Upregulated microRNA-125b-5p in patients with asthma-COPD overlap mediates oxidative stress and late apoptosis via targeting IL6R/TRIAP1 signaling.

BACKGROUND: Among patients with chronic obstructive pulmonary disease (COPD), some have features of both asthma and COPD-a condition categorized as asthma-COPD overlap (ACO). Our aim was to determine whether asthma- or COPD-related microRNAs (miRNAs) play a role in the pathogenesis of ACO. METHODS: A total of 22 healthy subjects and 27 patients with ACO were enrolled. We selected 6 miRNAs that were found to correlate with COPD and asthma. The expression of miRNAs and target genes was analyzed using quantitative reverse-transcriptase polymerase chain reaction. Cell apoptosis and intracellular reactive oxygen species production were evaluated using flow cytometry. In vitro human monocytic THP-1 cells and primary normal human bronchial epithelial (NHBE) cells under stimuli with cigarette smoke extract (CSE) or ovalbumin (OVA) allergen or both were used to verify the clinical findings. RESULTS: We identified the upregulation of miR-125b-5p in patients with ACO and in THP-1 cells stimulated with CSE plus OVA allergen. We selected 16 genes related to the miR-125b-5p pathway and found that IL6R and TRIAP1 were both downregulated in patients with ACO and in THP-1 cells stimulated with CSE plus OVA. The percentage of late apoptotic cells increased in the THP-1 cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p small interfering RNA (siRNA). The percentage of reactive oxygen species-producing cells increased in the NHBE cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p siRNA. In NHBE cells, siRNA transfection reversed the upregulation of STAT3 under CSE+OVA stimulation. CONCLUSIONS: Our study revealed that upregulation of miR-125b-5p in patients with ACO mediated late apoptosis in THP-1 cells and oxidative stress in NHBE cells via targeting IL6R and TRIAP1. STAT3 expression was also regulated by miR-125b-5p.

Standardized patients' experiences of portraying characters in difficult communication scenarios: Narrative inquiry.

BACKGROUND: There are limited studies that explored the preparation and challenges faced by standardized patients (SPs) in portraying characters in difficult communication scenarios, and the strategies used to overcome these challenges. The purpose of this study was to understand the experience of SPs in interpreting difficult communication situations and the learning needs of performing similar scenarios. And it allows the researchers to explore the meaning, beliefs, values, and aspiration associated with their role as SPs. The findings could shade light on the significance of their experiences and provide valuable insights for the development of future SP training programs. METHODS: The design of this study is framed by a narrative inquiry, using semi-structured guidelines to conduct in-depth interviews with 11 SPs who have participated in the performances of difficult communication situations. Research data were analyzed by Polkinghorne narrative analysis, and Riessman's four criteria were used to establish rigor. RESULTS: Analysis revealed the following five themes: scenarios to real life connections, process of preparing for a performance, methods to detach from character, obtaining unexpected rewards, and needs for performance training. There are two to three subthemes that are subsumed under each theme. CONCLUSIONS: To strengthen training in difficult communication for healthcare professionals, the use of SPs to interpret challenging difficult communication scenarios will continue to increase. Educators need to ensure that SPs are fully prepared physically and emotionally before, during and after their performance. Offering of continuing education and training in feedback techniques are crucial to extend the tenure of SPs, reduce their frustration, prevent attrition, and ultimately, reduce training costs. In the future, SP training should also include detachment and feedback techniques to alleviate SPs' stress.

Body Mass Index, Weight Loss, and Mortality Risk in Advanced-Stage Non-Small Cell Lung Cancer Patients: A Focus on EGFR Mutation.

Body mass index (BMI) influences the prognosis of patients with non-small cell lung cancer (NSCLC), including both early-stage and late-stage NSCLC patients that are undergoing chemotherapies. However, earlier research on the relationship between BMI and survival in patients taking epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) yielded contradictory results. These publications either had a limited number of patients or were getting TKIs in various lines of therapy, which might explain why the outcomes were contradictory. As a result, we undertook retrospective study to examine the effect of BMI on survival outcomes in patients with advanced EGFR mutant NSCLC receiving first-line EGFR-TKIs. We also compared the findings to those with wild-type EGFR. Between November 2010 and March 2014, 513 patients with advanced NSCLC were enrolled in the study. According to the adjusted BMI cut-off point for Asia, 35 out of 513 (6.8%) patients were underweight (BMI < 18.5 kg/m2), whereas 197 (38.4%) were overweight (BMI > 24 kg/m2). Overweight patients with wild-type EGFR exhibited longer progression-free survival (4.6 vs. 2.1 months, p = 0.003) and overall survival (OS) (8.9 vs. 4.3 months, p = 0.003) than underweight patients. Overweight patients with EGFR mutations had a longer OS than normal-weight patients (23.0 vs. 20.2 months, p = 0.025). Bodyweight reduction was related to a shorter OS in both the mutant EGFR patients (17.1 vs. 30.5 months, p < 0.001) and the wild-type EGFR patients (7.8 vs. 18.7 months, p < 0.001). In conclusion, advanced stages NSCLC patients with a lower BMI and early weight loss had a worse outcome that was independent of EGFR mutation status.

Disrupted Expression of Circadian Clock Genes in Patients with Bronchial Asthma.

PURPOSE: Circadian clock is synchronized to the 24-hour day by the daily light-dark cycle and proper function of circadian rhythm is essential for many physiological processes. Disruption of circadian rhythm can affect disease processes and influence disease severity, treatment responses, and even survivorship. In this retrospective case-controlled study, we tried to explore whether expression of circadian clock genes was disturbed in patients with bronchial asthma. PATIENTS AND METHODS: We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes (BMAL1, CK1ε, CLOCK, CRY1, CRY2, PER1, PER2, PER3, and TIM) in total leukocytes of peripheral blood collected at chest clinics from 120 patients with asthma and 60 health individuals. RESULTS: Expression levels of the nine circadian clock genes were significantly different between patients and healthy individuals, but not associated with the asthma control status. We also noted the difference of PER3 expression in asthmatic patients with and without nocturnal symptoms. In well-controlled asthmatics, expression of BMAL1, CK1ε, CLOCK, CRY1, CRY2, and PER1 was significantly lower in patients with nocturnal symptoms than those without nocturnal symptoms. However, in not well-controlled asthmatics, expression of only BMAL1, CK1ε, PER1, and PER2 was significantly different between patients with and without nocturnal symptoms. Binary logistic regression analysis selected BMAL1, CKIε, PER3, and TIM as independent factors for bronchial asthma and ROC curves showed the combined expression of these four genes enhanced the capability of predicting asthma (AUC=0.924; 95% CI=0.875-0.958; P<0.001). CONCLUSION: Our results showed altered expression of circadian clock genes in patients with bronchial asthma and down-regulated PER3 in patients with nocturnal symptoms. Altered expression of circadian clock genes was also observed in asthmatics with or without nocturnal symptoms in well- or not well-controlled subgroups. Combined expression of BMAL1, CKIε, PER3, and TIM could be a potential predictor for bronchial asthma.

Defective formyl peptide receptor 2/3 and annexin A1 expressions associated with M2a polarization of blood immune cells in patients with chronic obstructive pulmonary disease.

BACKGROUND: Controversy exists in previous studies on macrophage M1/M2 polarization in chronic obstructive pulmonary disease (COPD). We hypothesized that formyl peptide receptor (FPR), a marker of efferocytosis and mediator of M1/M2 polarization, may be involved in the development of COPD. METHODS: We examined FPR 1/2/3 expressions of blood M1/M2a monocyte, neutrophil, natural killer (NK) cell, NK T cell, T helper (Th) cell, and T cytotoxic (Tc) cell by flowcytometry method in 40 patients with cigarette smoking-related COPD and 16 healthy non-smokers. Serum levels of five FPR ligands were measured by ELISA method. RESULTS: The COPD patients had lower M2a percentage and higher percentages of NK, NK T, Th, and Tc cells than the healthy non-smokers. FPR2 expressions on Th/Tc cells, FPR3 expressions of M1, M2a, NK, NK T, Th, and Tc cells, and serum annexin A1 (an endogenous FPR2 ligand) levels were all decreased in the COPD patients as compared with that in the healthy non-smokers. FPR1 expression on neutrophil was increased in the COPD patient with a high MMRC dyspnea scale, while FPR2 expression on neutrophil and annexin A1 were both decreased in the COPD patients with a history of frequent moderate exacerbation (≥ 2 events in the past 1 year). In 10 COPD patients whose blood samples were collected again after 1-year treatment, M2a percentage, FPR3 expressions of M1/NK/Th cells, FPR2 expression on Th cell, and FPR1 expression on neutrophil were all reversed to normal, in parallel with partial improvement in small airway dysfunction. CONCLUSIONS: Our findings provide evidence for defective FPR2/3 and annexin A1 expressions that, associated with decreased M2a polarization, might be involved in the development of cigarette smoking induced persistent airflow limitation in COPD.

The impact of de novo liver metastasis on clinical outcome in patients with advanced non-small-cell lung cancer.

Liver metastasis has been found to affect outcome in prostate cancer and colorectal cancer, but its role in lung cancer is unclear. The current study aimed to evaluate the impact of de novo liver metastasis (DLM) on stage IV non-small cell lung cancer (NSCLC) outcomes and to examine whether tyrosine kinase inhibitors (TKI) reverse poor prognosis in patients with DLM and epidermal growth factor receptor (EGFR)-mutant NSCLC. Among 1392 newly diagnosed NSCLC patients, 490 patients with stage IV disease treated between November 2010 and March 2014 at Kaohsiung Chang Gung Memorial Hospital were included. Patients were divided into two groups according to DLM status. There were 75 patients in the DLM group and 415 patients in the non-DLM group. The DLM group included more patients with bone metastasis, fewer patients with a lymphocyte-to-monocyte ratio (LMR) > 3.1, and fewer patients with pleural metastasis. In the DLM group, Eastern Cooperative Oncology Group performance status 3-4 and LMR ≦3.1 were associated with poor outcome. In patients without DLM, overall survival (OS) was longer in patients with EGFR-mutant NSCLC than in those without (20.2 vs. 7.3 months, p < 0.001). Among DLM patients, OS was similar between the EGFR-mutant and wild-type EGFR tumor subgroups (11.9 vs. 7.7 months, p = 0.155). We found that DLM was a significant poor prognostic factor in the EGFR-mutant patients treated with EGFR-TKIs, whereas DLM did not affect the prognosis of EGFR-wild-type patients.

A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases.

In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC patients with de novo bone metastases. This retrospective study evaluated 1510 NSCLC patients diagnosed between November 2010 and March 2014. Among these patients, 234 patients had de novo bone metastases. We found that 121 of these 234 patients (51.7%) had positive EGFR mutation tests, and a positive EGFR mutation test significantly affected overall survival (OS) (EGFR mutant: 15.2 months, EGFR wild type: 6.5 months; p < 0.001). Other prognostic factors significant in the multivariable analysis for NSCLC with de novo bone metastases included Eastern Cooperative Oncology Group performance status (PS) (OS; PS 0-2: 11.2 months, PS 3-4: 4.9 months; p = 0.002), presence of extraosseous metastases (OS; with extraosseous metastases: 8.8 months, without extraosseous metastases: 14.0 months; p = 0.008), blood lymphocyte-to-monocyte ratio (LMR) (OS; LMR > 3.1: 17.1months, LMR ≤ 3.1: 6.9months; p < 0.001). A positive EGFR mutation status reversed the poor outcomes of NSCLC patients with de novo bone metastases. A simple and useful survival scoring system including the above clinical parameters was thus created for NSCLC patients with de novo bone metastases.

Impact of clinical parameters and systemic inflammatory status on epidermal growth factor receptor-mutant non-small cell lung cancer patients readministration with epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration to lung cancer patients is common owing to the few options available. Impact of clinical factors on prognosis of EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKI readministration after first-line EGFR-TKI failure and a period of TKI holiday remains unclear. Through this retrospective study, we aimed to understand the impact of clinical factors in such patients. METHODS: Of 1386 cases diagnosed between December 2010 and December 2013, 80 EGFR-mutant NSCLC patients who were readministered TKIs after failure of first-line TKIs and intercalated with at least one cycle of cytotoxic agent were included. We evaluated clinical factors that may influence prognosis of TKI readministration as well as systemic inflammatory status in terms of neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Baseline NLR and LMR were estimated at the beginning of TKI readministration and trends of NLR and LMR were change amount from patients receiving first-Line TKIs to TKIs readministration. RESULTS: Median survival time since TKI readministration was 7.0 months. In the univariable analysis, progression free survival (PFS) of first-line TKIs, baseline NLR and LMR, and trend of LMR were prognostic factors in patients receiving TKIs readministration. In the multivariate analysis, only PFS of first-line TKIs (p < 0.001), baseline NLR (p = 0.037), and trend of LMR (p = 0.004) were prognostic factors. CONCLUSION: Longer PFS of first-line TKIs, low baseline NLR, and high trend of LMR were good prognostic factors in EGFR-mutant NSCLC patients receiving TKI readministration.

Tanshinone IIA Modulates Low Density Lipoprotein Uptake via Down-Regulation of PCSK9 Gene Expression in HepG2 Cells.

Tanshinone IIA, one of the most pharmacologically bioactive phytochemicals isolated from Salvia miltiorrhiza Bunge, possesses several biological activities such as anti-inflammation, anti-cancer, neuroprotection and hypolipidemic activities. In this study, we aim to investigate the hypocholesterolemic effect of tanshinone IIA in hepatic cells. We demonstrated that tanshinone IIA significantly increased the amount of low-density lipoprotein receptor (LDLR) and LDL uptake activity in HepG2 cells at the post-transcriptional regulation. We further demonstrated that tanshinone IIA inhibited the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and mature protein, which may lead to an increase the cell-surface LDLR in hepatic cells. We further identified a regulatory DNA element involved in the tanshinone IIA-mediated PCSK9 down-regulation, which is located between the -411 and -336 positions of the PCSK9 promoter. Moreover, we found that tanshinone IIA markedly increased the nuclear forkhead box O3a (FoxO3a) level, enhanced FoxO3a/PCSK9 promoter complexes formation and decreased the PCSK9 promoter binding capacity of hepatocyte nuclear factor 1α (HNF-1α), resulting in suppression of PCSK9 gene expression. Finally, we found that the statin-induced PCSK9 overexpression was attenuated and the LDLR activity was elevated in a synergic manner by combination of tanshinone IIA treatment in HepG2 cells. Overall, our results reveal that the tanshinone IIA modulates LDLR level and activity via down-regulation of PCSK9 expression in hepatic cells. Our current findings provide a molecular basis of tanshinone IIA to develop PCSK9 inhibitors for cholesterol management.

Advanced non-Small cell lung cancer patients at the extremes of age in the era of epidermal growth factor receptor tyrosine kinase inhibitors.

OBJECTIVES: The clinical characteristics and survival of very young (≤40 years) and very old (>80years) patients with advanced non-small cell lung cancer (NSCLC) are distinct. However, the benefits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to patients at the extremes of age with NSCLC harboring EGFR mutation have not been well studied. We retrospectively studied the effect of extreme age on patients' clinical characteristics and prognosis. MATERIALS AND METHODS: Of 1510 lung cancer patients diagnosed between November 2010 and March 2014, 555 patients who were tested for EGFR mutations were included. Patients were divided into the following groups according to age: young (≤40 years), lower medium (41-60 years), higher medium (61-80years), and very old (>80years). RESULTS: Of the 555 patients, 20 (3.6%) patients were aged ≤40 years and 60 (10.8%) patients were aged >80years. Young NSCLC patients had a lower BMI (p=0.003), more brain (p=0.016) and bone metastases (p=0.002) Very young lung cancer patients still have poor prognosis even they were EGFR mutant. (EGFR mutant vs. wild type patients, OS: 12 vs. 7.3 months, p=0.215) Very old NSCLC patients had a lower BMI (p=0.003) and poor ECOG PS (p=0.028). Positive EGFR mutation test reverses poor prognosis of elderly NSCLC patients. (EGFR mutant vs. wild type patients, OS: 13.2 vs. 4.9 months, p=0.003) CONCLUSION: We observed EGFR mutations reverse the poor prognosis of old patients with NSCLC. However, young patients with lung cancer have a poor prognosis even if they harbor EGFR mutations.

Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

BACKGROUND: Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases. MATERIALS AND METHODS: This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users. RESULTS: Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases. CONCLUSION: Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.

Baseline and Trend of Lymphocyte-to-Monocyte Ratio as Prognostic Factors in Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer Patients Treated with First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

BACKGROUND: Patients with early-stage lung cancer who have a high baseline lymphocyte-to-monocyte ratio (LMR) have a favorable prognosis. However, the prognostic significance of LMR in patients with advanced-stage EGFR-mutant non-small cell lung cancer (NSCLC) receiving first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has not been established. We conducted a retrospective analysis to investigate the influence of LMR on clinical outcomes including progression-free survival (PFS) and overall survival (OS) in EGFR-mutant patients with NSCLC. MATERIALS AND METHODS: Of 1310 lung cancer patients diagnosed between January 2011 and October 2013, 253 patients receiving first-line EGFR-TKIs for EGFR-mutant NSCLC were included. The cut-off values for baseline and the 1-month-to-baseline ratio of LMR (MBR), determined by using receiver operating characteristic curves, were 3.29 and 0.63, respectively. Patients were divided into 3 prognostic groups: high LMR and MBR, high LMR or MBR, and low LMR and MBR. RESULTS: The mean patient age was 65.2 years, and 41% were men. The median PFS and OS were 10.3 and 22.0 months, respectively. The PFS in patients with high LMR and MBR, high LMR or MBR, and low LMR and MBR were 15.4, 7.1, and 2.0 months, respectively (p < 0.001), whereas the OS were 32.6, 13.7, and 5.1 months, respectively (p < 0.001). CONCLUSION: A combination of baseline and trend of LMR can be used to identify patients with a high mortality risk in EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs.

Bilateral Diaphragmatic Paralysis in a Patient With Critical Illness Polyneuropathy: A Case Report.

Bilateral diaphragmatic paralysis (BDP) manifests as respiratory muscle weakness, and its association with critical illness polyneuropathy (CIP) was rarely reported. Here, we present a patient with BDP related to CIP, who successfully avoided tracheostomy after diagnosis and management.A 71-year-old male presented with acute respiratory failure after sepsis adequately treated. Repeated intubation occurred because of carbon dioxide retention after each extubation. After eliminating possible factors, septic shock-induced respiratory muscle weakness was suspected. Physical examination, a nerve conduction study, and chest ultrasound confirmed our impression.Pulmonary rehabilitation and reconditioning exercises were arranged, and the patient was discharged with a diagnosis of BDP.The diagnosis of BDP is usually delayed, and there are only sporadic reports on its association with polyneuropathy, especially in patients with preserved limb muscle function. Therefore, when physicians encounter patients that are difficult to wean from mechanical ventilation, CIP associated with BDP should be considered in the differential diagnosis.

Urinary neutrophil gelatinase-associated lipocalin and clinical outcomes in chronic kidney disease patients.

BACKGROUND: Tubulointerstitial damage is a final common pathway of most renal diseases. Whether urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker for renal tubular damage, is of prognostic value for clinical outcomes in chronic kidney disease (CKD) patients has not been well investigated. METHODS: The uNGAL and proteinuria levels were measured among a cohort of 473 advanced CKD patients of various etiologies recruited during 2002-2009. RESULTS: The estimated glomerular filtration rate (eGFR) was 32.3±22.0 mL/min/1.73 m2 with a urine protein-to-creatinine ratio (UPCR) 680 (255-1248) mg/g and 132 (27.9%) participants had diabetes. The baseline uNGAL level was significantly associated with male gender, eGFR, UPCR, and hemoglobin. The hazard ratio (HR) of the highest uNGAL tertile for end-stage renal disease (ESRD) was 3.44 (95% CI 1.47-8.06, p=0.004). With the adjustment of urine creatinine and urine protein, HR of the highest urine NGAL-to-creatinine ratio (UNCR) tertile and the highest urine NGAL-to-protein ratio (UNPR) tertile was 3.06 (95% CI 1.19-7.90, p=0.02) and 2.10 (95% CI 1.13-3.89, p=0.02), respectively. UNPR increased the prediction of survival model for ESRD. HR of the highest UNCR tertile and UNPR tertile for cardiovascular (CV) events was 2.21 (95% CI 0.81-5.98, p=0.08) and 2.79 (95% CI 1.25-6.26, p=0.01), respectively. None of these were associated with all-cause mortality. CONCLUSIONS: Elevated uNGAL in CKD patients is associated with risks for ESRD and probably CV events. UNPR could improve the prediction for ESRD.

Influencing factors of successful eradication of multidrug-resistant Acinetobacter baumannii in the respiratory tract with aerosolized colistin.

BACKGROUND: The increased prevalence of multidrug-resistant Acinetobacter baumannii (MDRAB) poses a worldwide treatment challenge. Although aerosolized colistin therapy for MDRAB pneumonia has attracted increasing interest, factors influencing successful eradication remain unclear. METHODS: This retrospective study evaluated 135 consecutively admitted adult patients showing positive respiratory secretion cultures for MDRAB who underwent aerosolized colistin therapy between January 2007 and November 2011. Possible factors related to pneumonia and MDRAB eradication were collected for analysis. RESULTS: Patients with successful MDRAB eradication on Day 14 had a shorter interval between the day the positive MDRAB sputum cultures were yielded and the day colistin inhalation treatment began (4.0 ± 2.5 vs. 7.3 ± 6.5; p = 0.002). Patients with a worsening chest X-ray on Day 7 of the colistin inhalation had a lower chance of 14-day MDRAB eradication [1/44 (2.3%) vs. 8/37 (21.6%); p = 0.006]. Patients with diabetes mellitus also had a lower chance of early MDRAB eradication [13/44 (29.5%) vs. 20/37 (54.1%); p = 0.025]. CONCLUSIONS: Early intervention using aerosolized colistin in patients with MDRAB pneumonia or colonization can achieve better eradication.

Impact of serum biomarkers and clinical factors on intensive care unit mortality and 6-month outcome in relatively healthy patients with severe pneumonia and acute respiratory distress syndrome.

OBJECTIVES: This study aimed to identify the independent biomarkers and clinical factors that could predict ICU mortality and 6-month outcomes in relatively healthy patients with severe pneumonia and acute respiratory distress syndrome (ARDS). PATIENTS AND METHODS: We prospectively enrolled patients with severe pneumonia-related ARDS that required mechanical ventilation. Patients were excluded if they were unable to take care of themselves. Several biomarkers and clinical factors were evaluated prospectively on day 1 and day 3 after ICU admission. All biomarkers and clinical factors were collected for analysis. RESULTS: 56 patients were enrolled in this study. We determined that the initial appropriate antibiotics use was an independent clinical factor and day 1 high-mobility group protein B1 (HMGB1) concentration was an independent biomarker for ICU mortality. Interestingly, we also found that a low day 1 albumin level was an independent biomarker for predicting patient life dependence 6 months after a pneumonia event. CONCLUSION: Patients with severe pneumonia and ARDS requiring mechanical ventilation experience high rates of ICU mortality or disability, even if they were quite healthy before. Initial appropriate antibiotics use and day 1 level of HMGB1 were independent factors for predicting ICU mortality. Day 1 albumin level was predictive of 6-month patient life dependence.

Significantly Higher Percentage of Circulating CD27(high) Plasma Cells in Systemic Lupus Erythematosus Patients with Infection than with Disease Flare-Up

PURPOSE: To distinguish lupus flare-up from infection in systemic lupus erythematosus (SLE), we analyze the expression of circulating CD27(high) plasma cells in SLE patients with and without infection, in comparison to non-SLE patients with infection. MATERIALS AND METHODS: The percentage of circulating CD27(high) plasma cells was measured by flow cytometry in the following four groups: 36 SLE patients without infection, 23 SLE patients with infection, eight non-SLE patients with infection, and 26 healthy controls. RESULTS: The frequency of CD27(high) plasma cells had a correlation with the SLE disease activity index (SLEDAI) (r = 0.866, p < 0.05), level of anti-dsDNA (r = 0.886, p < 0.05), C3 (r = - 0.392, p < 0.05), and C4 (r = - 0.337, p < 0.05) in SLE patients without infection, but there was no correlation with disease activity in SLE patients with infection. Among three groups in particular-SLE without infection, SLE with infection, and non-SLE with infection-the percentages of CD27(high) plasma cells were elevated. The percentage of CD27(high) plasma cells was higher in SLE patients with infection, when compared to SLE patients without infection. CONCLUSION: The percentage of CD27(high) plasma cells is a biomarker for disease activity of SLE without infection, under correlation with SLEDAI, anti-dsDNA, and C3 and C4 level. However, when the SLE patients have an infection, the percentage of CD27(high) plasma cells is not an adequate biomarker for the survey of disease activity. The percentage of CD27(high) plasma cells may serve as a potential parameter to distinguish a lupus flare-up from infection.

Differential promoter usage of mouse mu-opioid receptor gene during development.

Previously, we demonstrated that mouse mu-opioid receptor (MOR) gene expression is regulated by both distal and proximal promoters, with the latter playing a major role in controlling MOR transcription in the adult mouse brain. Here, we report studies of the relative usages of the mouse MOR dual promoters during murine development. We used the reverse transcription-polymerase chain reaction (RT-PCR) method, which gave results similar to those using binding assays or in situ hybridization. However, due to the greater sensitivity of RT-PCR method, we were able to detect the emergence of MOR as early as at embryonic day 8.5 (E8.5). We found that both proximal and distal promoters were active at E8.5. The proximal promoter initiated approximately two-thirds of total MOR transcripts at E8.5, with the distal promoter directing transcription of the remaining one-third. This is the greatest relative contribution of the distal promoter to MOR transcription we have observed during any time in development. Thereafter, the percentage of transcripts directed by the distal promoter gradually declined, and remained at a low but detectable level (approximately 5% of total MOR transcripts) throughout development and adulthood. Conversely, a progressive increase of the contribution of the proximal promoter to MOR transcription was observed during development, reaching its maximum in the adult. In summary, our results demonstrated the pivotal role of the proximal promoter in directing MOR transcription during murine development.