Hen-I Lin

Diagnostic value of procalcitonin for bacterial infection in elderly patients in the emergency department.

OBJECTIVES: To evaluate the diagnostic performance of procalcitonin (PCT) in elderly patients with bacterial infection in the emergency department (ED).

Bacteremia caused by non-faecalis and non-faecium enterococcus species at a Medical center in Taiwan, 2000 to 2008

SUMMARY OBJECTIVES Human infections due to non-faecalis and non-faecium Enterococcus species are emerging but data on the characteristics of these infections are limited. METHODS We retrospectively reviewed the computerized database of the bacteriology laboratory at National Taiwan University Hospital from January 2000 through December 2008 to identify patients with non-faecalis and non-faecium enterococcal bacteremia. RESULTS Enterococcal bacteremia was diagnosed in 1887 patients during the study period and was caused by non-faecalis and non-faecium enterococci in 182 (9.6%) of these patients. The causative organisms included Enterococcus casseliflavus (n = 59, 3.1%), Enterococcus gallinarum (n = 58, 3.0%), Enterococcus avium (n = 45, 2.4%), Enterococcus hirae (n = 9, 0.5%), Enterococcus raffinosus (n = 9, 0.5%), Enterococcus durans (n = 2, 0.1%), Enterococcus cecorum (n = 2, 0.1%), and Enterococcus canintestini (n = 1, 0.5%). A commercially-available phenotypic identification system misidentified six isolates based upon sequence analysis of 16S and groESL genes. Among the 182 patients, 74 (40.7%) had catheter-associated bloodstream infection and 69 (37.9%) presented with biliary tract infection. Healthcare-associated enterococcal bacteremia comprised 99 (54.4%) episodes and a polymicrobial etiology was found in 106 (58.2%) episodes. The clinical manifestations varied between the infecting Enterococcus species. Multivariate logistic regression showed that immunocompromised status is the only risk factor for the all cause mortality. CONCLUSIONS Non-faecalis and non-faecium Enterococcus species can cause protean manifestations which vary with the infecting Enterococcus species. Misidentification of unusual enterococcal species might occur by the commercial identification methods and accurate identification with molecular methods is required.

Idiopathic pulmonary fibrosis in Taiwan - a population-based study.

BACKGROUND This study took advantage of a large population-based database of the Taiwan National Health Insurance (NHI) to investigate the epidemiology of idiopathic pulmonary fibrosis (IPF) in Taiwan. METHODS This is a retrospective cohort study based on secondary analysis of prospectively collected data in the NHI system and governmental data on death registry in Taiwan during 1997-2007. By using the broad and narrow definitions for IPF, we estimated incidence and prevalence rates of IPF, and its associated clinical outcomes. RESULTS The estimates of annual IPF incidence rates became more stable after 2000, ranging between 0.9 and 1.6 cases per 100,000 persons. The prevalence rates became more than twofold from 2000 to 2007 (from 2.8 to 6.4 cases per 100,000 persons for the broad definition, and from 2.0 to 4.9 cases per 100,000 persons for the narrow definition). Men of age older than 75 years had markedly higher incidence and prevalence rates than other groups. Around 40% of all incidences and about 30% of prevalent cases occurred in this population group. The median survival time after IPF diagnosis was 0.9 year (interquartile range (IQR), 0.2-2.5 years) and 0.7 year (IQR, 0.1-2.3 years) for the broad and narrow definitions, respectively. Progression of IPF was the leading cause of death, followed by cancer. CONCLUSIONS In Taiwan, elderly men were the major group suffering from IPF. Survival time was short after IPF diagnosis, and the poor survival was largely attributable to quick IPF progression after diagnosis.

Rhabdomyolysis and Acute Kidney Injury Associated With 2009 Pandemic Influenza A(H1N1)

o the Editor: Pandemic 2009 influenza A(H1N1) is an emerging disase first reported in April, 2009. Previous studies have ointed out that patients with pneumonia and respiratory ailure arising from pandemic H1N1 may have abnormal aboratory examination results, including elevated creatine inase (CK) levels. We report a patient with pandemic 1N1 infection who developed mild rhabdomyolysis and cute kidney injury (AKI). A 49-year-old man presented with fever, productive cough, yalgia, and shortness of breath. His vital signs included a emperature of 38.5°C, pulse rate of 116 beats/min, respiraory rate of 28 breaths/min, and blood pressure of 100/64 m Hg. There was a coarse crackle over bilateral lower lung elds on chest auscultation. The results of laboratory tests ere as follows: white blood cell count of 7.6 10/ L 7.6 10/L; 89% neutrophils, 2% lymphocytes); serum rea nitrogen, 75 mg/dL (26.78 mmol/L); serum creatinine, .85 mg/dL (252 mol/L); potassium, 4.1 mEq/L (4.1 mol/L); asparatate aminotransferase, 94 U/L (normal, 40 /L); lactate dehydrogenase, 339 U/L (normal, 98-192 /L); C-reactive protein, 15.77 mg/dL (normal, 0.8 mg/ L); and peak CK level, 3,551 U/L (normal, 40-290 U/L). A rine dipstick test for blood had positive findings in the bsence of red blood cells. Chest radiography showed ilateral consolidations over bilateral lower lobes. An inouse real-time reverse transcriptase–polymerase chain reacion (RT-PCR) from a nasopharyngeal swab sample was ositive for pandemic H1N1. He received a 5-day course of seltamivir (75 mg twice daily). He was treated with intense ydration and urine alkalization for rhabdomyolysis and KI. Eight days later, the CPK and creatinine level dereased to within normal range. The association of rhabdomyolysis with pandemic H1N1 nfection in a patient who did not develop AKI was previusly reported. In our report, the patient suffering from 1N1 pneumonia developed mild rhabdomyolysis and AKI. ther than the viral infection, we were unable to identify ther predisposing factors for rhabdomyolysis. However, we an only speculate as to whether volume depletion and epsis contributed to the AKI rather than mild rhabdomyolyis. In summary, we suggest that mild rhabdomyolysis and KI may be another clinical manifestation of pandemic 1N1 infection.

CIP2A mediates erlotinib-induced apoptosis in non-small cell lung cancer cells without EGFR mutation

BACKGROUND Epidermal growth factor receptor (EGFR) inhibitors show favorable clinical response in some patients with non-small cell lung cancer (NSCLC) who have no EGFR mutation, indicating alternative mechanisms for their tumoricidal effects. We previously showed erlotinib, a selective EGFR antagonist, inhibited the growth of sensitive hepatocellular carcinoma cells by inhibiting the cancerous inhibitor of protein phosphatase 2A (CIP2A) pathway. The aim of this study was to determine if erlotinib can also inhibit the growth of NSCLC cells by inactivating the CIP2A-dependent signaling pathway. METHODS Four NSCLC cell lines (H358 H441 H460 and A549) were treated with erlotinib to determine their sensitivity to erlotinib-induced cell death and apoptosis. Expression of CIP2A and the downstream AKT were analyzed. The effects of CIP2A on erlotinib-induced apoptosis were confirmed by overexpression of CIP2A and knockdown of CIP2A gene expression in the sensitive cells and resistant cells, respectively. In vivo efficacy of erlotinib against H358 xenograft tumor was also determined in nude mice. RESULTS Erlotinib induced significant cell death and apoptosis in H358 and H441 cells, as evidenced by increased caspase 3 activity and cleavage of pro-caspase 9 and PARP, but not in H460 or A549 cells. The apoptotic effect of erlotinib in the sensitive H358 cells was associated with downregulation of CIP2A, increase in PP2A activity and decrease in AKT phosphorylation. Overexpression of CIP2A and AKT protected the sensitive H358 cells from erlotinib-induced apoptosis. Knockdown of CIP2A gene expression by siRNA enhanced the erlotinib-induced apoptotic in the resistant H460 cells that resembled the sensitive H358 cells. Erlotinib also inhibited the growth of H358 tumors in nude mice. CONCLUSIONS The CIP2A-dependent pathway mediates the tumoricidal effects of erlotinib on NSCLC cells without EGFR mutations in vitro and in vivo. CIP2A may be a novel molecular target against NSCLC for future drug development.

Hyperbaric oxygen attenuates cell growth in skin fibroblasts cultured in a high-glucose medium

Hyperglycemia and hypoxia synergistically retard diabetic wound healing. We investigated the direct effect of hyperbaric and normobaric hyperoxia on skin fibroblasts cultured in a high‐glucose medium. Detroit 551 human dermal fibroblasts cultured in Dulbeccos modified Eagles medium containing d‐glucose had reduced cell survival compared with cells grown in normal glucose medium; survival was 27.5±3.8% lower in 25 mM glucose and 30.6±3.7% lower in 50 mM glucose. Cell survival decreased because of inhibition of cell proliferation and enhanced cell death. Daily hyperbaric oxygen therapy at 2.5 atmosphere absolute for 90 minutes on 3 consecutive days reduced cell proliferation and increased cell death in normal cultured fibroblasts. Hyperbaric oxygen therapy and high‐glucose medium had a synergistic effect and reduced survival by 37.6±4.4% (25 mM glucose) and 39.6±5.1% (50 mM glucose). The effects of hyperbaric oxygen and high‐glucose medium were associated with overproduction of reactive oxygen species. Our results suggest that direct exposure of skin fibroblasts to hyperbaric oxygen affects cell growth and superimposes the toxic effect of high glucose. This cytotoxicity may be related to the production of reactive oxygen species in the fibroblasts.

TD-19, an Erlotinib Derivative, Induces Epidermal Growth Factor Receptor Wild-Type Nonsmall-Cell Lung Cancer Apoptosis through CIP2A-Mediated Pathway

Some patients with nonsmall-cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) mutations still respond to gefitinib and erlotinib, suggesting that there may be a mechanism(s) other than the EGFR pathway that mediates the tumoricidal effects. In the current study, we tested the efficacy of TD-19, a novel compound chemically modified from erlotinib, which has more potent apoptotic effects than erlotinib in EGFR wild-type NSCLC cell lines. TD-19 induced significant cell death and apoptosis in H358, H441, H460, and A549 cells, as evidenced by increased caspase-3 activity and cleavage of procaspase-9 and poly (ADP-ribose) polymerase. The apoptotic effect of TD-19 in H460 cells, which were resistant to erlotinib, was associated with downregulation of cancerous inhibitor of protein phosphatase 2A (CIP2A), increased protein phosphatase 2A (PP2A) activity, and decreased AKT phosphorylation, but minimal effects on EGFR phosphorylation. Overexpression of CIP2A partially protected the H460 cells from TD-19–induced apoptosis. Okadaic acid, a known PP2A inhibitor, significantly reduced TD-19–induced apoptosis, while forskolin, which increased PP2A activity, increased the apoptotic effect of TD-19. TD-19 inhibited the growth of H460 xenograft tumors by ∼80%. We conclude that TD-19 exerted tumoricidal effects on NSCLC cells. TD-19 provides proof that the CIP2A pathway may be a novel target for the treatment of EGFR wild-type NSCLC.

Diagnostic value of an enzyme-linked immunospot assay for interferon-γ in genitourinary tuberculosis

The aim of this study was to evaluate the diagnostic performance of an enzyme-linked immunospot (ELISPOT) assay for interferon-γ in patients with suspected genitourinary tuberculosis (TB). A total of 30 patients with suspected genitourinary TB at the National Taiwan University Hospital, Taipei, Taiwan, were prospectively enrolled from January 2007 to December 2009, and 12 of whom had positive urine culture for Mycobacterium tuberculosis. Frequency and dysuria were the most common symptoms noted in 6 (50.0%) and 4 (33.3%) patients, respectively. Pyuria was the most common finding of urinalysis noted in 11 (91.7%) patients. Six (50.0%) patients had positive acid-fast stain in urine. Among the 30 patients, 13 patients had positive ELISPOT assay. Eleven patients with positive ELISPOT assay had culture-confirmed TB, and the remaining 2 patients without evidence of active TB had positive ELISPOT assay. The overall sensitivity, specificity, positive predictive value, and negative predictive value for genitourinary TB diagnosis by the ELISPOT assay were 91.7% (95% confidence interval [CI], 59.8-99.6%), 88.9% (95% CI, 63.9-98.1%), 84.6% (95% CI, 53.7-97.3%), and 94.1% (95% CI, 69.2-96.7%), respectively. In conclusion, ELISPOT assay can provide useful support in diagnosing genitourinary TB.

Risk of Colorectal Cancer in Type 2 Diabetic Patients: A Population-based Cohort Study

OBJECTIVE Most of the existing findings on the association between diabetes mellitus and colorectal cancer were generated from studies in Western societies. However, significant differences in cancer incidence and cancer-prone lifestyles are apparent between Asian and Western countries. This study aims to estimate the risks of colorectal cancer in the diabetic population in Taiwan by conducting a large-scale, controlled cohort study. METHODS From Taiwans Longitudinal Health Insurance Database 2005 (LHID2005), a total of 37 001 diabetic patients were identified. We also obtained data for four controls per patient, matched for sex, age and year of first entry into the LHID2005. All patients were followed up from the date of entry into the LHID2005 until they developed colorectal cancer or to the end of 2006, whichever was earlier. We used Coxs regression models to assess the risk of developing colorectal cancer, with adjustment for sex, age, comorbid disorders, and socioeconomic characteristics. RESULTS We identified 37 001 diabetic patients and 148 004 controls. The adjusted hazard ratio for colorectal cancer in diabetes mellitus patients was 2.1 (95% confidence interval, 1.82-2.42) compared with controls. The risk was significant to both men and women. The adjusted hazard ratios for colorectal cancer were 2.03 (95% confidence interval, 1.68-2.47) in male diabetes mellitus patients and 2.17 (95% confidence interval, 1.77-2.67) in female diabetes mellitus patients. CONCLUSIONS Our findings based on a large population-based cohort study provide evidence that diabetes mellitus may increase the risk of colorectal cancer in Asians.

Diagnostic usefulness of enzyme-linked immunospot assay for interferon-gamma for tuberculosis in cancer patients

Abstract The interferon-γ enzyme-linked immunospot assay (ELISPOT) has been demonstrated to be useful in the diagnosis of active tuberculosis (TB). In this study we aimed to evaluate the diagnostic performance of the ELISPOT assay in cancer patients with suspected pulmonary TB. Eighty-one cancer patients with suspected pulmonary TB were prospectively enrolled from April 2007 to December 2008, to investigate the diagnostic sensitivity and specificity of the ELISPOT assay. Of the 38 patients with TB, 33 (86.8%) had positive ELISPOT results. Of the 43 patients without TB, the results of the ELISPOT assay were negative in 35 (81.3%) patients. The overall sensitivity was 86.8%, specificity 81.3%, positive predictive value 80.5% and negative predictive value 87.5%. No significant difference was noted for the diagnostic performance of the ELISPOT assay for diagnosing TB between solid cancer and haematological cancer patients. In addition, a quantitative study did not show that TB patients with solid cancers have a better response than haematological cancer patients as measured by spot-forming cells per 106 peripheral blood mononuclear cells after exposure to early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10). In conclusion, the ELISPOT assay could be a useful supplementary tool for the diagnosis of pulmonary TB among cancer patients, irrespective of cancer type.