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Abstract Background Pathogenesis of acute respiratory distress syndrome (ARDS) involves immune cell death and removal from the injured lungs. ARDS severity is related to lung compliance. However, the correlation between the respiratory mechanics and alveolar immune cell death in patients with ARDS remains unclear. Methods Twenty-four patients with respiratory failure and ARDS were enrolled in the intensive care unit between November 2019 and November 2021. Neutrophil extracellular traps (NETs) and cell death of lymphocytes and monocytes in bronchoalveolar lavage fluid were detected on days 1 and 8. Results Lung compliance was positively correlated with the cell death percentage of alveolar CD4/CD8 lymphocytes and monocytes on day 8 (Pearson’s correlation coefficient (r) = 0.554, p = 0.005; r = 0.422, p = 0.040; r = 0.569, p = 0.004, respectively). There was no association between lung compliance and the percentage of alveolar NETs on days 1 and 8. The cell death percentages of alveolar CD4/CD8 lymphocytes and monocytes were negatively correlated with driving pressure (DP) on days 1 (r = − 0.440, p = 0.032; r = − 0.613, p = 0.001; r = -0.557, p = 0.005, respectively) and 8 (r = − 0.459, p = 0.024; r = − 0.407, p = 0.048; r = − 0.607, p = 0.002, respectively). The cell death percentages of alveolar CD4/CD8 lymphocytes and monocytes were also negatively correlated with mechanical power (MP) on days 1 (r = − 0.558, p = 0.005; r = − 0.593, p = 0.002; r = − 0.571, p = 0.004, respectively) and 8 (r = − 0.539, p = 0.007; r = − 0.338, p = 0.107; r = − 0.649, p

For patients on ventilation without acute respiratory distress syndrome (ARDS), there are, as yet, limited data on ventilation strategies. We hypothesized that driving pressure (DP) and mechanical power (MP) may play key roles for the late development of ARDS in patients without initial ARDS. A post hoc analysis of a database from our previous cohort was performed. The mean DP/MP was computed from the data before ARDS development or until ventilator support was discontinued within 28 days. The association between DP/MP and late development of ARDS within 28 days was determined. One hundred and twelve patients were enrolled, among whom seven developed ARDS. Univariate Cox regression showed that congestive heart failure (CHF) history and higher levels of mean MP and DP were associated with ARDS development. Multivariate models revealed that the mean MP and mean DP were still factors independently associated with ARDS development at hazard ratios of 1.177 and 1.226 after adjusting for the CHF effect. Areas under the receiver operating characteristic curves for mean DP/MP in predicting ARDS development were 0.813 and 0.759, respectively. In conclusion, high mean DP and MP values may be key factors associated with late ARDS development. The mean DP had a better predicted value for the development of ARDS than the mean MP.

Abstract Background We established 1-h and 1-day survival models after terminal extubation to optimize ventilator use and achieve a balance between critical care for COVID-19 and hospice medicine. Methods Data were obtained from patients with end-of-life status at terminal extubation from 2015 to 2020. The associations between APACHE II scores and parameters with survival time were analyzed. Parameters with a p-value ≤ 0.2 in univariate analysis were included in multivariate models. Cox proportional hazards regression analysis was used for the multivariate analysis of survival time at 1 h and 1 day. Results Of the 140 enrolled patients, 76 (54.3%) died within 1 h and 35 (25%) survived beyond 24 h. No spontaneous breathing trial (SBT) within the past 24 h, minute ventilation (MV) ≥ 12 L/min, and APACHE II score ≥ 25 were associated with shorter survival in the 1 h regression model. Lower MV, SpO2 ≥ 96% and SBT were related to longer survival in the 1-day model. Hospice medications did not influence survival time. Conclusion An APACHE II score of ≥ 25 at 1 h and SpO2 ≥ 96% at 1 day were strong predictors of disposition of patients to intensivists. These factors can help to objectively tailor pathways for post-extubation transition and rapidly allocate intensive care unit resources without sacrificing the quality of palliative care in the era of COVID-19. Trial registration They study was retrospectively registered. IRB No.: 202101929B0.

Sepsis may induce immunosuppression and result in death. S100A12 can bind to the receptor for advanced glycation end-products (RAGE) and Toll-like receptor (TLR)4 following induction of various inflammatory responses. It is unclear whether S100A12 significantly influences the immune system, which may be associated with sepsis-related mortality. We measured plasma S100A12 levels and cytokine responses (mean ± standard error mean) of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) after S100A12 inhibition in healthy controls and patients with sepsis on days one and seven. Day one plasma soluble RAGE (sRAGE) and S100A12 levels in patients with sepsis were significantly higher than those in controls (2481.3 ± 295.0 vs. 1273.0 ± 108.2 pg/mL, p < 0.001; 530.3 ± 18.2 vs. 310.1 ± 28.1 pg/mL, p < 0.001, respectively). Day seven plasma S100A12 levels in non-survivors were significantly higher than those in survivors (593.1 ± 12.7 vs. 499.3 ± 23.8 pg/mL, p = 0.002, respectively). In survivors, plasma sRAGE levels were significantly decreased after 6 days (2297.3 ± 320.3 vs. 1530.1 ± 219.1 pg/mL, p = 0.009, respectively), but not in non-survivors. Inhibiting S100A12 increased the production of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in stimulated PBMCs for both controls and patients. Therefore, S100A12 plays an important role in sepsis pathogenesis. S100A12 may competitively bind to TLR4 and RAGE, resulting in decreased IL-10 and TNF-α production.

Background: Ventilation limitation has a significant adverse effects on cardiovascular function and tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). High flow nasal cannula (HFNC) improve ventilation by washing out the anatomical dead space and providing oxygen at constant concentration. This study aimed to examine the effects of HFNC on the exercise performance and hemodynamic status in COPD patients. Methods: Fifteen patients with COPD performed two constant load exercise tests (CLET) at the 70% of maximum workload achieved at a previous incremental exercise test on arm ergometer. The CLET were performed with HFNC and with nasal cannula (NC) in random order. The hemodynamics parameters of subjects during exercises were measured by a bioelectrical impedance device. The tissue oxygenation status (oxygenated hemoglobin, deoxygenated hemoglobin (hHb), total hemoglobin) was measured by a near infrared spectrophotometer. Results: The exercise duration was longer for HFNC test than NC test (962.9 ± 281.7 s, vs 823.9 ± 184.9 s, p < 0.05). At the end of CLET, the PetCO2 was lower for HFNC than NC (29.3 ± 5.1 mmHg vs 32.1 ± 5.5 mmHg, p 0.05), stroke volume (NC:73.5 ± 21.0 vs HFNC 67.5 ± 16.3 ml, p > 0.05). The changes of hHb in muscle tissues was significantly lower in HFNC test than that in NC test (p

Abstract Pectobacterium carotovorum subsp. carotovorum (Pcc) causes soft-rot disease in a wide variety of plants resulting in economic losses worldwide. It produces various types of bacteriocin to compete against related plant pathogens. Studies on how bacteriocins are extracellularly secreted are conducted to understand the mechanism of interbacterial competition. In this study, the secretion of the low-molecular-weight bacteriocins (LMWB) Carocin S1 and Carocin S3 produced by a multiple-bacteriocin producing strain of Pcc, 89-H-4, was investigated. Tn5 insertional mutagenesis was used to generate a mutant, TH22–6, incapable of LMWBs secretion. Sequence and homology analyses of the gene disrupted by transposon Tn5 insertion revealed that the gene sctT, an essential component of the injectisome type III secretion machinery (T3aSS), is required for the secretion of the bacteriocins. This result raised a question regarding the nature of the secretion mechanism of Pcc bacteriocins which was previously discovered to be secreted via T3bSS, a system that utilizes the bacterial flagellum for extracellular secretions. Our previous report has shown that bacteriocin Carocin S1 cannot be secreted by mutants that are defective of T3bSS-related genes such as flhA, flhC, flhD and fliC. We knocked out several genes making up the significant structural components of both T3aSS and T3bSS. The findings led us to hypothesize the potential roles of the T3aSS-related proteins, SctT, SctU and SctV, as flagellar T3SS chaperones in the secretion of Pcc bacteriocins. This current discovery and the findings of our previous study helped us to conceptualize a unique Type III secretion system for bacteriocin extracellular export which is a hybrid of the injectisome and flagellar secretion systems.

Pectobacterium carotovorum subsp. carotovorum (Pcc) is known to produce different types of bacteriocins, active protein substances that inhibit or kill related strains and are known to be induced by several factors. In this paper, we report the discovery, isolation, characterization, and functional analysis of Carocin S4, a novel low-molecular-weight bacteriocin (LMWB) from Pcc. A 2750 bp gene fragment was isolated from the chromosomal DNA of Pcc mutant strain rif-TO6, a rifampicin-resistant strain of TO6. The gene contains caroS4K and caroS4I within two open reading frames, which encode CaroS4K and CaroS4I, with molecular weights of about 90 kD and 10 kD, respectively. The unique characteristics of Carocin S4 were revealed after homology analysis with the previously discovered bacteriocins from Pcc. CaroS4K, which shares 23% and 85% homology with CaroS1K and CaroS3K, respectively, is also a deoxyribonuclease. However, unlike the two which can only hydrolyze genomic DNA, CaroS4K hydrolyzes both genomic and plasmid DNA. On the other hand, CaroS4K was found to be 90% homologous with CaroS2K but works differently in killing the target cell, as the latter is a ribonuclease. The optimal reaction temperature for CaroS4K to hydrolyze dsDNA is approximately 50 °C and requires the divalent metal ions Mg2+, Ca2+, and Zn2+ to catalyze its DNase activity. This study reveals another nuclease type of bacteriocin in Pcc, with CaroS4K and CaroS4I functioning as killer and immunity proteins, respectively.

Purpose: Recent studies reported that driving pressure has been associated with increased mortality in acute respiratory distress syndrome (ARDS) patients. We aimed to explore the association between 28-day mortality and driving pressure in patients with severe pneumonia without ARDS. Methods: In total, 207 non-ARDS patients with severe pneumonia were enrolled. Serial driving pressures were recorded daily for either 21 days or until ventilator support was no longer required. The relationships between all variables and 28-day mortality were analyzed using binary logistic regression analyses. Results: Non-survivors (56 patients) demonstrated high incidences of shock (55.4% vs. 24.5%, p

Abstract Background Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Methods We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded. Results A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 [95% CI 1.214–4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018–1.104], p = 0.005) or MP referenced to PBW (HR 1.004 [95% CI 1.002–1.007], p 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H2O) (63.6% vs. 29.7%, p

Abstract Background Pectobacterium carotovorum subsp. carotovorum belongs to the Enterobacteriaceae family, which causes soft-rot disease in numerous plants worldwide resulting in significant economic losses. Results from our previous studies showed that the strain H-rif-8-6 produces low-molecular-weight bacteriocin (LMWB) Carocin S1. Interestingly, TH22–10, the caroS1K:Tn5 insertional mutant in H-rif-8-6, loses Carocin S1 producing ability, but still produces other LMWBs which the indicator strain SP33 can detect. The SP33 is one of the many strains that are sensitive toward the cytotoxic effects of Carocin S3K, but not Carocin S1. The result revealed that H-rif-8-6 is a multiple-bacteriocin producing strain. Results In this study, a 4.1-kb DNA fragment was isolated from the chromosomal DNA of Pcc strain, H-rif-8-6, by a DNA probe using the caroS1K gene as the template. DNA sequencing and analysis by GenBank revealed two complete open reading frames (ORFs), designated ORF1 and ORF2, which were identified within the sequence fragment. ORF1 and ORF2, similar to the identified carocin S2 genes, encode the killer (Carocin S3K) and the immunity (Carocin S3I) proteins, respectively, which were homologous to the colicin E3 gene. Carocin S3K and Carocin S3I were expressed, isolated, and purified in Escherichia coli BL21 after subcloning of the expression plasmid pGS3KI or pGSK3I. SDS-PAGE analysis showed that the relative masses of Carocin S3K and Carocin S3I were 95.6 kDa and 10.2 kDa, respectively. The results reveal that Carocin S3K has higher antimicrobial and specific antimicrobial activities for Pcc along with a nuclease activity than Carocin S3I. However, Carocin S3I inhibits the activity of Carocin S3K. Interestingly, a high concentration of Carocin S3I protein is also a DNA nuclease, and Carocin S3K also inhibits its activity. Conclusion This study showed that another type of bacteriocin was found in Pectobacterium carotovorum. This new type of bacteriocin, Carocin S3, has the killer protein, Carocin S3K, and the immunity protein, Carocin S3I.

Driving pressure (ΔP) and mechanical power (MP) are associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). We aimed to investigate which was better to predict mortality between changes in ΔP and MP. We reanalyzed data from a prospective observational cohort study of patients with ARDS in our hospital. Serial ΔP and MP values were calculated. The factors associated with survival were analyzed. Binary logistic regression showed that age (odds ratio (OR), 1.012; 95% confidence interval (CI), 1.003–1.022), Sequential Organ Failure assessment (SOFA) score (OR, 1.144; 95% CI, 1.086–1.206), trauma (OR, 0.172; 95% CI, 0.035–0.838), ΔP (OR, 1.077; 95% CI, 1.044–1.111), change in ΔP (OR, 1.087; 95% CI, 1.054–1.120), and change in MP (OR, 1.018; 95% CI, 1.006–1.029) were independently associated with 30-day mortality. Change in MP, change in ΔP, and SOFA scores were superior to ΔP in terms of the accuracy of predicting 30-day mortality. In conclusion, calculating change in ΔP is easy for respiratory therapists in clinical practice and may be used to predict mortality in patients with ARDS.

ARDS is a potentially lethal syndrome. HLA-DR expression in monocytes reflects their activation and antigen-presenting capacity. However, the correlation between clinical outcomes and HLA-DR expression in alveolar monocytes/macrophages in patients with pneumonia-related ARDS remains unclear. Thus, we determined the trends of HLA-DR and cytokine expressions in alveolar monocytes using repeated measurements to answer this question. Thirty-one pneumonia patients with respiratory failure and ARDS without coronavirus disease 2019 between November 2019 and November 2021 were enrolled in our intensive care unit and three without complete data were excluded. Interleukin (IL)-10, IL-12, and HLA-DR expression in bronchoalveolar lavage (BAL) monocytes were determined on days one and eight. Monocyte HLA-DR expression (mHLA-DR) and CD4 T lymphocytes percentages in BAL cells of survivors increased remarkably after seven days. Monocyte IL-10 expression and monocytes percentages in BAL cells of survivors decreased substantially after seven days. The mHLA-DR was negatively correlated with disease severity scores on day one and eight. In conclusion, serial increases in HLA-DR expression and decreases in IL-10 expression were observed in BAL monocytes of survivors of pneumonia-related ARDS. More studies are needed to confirm this point of view, and then development of a therapeutic agent restoring mHLA-DR and preventing IL-10 production can be considered.

Background and objectives: Acute kidney injury (AKI) is common in critically ill patients, especially those with sepsis. Persistently low human leukocyte antigen (HLA)-DR expression in monocytes reflects the decreased function of antigen-presenting cells, contributing to poor outcomes in sepsis. This study aimed to establish an association between AKI and HLA-DR expression in monocytes of patients with sepsis. Materials and Methods: We detected HLA-DR expression in monocytes and measured plasma levels of S100A12, high-mobility group box 1 (HMGB1), advanced glycation end products (AGE), and soluble receptor for AGE (sRAGE) from septic patients and healthy controls. Results: HLA-DR expression in monocytes was decreased in patients with AKI than in those without AKI (29.8 ± 5.0% vs. 53.1 ± 5.8%, p = 0.005). Compared with AKI patients, the mean monocyte HLA-DR expression in patients with end-stage renal disease was increased without statistical significance. There were no differences in the AGE/sRAGE ratio and plasma levels of S100A12, HMGB1, AGE, and sRAGE between patients with and without AKI. Conclusions: Compared with septic patients without AKI, patients with AKI had significantly lower HLA-DR expression in monocytes. The role of hemodialysis in monocyte HLA-DR expression needs further studies to explore.

Background. Apoptosis is one of the causes of immune depression in sepsis. Pyroptosis also occurs in sepsis. The toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) have been shown to play important roles in apoptosis and pyroptosis. However, it is still unknown whether TLR4 inhibition decreases apoptosis in sepsis. Methods. Stimulated peripheral blood mononuclear cells (PBMCs) with or without lipopolysaccharides (LPS) and high-mobility group box 1 (HMGB1) were cultured with or without TLR4 inhibition using monoclonal antibodies from 20 patients with sepsis. Caspase-3, caspase-8, and caspase-9 activities were measured. The expression of B cell lymphoma 2 (Bcl2) and Bcl2-associated X (Bax) was measured. The cell death of PBMCs was detected using a flow cytofluorimeter. Results. After TLR4 inhibition, Bcl2 to Bax ratio elevated both in LPS and HMGB1-stimulated PBMCs. The activities of caspase-3, caspase-8, and caspase-9 did not change in LPS or HMGB1-stimulated PBMCs. The cell death of LPS and HMGB1-stimulated CD8 lymphocytes and monocytes increased after TLR4 inhibition. The cell death of CD4 lymphocytes was unchanged. Conclusion. The apoptosis did not decrease, while TLR4 was inhibited. After TLR4 inhibition, there was an unknown mechanism to keep cell death in stimulated PBMCs in patients with sepsis.

Background: Disease severity may change in the first week after acute respiratory distress syndrome (ARDS) onset. The aim of this study was to evaluate whether the reclassification of disease severity after 48 h (i.e. day 3) of ARDS onset could help in predicting mortality and determine factors associated with ARDS persistence and mortality. Methods: We performed a secondary analysis of a 3-year prospective, observational cohort study of ARDS in a tertiary care referral center. Disease severity was reclassified after 48 h of enrollment, and cases that still fulfilled the Berlin criteria were regarded as nonresolving ARDS. Results: A total of 1034 ARDS patients were analyzed. Overall hospital mortality was 57.7% (56.7%, 57.5%, and 58.6% for patients with initial mild, moderate, and severe ARDS, respectively, p = 0.189). On day 3 reclassification, the hospital mortality rates were as follows: resolved (42.1%), mild (47.9%), moderate (62.4%), and severe ARDS (76.1%) ( p

Recent studies have reported that mechanical power (MP) is associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). We aimed to investigate the association between 28-day mortality and MP in patients with severe pneumonia. In total, the data of 313 patients with severe pneumonia were used for analysis. Serial MP was calculated daily for either 21 days or until ventilator support was no longer required. Compared with the non-ARDS group, the ARDS group (106 patients) demonstrated lower age, a higher Acute Physiology and Chronic Health Evaluation II score, lower history of diabetes mellitus, elevated incidences of shock and jaundice, higher MP and driving pressure on Day 1, and more deaths within 28 days. Regression analysis revealed that MP was an independent factor associated with 28-day mortality (odds ratio, 1.048; 95% confidence interval, 1.020–1.077). MP was persistently high in non-survivors and low in survivors among the ARDS group, the non-ARDS group, and all patients. These findings indicate that MP is associated with the 28-day mortality in ventilated patients with severe pneumonia, both in the ARDS and non-ARDS groups. MP had a better predicted value for the 28-day mortality than the driving pressure.

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome caused by direct (local damage to lung parenchyma) or indirect lung injury (insults from extrapulmonary sites with acute systemic inflammatory response), the clinical and biological complexity can have a profound effect on clinical outcomes. We performed a retrospective analysis of 152 severe ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Our objective was to assess the differences in clinical characteristics and outcomes of direct and indirect ARDS patients receiving ECMO. Overall hospital mortality was 53.3%. A total of 118 patients were assigned to the direct ARDS group, and 34 patients were assigned to the indirect ARDS group. The 28-, 60-, and 90-day hospital mortality rates were significantly higher among indirect ARDS patients (all p < 0.05). Cox regression models demonstrated that among direct ARDS patients, diabetes mellitus, immunocompromised status, ARDS duration before ECMO, and SOFA score during the first 3 days of ECMO were independently associated with mortality. In indirect ARDS patients, SOFA score and dynamic compliance during the first 3 days of ECMO were independently associated with mortality. Our findings revealed that among patients receiving ECMO, direct and indirect subphenotypes of ARDS have distinct clinical outcomes and different predictors for mortality.

Background: Patients with severe sepsis frequently require intensive care unit (ICU) admission and different ICU care models may influence their outcomes. The mortality of severe septic patients between physician's high and low care volume remains unclear. Methods: We analyzed the data from a three-year prospective observation study, which was performed in an adult medical ICU of Chung Gung Memorial Hospital, Keelung. The data included initial bundle therapies based on the Surviving Sepsis Campaign (SSC) guidelines for patients with severe sepsis. Results: Clinical data of total 484 patients with severe sepsis were recorded. Cox regression model showed that physician's care volume was an independent factor for lowering mortality in ICU patients with severe sepsis (hazard ratio 0.708; 95% confidence interval 0.514–0.974; p = 0.034). Patients treated by high care volume physician had four out of nine bundle therapies that were significantly higher in percentage following the SSC guidelines. These four therapies were renal replacement therapy, administration of low-dose steroids for septic shock, prophylaxis of gastro-intestinal bleeding, and control of hyperglycemia. Conclusion: High care volume physician may decrease mortality in ICU patients with severe sepsis through fitting bundle therapies for sepsis.

The high mortality rate of patients with severe acute respiratory distress syndrome (ARDS) warrants aggressive clinical intervention. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for life-threatening hypoxemia. Randomized controlled trials of ECMO for severe ARDS comprise a number of ethical and methodological issues. Therefore, indications and optimal timing for implementation of ECMO, and predictive risk factors for outcomes have not been adequately investigated. We performed propensity score matching to match ECMO-supported and non-ECMO-supported patients at 48 h after ARDS onset for comparisons based on clinical outcomes and hospital mortality. A total of 280 severe ARDS patients were included, and propensity score matching of 87 matched pairs revealed that the 90-d hospital mortality rate was 56.3% in the ECMO group and 74.7% in the non-ECMO group (p = 0.028). Subgroup analysis revealed that greater severity of ARDS, higher airway pressure, or a higher Sequential Organ Failure Assessment score tended to benefit from ECMO treatment in terms of survival. Multivariate logistic regression revealed that hospital mortality was significantly lower among patients who received ECMO than among those who did not. Our findings suggested that early initiation of ECMO (within 48 h) may increase the likelihood of survival for patients with severe ARDS.

Interleukin (IL)-17 family members (IL-17A to IL-17F) are appearing to play key roles in host defense and inflammatory disease. Recently, several cytokines, such as IL-6, IL-10, IL-12, and transforming growth factor (TGF)-β1, were shown to have vital roles in severe sepsis. However, the influence of IL-17 on these cytokine responses from peripheral blood mononuclear cells (PBMCs) is unclear. Methods: Fifty-two patients who were admitted to our intensive care unit (ICU) because of severe sepsis were enrolled into this study. To validate experimental findings, 25 healthy controls were enrolled. Lipopolysaccharide-stimulated PBMCs with IL-17 or anti-IL-17 treatments were cultured for 24 hours. IL-6, IL-10, IL-12, and TGF-β1 levels in supernatants were measured. Results: The IL-12 production from stimulated PBMCs was increased after IL-17 treatment in both control and patient groups. Additional treatment of anti-IL-17 enhanced IL-10 production but decreased IL-12 production from stimulated PBMCs of healthy controls and patients with severe sepsis. Conclusion: IL-17 was helpful for inflammation in severe sepsis. Lack of IL-17 decreased IL-12 and enhanced IL-10 production from PBMCs, which resulted in immune imbalance.

Background: Lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) of type 2 diabetes patients produce more interleukin (IL)-12 under glucose treatment. The aim of this study was to determine whether increased IL-12 response in hyperglycemic LPS-stimulated PBMCs is due to increased gene expression or osmolarity. Methods: LPS-stimulated PBMCs of 13 type 2 diabetes patients and 8 healthy controls were used for culture in the presence or absence of glucose or mannitol for 24 h. The IL-12 gene expressions of PBMCs and IL-12 protein levels in supernatants were evaluated. Results: After 24 h, the stimulated PBMCs of diabetes patients expressed more IL-12 mRNA and produced more IL-12 protein following glucose treatment than those without glucose treatment and with mannitol treatment. Stimulated PBMCs of controls did not express more IL-12 mRNA and produce more IL-12 protein following glucose treatment than those without glucose treatment and with mannitol treatment. Conclusions: Glucose increases the IL-12 production in stimulated PBMCs of diabetes patients through increased IL-12 gene expression.

Background. The risk factors for Staphylococcus aureus (S. aureus) pneumonia are not fully identified. The aim of this work was to find out the clinical characteristics associated with S. aureus infection in patients with healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), which may be applicable for more appropriate selection of empiric antibiotic therapy. Methods. From July 2007 to June 2010, patients who were admitted to the intensive care unit with severe HCAP/HAP and severe sepsis were enrolled in this study. Lower respiratory tract sample was semiquantitatively cultured. Initial broad-spectrum antibiotics were chosen by Taiwan or American guidelines for pneumonia management. Standard bundle therapies were provided to all patients according to the guidelines of the Surviving Sepsis Campaign. Results. The most frequently isolated pathogens were Pseudomonas aeruginosa, S. aureus, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Patients with positive isolation of S. aureus in culture had significantly higher history of liver cirrhosis and diabetes mellitus, with odds ratios of 3.098 and 1.899, respectively. The S. aureus pneumonia was not correlated with history of chronic obstructive pulmonary disease, hypertension, and hemodialysis. Conclusion. Liver cirrhosis and diabetes mellitus may be risk factors for S. aureus infection in patients with severe HCAP or HAP.

Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients.

Macrophage activation assisted by interferon-gamma (IFN-γ) is a primary mechanism by which Mycobacterium tuberculosis is killed, but IFN-γ (production is inhibited in tuberculosis (TB) patients. The production of IFN-γ is influenced by many factors, such as interleukin (IL)-10, IL-12, IL-18, and clinical diseases; but the relative importance of each factor is unclear. Methods: We evaluated the effects of these factors in 46 healthy individuals, 81 patients with TB, and 88 patients with non-TB pneumonia. The responses of IFN-γ, IL-10, IL-12 and IL-18 were determined from phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs). Results: General linear model analysis showed that disease status and IL-12 response were the independent factors associated with the IFN-γ response. The production of IFN-γ was not affected by IL-10 and IL-18. There was a significant relationship between the IFN-γ response and the IL-12 response among patients with non-TB pneumonia, patients with TB, and healthy participants (Pearson's correlation coefficients of 0.466, 0.483, and 0.464, respectively). Conclusion: Production of IFN-γ in PBMCs was associated with active pulmonary TB and IL-12 response.

Pro- and anti-inflammatory cytokines, such as interferon (IFN)-γ, interleukin (IL)-6, IL-10, IL-12 and transforming growth factor (TGF)-β1, have been shown to be mediators associated with severe community-acquired pneumonia (CAP). It is unknown whether plasma TGF-β1 level can help physicians to judge disease severity. In this study, we investigated the value of predicting mortality in patients with severe CAP by the plasma levels of IFN-γ, IL-6, IL-10, IL-12 and TGF-β1 on admission day. Methods: Patients who were admitted to the emergency department and soon transferred to the ICU because of severe CAP were enrolled in this study. Plasma levels of IFN-γ, IL-6, IL-10, IL-12 and TGF-β1 on the day of admission were determined in 49 survivors and 14 non-survivors within 28 days by ELISA. Clinical characteristics were also recorded. Results: Plasma IL-6, IL-10 and TGF-β1 levels on admission were significantly different between survivors and non-survivors. Conversely, there was no significant difference in plasma IFN-γ and IL-12 levels between the survivors and non-survivors. Furthermore, the plasma TGF-β1 level was the only independent factor associated with mortality. The value of predicting mortality in patients with severe CAP was similar for IL-6, IL-10 and TGF-β1. Plasma IL-6 level was not related to the Acute Physiology and Chronic Health Evaluation (APACHE) II score. However, plasma IL-10 and TGF-β1 levels were correlated with APACHE II score. Conclusion: A severity scoring system, including TGF-β1 level on admission, may be considered as a useful parameter to predict outcomes of patients with severe CAP.