LIGHT is a crucial mediator of airway remodeling.

Chronic inflammatory airway diseases like asthma and chronic obstructive pulmonary disease are major health problems globally. Airway epithelial cells play important role in airway remodeling, which is a critical process in the pathogenesis of diseases. This study aimed to demonstrate that LIGHT, an inflammatory factor secreted by T cells after allergen exposure, is responsible for promoting airway remodeling. LIGHT increased primary human bronchial epithelial cells (HBECs) undergoing epithelial-mesenchymal transition (EMT) and expressing MMP-9. The induction of EMT was associated with increased NF-κB activation and p300/NF-κB association. The interaction of NF-κB with p300 facilitated NF-κB acetylation, which in turn, was bound to the promoter of ZEB1, resulting in E-cadherin downregulation. LIGHT also stimulated HBECs to produce numerous cytokines/chemokines that could worsen airway inflammation. Furthermore, LIGHT enhanced HBECs to secrete activin A, which increased bronchial smooth muscle cell (BSMC) migration. In contrast, depletion of activin A decreased such migration. The findings suggest a new molecular determinant of LIGHT-mediated pathogenic changes in HBECs and that the LIGHT-related vicious cycle involving HBECs and BSMCs may be a potential target for the treatment of chronic inflammation airway diseases with airway remodeling.

In vitro efficacies and resistance profiles of rifampin-based combination regimens for biofilm-embedded methicillin-resistant Staphylococcus aureus.

To compare the in vitro antibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistant Staphylococcus aureus (MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.

Comparative efficacies of various corticosteroids for preventing postextubation stridor and reintubation: a systematic review and network meta-analysis.

Objectives: We assessed the efficacies of various corticosteroid treatments for preventing postexubation stridor and reintubation in mechanically ventilated adults with planned extubation. Methods: We searched the Pubmed, Embase, the Cochrane databases and ClinicalTrial.gov registration for articles published through September 29, 2022. Only randomized controlled trials (RCTs) that compared the clinical efficacies of systemic corticosteroids and other therapeutics for preventing postextubation stridor and reintubation were included. The primary outcome was postextubation stridor and the secondary outcome was reintubation. Results: The 11 assessed RCTs reported 4 nodes: methylprednisolone, dexamethasone, hydrocortisone, and placebo, which yielded 3 possible pairs for comparing the risks of post extubation stridor and 3 possible pairs for comparing the risks of reintubation. The risk of postextubation stridor was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients (dexamethasone: OR = 0.39; 95% CI = 0.22-0.70; methylprednisolone: OR = 0.22; 95% CI = 0.11-0.41). The risk of postextubation stridor was significantly lower in methylprednisolone-treated patients than in hydrocortisone-treated: OR = 0.24; 95% CI = 0.08-0.67) and dexamethasone-treated patients: OR = 0.55; 95% CI = 0.24-1.26). The risk of reintubation was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients: (dexamethasone: OR = 0.34; 95% CI = 0.13-0.85; methylprednisolone: OR = 0.42; 95% CI = 0.25-0.70). Cluster analysis showed that dexamethasone- and methylprednisolone-treated patients had the lowest risks of stridor and reintubation. Subgroup analyses of patients with positive cuff-leak tests showed similar results. Conclusions: Methylprednisolone and dexamethasone were the most effective agents against postextubation stridor and reintubation.

Use of Carbapenems against clinical, nontyphoid Salmonella isolates: results from in vitro and in vivo animal studies.

The emergence of multidrug-resistant Salmonella isolates has created the need for new therapeutic agents. We evaluated the intracellular activity of four carbapenem compounds against clinical nontyphoid Salmonella (NTS) isolates in vitro and ex vivo. Subsequently, the efficacy of carbapenem treatment against selected Salmonella isolates in vivo was assessed using a murine peritonitis model. The MIC(50) and MIC(90) for doripenem, ertapenem, imipenem, and meropenem against 126 NTS isolates were found to be 0.062 and 0.062, 0.015 and 0.015, 0.5 and 1, and 0.031 and 0.031 µg/ml, respectively. The intracellular killing effect of ertapenem was sustained for 24 h and was superior to that of imipenem, meropenem, and doripenem; its effect was comparable to that of ceftriaxone. Ertapenem demonstrated an excellent pharmacokinetic profile with a percent time above the MIC of 75.5% and an area under the concentration-time curve/MIC ratio of 20,733. When peritoneal exudate cells were examined directly ex vivo from mice with Salmonella-induced peritonitis, cells from mice treated with ertapenem and ceftriaxone had intracellular and extracellular bacterial counts reduced 10(2)- to 10(4)-fold and exhibited killing effects similar to each other. The survival rates of mice inoculated with 1 × 10(5) and 10(6) CFU of a ceftriaxone-susceptible Salmonella isolate that were subsequently treated with ertapenem or ceftriaxone were 100% and 90%, respectively. When mice were inoculated with 5 × 10(4) and 10(5) CFU of a ceftriaxone-resistant and ciprofloxacin-resistant Salmonella isolate, mice treated with ertapenem had a higher survival rate than mice treated with ceftriaxone (70% versus 0% and 50% versus 0%, respectively; P < 0.001). Our results suggest that ertapenem is at least as effective as ceftriaxone in treating murine Salmonella infections and show that further clinical investigations on the potential use of ertapenem in treatment of human Salmonella infections are warranted.

In vitro efficacy of fosfomycin-containing regimens against methicillin-resistant Staphylococcus aureus in biofilms.

OBJECTIVES: To compare the in vitro antibacterial efficacy of antistaphylococcal antibiotics in combination with fosfomycin or rifampicin, using a biofilm model. METHODS: The antibacterial activities of fusidic acid, linezolid, vancomycin, teicoplanin, rifampicin, minocycline, fosfomycin and tigecycline, individually and in fosfomycin or rifampicin combinations, were measured against planktonic or biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) with susceptible and resistant breakpoint concentrations (SBCs and RBCs, respectively), using the MTT-staining method and by counting the number of cfu in the biofilms. RESULTS: Linezolid alone at its SBC, and fosfomycin, linezolid, minocycline and tigecycline at their RBCs, exhibited killing effects on biofilm-embedded MRSA (P < 0.0001). Of the eight fosfomycin combinations studied, fosfomycin combined with linezolid, minocycline, vancomycin or teicoplanin at their respective SBCs, exhibited enhanced antibacterial activities (P < 0.0001) when compared with the control group, and outperformed rifampicin combinations (P < 0.01). The killing effects of fosfomycin combinations at their respective RBCs were better than those at their respective SBCs (P < 0.05). Significantly enhanced killing effects were observed with fosfomycin in combination with vancomycin or teicoplanin, compared with vancomycin or teicoplanin alone. For 10 randomly selected MRSA isolates, the results of colony counting in biofilms were comparable with those of the MTT-staining method. CONCLUSIONS: Fosfomycin enhanced the activities of linezolid, minocycline, vancomycin and teicoplanin. These combinatorial treatments were even better than rifampicin combination regimens, and may provide therapeutic advantages in catheter-related or prosthetic joint infections.

In vitro and in vivo intracellular killing effects of tigecycline against clinical nontyphoid Salmonella isolates using ceftriaxone as a comparator.

Salmonella is an important, worldwide food-borne pathogen. Resistance to fluoroquinolones and cephalosporins has been increasingly reported, and new therapeutic agents are desperately needed. In this study, we evaluated the in vitro antimicrobial susceptibility of clinical nontyphoidal Salmonella isolates to tigecycline. Antibacterial activity of tigecycline, ceftriaxone, and ciprofloxacin were investigated by time-kill studies and the murine peritonitis model. The MIC50/MIC90 values of tigecycline, ceftriaxone, and ciprofloxacin against 76 Salmonella isolates were 0.25/0.5, 1/8, and 0.125/0.5 µg/ml, respectively. The intracellular inhibitory activity of tigecycline at 0.5 µg/ml (1 × MIC) against Salmonella isolates in human peripheral blood mononuclear cells was sustained for 24 h. In a mouse peritonitis model, tigecycline reduced the extracellular and intracellular bacterial counts from 107 CFU/ml and 105 CFU/ml, respectively, to an undetectable level within 96 h. The results were similar to those obtained with ceftriaxone. The survival rate of mice exposed to tigecycline after being infected by an inoculum of 1 × 105 CFU was 80%, and that of mice exposed to ceftriaxone was 100%. When the inoculum was increased to 1.3 × 106 CFU, the survival rate of mice treated by tigecycline was 20%, and that of mice exposed to ceftriaxone was 0% (P = 0.2). When a ceftriaxone- and ciprofloxacin-resistant but tigecycline-susceptible isolate was tested, mice treated by tigecycline had a higher survival rate than those treated by ceftriaxone (15/20 [75%] versus 6/20 [30%]; P = 0.011). Our results suggest that tigecycline is at least as effective as ceftriaxone for murine Salmonella infections and warrants further clinical investigations to delineate its potential against human Salmonella infections.

Antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae.

BACKGROUND: This study aims to investigate the antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae (CPE). METHODS: Five Lactobacillus spp. strains and 18 CPE clinical isolates were collected. Their anti-CPE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test. Finally, the specific anti-CPE mechanism, especially for the effect of organic acids was determined using broth microdilution method. RESULTS: All of five Lactobacilli isolates displayed the potent activity against most CPE isolates with mean zones of inhibition ranging 10.2-21.1 mm. The anti-CPE activity was not affected by heating, catalase, and proteinase treatment. Under the concentration of 50% LUC0180 cell-free supernatant (CFS), lactic acid, and mix acid could totally inhibit the growth of carbapenem-resistant Klebsiella pneumoniae (CPE0011), and acetic acid could inhibit 67.8%. In contrast, succinic acid and citric acid could not inhibit the growth of CPE0011. While we decreased the concentration to 25%, only lactic acid and mix acid displayed 100% inhibition. In contrast, succinic acid, citric acid and acetic acid did not show any inhibitory effect. CONCLUSIONS: Lactobacillus strains exhibit potent anti-CPE activity, and lactic acid produced by Lactobacillus strains is the major antimicrobial mechanism.

Correlation of Body Mass Index with Oncologic Outcomes in Colorectal Cancer Patients: A Large Population-Based Study.

It has been acknowledged that excess body weight increases the risk of colorectal cancer (CRC); however, there is little evidence on the impact of body mass index (BMI) on CRC patients' long-term oncologic results in Asian populations. We studied the influence of BMI on overall survival (OS), disease-free survival (DFS), and CRC-specific survival rates in CRC patients from the administrative claims datasets of Taiwan using the Kaplan-Meier survival curves and the log-rank test to estimate the statistical differences among BMI groups. Underweight patients (<18.50 kg/m2) presented higher mortality (56.40%) and recurrence (5.34%) rates. Besides this, they had worse OS (aHR:1.61; 95% CI: 1.53-1.70; p-value: < 0.0001) and CRC-specific survival (aHR:1.52; 95% CI: 1.43-1.62; p-value: < 0.0001) rates compared with those of normal weight patients (18.50-24.99 kg/m2). On the contrary, CRC patients belonging to the overweight (25.00-29.99 kg/m2), class I obesity (30.00-34.99 kg/m2), and class II obesity (≥35.00 kg/m2) categories had better OS, DFS, and CRC-specific survival rates in the analysis than the patients in the normal weight category. Overweight patients consistently had the lowest mortality rate after a CRC diagnosis. The associations with being underweight may reflect a reverse causation. CRC patients should maintain a long-term healthy body weight.

The prognosis in extremely elderly patients receiving orotracheal intubation and mechanical ventilation after planned extubation.

The main objective of this study was to evaluate the outcomes of extremely elderly patients receiving orotracheal intubation and mechanical ventilation after planned extubation. This retrospective cohort study included extremely elderly patients (>90 years) who received mechanical ventilation and passed planned extubation. We reviewed all intensive care unit patients in a medical center between January 1, 2010, and December 31, 2017. There were 19,518 patients (aged between 20 and 105 years) during the study period. After application of the exclusion criteria, there were 213 patients who underwent planned extubation: 166 patients survived, and 47 patients died. Compared with the mortality group, the survival group had lower Acute Physiology and Chronic Health Evaluation II scores and higher Glasgow Coma Scale (GCS) scores, with scores of 19.7 ±â€Š6.5 (mean ±â€Šstandard deviation) vs 22.2 ±â€Š6.0 (P = .015) and 9.5 ±â€Š3.5 vs 8.0 ±â€Š3.0 (P = .007), respectively. The laboratory data revealed no significant difference between the survival and mortality groups except for blood urea nitrogen (BUN) and hemoglobin. After multivariate logistic regression analysis, a lower GCS, a higher BUN level, weaning beginning 3 days after intubation and reintubation during hospitalization were associated with poor prognosis. In this cohort of extremely elderly patients undergoing planned extubation, a lower GCS, a higher BUN level, weaning beginning 3 days after intubation and reintubation during hospitalization were associated with mortality.

Outcome of liver cirrhosis patients requiring prolonged mechanical ventilation.

Acute respiratory failure requiring mechanical ventilation is a major indicator of intensive care unit (ICU) admissions in cirrhotic patients and is an independent risk factor for ICU mortality. This retrospective study aimed to investigate the outcome and mortality risk factors in patients with liver cirrhosis (LC) who required prolonged mechanical ventilation (PMV) between 2006 and 2013 from two databases: Taiwan's National Health Insurance Research Database (NHIRD) and a hospital database. The hospital database yielded 58 LC patients (mean age: 65.3 years; men: 65.5%). The in-hospital mortality was significantly higher than in patients without LC. Based on the NHIRD database of PMV cases, patients were age-gender matched in a ratio of 1:2 for patients with and without LC. Model for End-Stage Liver Disease (MELD) score was calculated. The mortality was higher in patients with LC (19.5%) than those without LC (18.12%), though not statistically significant (p = 0.0622). Based on the hospital database, risk factor analysis revealed that patients who died had significant higher MELD score than the survivors (18.9 vs 13.7, p = 0.036) and patients with MELD score of >23 had higher risk of mortality than patients with MELD score of ≤23 (adjusted OR:9.26, 95% CI: 1.96-43.8). In conclusion, the in-hospital mortality of patients with high MELD scores who required PMV was high. MELD scores may be useful predictors of mortality in these patients.

The association between depression and length of stay in the intensive care unit.

Depression is common after patients are discharged from the intensive care unit (ICU) and has a negative impact on quality of life and mortality. There is inconsistent information about ICU admission and the risk of depression. The aim of our study was to investigate the association between the risk of depression and length of ICU stay.ICU survivors between 20 and 65 years old were enrolled in this study using data from Taiwan's nationwide population database. All study subjects were followed for a maximum of 1 year or until they were diagnosed with new-onset depression. The association between the length of ICU stay and the depression risk among ICU survivors was estimated using a Cox regression model. The screened diagnostic records of ICU survivors with depression were also investigated to find the potential disease effect of depression.Compared to patients with ICU stays between 8 and 14 days, the adjusted HR (95% confidence interval) for depression in patients with ICU stays between 1 to 3 days, 4 to 7 days, 15 to 21 days, and ≥22 days were 1.08 (1.03-1.13), 1.01 (0.96-1.05), 1.08 (1.01-1.14), and 1.12 (1.06-1.19), respectively. For patients with depression after discharge from the ICU, the most common primary diagnosis was intracerebral hemorrhage.There is a risk of depression after ICU discharge, and the incidence of depression may be higher among patients between 20 and 49 years old. The risk of depression was U-shaped, with higher risks associated with ICU stays of 1 to 3 days and more than 15 days.

Does radiotherapy increase the risk of colorectal cancer among prostate cancer patients? A large population-based study.

Objective: The survival of prostate cancer (PC) patients after radiotherapy (RT) has improved over time, but it raises the debate of increased risk of secondary colorectal cancer (SCRC). This study aimed to assess whether RT for PC treatment increases the risk of SCRC in comparison with radical prostatectomy (RP). Methods: A population-based cohort of PC patients treated only with RT or only with RP between January 2007 and December 2015 was identified from the Taiwan Cancer Registry. The incidence rate of SCRC development was estimated using Cox regression model. Results: In this study, total 8,797 PC patients treated with either RT (n = 3,219) or RP (n =5,578). Patients subjected to RT were elder (higher percentage of 70≧years, p < 0.0001) and more advanced clinically (stage III: 22.90% vs. 11.87%; stage IV: 22.15% vs. 13.80%, p < 0.0001), compared to those subjected to RP. More patients subjected to RT had a much higher percentage of autoimmune disease (22.34% vs. 18.75%, p < 0.0001) and osteoarthritis and allied disorders (16.31% vs. 12.98%, p < 0.0001). Besides, RT patients had a higher percentage of underlying Crohn's disease (0.25% vs. 0.05%, p = 0.0230). Although almost all selected factors were not statistically significant, they presented the positive risk of SCRC for those under RP compared with those among RT. Besides, for PC patients in clinical stage I and II, patients with RP may have borderline significantly protective effects of SCRC compared with those under RT (stage I, HR: 0.14; 95% C.I.:0.01-1.39; p = 0.0929; stage II, HR: 1.92; 95% C.I.:0.93-3.95; p = 0.0775). Kaplan-Meier curves for a 3-year-period, which demonstrated no statistical difference in the risk of SCRC free between PC patients undergoing RT and RP (p = 0.9766). Conclusion: Whether or not pelvic RT for PC is associated with an increased risk for SCRC on a population-based level remains a matter of considerable debate. From a clinical perspective, these PC survivors should be counseled accordingly and received continued cancer surveillance with regular colonoscopy follow-up.

Intratracheal colistin sulfate for BALB/c mice with early pneumonia caused by carbapenem-resistant Acinetobacter baumannii.

OBJECTIVES: : To study the efficacy of intratracheal colistin sulfate therapy in a murine model of acute pneumonia caused by a clinical CRAB strain, Ab396. Colistin therapy has currently achieved a favorable outcome in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but parenteral colistin may have limited therapeutic efficacy for CRAB pneumonia. DESIGN: : A controlled, in vivo experimental study. SETTING: : Research laboratory of a medical center. SUBJECTS: : Female BALB/c mice. INTERVENTIONS: : The minimal inhibitory concentrations of antibiotics were measured. Acute pneumonia was established by intratracheal inoculation with an inoculum size of 2.5 x 10 colony-forming units Ab396 plus 10% porcine mucin into the lungs of mice, verified by histopathological examinations, and then treated with or without antibiotics. Mice received intratracheal saline treatment as a control group, intraperitoneal administration (IP) imipenem/cilastatin plus sulbactam (IP IS group, 80/80 mg/kg and 40 mg/kg every 8 hrs, n = 30), IP colistin sulfate (IP CS group, 150,000 U/kg every 8 hrs, n = 30), and intratracheal colistin sulfate (intratracheal CS group, 75,000 U/kg every 8 hrs, n = 30) at 2 hrs after intratracheal inoculation of Ab396. MEASUREMENTS AND MAIN RESULTS: : The minimal inhibitory concentrations of colistin sulfate, imipenem/cilastatin, or sulbactam for Ab396 were 2 microg/mL, 128 microg/mL, or 32 microg/mL, respectively. Compared with the mice in the control, IP IS, and IP CS groups, those in intratracheal CS group had a significantly favorable outcome at 72 hrs after infection (survival rate = 0%, 10%, 0% and 100%, respectively; all p < .001, log-rank test). Furthermore, intratracheal therapy decreased significantly the bacterial loads in the lungs and normalized the wet lung/body weight ratios in mice with acute pneumonia. CONCLUSIONS: : The intratracheal colistin sulfate therapy led to more favorable outcomes than therapies by IP colistin sulfate or imipenem/cilastatin plus sulbactam in mice with early CRAB pneumonia.

Bergapten induces G1 arrest of non­small cell lung cancer cells, associated with the p53­mediated cascade.

The principal subtype of lung cancer, non­small cell lung cancer (NSCLC) is a life­threatening malignancy that causes high mortality rates. Bergapten (5­methoxypsoralen) has been identified to possess anticancer activity against a number of carcinomas. In the present study, the effects of bergapten on NSCLC cells were investigated. The cell viability was determined by MTT assay. Cell cycle distribution was analyzed using flow cytometry. Protein expression and kinase cascade were demonstrated using western blot analysis. The results demonstrated that treatment with bergapten (50 µM for 48 h) inhibited the viability of A549 and NCI­H460 NSCLC cells to 79.1±2.8% and 74.5±3.1%, respectively, compared with the controls. It was identified that bergapten induced G1 phase accumulation in A549 and NCI­H460 cells between ~58 and 75% (P<0.01). In addition, bergapten significantly increased the sub­G1 phase ratio to ~9% (P<0.05) in the two cell types. Further investigation demonstrated that bergapten upregulated the expression of cellular tumor antigen p53 (p53) and its downstream proteins cyclin­dependent kinase inhibitor 1 and cyclin­dependent kinase inhibitor 1B, whereas, it downregulated the expression of cyclin D1 and CDK4. Overall, these results suggested that bergapten may inhibit cell viability and trigger G1 arrest and apoptosis in A549 and NCI­H460 cells, which may be attributed to the activation of p53­mediated cascades. Therefore, bergapten may be beneficial for NSCLC treatment.

Prognosis of patients with acute respiratory failure and prolonged intensive care unit stay.

BACKGROUND: Reasons for the prolonged critical care support include uncertainty of outcome, the complex dynamic created between physicians with care team members and the patient's family over a general unwillingness to surrender to unfavorable outcomes. The purpose of this study was to investigate outcomes and identify risk factors of patients with acute respiratory failure (ARF) who required a prolonged intensive care unit (ICU) stay (≥21 days). It may provide reference to screen patients who are suitable for hospice care. METHODS: The medical records of all ARF patients with a prolonged ICU stay were retrospectively reviewed. The primary outcome was in-hospital mortality. RESULTS: We identified 1,189 patients. Sepsis (n=896, 75.4%) was the most common cause of prolonged ICU stays, following by renal failure (n=232, 19.5%), and unstable hemodynamic status vasopressors or arrhythmia (n=208, 17.5%). Using multivariable logistic regression, we identified eight risk factors of death: age >75 years, ICU stay for more than 28 days, APACHE II score ≥25, unstable hemodynamic status, renal failure, hepatic failure, massive gastrointestinal tract bleeding, and using a fraction of inspired oxygen (FiO2) ≥40%. The overall in-hospital mortality rate was 53.6% (n=637), and it up to 75.3% (216/287) for patients with at least three risk factors. CONCLUSIONS: The outcome of patients with ARF who required prolonged ICU stay was poor. They had a high risk of in-hospital mortality. Palliative care should be considered as a reasonable option for the patients at high risk of death.

The effects of human parvovirus VP1 unique region in a mouse model of allergic asthma.

Evidence has indicated that viral infection increases the risk of developing asthma. Although the association of human parvovirus B19 (B19V) or human bocavirus (HBoV) with respiratory diseases has been reported, little is known about the influence of the B19V-VP1u and HBoV-VP1u proteins on the symptoms of asthma. Herein, we investigated the systemic influence of subcutaneously injected B19V-VP1u and HBoV-VP1u recombinant proteins in an OVA-sensitized asthmatic mouse model. A significantly higher Penh ratio and IgE level were detected in the serum, bronchoalveolar lavage fluid (BALF) and the supernatant of a lymphocyte culture from mice treated with HBoV-VP1u or B19V-VP1u than in a lymphocyte culture from OVA-sensitized mice. Significantly higher levels of serum and BALF IgE, total IgG, IgG1, OVA-specific IgE and OVA-specific IgG1 were detected in mice treated with HBoV-VP1u or B19V-VP1u than in OVA-sensitized mice. Conversely, a significantly lower IgG2a level was detected in mice from the HBoV-VP1u or B19V-VP1u groups than in mice from the OVA group. The mice treated with HBoV-VP1u or B19V-VP1u exhibited more significant lung inflammatory indices, including elevated serum and BALF IL-4, IL-5, IL-10 and IL-13 levels; BALF lymphocyte, neutrophil and eosinophil counts, MMP-9 and MMP-2 activity; and the amount of lymphocyte infiltration, relative to those in the control mice or in those sensitized with OVA. These findings demonstrate that the subcutaneous injection of HBoV-VP1u or B19V-VP1u proteins in OVA-sensitized mice result in elevated asthmatic indices and suggest that human parvoviruses may increase the risk of developing airway inflammation in a mouse model of asthma.

Colistin-sparing regimens against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae isolates: Combination of tigecycline or doxycycline and gentamicin or amikacin.

BACKGROUND/PURPOSE: In vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens. METHODS: Thirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies. RESULTS: Treatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84-100% in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69-100% in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens. CONCLUSION: Enhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application.

Inhibition of poly(adenosine diphosphate-ribose) polymerase attenuates ventilator-induced lung injury.

BACKGROUND: Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury. METHODS: Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34. RESULTS: The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor alpha and interleukin 6, and attenuated the degree of apoptosis in the kidney. CONCLUSION: The pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase reduces ventilator-induced lung injury and protects kidney function.

Idiopathic pulmonary hemosiderosis: favorable response to corticosteroids.

A 50-year-old Taiwanese woman had a history of massive hemoptysis occurring every 6 months for the past 4 years. After each bout of hemoptysis, chest roentgenography would show diffuse alveolar infiltration of bilateral lungs, which would usually resolve within 7 days. Transbronchial biopsy revealed diffuse alveolar hemorrhage and hemosiderin-laden macrophage infiltration. Idiopathic pulmonary hemosiderosis was diagnosed by excluding other glomerular, cardiac and immunological disorders. An initial dose of 20 mg prednisolone daily was tapered to 10 mg daily 1 month later. The patient is currently undergoing steroid therapy, and there have been no further episodes of hemoptysis.

Critical care medicine in Taiwan from 1997 to 2013 under National Health Insurance.

BACKGROUND: Monitoring of trends in the use of the intensive care unit (ICU) and the outcomes of ICU patients is essential for the assessment of the effective use of ICU. This study aims to investigate the incidence and outcome of critical care admissions in Taiwan from 1997 to 2013. METHODS: Patients >18 years who had ICU admission between January 1997 and December 2013 were identified from the National Health Insurance Research Database in Taiwan. The main outcomes including ICU mortality and ICU length of stay (LOS) were measured. RESULTS: A total of 3,451,157 patients with ICU admission were identified during the study period. The mean ICU LOS was 5.9±9.0 days and the overall ICU-mortality rate was 19.8%. The mean age of the patients was 65.4 years old, 58.0% were elderly (≥65 years old), 61.1% were male. Annual incidence of ICU admissions increased from 115,754 in 1997 (age-adjusted incidence: 1,130/100,000 population) to 244,820 in 2013 (incidence: 1,483/100,000 population) (P<0.0001). The admission rate was highest for patients 75-104 years old (8,074 per 100,000 population), and lowest for those 18-44 years old (298 per 100,000 population). Among ICU admission patients, the percentage of patients ≥75 years old significantly increased from 25.2% in 1997 to 38.3% in 2013 (P<0.0001). ICU LOS remained stable during the study period, but the annual mortality rate significantly decreased from 23.0% in 1997 to 16.3% in 2013. CONCLUSIONS: ICU admissions significantly increased from 1997 to 2013, especially for elderly patients, in contrast, the mortality rate of ICU patients significantly declined with time. In addition, the ICU LOS did not change during the study period.