Inn-Wen Chong

Impact of type 2 diabetes on manifestations and treatment outcome of pulmonary tuberculosis.

Diabetes mellitus (DM) is a known risk factor for pulmonary tuberculosis (PTB). This study aimed to determine if type 2 DM alters manifestations and treatment outcome of PTB. Records of 217 consecutive culture-proven PTB patients were analysed retrospectively. The manifestations and treatment outcomes of 74 patients with type 2 DM (PTB-DM group) were compared to 143 patients without DM (PTB group). PTB-DM patients showed higher frequencies of fever, haemoptysis, positive acid-fast bacilli sputum smears, and consolidation, cavity, and lower lung field lesions on chest radiographs, and higher mortality rate. Furthermore, type 2 DM, age 65 years, and extensive radiographic disease were factors independently associated with an unfavorable outcome. This study confirmed that clinical manifestations and chest radiographs of PTB patients associated with type 2 DM significantly depart from the typical presentation. Type 2 DM seems to have a negative effect on treatment outcome of PTB.

Combination of multiple mRNA markers (PTTG1, survivin, UbcH10 and TK1) in the diagnosis of taiwanese patients with breast cancer by membrane array

Objective: Early detection is a prerequisite to the effective reduction of morbidity and mortality from breast cancer. The present study intended to employ a high-throughput membrane array to detect a panel of mRNA markers expressed by circulating tumor cells (CTCs) in the peripheral blood of female patients with breast cancer. Methods: Peripheral blood was sampled from 92 breast cancer patients and 100 normal persons. CTCs were detected by using a membrane array technique. The markers used included the pituitary tumor transforming gene 1, survivin, UbcH10 and thymidine kinase 1. Results: The results showed that the membrane array could positively detect 5 cancer cells per 1 ml of peripheral blood in breast cancer cell dilution experiments. For the panel of 4 mRNA markers, sensitivity and specificity were elevated up to 86 and 88%, respectively. Furthermore, it was found that the patients’ clinicopathological characteristics tumor size (p = 0.006), histologic grade (p = 0.012), lymph node metastasis (p = 0.001) and TNM stage (p = 0.006) significantly correlated with the positive detection rate of the multimarker panel. Conclusions: These findings demonstrated that our multimarker membrane array method could detect CTCs in the circulation of breast cancer patients with considerably high sensitivity and specificity.

High expression of heme oxygenase-1 is associated with tumor invasiveness and poor clinical outcome in non-small cell lung cancer patients

BackgroundHeme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, is known to play a role in the protection of cells against oxidative stress, inflammation, anomalous proliferation and apoptosis. As yet, the role of HO-1 expression in non-small cell lung cancer (NSCLC) development and metastasis remains unclear and insufficient data are available regarding its impact on the prognosis of NSCLC patients.MethodsSeventy NSCLC patients who underwent surgical resection were included in this HO-1 expression study and, concomitantly, clinical parameters were collected. Two lung adenocarcinoma cell lines (A549 and H441) were used to assess both invasive and migratory parameters in vitro.ResultsNSCLC patients with a high HO-1 expression ratio (tumor tissue/normal tissue) (> 1) exhibited a significantly poorer prognosis and a higher metastatic rate compared to those with a low HO-1 expression ratio (p < 0.05). The invasive and migratory abilities of A549 and H441 cells significantly increased after exogenous HO-1 over-expression and significantly decreased after siRNA-mediated HO-1 expression silencing. HO-1 up- and down-regulation also positively correlated with the expression of metastasis-associated proteins EGFR, CD147 and MMP-9. In addition, we found that HO-1 expression can be inhibited by PI3K and AKT inhibitors, but not by MAPK inhibitors.ConclusionsHO-1 is a poor prognostic NSCLC predictor and its over-expression may increase the metastatic potential of NSCLC. Based on our findings and those of others, HO-1 may be considered as a novel NSCLC therapeutic target.

The Impact of Age on the Demographic, Clinical, Radiographic Characteristics and Treatment Outcomes of Pulmonary Tuberculosis Patients in Taiwan

Background:The characteristics of pulmonary tuberculosis (TB) in the elderly are different from young patients. This leads to delay in diagnosis and higher mortality from TB in the aged population. The aim of this study was to investigate the impact of age on the demographic, clinical, radiographic characteristics, and treatment outcomes of pulmonary TB patients in Taiwan.Materials and Methods:We performed a retrospective analysis of the medical charts and chest radiographs of 83 elderly (≥60 years old) and 74 young (< 60 years old) culture-proven pulmonary TB patients from 1 August 2003 to 31 July 2006.Results:Elderly patients showed lower frequencies of infectious TB contact history, alcoholism, cavity, and positive acid-fast bacilli sputum smears. In contrast, the elderly population had higher frequencies of chronic obstructive lung disease, heart failure, stroke, dyspnea, lower lung field involvement, pleural effusion and mortality. There were no differences between these two groups regarding sex, initial body weight, previous TB disease, hospital admission, diabetes mellitus, end-stage renal disease, neoplasm, liver cirrhosis, upper lung field involvement, cure, and treatment completion. Furthermore, age of 60 and older, lower initial body weight less than 50 kg, coexisting medical diseases, and extensive radiographic disease were factors independently associated with unfavorable outcomes.Conclusions:Elderly patients with pulmonary TB are more likely to present with negative sputum smears, cavitynegative lesions, lower lung field involvement and pleural effusion on chest radiographs. The prognosis is poor for the elderly pulmonary TB patients with lower body weight, coexisting medical diseases, and extensive radiographic disease.

Decreased expression of thrombomodulin is correlated with tumor cell invasiveness and poor prognosis in nonsmall cell lung cancer

Thrombomodulin (TM) plays a role in coagulation, inflammation, and cell adhesion. Reduction of TM expression plays an important role in the tumor metastatic process; however, insufficient information is available regarding the expression of TM in nonsmall cell lung cancer (NSCLC). Sixty NSCLC patients who underwent surgery were reviewed for TM expression and multiple variables were assessed by univariate and multivariate analyses. The expression level of TM and its metastatic ability were examined in vitro using the human NSCLC A549 cell line. TM expression in NSCLC was significantly correlated with survival; the 5‐yr survival rates of patients with high and low TM expression were 23% and 18% (P < 0.01), respectively. Distribution of TM was detected predominantly in the normal lung tissue compared with lung cancer tissue. Western blot analysis showed, on average, decreased expression levels of TM protein in the lung cancer tissues of patients with NSCLC. An in vitro study also showed that overexpression of TM can inhibit the invasiveness and migration ability of the A549 cell line, whereas silencing of TM significantly enhanced these processes. This inhibition of cellular migration by overexpression of TM was significantly prevented by the selective inhibitors of PI3K and Akt, but not by MAPK inhibitors. This study demonstrates that a decrease in TM expression may be an indicator in the prognosis of NSCLC patients and provides new insights into the molecular mechanisms of TM in the metastasis of NSCLC.

Overexpression of Circulating c-Met Messenger RNA Is Significantly Correlated With Nodal Stage and Early Recurrence in Non-Small Cell Lung Cancer

BACKGROUND The c-met receptor and its ligand hepatocyte growth factor have been shown to be involved in tumor invasiveness and metastasis. Overexpression of c-met has been demonstrated in lung cancer tissues and cell lines, but the expression of c-met in peripheral blood (circulating c-met) has not been addressed. The molecular monitoring of circulating c-met could be helpful for selecting patients for adjuvant therapy. OBJECTIVES To investigate the expression of circulating c-met in non-small cell lung cancer (NSCLC) patients and to assess its prognostic implications. METHODS We quantified the levels of c-met messenger RNA (mRNA) in paired tumor and normal lung tissues and their peripheral bloods in 45 patients with NSCLC by real-time polymerase chain reaction (PCR). The expression status of c-met protein in tumor tissues was further evaluated by immunohistochemistry. RESULTS c-Met mRNA was significantly higher by 1.5 to 11 times in 34 of 45 tumor tissues (75.5%) than it was in their normal counterparts by real-time PCR. A comparison of this assay to immunohistochemistry suggested that real-time PCR was more sensitive than immunohistochemistry (27 of 45 tumor tissues, 60.0%) for the detection of c-met (p = 0.016). Of these patients with overexpression of c-met in tumors, 67.6% (23 of 34 patients) expressed higher amounts of circulating c-met by 1.4 to 8 times that of the normal control subjects. In addition, overexpression of circulating c-met was significantly correlated with nodal (N) stage (p = 0.011), but weakly correlated with tumor (T) stage (p = 0.056) and overall stages (p = 0.054) in patients with NSCLC. However, no correlations were found among circulating c-met and other factors such as age, gender, and pathologic types. Moreover, by univariate analysis, circulating c-met overexpression and pathologic stages (including T and N stages) were the most important factors correlated with early recurrence (p < 0.05). Only the circulating c-met remained as an independent predictor of early recurrence (hazard ratio, 3.94; 95% confidence interval, 1.17 to 13.33; p = 0.027) after Cox regression multivariate analysis. CONCLUSIONS Overexpression of circulating c-met is significantly correlated with the N stage and early recurrence. Moreover, early recurrence is frequently noted in patients with overexpression of circulating c-met, indicating that circulating c-met is an independent negative prognostic indicator in NSCLC.

Admission Time and Outcomes of Patients in a Medical Intensive Care Unit

Studies have shown that weekend or night admissions to intensive care units (ICUs) are associated with increased mortality in critically ill patients. Our study aimed to evaluate the effects of admission time and day on patient outcomes in a medical ICU equipped with patient management guidelines, and staffed by intensivists on call for 24 hours, who led the morning rounds on all days of the week but did not stay in‐house overnight. The study enrolled 611 consecutive patients admitted to a 26‐bed medical ICU in a university hospital during a 7‐month period. We divided them into two groups, which we labeled as “office hours” (08:00–18:00 on weekdays) and “non‐office hours” (18:00–08:00 on weekdays, and all times on weekends) according to their ICU admission times. The clinical outcomes were compared between the groups. The effects of admission on weekends, at night, and various days of the week on hospital mortality were also evaluated. Our results showed that there were no significant differences in ICU and hospital mortalities between patients admitted during office hours and those admitted during non‐office hours (27.2% vs. 27.4%, p = 1.000; 38.9% vs. 37.6%, p = 0.798). The ICU length of stay, ICU‐free time within 21 days, and length of stay in the hospital were also comparable in both groups. Among the 392 patients requiring mechanical ventilation, the ventilator outcomes were not significantly different between those in the office‐hour group and the non‐office‐hour group. Multivariate logistic regression analyses showed that the adjusted odds of hospital mortality were not significantly higher for patients admitted to our ICU on weekends, at night, or on any days of the week. In conclusion, our results showed that non‐office‐hour admissions to our medical ICU were not associated with poorer ICU, hospital, and ventilator outcomes, compared with office‐hour admissions. Neither were time of day and day of the week admissions to our ICU associated with significant differences in hospital mortality.

ORGANOPHOSPHATE POISONING: 10 YEARS OF EXPERIENCE IN SOUTHERN TAIWAN

Poisoning due to organophosphate pesticides is an important cause of morbidity and mortality worldwide. Although standard treatments involving the administration of atropine and oximes have been used, there remain many controversial areas concerning organophosphate poisoning (OPP). Herein, we present our 10 years of experience in assessing the severity of OPP in southern Taiwan. A retrospective study was performed on patients admitted with OPP. A total of 75 patients (50 males and 25 females) were studied between January 1996 and December 2005. Diagnosis was based on a clinical assessment and serum acetylcholinesterase (AChE) level at the time of hospital admission. The severity of OPP was assessed using the grading system of Bardin et al. The duration and dosage of atropine and palidroxime were recorded. All the biochemical data were analyzed. Sixty‐one of the patients had attempted suicide and 14 patients had accidental exposure. The overall mortality rate was 8%. Muscarinic effects were observed in 66 (88%) of the OPP patients and the most frequent symptom was bronchial hypersecretion (52%). Among these three different severity groups, prolonged length of stay, higher infection rates, and higher mortality were found in the life‐ threatened group. The initial serum C‐reactive protein (CRP) level was strongly correlated to the severity grading of the OPP. Nearly half of the patients were admitted to the intensive care unit (ICU) and, of this, 21 patients developed respiratory failure within 72 hours. Low serum AChE levels support the diagnosis of OPP, but no significant association was found between the severity of OPP and serum AChE levels. The grading system of Bardin et al is very helpful for physicians to facilitate the recognition of seriously poisoned subjects, and to permit their early admission to an ICU. Initial serum CRP, an acute phase reactant, had significant value in assessing the severity of the OPP. Although the management of acute OPP is supportive and the recovery rate is high, anti‐cholinergic therapy should be used as soon as possible to counteract muscarinic effects. Physicians must be aware of the potential dangers of respiratory failure, which could occur within 72 hours of OPP.

Correlation between EGFR mutation status and computed tomography features in patients with advanced pulmonary adenocarcinoma.

Purpose: To correlate computed tomography (CT) imaging features and epidermal growth factor receptor (EGFR) mutation status in patients with advanced lung adenocarcinoma. Materials and Methods: Patients with advanced pulmonary adenocarcinoma who were diagnosed between January 1, 2009 and December 31, 2011 and who had available chest CT and their tumors analyzed for EGFR mutations at a university hospital were enrolled in this retrospective study. Two radiologists independently evaluated the CT images and recorded the target lesions size, shape, margin, density, and the presence or absence of an air bronchogram and calcification. Results: One hundred and forty-nine patients were enrolled into this study (66 men, 83 women), with a mean age of 63±11 years (range 32 to 89 y). Seventy-eight (52.3%) patients had EGFR mutations. The tumors in the patients harboring no EGFR mutations (EGFR wild type) were larger than in those whose tumors harbored EGFR mutations (P=0.01). An irregular shape was more common in the tumors with wild-type EGFR (P=0.01), and an oval shape was more common in tumors with EGFR mutations. Tumors with exon 21 mutations were larger than those with exon 19 deletions (P=0.02). Air bronchograms were more common in tumors with exon 19 deletions than in those with wild-type EGFR or exon 21 mutations (P=0.004 and 0.01, respectively). Calcification was more common in the tumors with wild-type EGFR than in those with EGFR mutations (P=0.03). Conclusions: Adenocarcinomas with wild-type EGFR were significantly associated with larger tumors and an irregular shape. In particular, calcification was more common in the tumors with wild-type EGFR than in those with EGFR mutations. In addition, air bronchograms were more common in the tumors with exon 19 deletions.

Regulation of chemokine mRNA expression in a rat model of vanadium-induced pulmonary inflammation.

Environmental and occupational exposure to vanadium dusts results in toxic effects mainly confined to the respiratory system. Using a rat model of acute lung inflammation induced by intratracheal instillation of sodium metavanadate (NaVO3) at the dose of 200 μg V/kg, we investigated the relationship between the cytologic characterization of pulmonary inflammation and the expression of chemokine mRNA. Significant polymorphonuclear leukocyte (PMN) influx (P < 0.01) into the lung was noted 4 h after NaVO3 instillation, whereas alveolar macrophages (AMs) in bronchoalveolar lavage (BAL) cells appeared to decrease significantly. In contrast, neither PMNs nor AMs changed substantially 1 h after NaVO3 instillation. By Northern analysis, macrophage inflammatory protein (MIP)-2 mRNA in BAL cells increased markedly 1 h after NaVO3 instillation and reduced a little bit at 4 h, whereas MIP-1α mRNA in BAL cells was expressed relatively high 1 h after NaVO3 instillation, although a basal expression was detected in control group, and returned rapidly nearly to control level at 4 h. Since MIP-2 is a potent PMN chemoattractant and MIP-1α is a potent macrophage/monocyte chemoattractant has been well known. The facts that PMN influx was preceded by increased MIP-2 mRNA expression, suggesting that MIP-2 is involved in the development of NaVO3-induced pulmonary inflammation, whereas increased MIP-1α mRNA expression was followed by decreased AMs in BAL cells, suggesting AMs might be activated by MIP-1α, adherent to the lining surface of the airways and then resistant to be washed out. To delineate the mechanisms of transcriptional activation, we recently cloned the 5′-flanking region of the MIP-2 gene. The promotor region contains consensus binding sites for transcription factor nuclear factor κβ (NF-κB) and activator protein-1 (AP-1). Using electrophoretic mobility shift assay, increased nuclear NF-κB, not AP-1, binding activity was detected 1 h after NaVO3 instillation, which correlated with the induction of MIP-2 mRNA. p65 (Rel A) and p50 protein appears to be involved in MIP-2 NF-κB binding. Taken together, our studies suggest that MIP-2 is an important mediator of NaVO3-induced pulmonary inflammation in the rat model. In addition, elevated MIP-2 mRNA levels are accompanied by increased NF-κB binding activity in BAL cells, suggesting possible MIP-2 transcriptional regulation through NF-κB.