of readmission and in-hospital mortality was calculated by logistic regression analysis. RESULTS: Totally, 29,503 patients were included in the study group, of which 2,711 (9.2%) had ICU readmissions. Of the 2,711 readmitted patients, 472 patients were readmitted more than once (readmitted 2 or more times to the ICU, 17.4%). In the readmitted patient group, there were more males, higher sequential organ failure assessment (SOFA) scores, and hospitalized for medical reasons. Length of stay (LOS) in ICU and in-hospital were longer, and 28-day and in-hospital mortality was higher in readmitted patients than in nonreadmitted patients. Risk factors of ICU readmission included the ICU admission due to medical reason, SOFA score, presence of chronic heart disease, diabetes mellitus, chronic kidney disease, transplantation, use of mechanical ventilation, and initial ICU LOS. ICU readmission and age (over 85 years) were independent predictors of in-hospital mortality on multivariable analysis. The delayed ICU readmission group (>72 h) had higher in-hospital mortality than the early readmission group (≤72 h) (20.6 vs. 16.2%, p = 0.005). CONCLUSIONS: ICU readmissions occurred in 9.2% of elderly patients and were associated with poor prognosis and higher mortality.

Prognostic implication of bronchoalveolar lavage fluid analysis in patients with Pneumocystis jirovecii pneumonia without human immunodeficiency virus infection.

BACKGROUND: The prognostic value of bronchoalveolar lavage (BAL) fluid analysis in non-human immunodeficiency virus (HIV)-infected patients with Pneumocystis jirovecii pneumonia (PJP) has not been well elucidated. We aimed to investigate the prognostic implication of BAL fluid analysis in non-HIV patients with PJP. METHODS: The data of 178 non-HIV patients diagnosed with PJP based on the results of the polymerase chain reaction assay of BAL fluid specimens between April 2018 and December 2020 were retrospectively reviewed. The clinical characteristics, laboratory findings, and BAL fluid analysis results of patients who died within 90 days after hospital admission were compared. RESULTS: Twenty patients (11.2%) died within 90 days from admission. The neutrophil count in BAL fluid was significantly higher (median 22.0%, interquartile range [IQR] 2.0-46.0% vs. median 6.0%, IQR 2.0-18.0%, P = 0.044), while the lymphocyte count was significantly lower (median 24.0%, IQR 7.0-37.0% vs. median 41.0%, IQR 22.5-60.5%, P = 0.001) in the non-survivor group compared with that in the survivor group. In the multivariate analysis, the C-reactive protein level (odds ratio [OR] 1.093, 95% confidence interval [CI] 1.020-1.170, P = 0.011) and a BAL fluid lymphocyte count of ≤ 30% (OR 3.353, 95% CI 1.101-10.216, P = 0.033) were independently associated with mortality after adjusting for albumin and lactate dehydrogenase levels. CONCLUSION: A low lymphocyte count in BAL fluid may be a predictor of mortality in non-HIV patients with PJP.

Severe Human Bocavirus-Associated Pneumonia in Adults at a Referral Hospital, Seoul, South Korea.

We report a case series of severe human bocavirus-associated pneumonia in adults in Seoul, South Korea. The virus accounted for 0.5% of all severe pneumonia cases. Structural lung disease and hematologic malignancy were common underlying diseases. Overall death rate was 54.5%. Higher death rates were associated with co-infection (83.3%) and immunocompromise (80.0%).

Attributable mortality of acute respiratory distress syndrome: a systematic review, meta-analysis and survival analysis using targeted minimum loss-based estimation.

BACKGROUND: Although acute respiratory distress syndrome (ARDS) is associated with high mortality, its direct causal link with death is unclear. Clarifying this link is important to justify costly research on prevention of ARDS. OBJECTIVE: To estimate the attributable mortality, if any, of ARDS. DESIGN: First, we performed a systematic review and meta-analysis of observational studies reporting mortality of critically ill patients with and without ARDS matched for underlying risk factor. Next, we conducted a survival analysis of prospectively collected patient-level data from subjects enrolled in three intensive care unit (ICU) cohorts to estimate the attributable mortality of critically ill septic patients with and without ARDS using a novel causal inference method. RESULTS: In the meta-analysis, 44 studies (47 cohorts) involving 56 081 critically ill patients were included. Mortality was higher in patients with versus without ARDS (risk ratio 2.48, 95% CI 1.86 to 3.30; p<0.001) with a numerically stronger association between ARDS and mortality in trauma than sepsis. In the survival analysis of three ICU cohorts enrolling 1203 critically ill patients, 658 septic patients were included. After controlling for confounders, ARDS was found to increase the mortality rate by 15% (95% CI 3% to 26%; p=0.015). Significant increases in mortality were seen for severe (23%, 95% CI 3% to 44%; p=0.028) and moderate (16%, 95% CI 2% to 31%; p=0.031), but not for mild ARDS. CONCLUSIONS: ARDS has a direct causal link with mortality. Our findings provide information about the extent to which continued funding of ARDS prevention trials has potential to impart survival benefit. PROSPERO REGISTRATION NUMBER: CRD42017078313.

Usefulness of ICU criteria for diagnosis of invasive pulmonary aspergillosis in nonhematologic critically ill patients.

Invasive pulmonary aspergillosis (IPA) is a life-threatening disease in the intensive care unit (ICU). The ICU criteria were proposed to diagnose IPA in critically ill patients. This study aims to evaluate the usefulness of ICU criteria for diagnosis and treatment of IPA in nonhematologic patients in the ICU. We retrospectively reviewed 103 ICU patients with positive galactomannan test in blood and respiratory tract from January 1, 2016, to May 31, 2017. We excluded patients with hematologic malignancy. We divided the treatment and non-treatment groups according to the IPA treatment. We compared the baseline characteristics and outcomes between two groups and the agreement with ICU criteria. There were 49 patients in treatment groups and 54 patients in non-treatment groups. There were more cases of solid organ transplantation (P = .003), immunosuppressive therapy (P < .001) and bacterial viral coinfection (P = .048) in the treatment group compared to nontreatment group. There was no statistically significant difference in mortality, the use of ventilator, and septic shock between the two groups. The agreement rate between the putative group and treatment was low (59.2%). There was no statistically significant difference in outcome between the putative and colonization groups according to the ICU criteria in each group. The treatment of IPA based on the symptom, radiologic finding and galactomannan test did not showed the better outcome. Also, the treatment based on the ICU criteria didn't show the difference of outcome. The new criteria for diagnosis of IPA in critically ill patients are needed.

Prognosis of Acute Respiratory Distress Syndrome in Patients With Hematological Malignancies.

INTRODUCTION: The intensive care unit (ICU) admission of patients with hematologic malignancies is gradually increasing. Life-threatening events are common, and acute respiratory distress syndrome (ARDS) is one of the most critical conditions. The aim of this study was to investigate the clinical characteristics and outcomes of ARDS in patients with hematological malignancies admitted to the ICU. METHODS: A retrospective study was performed on all patients with ARDS with hematological malignancies in a single tertiary teaching hospital between 2008 and 2015. Data on the treatment of and the outcomes of ARDS were collected to determine the clinical characteristics associated with ICU mortality. RESULTS: During the 8-year study period, among a total of 821 patients with ARDS admitted to the ICU, all 185 patients with hematological malignancies were included in the analysis. Most of the patients (88.1%) had moderate-to-severe ARDS, and the median PaO2/FiO2 ratio was 122 (interquartile range: 88-157). The overall ICU mortality rate was 57.3% (50.0% for mild, 52.0% for moderate, and 67.7% for severe ARDS). After the univariate and the multivariate logistic regressions, the factors independently associated with a higher ICU mortality were severe ARDS (odds ratio [OR]: 2.47; 95% confidence interval [CI]: 1.17-5.25), identification of carbapenem-resistant gram-negative bacteria (OR: 6.61; 95% CI: 1.31-33.41), the amount of blood product transfusion (OR: 1.25; 95% CI: 1.13-1.38), and the progressive or refractory disease (OR: 3.01; 95% CI: 1.31-6.91). Mortality was independently lower in patients who received the initial low tidal volume ventilation (OR: 0.37, 95% CI: 0.14-0.96). CONCLUSION: The outcome of ARDS in patients with hematological malignancies is associated with the severity of the underlying diseases, the presence of multidrug-resistance pathogens, and the amount of transfusion; however, strict application of low tidal volume ventilation may improve the outcome of these patients at the time of diagnosis.