Hsi-Hsun Lin

Plasma Interleukin-6 Levels in Patients with Cirrhosis Relationship to Endotoxemia, Tumor Necrosis Factor-α, and Hyperdynamic Circulation

BACKGROUND Liver cirrhosis with portal hypertension is associated with hyperdynamic circulation characterized by generalized vasodilatation and increased cardiac output and regional blood flows. Patients with liver cirrhosis present with increased levels of interleukin-6 (IL-6), which may inhibit vascular smooth-muscle contraction. We investigated whether increased plasma IL-6 levels contribute to the pathogenesis of hyperdynamic circulation observed in cirrhotic patients and whether they are correlated with plasma tumor necrosis factor-alpha (TNF-alpha) and endotoxin concentrations. METHODS In 58 consecutive cirrhotic patients and 34 healthy subjects the plasma concentrations of TNF-alpha and IL-6 were measured with enzyme-linked immunosorbent assay, and endotoxin determinations with a limulus assay. In addition, 52 cirrhotic patients underwent a hemodynamic study using Swan-Ganz catheterization. RESULTS Plasma TNF-alpha, IL-6, and endotoxin levels were significantly higher in cirrhotic patients than in healthy subjects (7.3 +/- 0.2 versus 5.8 +/- 0.1 pg/ml, 6.4 +/ 0.8 versus 2.0 +/- 0.2 pg/ml, and 7.6 +/- 1.2 versus 2.8 +/- 0.3 pg/ml, respectively; p < 0.01). In cirrhotic patients the plasma levels of TNF-alpha IL-6, and endotoxin progressively increased in relation to the severity of liver dysfunction (graded by Pughs classification). A significant correlation was observed between plasma TNF-alpha and IL-6 levels (r = 0.48, p < 0.001), whereas no correlation was observed between plasma endotoxin levels and plasma TNF-alpha and IL-6 levels. Plasma IL-6 levels correlated negatively with systemic vascular resistance in patients with cirrhosis (r = 0.5, p < 0.01). CONCLUSIONS Plasma IL-6 levels are increased in patients with cirrhosis. The severity of liver cirrhosis is an important factor for the occurrence of increased IL-6 levels. IL-6 may play a role in the hyperdynamic circulation observed in patients with cirrhosis.

Bacteremia Caused by Extended-Spectrum-β-Lactamase-Producing Escherichia coli Sequence Type ST131 and Non-ST131 Clones: Comparison of Demographic Data, Clinical Features, and Mortality

ABSTRACT Escherichia coli producing the highly virulent, multidrug-resistant, CTX-M-15 extended-spectrum β-lactamase (ESBL), sequence type 131 (ST131), has emerged on three continents since the late 2000s. We described the molecular epidemiology, clinical features, and outcome of ESBL-producing E. coli bacteremia in Taiwan from 2005 to 2010. This study aims to determine whether the risk factors, clinical features, and outcomes of the ST131 isolate differ from those of non-ST131 isolates. From 2005 to 2010, we collected 122 nonduplicated, consecutive, ESBL-producing E. coli isolates from bloodstream infections in a 1,200-bed hospital in Taiwan. Isolates were characterized using multilocus sequence typing. Demographic data, clinical features, and outcomes were collected from medical chart records. Thirty-six (29.5%) patients with bacteremia with ESBL-producing E. coli ST131 were identified. Patients with clone ST131 were more likely to have secondary bacteremia and noncatheterized urinary tract infections (P < 0.05). Secondary bacteremia (odds ratio [OR], 5.05; 95% confidence interval [CI], 1.08 to 23.56) and urinary catheter nonuse (OR, 3.77; 95% CI, 1.17 to 12.18) were independent risk factors for the ST131 clone after adjustment. Mortality rates at day 28 were similar in ST131 and non-ST131 populations. Independent risk factors predicting mortality at day 28 included malignancy, shock, and hospital-acquired bacteremia. In ESBL-producing E. coli bloodstream infections, the ST131 clone was not associated with health-care-associated risk factors, such as urinary catheter use or antibiotic exposure. Although highly virulent and multidrug resistant, the ST131 clone was not associated with higher mortality than non-ST131 clones.

Sphingomonas paucimobilis Bacteremia in Humans: 16 Case Reports and a Literature Review

BACKGROUND/PURPOSE Sphingomonas paucimobilis is a glucose-nonfermenting Gram-negative bacillus that is widely distributed in both natural environment and hospitals. Various infections in humans have been reported, but most have been limited to sporadic case reports. The aim of this study was to describe the clinical characteristics and manifestations of S. paucimobilis bacteremia. We also reviewed the literature on S. paucimobilis bacteremia. METHODS Cases of S. paucimobilis bacteremia were identified retrospectively at a university-affiliated hospital in Taiwan. In addition, relevant case reports were identified through PubMed and reviewed. RESULTS From April 2004 to April 2008, 42 cases of S. paucimobilis bacteremia were identified in this study. Among them, 16 cases were identified from E-Da hospital, Kaohsiung, Taiwan and 26 cases from the literature review. The median age of patients was 48.5 years and 57.1% were male. The most common comorbidities included malignancy (57.1%), immunosuppressant use (40.5%), and diabetic mellitus (11.9%). Hospital-acquired bacteremia accounted for 69.0% of infections. Primary bacteremia and catheter-related bloodstream infection were found in 35.7% and 33.3% respectively. The most effective antibiotics were fluoroquinolones, carbapenems, and beta-lactam/beta-lactamase inhibitor combinations. All 42 patients survived the S. paucimobilis bacteremic episodes, but three patients experienced septic shock. CONCLUSION S. paucimobilis can cause infections in healthy as well as immunocompromised individuals. Although it is an organism of low clinical virulence, infection caused by S. paucimobilis can lead to septic shock. Further clinical research is required to characterize this infection.

Risk factors for mortality of bacteremic patients in the emergency department.

OBJECTIVES Patients with bacteremia have a high mortality and generally require urgent treatment. The authors conducted a study to describe bacteremic patients in emergency departments (EDs) and to identify risk factors for mortality. METHODS Bacteremic patients in EDs were identified retrospectively at a university hospital from January 2007 to December 2007. Demographic characteristics, underlying illness, clinical conditions, microbiology, and the source of bacteremia were collected and analyzed for their association with 28-day mortality. RESULTS During the study period, 621 cases (50.2% male) were included, with a mean (+/-SD) age of 62.8 (+/-17.4) years. The most common underlying disease was diabetes mellitus (39.3%). Escherichia coli (39.2%) was the most frequently isolated pathogen. The most common source of bacteremia was urinary tract infection (41.2%), followed by primary bacteremia (13.2%). The overall 28-day mortality rate was 12.6%. Multivariate stepwise logistic regression analysis showed age > 60 years (odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.29 to 4.92, p = 0.007), malignancy (OR = 2.66, 95% CI = 1.44 to 4.91, p = 0.002), liver cirrhosis (OR = 2.08, 95% CI = 1.02 to 4.26, p = 0.044), alcohol use (OR = 5.73, 95% CI = 2.10 to 15.63, p = 0.001), polymicrobial bacteremia (OR = 3.99, 95% CI = 1.75 to 9.10, p = 0.001), anemia (OR = 2.33, 95% CI = 1.34 to 4.03, p = 0.003), and sepsis (OR = 1.94, 95% CI = 1.16 to 3.37, p = 0.019) were independent risk factors for 28-day mortality. CONCLUSIONS Bacteremic patients in the ED have a high mortality, particularly with these risk factors. It is important for physicians to recognize the factors that potentially contribute to mortality of bacteremic patients in the ED.

Portal hypertensive colopathy in patients with cirrhosis

BACKGROUND Colonic vascular ectasias and colorectal varices have been observed in patients with cirrhosis. However, the pathogenesis of these vascular lesions has not been established. METHODS We enrolled 35 cirrhotic patients and 20 normal controls in this study. All received colonoscopic examinations and measurements of plasma glucagon levels. Portal pressure measurements were performed in all the cirrhotic patients. RESULTS Colonic vascular ectasias occurred more commonly in cirrhotic patients than in controls (17 of 35 versus 0 of 20; p = 0.009) and more commonly in cirrhotic patients with ascites than in those without (15 of 24 versus 2 of 11; p = 0.038). However, the presence of colonic vascular ectasias was not related to the hepatic venous pressure gradient or plasma glucagon levels. Colorectal varices also occurred more commonly in cirrhotic patients than in controls (16 of 35 versus of 1 of 20; p = 0.034), but the hepatic venous pressure gradient, plasma glucagon levels, and severity of cirrhosis were not related to the presence of colorectal varices. CONCLUSIONS Portal hypertension per se and increased plasma glucagon levels may not play an important role in the pathogenesis of colonic vascular ectasias or colorectal varices in patients with cirrhosis.

Evaluation of Macrolide Resistance and Enhanced Molecular Typing of Treponema pallidum in Patients with Syphilis in Taiwan: a Prospective Multicenter Study

ABSTRACT Studies of macrolide resistance mutations and molecular typing using the newly proposed enhanced typing system for Treponema pallidum isolates obtained from HIV-infected patients in the Asia-Pacific region are scarce. Between September 2009 and December 2011, we conducted a survey to detect T. pallidum using a PCR assay using clinical specimens from patients with syphilis at six major designated hospitals for HIV care in Taiwan. The T. pallidum strains were genotyped by following the enhanced molecular typing methodology, which analyzed the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and the sequence of base pairs 131 to 215 in the tp0548 open reading frame of T. pallidum. Detection of A2058G and A2059G point mutations in the T. pallidum 23S rRNA was performed with the use of restriction fragment length polymorphism (RFLP). During the 2-year study period, 211 clinical specimens were obtained from 136 patients with syphilis. T. pallidum DNA was isolated from 105 (49.8%) of the specimens, with swab specimens obtained from chancres having the highest yield rate (63.2%), followed by plasma (49.4%), serum (35.7%), and cerebrospinal fluid or vitreous fluid (18.2%) specimens. Among the 40 fully typed specimens, 11 subtypes of T. pallidum were identified. Subtype 14f/f (18 isolates) was the most common isolates, followed by 14f/c (3), 14b/c (3), and 14k/f (3). Among the isolates examined for macrolide resistance, none had the A2058G or A2059G mutation. In conclusion, we found that type 14 f/f was the most common T. pallidum strain in this multicenter study on syphilis in Taiwan and that none of the isolates exhibited 23S rRNA mutations causing resistance to macrolides.

Correlation between Pyrazinamide Activity and pncA Mutations in Mycobacterium tuberculosis Isolates in Taiwan

ABSTRACT A total of 76 clinical Mycobacterium tuberculosis isolates from Taiwan were tested for pyrazinamidase activity, pyrazinamide susceptibility, and pncA mutations. Frequency of resistance to PZA rose with increases in resistance to first-line drugs. Of 17 pyrazinamide-resistant strains, 7 (3 of which had not been previously described) possessed mutations in the pncA gene.

Clinical significance of serum type-III procollagen aminopropeptide in hepatitis B virus-related liver diseases

Serum type-III procollagen aminopropeptide (PIIIP) has been considered a marker of hepatic fibrogenesis. In an attempt to evaluate the clinical significance of serum PIIIP in patients with hepatitis B virus (HBV)-related liver diseases, the levels of the peptide were measured in 66 healthy adults and 200 patients with HBV-related liver diseases. As compared with the healthy adults (12.3 +/- 3.1 ng/ml), the serum PIIIP levels were significantly elevated in patients with acute hepatitis (17.4 +/- 6.6 ng/ml), chronic persistent hepatitis (18.3 +/- 4.9 ng/ml), and inactive liver cirrhosis (22.1 +/- 7.1 ng/ml). The PIIIP levels in patients with chronic active hepatitis (CAH) (33.9 +/- 23.1 ng/ml) were the highest among HBV-related liver diseases and had a tendency to increase with the severity of CAH. Of the liver-diseased patients with serum PIIIP levels greater than 30 ng/ml, 91% had a recent episode of severe hepatocellular damage, whereas 56% of patients with greatly elevated serum liver aminotransferase levels had no associated high increase in serum PIIIP levels. Thus, we suggest that fibrogenesis in HBV-related liver diseases is initiated by severe hepatocellular damage, but liver damage can also take place without prominent hepatic fibrogenesis. Serum PIIIP may be a serum marker to predict the active fibrogenesis of HBV-related liver diseases.

High prevalence of latent tuberculosis infection in dialysis patients using the interferon-{gamma} release assay and tuberculin skin test

BACKGROUND AND OBJECTIVES Patients in ESRD on hemodialysis with latent tuberculosis (TB) infection have 10 to 25 times the risk of reactivation into active disease compared with healthy adults. This study investigates the prevalence of latent TB infection in dialysis patients from a country with an intermediate burden of TB and its associated risk factors using the QuantiFERON-TB Gold in-tube test (QGIT) and the tuberculin skin test (TST). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a prospective, cross-sectional study performed at a medical center in Taiwan on dialysis patients. Each patient underwent QGIT, two-step TST using 2 tuberculin units (TU) of PPD RT-23, a chest x-ray to exclude active TB, and an interview to determine TB risk factors. RESULTS Ninety-three of 190 eligible patients were enrolled: 35 men and 58 women. 64.8% were vaccinated with the Bacille-Calmette-Guérin (BCG) vaccination. Overall, 34.4% were positive by QGIT and 10.8% were indeterminate. Using a 10-mm TST cutoff, 53.9% were positive. There was poor correlation between TST and QGIT at any TST cutoff criteria. There was a significant increasing trend of QGIT positivity with age in those younger than 70 years, and, conversely, a decreasing trend of TST reactivity with age. Significant risk factors for QGIT positivity included age and past TB disease. CONCLUSIONS This study shows a high prevalence of latent TB infection in dialysis patients in a country with an intermediate burden of TB. QGIT in dialysis patients correlated better than TST with the risk of TB infection and past TB disease.

Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function.

BACKGROUND Spider angioma is a common sign in patients with liver cirrhosis, but the pathogenesis is still unclear. Alcohol and hyperestrogenemia are both possible etiologies. This study was designed to investigate the relationship of spider angiomas in patients with liver cirrhosis to alcohol, liver function test results, and plasma levels of sex hormones. METHODS Eighty-two patients with liver cirrhosis and 18 healthy subjects were enrolled in this study. The number, size, and location of the spider angiomas were recorded for all subjects. Plasma levels of estradiol and testosterone were measured. RESULTS Cirrhotic patients had significantly higher estradiol/testosterone ratios (26.8 +/- 5.1 x 10(-3) versus 8.8 +/- 2.0 x 10(-3); P = 0.002) than healthy controls. Twenty-seven (33%) of the 82 cirrhotic patients had spider angiomas. Cirrhotic patients with spider angiomas were younger (56 +/- 3 versus 66 +/- 1 years; P = 0.002) and had higher serum bilirubin levels (3.3 +/- 0.6 versus 1.7 +/- 0.2 mg/dl; P = 0.002), longer prothrombin time (16.8 +/- 0.8 versus 14.8 +/- 0.4 sec; P = 0.01), and higher prevalence of alcoholism (41% versus 20%; P = 0.04) than those without. Stepwise logistic regression showed that alcoholism and serum bilirubin level were the only significant and independent predictors associated with the presence of spider angiomas in cirrhotic patients (odds ratio = 3.5; 95% confidence interval = 1.2-10.8; P = 0.03, and odds ratio = 2.8; 95% confidence interval = 1.3-5.7; P = 0.006, respectively). CONCLUSIONS Alcoholism and impaired liver function are important predictors of the presence of spider angiomas in patients with liver cirrhosis.