The Prognostic Factors of Bloodstream Infection in Immunosuppressed Elderly Patients: A Retrospective, Single-center, Five-year Cohort Study.

Introduction: Elderly patients with immunosuppressive status may have increased risk of mortality. At present, few studies have explored the clinical characteristics of the elderly immunosuppressed population with bloodstream infection. Our objectives were to evaluate the prognostic factors in immunosuppressed elderly patients with bloodstream infection. Methods: Three hundred and seventy-six elderly patients who were diagnosed with bloodstream infection in immunosuppressive status while receiving treatment in our hospital were selected from 2015 to 2019. The demographic data, underlying diseases, comorbidity, inducement, complications, pathogen sources, etiologies and the antibiotic therapy were analyzed between 90-day survival groups and 90-day mortality groups. The prognostic factors of 90-day mortality were evaluated by univariate logistic regression analysis and multivariate logistic regression analysis. Results: The clinical characteristics of 376 immunosuppressed elderly people diagnosed with bloodstream infection were analyzed, and among those people about 111 were 90-day mortality. By univariate logistic regression analysis and multivariate logistic regression analysis, we found ICU admission (OR: 2.052, 95%CI: 1.088-3.871, p=0.026), the decrease in BMI (OR: 0.307, 95%CI: 0.130-0.723, p=0.007), coronary heart disease (OR: 2.028, 95%CI: 1.078-3.816, p=0.028), biliary infection (OR: 4.406, 95%CI: 1.794-10.821, p=0.001) and the use of tigecycline (OR: 2.480, 95%CI: 1.195-5.147, p=0.015) were significantly different between the 90-day survival and 90-day mortality groups. Conclusion: ICU admission, coronary heart disease, biliary infection, and the use of tigecycline were the independent prognostic risk factors of 90-day mortality in immunosuppressed elderly people, and the decrease in BMI was the protective factor, which would have the benefit of discriminating the prognostic factors in immunosuppressed elderly people with bloodstream infection.

Prognostic Risk Factors of Carbapenem-Resistant Gram-Negative Bacteria Bloodstream Infection in Immunosuppressed Patients: A 7-Year Retrospective Cohort Study.

Purpose: Carbapenem-resistant Gram-negative bacteria bloodstream infection (CRGNB-BSI) has gradually become a major threat worldwide due to its treatment difficulty and high mortality. This study aimed to determine the risk factors for CRGNB-BSI in immunosuppressed patients. Patients and Methods: A total of 427 immunosuppressed patients with CRGNB-BSI were retrospectively investigated from 2015 to 2021. Both univariate and multivariate logistic regression analyses were applied to evaluate independent risk factors for CRGNB-BSI. Results: The most common etiology was Klebsiella Pneumoniae (50.59%; 216/427), while the Acinetobacillus baumannii infection was associated with the highest mortality (58.25%) among all etiologies. The 60-day mortality of immunosuppressed patients with CRGNB-BSI was 52.48% (224/427). Procalcitonin (PCT) > 0.5 µg/L (OR = 2.32, 95% CI: 1.28-4.19, P = 0.005) and age > 55 years (OR = 2.06, 95% CI: 1.17-3.64, P = 0.012) were found to be predictors of 60-day mortality of CRGNB-BSI, and tigecycline regimen (OR = 3.20, 95% CI: 1.81-5.67, P < 0.001) was associated with higher mortality. Multivariate analysis also revealed that patients who developed acute kidney injury (AKI) (OR = 2.19, 95% CI: 1.11-4.30, P = 0.023), gastrointestinal bleeding (OR = 3.18, 95% CI: 1.10-9.16, P = 0.032), multiple organ dysfunction syndrome (MODS) (OR = 12.11, 95% CI: 2.61-56.19, P = 0.001), and septic shock (OR = 3.24, 95% CI: 1.77-5.94, P < 0.001) showed worse outcomes. The risk factors were also significantly associated with mortality in the different subgroups. Conclusion: This study demonstrated that PCT > 0.5 µg/L, age > 55 years, and the tigecycline regimen were significantly associated with higher 60-day mortality among immunosuppressed patients with CRGNB- BSI. Patients developing MODS, septic shock, or AKI had worse clinical outcomes. .

Clinical Characteristics of Bloodstream Infection in Immunosuppressed Patients: A 5-Year Retrospective Cohort Study.

Introduction: Immunosuppressed patients with bloodstream infection are at risk of mortality. Our objective was to assess the independent risk factors of bloodstream infection with mortality in immunosuppressive states. Methods: The medical data of a total of 896 patients who were hospitalized in our hospital were collected from January 2015 to December 2019. Evaluation of the independent risk factors of mortality was done by univariate and multivariate logistic regression analyses. Results: Of the 896 immunosuppressed patients with bloodstream infection, 698 had over 60-day survivals and 198 had 60-day mortality. In our study, PCT (mean ±; standard: 11.40 ±; 31.89 µg/l vs. 62.45 ±; 17.10 µg/l, p = 0.007) and presence of age >60 years (40% vs. 14.19%, p = 0.001) were significantly different between situations with and without 60-day survivals in both univariate and multivariate logistic regression analyses. Age >60 years and PCT could be used as indicators for bloodstream infection with 60-day death in immunosuppressive states; the OR (95% CI) were 1.532 (1.099-2.135) and 2.063 (1.413-3.013), respectively. In different subgroups, PCT and age were also independent risk factors of blood system diseases, Klebsiella pneumoniae infection, diabetes, and ICU-stay subgroups. Conclusions: Age and PCT were independently associated with mortality in immunosuppressive states, which may help to identify the highly risky situation of bloodstream infection in immunosuppressive states.

A Microbial World: Could Metagenomic Next-Generation Sequencing Be Involved in Acute Respiratory Failure?

Background: The usefulness of metagenomic next-generation sequencing (mNGS) in identifying pathogens is being investigated. We aimed to compare the power of microbial identification between mNGS and various methods in patients with acute respiratory failure. Methods: We reviewed 130 patients with respiratory failure, and 184 specimens including blood, bronchoalveolar lavage fluid (BALF), sputum, pleural effusion, ascitic fluid, and urine were tested by mNGS and conventional methods (culture, PCR). We also enrolled 13 patients to evaluate the power of mNGS and pathogen targets NGS (ptNGS) in microbial identifications. Clinical features and microbes detected were analyzed. Results: mNGS outperformed the conventional method in the positive detection rate of Mycobacterium tuberculosis (MTB) (OR, ∞; 95% CI, 1-∞; P < 0.05), bacteria (OR, 3.7; 95% CI, 2.4-5.8; P < 0.0001), fungi (OR, 4.37; 95% CI, 2.7-7.2; P < 0.0001), mycoplasma (OR, 10.5; 95% CI, 31.8-115; P = 0.005), and virus (OR, ∞; 95% CI, 180.7-∞; P < 0.0001). We showed that 20 patients (28 samples) were detected with Pneumocystis jirovecii (P. jirovecii) by mNGS, but not by the conventional method, and most of those patients were immunocompromised. Read numbers of Klebsiella pneumoniae (K. pneumoniae), Acinetobacter baumannii (A. baumannii), Pseudomonas aeruginosa (P. aeruginosa), P. jirovecii, cytomegalovirus (CMV), and Herpes simplex virus 1 (HSV1) in BALF were higher than those in other sample types, and the read number of Candida albicans (C. albicans) in blood was higher than that in BALF. We found that orotracheal intubation and type 2 diabetes mellitus (T2DM) were associated with a higher detection rate of bacteria and virus by mNGS, immunosuppression was associated with a higher detection rate of fungi and virus by mNGS, and inflammatory markers were associated with mNGS-positive detection rate of bacteria. In addition, we observed preliminary results of ptNGS. Conclusion: mNGS outperformed the conventional method in the detection of MTB, bacteria, fungi, mycoplasma, and virus. Orotracheal intubation, T2DM, immunosuppression, and inflammatory markers were associated with a higher detection rate of bacteria, fungi, and virus by mNGS. In addition, ptNGS results were consistent with the detection of abundant bacteria, fungi, and mycoplasma in our specimens.

Role of miR-466 in mesenchymal stromal cell derived extracellular vesicles treating inoculation pneumonia caused by multidrug-resistant Pseudomonas aeruginosa.

RATIONALE: The effects of mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (MSC EVs) on multidrug-resistant pseudomonas aeruginosa (MDR-PA)-induced pneumonia remain unclear. MATERIALS AND METHODS: MicroRNA array and RT-PCR were used to select the major microRNA in MSC EVs. Human peripheral blood monocytes were obtained and isolated from qualified patients. The crosstalk between MSCs/MSC EVs and macrophages in vitro was studied. MDR-PA pneumonia models were further established in C57BL/6 mice and MSC EVs or miR-466 overexpressing MSC EVs were intratracheally instilled. RESULTS: MiR-466 was highly expressed in MSC EVs. MSCs and miR-466 promoted macrophage polarization toward Type 2 phenotype through TIRAP-MyD88-NFκB axis. Moreover, cocultured macrophages with miR-466 overexpressing MSCs significantly increased the phagocytosis of macrophages. MSC EVs significantly reduced mortality and decreased influx of BALF neutrophils, proinflammatory factor levels, protein, and bacterial load in murine MDR-PA pneumonia. Administration of miR-466 overexpressing MSC EVs further alleviated the inflammatory severity. CONCLUSIONS: MSC-derived EVs containing high levels of miR-466 may partly participate in host immune responses to MDR-PA. Both MSCs and MSC EVs have therapeutic effects in treating MDR-PA-induced pneumonia.

The mNCP-SPI Score Predicting Risk of Severe COVID-19 among Mild-Pneumonia Patients on Admission.

PURPOSE: To predict the risk of developing severe pneumonia among mild novel coronavirus pneumonia (mNCP) patients on admission. METHODS: A retrospective cohort study was conducted at three hospitals in Shanghai and Wuhan from January 2020 to February 2020. Real-time polymerasechain-reaction assays were used to detect COVID-19. A total of 529 patients diagnosed with NCP were recruited from three hospitals and classified by four severity types during hospitalization following the standards of the Chinese Diagnosis and Treatment of Pneumonia Caused by New Coronavirus Infection (eighth version). Patients were excluded if admitted by ICU on admission (n=92, on a general ward while meeting the condition of severe or critical type on admission (n=25), or there was insufficient clinical information (n=64). In sum, 348 patients with mNCP were finally included, and 68 developed severe pneumonia. RESULTS: mNCP severity prognostic index values were calculated based on multivariate logistic regression: history of diabetes (OR 2.064, 95% CI 1.010-4.683; p=0.043), time from symptom onset to admission ≥7 days (OR 1.945, 95% CI 1.054-3.587; p=0.033), lymphocyte count ≤0.8 (OR 1.816, 95% CI 1.008-3.274; p=0.047), myoglobin ≥90 mg/L (OR 2.496, 95% CI 1.235-5.047; p=0.011), and D-dimer ≥0.5 mg/L (OR 2.740, 95% CI 1.395-5.380; p=0.003). This model showed a c-statistics of 0.747, with sensitivity and specificity 0.764 and 0.644, respectively, under cutoff of 165. CONCLUSION: We designed a clinical predictive tool for risk of severe pneumonia among mNCP patients to provided guidance for medicines. Further studies are required for external validation.

COVID-19 with Different Severities: A Multicenter Study of Clinical Features.

Rationale: The coronavirus disease (COVID-19) pandemic is now a global health concern.Objectives: We compared the clinical characteristics, laboratory examinations, computed tomography images, and treatments of patients with COVID-19 from three different cities in China.Methods: A total of 476 patients were recruited from January 1, 2020, to February 15, 2020, at three hospitals in Wuhan, Shanghai, and Anhui. The patients were divided into four groups according to age and into three groups (moderate, severe, and critical) according to the fifth edition of the Guidelines on the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of China.Measurements and Main Results: The incidence of comorbidities was higher in the severe (46.3%) and critical (67.1%) groups than in the moderate group (37.8%). More patients were taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the moderate group than in the severe and critical groups. More patients had multiple lung lobe involvement and pleural effusion in the critical group than in the moderate group. More patients received antiviral agents within the first 4 days in the moderate group than in the severe group, and more patients received antibiotics and corticosteroids in the critical and severe groups. Patients >75 years old had a significantly lower survival rate than younger patients.Conclusions: Multiple organ dysfunction and impaired immune function were the typical characteristics of patients with severe or critical illness. There was a significant difference in the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with different severities of disease. Involvement of multiple lung lobes and pleural effusion were associated with the severity of COVID-19. Advanced age (≥75 yr) was a risk factor for mortality.

Use of real-time polymerase chain reaction for the diagnosis of Pneumocystis pneumonia in immunocompromised patients: a meta-analysis.

BACKGROUND: The diagnosis of Pneumocystis pneumonia (PCP) in immunocompromised patients is still challenging today due to the absence of an in vitro culture system and the low diagnostic accuracy of microscopic examinations. Herein, we performed a meta-analysis to evaluate the accuracy of real-time polymerase chain reaction (PCR) in the diagnosis of PCP. METHODS: We searched Web of Knowledge and Medline from 1990 to May 2010 for studies reporting diagnostic accuracy data regarding the use of real-time PCR in the diagnosis of PCP in immunocompromised patients. RESULTS: Ten individual studies were included. Overall, the sensitivity of real-time PCR was 97% (95%CI: 93% - 99%); the specificity was 94% (95%CI: 90% - 96%). The area under the HSROC curve (95%CI) for real-time PCR was 0.99 (0.97 - 0.99). In a subgroup analysis regarding studies involving HIV patients among the study population, the sensitivity and specificity were 97% (95%CI: 93% - 99%) and 93% (95%CI: 89% - 96%), respectively. Regarding studies using Bronchoalveolar lavage (BAL) samples only: sensitivity = 98% (95%CI: 94% - 99%); specificity = 93% (95%CI: 89% - 96%), respectively. Regarding studies using microscopy as a reference standard: sensitivity = 97% (95%CI: 92% - 99%); specificity = 93% (95%CI: 88% - 96%). However, high between-study statistical heterogeneity was observed in all analyses. CONCLUSIONS: Real-time PCR has a good diagnostic accuracy and may provide a useful adjunctive tool for the diagnosis of PCP in immunocompromised patients. Further studies are needed in order to identify any differences in the diagnostic performance of real-time PCR in HIV and non-HIV immunocompromised patients.

Nicotinic acetylcholine receptor variants associated with susceptibility to chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: Only 10-15% of smokers develop chronic obstructive pulmonary disease (COPD) which indicates genetic susceptibility to the disease. Recent studies suggested an association between COPD and polymorphisms in CHRNA coding subunits of nicotinic acetylcholine receptor. Herein, we performed a meta-analysis to clarify the impact of CHRNA variants on COPD. METHODS: We searched Web of Knowledge and Medline from 1990 through June 2011 for COPD gene studies reporting variants on CHRNA. Pooled odds ratios (ORs) were calculated using the major allele or genotype as reference group. RESULTS: Among seven reported variants in CHRNA, rs1051730 was finally analyzed with sufficient studies. Totally 3460 COPD and 11437 controls from 7 individual studies were pooled-analyzed. A-allele of rs1051730 was associated with an increased risk of COPD regardless of smoking exposure (pooled OR = 1.26, 95% CI 1.18-1.34, p < 10⁻5). At the genotypic level, the ORs gradually increased per A-allele (OR = 1.27 and 1.50 for GA and AA respectively, p < 10⁻5). Besides, AA genotype exhibited an association with reduced FEV1% predicted (mean difference 3.51%, 95%CI 0.87-6.16%, p = 0.009) and increased risk of emphysema (OR 1.93, 95%CI 1.29-2.90, p = 0.001). CONCLUSIONS: Our findings suggest that rs1051730 in CHRNA is a susceptibility variant for COPD, in terms of both airway obstruction and parenchyma destruction.

Pleural fluid soluble triggering receptor expressed on myeloid cells-1 as a marker of bacterial infection: a meta-analysis.

BACKGROUND: Pleural infection is a common clinical problem. Its successful treatment depends on rapid diagnosis and early initiation of antibiotics. The measurement of soluble triggering receptor expressed in myeloid cells-1 (sTREM-1) level in pleural effusions has proven to be a valuable diagnostic tool for differentiating bacterial effusions from effusions of other etiologies. Herein, we performed a meta-analysis to assess the accuracy of pleural fluid sTREM-1 in the diagnosis of bacterial infection. METHODS: We searched Web of Knowledge and Medline from 1990 through March 2011 for studies reporting diagnostic accuracy data regarding the use of sTREM-1 in the diagnosis of bacterial pleural effusions. Pooled sensitivity and specificity and summary measures of accuracy and Q* were calculated. RESULTS: Overall, the sensitivity of sTREM-1was 78% (95% CI: 72%-83%); the specificity was 84% (95% CI: 80%-87%); the positive likelihood ratio was 6.0 (95% CI: 3.3-10.7); and the negative likelihood ratio was 0.22 (95% CI: 0.12-0.40). The area under the SROC curve for sTREM-1 was 0.92. Statistical heterogeneity and inconsistency were found for sensitivity (p = 0.015, χ2 = 15.73, I2 = 61.9%), specificity (p = 0.000, χ2 = 29.90, I2 = 79.9%), positive likelihood ratio (p = 0.000, χ2 = 33.09, I2 = 81.9%), negative likelihood ratio (p = 0.008, χ2 = 17.25, I2 = 65.2%), and diagnostic odds ratio (p = 0.000, χ2 = 28.49, I2 = 78.9%). A meta-regression analysis performed showed that the Quality Assessment of Diagnostic Accuracy Studies score (p = 0.3245; RDOR, 4.34; 95% CI, 0.11 to 164.01), the Standards for Reporting of Diagnostic Accuracy score (p = 0.3331; RDOR, 1.70; 95% CI, 0.44 to 6.52), lack of blinding (p = 0.7439; RDOR, 0.60; 95% CI, 0.01 to 33.80), and whether the studies were prospective or retrospective studies (p = 0.2068; RDOR, 7.44; 95% CI, 0.18 to 301.17) did not affect the test accuracy. A funnel plot for publication bias suggested a remarkable trend of publication bias. CONCLUSIONS: Our findings suggest that sTREM-1 has a good diagnostic accuracy and may provide a useful adjunctive tool for the diagnosis of bacterial pleural effusions. However, further studies are needed in order to identify any differences in the diagnostic performance of sTREM-1 of parapneumonic effusions and empyemas.

Plasma orexin-a levels in COPD patients with hypercapnic respiratory failure.

Orexins have previously been shown to promote wakefulness, regulate lipid metabolism and participate in energy homeostasis. The aim of the study was to determine the relationship between plasma orexin-A and body composition in COPD in-patients with hypercapnic respiratory failure. 40 patients with hypercapnic respiratory failure and 22 healthy individuals were enrolled prospectively in this study. Plasma orexin-A levels, BMI, SaO(2), PaCO(2) and PaO(2) were noted for all the patients. Plasma orexin-A levels were higher in the underweight (UW) group, normal weight (NW) group and overweight (OW) group of COPD patients as compared with UW, NW and OW group of the control group (P < .05). Plasma orexin-A in COPD patients were higher in the OW group than in the NW group and the UW group. Plasma orexin-A levels showed significant correlation with body mass index (BMI), independent of PaO(2) (r = 0.576; P < .05) and %fat (r = 0.367; P < .05); a negative correlation was noted between plasma orexin-A levels and PaO(2) (r = -0.738; P < .05) and SaO(2) (r = -0.616; P < .05). Our results suggest that orexin-A levels are high in COPD patients with hypercapnic respiratory failure, and vary according to BMI and body composition. Orexin-A may be associated with the severity of hypoxemia in COPD patients with hypercapnic respiratory failure.

Intrapleural delivery of mesenchymal stem cells: a novel potential treatment for pleural diseases.

AIM: To develop a method to deliver mesenchymal stem cells (MSCs) into the pleural cavity for the treatment of pleural diseases. METHODS: MSCs were isolated from rat bone marrow of rats and labeled with 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) or green fluorescent protein (GFP) using a lentiviral vector. Eighteen Sprague-Dawley (SD) rats were inoculated intrapleurally with 1×10(6) MSCs-DAPI. The distribution of the fluorescent cells was observed using fluorescent microscopy for the following 30 d. Another 12 rats inoculated intrapleurally with 1×10(6) MSCs-GFP were observed for 14 d. RESULTS: The isolated cells were typical MSC phenotypes and could differentiate into adipocytes, osteoblasts, and chondroblasts in vitro. Microscopic analysis revealed that the labeled cells adhered to the surface of the pleural cavity. The highest number of the labeled cells was found to be adhered to all specimens from the mediastinal pleura, but no labeled cells were detected in the lung parenchyma or other tissues/organs, such as the liver, kidney, spleen, and mesenterium. Incidentally, stomas were found in the mediastinal pleura. The recovered MSCs-GFP from the pleural cavity retained their ability to adhere and proliferate. CONCLUSION: We have established a novel method for intrapleural delivery of MSCs. The distribution of intrapleurally delivered MSCs was found to be limited to the pleurae and the pleural cavity, thereby providing us with a new approach to further investigation of the therapeutic roles of MSCs in pleural diseases.

LPS pretreatment ameliorates multiple organ injuries and improves survival in a murine model of polymicrobial sepsis.

OBJECTIVE: The endotoxin tolerance phenotype is characterized with decreased inflammation and increased phagocytosis. We hypothesized that endotoxin tolerance would provide protective effects on experimental sepsis with multiple organ injuries induced by cecal ligation and puncture (CLP). METHODS: Endotoxin tolerance was induced in male Sprague-Dawley rats with daily intraperitoneal injection of either 0.6 mg/kg of lipopolysaccharide (LPS) or vehicle for four consecutive days before subsequent CLP. Biochemical parameters, histological changes, inflammatory cytokine production, and lung tissue nuclear factor-κB (NF-κB) activation were assessed post-CLP. In a separate experiment, survival rate was monitored for 7 days after CLP. RESULTS: In vehicle-treated animals, CLP caused multiple organ injuries confirmed by the biochemical variables and histological examination. This was accompanied by an early activation of NF-κB in the lung and a substantial increase in plasma levels of tumor necrosis factor-α, interleukin-6, and interleukin-10. In contrast, pretreatment with LPS not only alleviated the development of multiple organ injuries after CLP, but also decreased sepsis-induced activation of pulmonary NF-κB and reduced plasma cytokines production. In addition, LPS pretreatment improved the survival in rats subjected to CLP. CONCLUSIONS: The beneficial effects of endotoxin tolerance indicate the potential of immunomodulatory strategies in the management of severe sepsis.

Protective effects of imipramine in murine endotoxin-induced acute lung injury.

The tricyclic antidepressant imipramine has recently emerged as a cytoprotective agent, exerting beneficial effects in inflammatory tissue injury. The present study aimed to investigate therapeutic effects of imipramine in murine model of endotoxin-induced acute lung injury. Mice were administrated intraperitoneally with LPS (lipopolysaccharide) from Escherichia coli or vehicle. Imipramine was administrated intraperitoneally 30 min before LPS challenge. Pretreatment of mice with imipramine reduced lethality. Impramine also significantly attenuated lung inflammation, lung edema, MPO (myeloperoxidase) activity, lung tissue pathological changes and nuclear factor-kappaB DNA binding activity. The results of this study suggest that imipramine can exert protective effects in endotoxin-induced acute lung injury by suppressing nuclear factor-kappaB-mediated expression of inflammatory genes. Thus, imipramine could be a potential novel therapeutic agent for the treatment for acute lung injury.

Up-regulation of growth factor independence 1 in endotoxin tolerant macrophages with low secretion of TNF-alpha and IL-6.

OBJECTIVE: Endotoxin tolerance refers to a low response to lipopolysaccharide (LPS). We hypothesized that growth factor independence 1 (Gfi1) involves in the endotoxin tolerance in macrophages. METHODS: Endotoxin tolerance was induced in the RAW264.7 cell line and thioglycolate-elicited murine peritoneal macrophages by incubation with 100 ng/ml LPS for 20 h. Macrophages without the pretreatment were set as control. Both endotoxin tolerant and control cells were then stimulated with 1,000 ng/ml LPS for indicated period of incubation. Gfi1 mRNA expression and protein production were investigated by real-time PCR and Western blotting, respectively. ELISA was performed to quantify the secretion of TNF-alpha and IL-6. RESULT: Compared with non-endotoxin tolerant macrophages, endotoxin tolerant cells secreted a lower amount of TNF-alpha and IL-6. The mRNA expression of Gfi1 in endotoxin tolerant macrophages was higher than that of control in both RAW264.7 cells and thioglycolate-elicited murine peritoneal macrophages. The protein production was accordingly up-regulated in endotoxin tolerant RAW264.7 cells. CONCLUSION: In in vitro endotoxin tolerant macrophages, the expression of Gfi1 mRNA and protein were up-regulated after high dose LPS stimulation, accompanied with a blunted TNF-alpha and IL-6 secretion. Gfi1 might participate in the mechanism of endotoxin tolerance.

Biomarkers: a definite plus in pneumonia.

During the past few years, biomarkers have emerged as an indispensible tool in the diagnosis of pneumonia. To find an ideal diagnostic biomarker for pneumonia is not an easy task. Not only should it allow an early diagnosis of the condition, but it should also allow differential diagnosis from other noninfectious conditions. Ongoing research is being done in this field so as to put an array of biomarkers at the disposal of doctors to improve the diagnosis of pneumonia when patients present to them with cough or nonspecific symptoms which could easily be misinterpreted as symptoms of other conditions. Procalcitonin and soluble triggering receptor expressed on myeloid cells-1 have emerged as reliable diagnostic markers in pneumonia, and are better when compared to other markers, namely, C-reactive protein, leukocyte count, and proinflammatory cytokines. Many other biomarkers are being studied for their probable use in diagnosing pneumonia but have yet to prove their benefit.