Jhi-Jhu Hwang

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.

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.

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.

Clinical and Radiographic presentations of pulmonary cryptococcosis in immunocompetent patients.

Pulmonary cryptococcosis is often noted in immunocompromized patients, especially in HIV-seropositive patients and post-transplant patients. Only a few case reports and small-scale studies on pulmonary cryptococcosis in immunocompetent patients have been published in the English literature. However, there are several areas of uncertainty in this group of patients including image presentations and management strategy. This retrospective study including 17 patients is designed to share our 7 y of experience in clarifying the characteristics of pulmonary cryptococcosis in immunocompetent patients, including initial symptoms, diagnostic criteria, pulmonary imaging, treatment and outcome in a tertiary teaching hospital in Taiwan.

Combined detection of CEA, CK-19 and c-met mRNAs in peripheral blood: a highly sensitive panel for potential molecular diagnosis of non-small cell lung cancer.

Objective: Detection of tumor-related mRNA in blood has become a potential cancer diagnostic approach. However, the sensitivity of single-marker assays is not high enough for clinical applications. The present study was aimed to evaluate the efficacy of a multimarker panel for molecular diagnosis of non-small cell lung cancer (NSCLC). Methods: Carcinoembryonic antigen (CEA), cytokeratin 19 (CK-19), c-met and heterogeneous nuclear ribonucleoprotein (hnRNP) B1 mRNAs were quantified by quantitative real-time reverse transcriptase polymerase chain reaction in 34 tumor tissues and 69 peripheral blood samples of NSCLC patients. Results: All four markers displayed high overexpression rates (range 82.3–97.1%) in NSCLC tumors. When used as single markers in blood for NSCLC diagnosis, CEA, CK-19, c-met and hnRNP B1 could only reach sensitivities of 52.2, 50.7, 42 and 17.4%, respectively. However, the sensitivity was enhanced up to 85.5% when CEA, CK-19 and c-met were combined in a 3-marker panel. Moreover, the expression of c-met and hnRNP B1 in blood was significantly correlated with patients’ pathological stages. Conclusions:The combined detection of CEA, CK-19 and c-met mRNAs in blood provided a valuable tool for molecular diagnosis of NSCLC. In addition, our results also suggested that hnRNP B1 was not a valuable diagnostic marker but a potential prognostic marker for NSCLC.

Second-hand smoke and chronic bronchitis in Taiwanese women: a health-care based study.

BackgroundCigarette smoking cannot fully explain the epidemiologic characteristics of chronic obstructive pulmonary disease (COPD) in women, particularly for those who rarely smoke, but COPD risk is not less than men. The aim of our study is to investigate the relationship between second-hand smoke (SHS) exposure and chronic bronchitis in Taiwanese women.MethodsWe used Taiwans National Health Insurance Bureau claims data in 1999, and cross-checked using criteria set by the American Thoracic Society; there were 33 women with chronic bronchitis, 182 with probable chronic bronchitis, and 205 with no chronic bronchitis during our interview time between 2000 and 2005. We measured second-hand smoke (SHS) exposure by self-reported measures (household users and duration of exposure), and validated this by measuring urinary cotinine levels of a subset subjects. Classification of chronic bronchitis was also based on spirometry defined according to the GOLD guidelines to get the severity of COPD.ResultsWomen who smoked and women who had been exposed to a lifetime of SHS were 24.81-fold (95% CI: 5.78-106.38) and 3.65-fold (95% CI: 1.19-11.26) more likely to have chronic bronchitis, respectively, than those who had not been exposed to SHS. In addition, there was a significant increasing trend between the severity of COPD and exposure years of SHS (p < 0.01). The population attributable risk percentages of chronic bronchitis for smokers and those exposed to SHS were 23.2 and 47.3% respectively.ConclusionsThese findings indicate that, besides cigarette smoking, exposure to SHS is a major risk factor for chronic bronchitis in Taiwanese women.

Predictors for Identifying the Most Infectious Pulmonary Tuberculosis Patient

BACKGROUND/PURPOSE Clinicians need to decide whether to begin isolation and empiric therapy for patients suspected of having infectious tuberculosis (TB). This study aimed to identify the demographic, clinical and radiographic characteristics of acid-fast bacilli (AFB) smear-positive patients and to create a smear-positive TB prediction rule, which clinicians may use to predict risk. METHODS This was a retrospective study involving 105 patients with AFB smear-positive TB and 52 patients with AFB smear-negative TB at Kaohsiung Municipal Hsiao-Kang Hospital in southern Taiwan from August 1, 2003 to July 31, 2006. All of the patients had at least one sputum culture that was positive for Mycobacterium tuberculosis. Demographic, clinical and radiographic data of patients with AFB smear-positive TB were compared to those of patients with AFB smear-negative TB. RESULTS On univariate analysis, young age (p = 0.033), alcoholism (p = 0.036), weight loss (p = 0.003), fever (p = 0.018), consolidation (p = 0.001), infiltration (p = 0.012), cavitary pattern (p = 0.005), right upper lung field (p < 0.001) and left upper lung field (p = 0.001) lesions on chest radiographs were found to be predictive of smear-positive TB patients. In contrast, end-stage renal disease (p = 0.035) and normal chest radiograph (p = 0.006) were predictive of smear-negative TB patients. On multivariate analysis, age less than 65 years (p = 0.004), fever (p = 0.004), right upper lung field (p = 0.044), left upper lung field (p = 0.041), consolidation (p = 0.018) and cavitary (p = 0.049) lesions on chest radiograph were independently associated with an increased risk of an AFB positive smear finding. The smear-positive TB prediction model was created based on the results of the multivariate analysis that had an area of 0.788 under the receiver operating characteristic curve. CONCLUSION The smear-positive TB prediction model may help clinicians decide if a patient with pending sputum smear results should first be placed in isolation and empiric anti-tuberculous therapy started.