Yao-Wen Kuo

Acinetobacter baumannii and Acinetobacter genospecies 13TU and 3 bacteraemia: comparison of clinical features, prognostic factors and outcomes

OBJECTIVES To investigate the clinical impact of different genospecies of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB complex; A. baumannii, Acinetobacter gen. sp. 13TU and Acinetobacter gen. sp. 3) on the severity of bacteraemia. METHODS We retrospectively compared the clinical features and outcomes of patients with bacteraemia caused by A. baumannii, Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3. The genospecies were identified using oligonucleotide array sequence analysis (interspacer sequence), and the clonality of Acinetobacter gen. sp. 13TU and 3 isolates was determined by PFGE analysis. RESULTS A total of 215 patients with bacteraemia due to ACB complex were evaluated. Among them, 117 (54.4%) had A. baumannii bacteraemia, 77 (35.8%) had Acinetobacter gen. sp. 13TU bacteraemia and 21 (9.8%) had Acinetobacter gen. sp. 3 bacteraemia. A. baumannii bacteraemia was associated with a higher 14 day mortality rate (P < 0.001), a higher 30 day mortality rate (P < 0.001) and a higher in-hospital mortality rate than bacteraemia due to Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3. Independent prognostic factors for the 30 day mortality included the Charlson co-morbidity index (P < 0.001) and Pitt bacteraemia score (P < 0.001). Bloodstream infection caused by a multidrug-resistant A. baumannii isolate appeared to be associated with a poor outcome (P = 0.069). There was no clonal spread of Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3 during the study period. CONCLUSIONS Bacteraemia due to multidrug-resistant strains but not A. baumannii per se appears to be associated with poor outcome.

EML4-ALK Translocation Predicts Better Outcome in Lung Adenocarcinoma Patients with Wild-Type EGFR

Introduction: The echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion represents a novel target in a subset of non-small cell lung cancer, especially adenocarcinoma. EML4-ALK fusion is mutually exclusive with epidermal growth factor receptor (EGFR) mutations. To understand the impact of EML4-ALK on the prognosis of non-small cell lung cancer, we examined EML4-ALK fusion in lung adenocarcinoma from patients with wild-type EGFR and analyzed their clinical treatment outcomes. Methods: Lung adenocarcinoma patients with malignant pleural effusions having wild-type EGFR and measurable target lesions were enrolled for EML4-ALK analysis by reverse transcription-polymerase chain reaction and direct sequencing. Demographic data, EML4-ALK status, and survival data were analyzed. We also performed fluorescence in situ hybridization on some available tumor samples to validate the PCR result. In addition, K-ras mutation was analyzed for patients without EML4-ALK fusion genes. Results: A total of 116 patients with wild-type EGFR sequencing results had complete clinical data for analysis. No patients received ALK inhibitor therapy. There were 39 patients (34%) with the EML4-ALK fusion gene. The concordance rate between reverse transcription-polymerase chain reaction and fluorescence in situ hybridization was 85%. The K-ras mutation rate for patients without EML4-ALK fusion gene was 6.5%. By multivariate analysis, patients who had better performance status (p < 0.001) and EML4-ALK translocation (p = 0.017) had longer overall survival. Comparing patients with tumors harboring variant 1 with those harboring nonvariant 1 EML4-ALK fusion genes, there were no significant differences in clinical factors and survival outcome. Conclusion: For lung adenocarcinoma patients with wild-type EGFR, EML4-ALK translocation is associated with longer overall survival.

Good Response to Gefitinib in Lung Adenocarcinoma Harboring Coexisting EML4-ALK Fusion Gene and EGFR Mutation

A 72-year-old female nonsmoker presented with dry cough and progressive exertional dyspnea for 4 months. Chest radiography disclosed multiple nodular opacities in bilateral lung fields and right pleural effusion. A computed tomography (CT) of the chest after the drainage of pleural effusion (Figure 1A) showed an irregular mass at right upper lung. Serum carcinoembryonic antigen (CEA) level was 442.1 ng/ml. The cytology of echoguided lung aspiration and right pleural effusion both yielded adenocarcinoma. The bronchial biopsy specimens showed neoplastic glands with immunoreactivity to thyroid transcription factor-1 protein and cytokeratin 7. Stage IV lung adenocarcinoma with metastasis to brain and bone was diagnosed. A repeated chest CT (Figure 1B) 92 days after gefitinib treatment showed dramatic shrinkage of right upper lobe mass. The CEA declined to 87.6 ng/ml 196 days after gefitinib treatment. The RNA extracted from cancer cells of echo-guided lung aspiration at the diagnosis of lung cancer was assessed for epidermal growth factor receptor (EGFR) mutation and echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion by reverse transcriptionpolymerase chain reaction and sequencing assays as previously described.1,2 Besides a variant 1 of EML4-ALK translocation, a mutant form of EGFR del 2235–2249 (del E746-A750) in exon 19 was identified (Figure 2). After 232 days of gefitinib treatment, the patient showed disease progression. The trend of lung cancer treatment has been toward personalized therapy. Identifying molecular genetic marker to guide treatment has been successfully demonstrated in the treatment of lung adenocarcinoma in East Asia. Patients with the characteristics of being female, nonsmoker or former light smoker, previously untreated, and advanced stage, and especially the presence of mutation of the EGFR gene, benefited much from EGFR tyrosine kinase inhibitor (TKI) compared with conventional cytotoxic chemotherapy.3 Recently, the EML4-ALK, a fusion gene first described in 2007, possesses oncogenic activity that can be blocked by ALK kinase inhibitor and represents a new therapeutic target in non-small cell lung cancer (NSCLC). EML4-ALK has been identified in 0.4 to 13.5% of unselected NSCLC patients.4 This subset of patients are often light or never smokers and mostly with adenocarcinoma,4 similar to those with EGFR mutations. The EML4-ALK fusions are almost in mutual exclusion to EGFR mutation,4 with

Revisiting tuberculous pleurisy: pleural fluid characteristics and diagnostic yield of mycobacterial culture in an endemic area

Background Tuberculous pleurisy is traditionally indicated by extreme lymphocytosis in pleural fluid and low yield of effusion culture. However, there is considerable inconsistency among previous study results. In addition, these data should be updated due to early effusion studies and advances in culture methods. Methods From January 2004 to June 2009, patients with tuberculous pleurisy were retrospectively identified from the mycobacteriology laboratories and the pathology and tuberculosis registration databases of two hospitals in Taiwan where tuberculosis is endemic. Pleural fluid characteristics and yields of mycobacterial cultures using liquid media were evaluated. Results A total of 382 patients with tuberculous pleurisy were identified. The median lymphocyte percentage of total cells in pleural fluids was 84% (IQR 64–95%) and 17% of cases had a lymphocyte percentage of <50%. The lymphocyte percentage was negatively associated with the probability of a positive effusion culture (OR 0.97; 95% CI 0.96 to 0.99). The diagnostic yields were 63% for effusion culture, 48% for sputum culture, 79% for the combination of effusion and sputum cultures, and 74% for histological examination of pleural biopsy specimens. Conclusion The degree of lymphocyte predominance in tuberculous pleurisy was lower than was previously thought. The lymphocyte percentage in pleural fluid was negatively associated with the probability of a positive effusion culture. With the implementation of a liquid culture method, the sensitivity of effusion culture was much higher than has been previously reported, and the combination of effusion and sputum cultures provided a good diagnostic yield.

Infections due to Candida haemulonii: species identification, antifungal susceptibility and outcomes

Here we report the clinical features and treatment outcomes of three patients with Candida haemulonii infection. Candida haemulonii was confirmed by sequence analysis of the internal transcribed spacer (ITS) regions of the rRNA genes and the 18S rRNA genes. Two of the three isolates were associated with fungaemia and reduced susceptibility to fluconazole [minimum inhibitory concentrations (MICs) of 16 mg/L] and amphotericin B (MICs of 2 mg/L). However, one of these two patients responded to fluconazole therapy. Echinocandins, voriconazole and posaconazole demonstrated excellent in vitro potency against the isolates.

Afatinib combined with cetuximab for lung adenocarcinoma with leptomeningeal carcinomatosis

We report a patient with non-small cell lung cancer (NSCLC) developed leptomeningeal carcinomatosis (LMC) after 4 years of multiple treatments. High-dose tyrosine kinase inhibitor (TKI) was given for LMC at first but was not effective. She then received dual therapy combining of afatinib and cetuximab. Brain magnetic resonance imaging (MRI) showed a partial response of disease and the patient experienced a clinical benefit. Our case suggests that dual targeting of epidermal growth factor receptor (EGFR) by a combination of afatinib and cetuximab can be a potential novel treatment option in treating LMC when high-dose TKI failed.

The Prognostic Value of the Simplified Comorbidity Score in the Treatment of Small Cell Lung Carcinoma

Introduction: Comorbidity may be an important prognostic factor in the treatment of small cell lung carcinoma (SCLC). This study aimed to investigate the prognostic values of simplified comorbidity score (SCS) in the treatment of patients with SCLC. Methods: The patients with SCLC admitted to the National Taiwan University Hospital during the period from January 2000 to December 2006 were included. The medical records were reviewed and analyzed. The SCS was used to evaluate comorbidities of the patients. A Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) for age, gender, and factors significantly associated with survival identified in univariate analyses. Results: A total of 172 patients were included; 56 patients had limited-stage disease and 116 had extensive-stage disease. Patients with an SCS more than 9 had shorter overall survival than those with SCS ≤9 both in limited-stage (372 days versus 581 days, p = 0.01) and extensive-stage disease (215 days versus 324 days, p = 0.001). Multivariate analysis indicated that SCS more than 9 was associated with a worse prognosis in patients with limited-stage disease (HR: 2.17, 95% CI: 1.12–4.21) and extensive-stage disease (HR: 1.74, 95% CI: 1.12–2.72), respectively. For patients with extensive-stage disease, SCS more than 9 was associated with poor treatment response (>9 versus ≤9, disease response rate: 60.0% versus 82.4%, p = 0.02). Conclusions: The SCS may be an independent prognostic factor for patients with SCLC. Large-scale prospective studies may be required to validate the prognostic value of the SCS for SCLC.

Invasive infections caused by non-Aspergillus moulds identified by sequencing analysis at a tertiary care hospital in Taiwan, 2000- 2008

The clinical and microbiological characteristics of 103 patients with cultures positive for non-Aspergillus moulds in the period 2000 to 2008 were described. Among these patients, 27 had proven or probable invasive infections caused by Fusarium (n = 12), Paecilomyces (n = 7), Zygomycetes (n = 5) and Scedopsorium species (n = 3). The incidence of invasive infections caused by these moulds has not increased during the study period. Lung was the most common infection site and disseminated disease was observed in three leukaemic patients. The overall mortality rate was 40.7%, and was highest in cases zygomycosis. Antifungal susceptibility varied considerably among species. Amphotericin B and posaconazole demonstrated greatest activity against these moulds.

Risk Factors of Pneumothorax after Endobronchial Ultrasound-Guided Transbronchial Biopsy for Peripheral Lung Lesions

Background The risk of endobronchial ultrasound-guided transbronchial biopsy-related pneumothorax is a major concern and warrants further studies. The aim of our study was to estimate the risk of pneumothorax after this procedure and identify its risk factors. Methods From 2007 to 2011, 399 patients who underwent endobronchial ultrasound-guided transbronchial biopsy for peripheral lung lesions were included in this study. The variables analyzed included patient factors, lesion factors and procedure factors. Multivariate logistic regression analysis was used to identify independent risk factors for pneumothorax. Results The incidence of pneumothorax was 3.3% (13/399). Chest tube placement was required for 31% (4/13) of pneumothoraces. Independent risk factors for pneumothorax included pulmonary emphysema (OR, 55.09; 95% CI, 9.37–324.03; p<0.001) and probe position adjacent to the lesion (OR, 17.01; 95% CI, 2.85–101.64; p = 0.002). The number of biopsy specimens, age, sex, history of prior lung surgery and lesion size, location and character did not influence the risk of pneumothorax in our analyses. Conclusions The risk of pneumothorax after endobronchial ultrasound-guided transbronchial biopsy is low. To further reduce the risk of pneumothorax, every effort should be made to advance the endobronchial ultrasound probe into the bronchus where it is imaged within the target lesion before embarking on transbronchial biopsy.

Compliance and barriers to implementing the sepsis resuscitation bundle for patients developing septic shock in the general medical wards

BACKGROUND/PURPOSE This two-part study aimed to investigate compliance with the sepsis resuscitation bundle (SRB) and the barriers to its implementation for patients developing septic shock in the general medical wards. METHODS In the first part, medical records of patients who were admitted to the intensive care unit from the general medical wards due to septic shock were reviewed. Compliance rates with the six SRB components were assessed. In the second part, responsible junior physicians (first-year and second-year residents) in the general wards and senior physicians (third-year residents and fellows) were randomly invited for questionnaire-based interviews. RESULTS In the first part, during the 6-month study period, 40 patients were included. Overall compliance with the SRB within 6 h was only 2.5%, mainly due to femoral catheterization (42.5%) and the lack of measuring central venous oxygen saturation (ScvO₂). Delayed completion of SRB components contributed little to the low compliance rate. In the second part, based on the questionnaire results of 71 junior physicians and 64 senior physicians, the junior physicians were less familiar with the SRB guidelines, particularly regarding the meaning of ScvO₂ (p = 0.01) and management of low ScvO₂ (p = 0.04). Junior physicians were also more reluctant to measure the central venous pressure (CVP; p = 0.04) and the ScvO₂ (p = 0.01), and were also less confident with internal jugular vein or subclavian vein catheterization (p < 0.001). CONCLUSION Compliance with the SRB for patients developing septic shock in the general medical wards is very low. Besides providing educational programs to improve awareness and acceptance of the SRB, measures to help in central venous catheterization and completion of SRB may be considered.