Incidence and Outcomes of Central Venous Catheter-related Blood Stream Infection in Patients with Inflammatory Bowel Disease in Routine Clinical Practice Setting.

BACKGROUND: Patients with inflammatory bowel disease (IBD) occasionally require central venous catheter (CVC) placement to support a therapeutic plan. Given that CVC can predispose patients to infection, this investigation was undertaken to assess the incidence, risk factors, and outcomes of CVC-related blood stream infection (CRBSI) in patients with IBD during routine clinical practice. METHODS: Data were compiled using retrospective chart reviews of 1367 patients treated at our IBD center between 2007 and 2012 during routine clinical practice. Among the 1367 patients, 314 who had received CVC placements were included. Patients with positive blood culture were considered as "definite" CRBSI, whereas "possible" CRBSI was defined as patients in whom fever alleviated within 48 hours post-CVC without any other infection. Patients' demographic variables including age, body mass index, serum albumin, duration of CVC placement, use of antibiotics, medications for IBD, and perioperative status between CRBSI and non-CRBSI subgroups were compared by applying a multivariate Poisson logistic regression model. RESULTS: Among the 314 patients with CVC placement, there were 83 CRBSI cases (26.4%). The average time to the onset of CRBSI was 22.5 days (range 4-105 days). The jugular vein access was found to be the most serious risk of CRBSI (risk ratio 2.041 versus subclavian vein). All patients with CRBSI fully recovered. CONCLUSIONS: In this investigation, regardless of the patients' demographic features including immunosuppressive therapy, up to 30% of febrile IBD patients with CVC showed CRBSI. It is believed that CVC placement per se is a risk of CRBSI in patients with IBD.

Doppler ultrasound findings correlate with tissue vascularity and inflammation in surgical pathology specimens from patients with small intestinal Crohn's disease.

BACKGROUND: Crohn's disease (CD) is routinely evaluated using clinical symptoms, laboratory variables, and the CD activity index (CDAI). However, clinical parameters are often nonspecific and do not precisely reflect the actual activity of CD small-intestinal lesions. The purposes of this prospective study were to compare color Doppler ultrasound (US) findings with histological findings from surgically resected specimens and confirm the hypothesis that color Doppler US can distinguish tissue inflammation and fibrosis. METHODS: Among 1764 consecutive patients who underwent color Doppler US examinations, 10 patients with CD (12 small-intestinal CD lesions) who underwent US examinations before elective small-intestine resection were evaluated in the present study. Areas of thickened intestinal walls were evaluated in terms of blood flow using color Doppler US imaging. The blood flow was semiquantitatively classified as "hyper-flow" and "hypo-flow" according to the Limberg score. Resected lesions were macroscopically and histopathologically processed. Inflammatory cell infiltration, fibrosis and vascularity were evaluated by myeloperoxidase (granulocytes), CD163 (macrophages), CD79a (B cells), CD3 (T cells), Masson's trichrome (fibrosis), and factor VIII staining (vascular walls). All histopathological images were entered into virtual slide equipment and quantified using a quantitative microscopy integrated system (TissueMorph™). RESULTS: There were no significant differences in disease features or laboratory findings between "hypo-flow" lesions (n = 4) and "hyper-flow" lesions (n = 8). Histopathologically, "hyper-flow" lesions showed significantly greater bowel wall vascularity (factor VIII) (p = 0.047) and inflammatory cell infiltration, including CD163 macrophages (p = 0.008), CD3 T cells, and CD79a B cells (p = 0.043), than did "hypo-flow" lesions. There was no apparent association between the blood flow and CDAI. CONCLUSIONS: In this study, active CD lesions were macroscopically visible in surgical specimens of patients with increased blood flow on preoperative color Doppler US imaging. Additionally, these CD lesions exhibited significantly greater vascularity and numbers of inflammatory leukocytes microscopically. Color Doppler US may predict tissue inflammation and fibrosis in small-intenstinal CD lesions.

Use of color Doppler ultrasonography for evaluating vascularity of small intestinal lesions in Crohn's disease: correlation with endoscopic and surgical macroscopic findings.

OBJECTIVE. Ultrasonography (US) is a simple, inexpensive and minimally invasive method. We evaluated the vascularity of small intestinal lesions in Crohn's disease using color Doppler US (CD-US) and retrospectively compared them with endoscopic and surgical macroscopic findings. MATERIAL AND METHODS. In order to compare CD-US and endoscopic findings, 108 Crohn's disease patients who underwent examination of the terminal ileum by both colonoscopy and CD-US were included in the study. Vascularity was evaluated in CD-US using a semiquantitative method, the Limberg score. We analyzed correlations between Limberg score and simple endoscopic score for Crohn's disease (SES-CD), an index reflecting endoscopic activity. Scores of SES-CD 3 and higher were defined as endoscopically active. For comparison with surgical macroscopic findings, 22 Crohn's disease patients who received CD-US and subsequent iliectomies were included. Lesions with apparent open ulcers were defined as active, and those without as non-active. These findings were compared with the Limberg score. RESULTS. A substantial positive correlation was observed between Limberg scores and SES-CD (ρ = 0.709 [p < 0.001]). Notably, all 27 cases with a Limberg score of 3 or 4 were classified as endoscopically active. Compared to surgical macroscopic activity, Limberg scores of active lesions were significantly higher than those of non-active lesions (p = 0.005). In particular, all 11 cases with a Limberg score of 3 or 4 were classified as active lesions. CONCLUSION. Vascularity of small intestinal lesions of Crohn's disease evaluated by CD-US with Limberg score is well correlated with endoscopic and surgical macroscopic findings.

Effects of IL-28B gene polymorphism on response to peginterferon plus ribavirin combination therapy for genotype 2 chronic hepatitis C.

AIM: Interleukin (IL)-28B gene polymorphism is closely linked with treatment response to peginterferon plus ribavirin combination therapy for hepatitis C virus genotype 1. However, few studies have reported its effects on therapy for genotype 2. We aimed to examine the effects of IL-28B gene polymorphism on treatment response in hepatitis C virus genotype 2 patients. METHODS: In a retrospective study of 101 patients infected with either genotype 2a (n = 65) or 2b (n = 36) and treated with peginterferon plus ribavirin, we investigated predictive factors for a sustained virological response (SVR), including genetic variations near the IL-28B gene (rs8099917, rs11881222 and rs8103142) and clinical variables such as age, sex, body mass index, stage of fibrosis and drug adherence. RESULTS: Ultra-rapid virological response, rapid virological response (RVR), end-of-treatment response, SVR and relapse rates were 22.2%, 61.4%, 95.0%, 87.1% and 7.9%, respectively. In univariate analysis, RVR and IL-28B single nucleotide polymorphisms (SNP) (rs8099917, rs11881222 and rs8103142) were significantly associated with SVR. In subgroup analysis, IL-28B SNP were significantly associated with SVR in genotype 2a patients but not in genotype 2b patients. In multiple logistic regression analysis, RVR and IL-28B SNP (rs8099917) were independently associated with SVR. Furthermore, IL-28B SNP was significantly associated with relapse but RVR was not. CONCLUSION: In genotype 2 patients treated with peginterferon plus ribavirin combination therapy, IL-28B gene polymorphism was a significant independent predictor of SVR as well as RVR. IL-28B major allele may favor reduced relapse rates in patients with genotype 2 chronic hepatitis C.

Novel Lens culinaris agglutinin-reactive fraction of α-fetoprotein: a biomarker of hepatocellular carcinoma recurrence in patients with low α-fetoprotein concentrations.

BACKGROUND: Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) is a specific marker used to detect hepatocellular carcinoma (HCC). However, its clinical utility is not sufficient in patients with low total AFP concentrations because of limitations in instrument sensitivity. Recent advances have led to the introduction of a highly sensitive AFP-L3% assay (sensitive AFP-L3%), provided by a novel on-chip, liquid-phase binding assay. This cross-sectional study was conducted to evaluate the clinical significance of the sensitive AFP-L3% in determining HCC recurrence in patients with low total AFP concentrations. METHODS: A total of 370 consecutive patients with HCC were screened within 1-3 months of locoregional treatment, and 215 of the 370 patients showed serum AFP <20 ng/ml. Total AFP, sensitive AFP-L3%, and des-gamma-carboxy prothrombin (DCP) were measured in those 215 patients and HCC recurrence was evaluated by radiological findings. Optimal cutoff values of the markers for detecting HCC recurrence were obtained on the basis of receiver operating characteristic (ROC) curve. RESULTS: The area under the ROC curve of the total AFP, sensitive AFP-L3%, and DCP in HCC patients with serum AFP <20 ng/ml were 0.638, 0.724, and 0.779, respectively. The diagnostic accuracies of the total AFP, sensitive AFP-L3%, and DCP were 60.9% (cutoff value 5 ng/ml), 67.7% (cutoff value 7%), and 64.6% (cutoff value 40 ng/ml), respectively. CONCLUSIONS: The new sensitive AFP-L3% assay provides great utility in determining HCC recurrence in patients with low AFP concentrations. Further studies focusing on the combinatorial use of the markers (total AFP, sensitive AFP-L3%, and DCP) are required.

Clostridium difficile infection in patients with ulcerative colitis: investigations of risk factors and efficacy of antibiotics for steroid refractory patients.

BACKGROUND AND OBJECTIVE: The incidence of Clostridium difficile infection (CDI) has increased throughout the world and patients with ulcerative colitis (UC) are at a high risk for CDI. Potentially, CDI can exacerbate UC. Therefore, knowledge on the prevalence of CDI should contribute to better management of UC patients. METHODS: The presence of toxin A antigen was defined as CDI, and the outcome of the test in patients with active UC during 2006-2009 was reviewed for identifying patients with CDI. Demographic data (disease profile, clinical response to medications and the need for colectomy) in UC patients with CDI were compared with the data from CDI free UC patients. RESULTS: Fifty-five of 137 patients (40.1%) were CDI positive. Univariate and multivariate analyses revealed that CDI was not associated with any demographic factor. Intensive antibiotic therapy spared five of 17 (29.4%) steroid refractory patients with CDI from steroids. CDI was not a predictor of colectomy although this could be an outcome of efficient eradication strategy. CONCLUSION: CDI was not associated with any demographic factor or colectomy rate. However, CDI eradication therapy allowed some refractory patients to withdraw from steroids. Patients with active UC benefit from regular CDI test and eradication treatment for CDI.

Hydroxyurea suppresses HCV replication in humans: a Phase I trial of oral hydroxyurea in chronic hepatitis C patients.

BACKGROUND: HCV is the main causative agent of chronic liver disease, which could progress to liver cirrhosis and hepatocellular carcinoma. By using a recently developed genome-length HCV RNA replication reporter assay system, we found that hydroxyurea (HU), an inhibitor of DNA synthesis, inhibited HCV RNA replication. METHODS: To test the hypothesis that HU suppresses HCV replication in humans, we conducted a Phase I trial involving Japanese patients with chronic hepatitis C (CHC) and investigated the safety and effectiveness of a 4-week course of oral HU. RESULTS: A total of nine patients were treated with an HU dose level of 500 mg three times daily. Dose-limiting toxicity was not observed at this dose level. Of the nine patients, eight exhibited a moderate decrease in serum HCV RNA levels during the trial. A decrease in HCV RNA levels to nadir levels was achieved for the eight patients (median -0.27 log(10) IU/ml [range -0.08--0.44]) at various times during the 4 weeks after therapy initiation. CONCLUSIONS: The results of this Phase I trial suggest that HU has potential as an anti-HCV agent that could be effective for the treatment of CHC patients.

Hydroxyurea as an inhibitor of hepatitis C virus RNA replication.

Hepatitis C virus (HCV) is the main causative agent of chronic liver disease, which may develop into liver cirrhosis and hepatocellular carcinoma. By using a recently developed reporter assay system in which genome-length HCV RNA replicates efficiently, we found that hydroxyurea (HU), a DNA synthesis inhibitor, inhibited HCV RNA replication. Moreover, we demonstrated that the anti-HCV activity of the combination of IFN-alpha and HU was higher than that of IFN-alpha alone. These results suggest that HU may be an effective anti-HCV reagent that can be used not only singly but also in combination with IFN-alpha to treat chronic hepatitis C.

Clinical evaluation of TRCRapid M.TB for detection of Mycobacterium tuberculosis complex in respiratory and nonrespiratory specimens.

The rapid and accurate diagnosis of tuberculosis is crucial to providing optimal treatment and reducing the spread of infection. We evaluated respiratory and nonrespiratory clinical specimens using a new automated Mycobacterium tuberculosis complex (MTBC) rRNA detection kit (TRCRapid M.TB; Tosoh Bioscience, Tokyo, Japan), which is based on the transcription-reverse transcription concerted reaction (TRC). TRC enables the rapid and completely homogeneous real-time monitoring of isothermal RNA sequence amplification without any postamplification procedures. The results were compared with those obtained by M. tuberculosis culture. A total of 1,155 respiratory specimens and 420 nonrespiratory specimens collected from 1,282 patients were investigated. Of the 45 specimens culture positive for MTBC, 42 were TRC positive, and of the 1,530 specimens culture negative for MTBC, 1,523 were TRC negative. Compared to the results of culture, the overall sensitivity and specificity of TRC were 96.6% and 99.9%, respectively, for respiratory specimens and 87.5% and 98.5%, respectively, for nonrespiratory specimens. The sensitivities of TRC were 100% for smear-positive respiratory and nonrespiratory specimens, 88.9% for smear-negative respiratory specimens, and 80% for smear-negative nonrespiratory specimens. No significant differences in test performance between respiratory and nonrespiratory specimens were observed. The TRC method proved to be clinically useful for the rapid identification of MTBC in respiratory and nonrespiratory specimens and in both smear-positive and smear-negative samples.

[In vitro susceptibilities to levofloxacin and various antibacterial agents of 12,919 clinical isolates obtained from 72 centers in 2007].

We have reported in this journal in vitro susceptibilities of clinical isolates to antibiotics every year since 1992. In this paper, we report the results of an analysis of in vitro susceptibilities of 12,919 clinical isolates from 72 centers in Japan to selected antibiotics in 2007 compared with the results from previous years. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae maintained a high susceptibility to fluoroquinolones (FQs). The resistance of S. pyogenes to macrolides has been increasing every year and this was especially clear this year. Most strains of Enterobacteriaceae except for Escherichia coli showed a high susceptibility to FQs. Almost 30% of E. coli strains were resistant to FQs and the resistance increased further this year. FQs resistance of methicillin-resistant Staphylococcus aureus (MRSA) was approximately 95% with the exception of 45% for sitafloxacin (STFX). FQs resistance of methicillin-susceptible S. aureus (MSSA) was low at about 10%. FQs resistance of methicillin-resistant coagulase negative Staphylococci (MRCNS) was higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), but it was lower than that of MRSA. However, FQs resistance of MSCNS was higher than that of MSSA. FQs resistance of Enterococcus faecalis was 22.5% to 29.6%, while that of Enterococcusfaecium was more than 85% except for STFX (58.3%). In clinical isolates of Pseudomonas aeruginosa derived from urinary tract infections, FQs resistance was 21-27%, which was higher than that of P. aeruginosa from respiratory tract infections at 13-21%, which was the same trend as in past years. Multidrug resistant strains accounted for 5.6% in the urinary tract and 1.8% in the respiratory tract. Acinetobacter spp. showed high susceptibility to FQs. The carbapenem resistant strains, which present a problem at present, accounted for 2.7%. Neisseria gonorrhoeae showed high resistance of 86-88% to FQs. The results of the present survey indicated that although methicillin-resistant Staphylococci, Enterococci, E. coli, P. aeruginosa, and N. gonorrhoeae showed resistance tendencies, and other species maintained high susceptibility rates more than 90% against FQs, which have been used clinically for over 15 years.

[Comparison of Tosoh TRCRapid M.TB assay by transcription-reverse transcription concerted reaction (TRC) with Roche COBAS AMPLICOR assay by PCR and with culture for detection of Mycobacterium tuberculosis complex].

The aim of this study was to test the performance of a new reagent kit Tosoh TRCRapid M.TB using by transcription-reverse transcription concerted reaction(TRC) for detection of Mycobacterium tuberculosis complex (MTC) by comparing both its sensitivity and specificity for detecting MTC with those of Roche COBAS AMPLICOR Mycobacterium assay using polymerase chain reaction (PCR) and comparing with culture. TRC is a novel method, that is rapid and provides real-time monitoring of the isothermal sequence of RNA amplification without any post-amplification procedure, and the resulting detection time was about 30 min. A total of 157 clinical samples from patients were tested. Of the 74 MTC culture-positive samples, TRC was positive in 59(sensitivity, 80%), whereas PCR was positive in 47(sensitivity, 63%). The 26 samples that were positive for Mycobacteria other than tuberculosis (MOTT) were negative by TRCRapid M.TB assay, and the 50 samples that were negative for smear, culture and Roche PCR were also negative by TRCRapid M.TB. The percent agreement between Tosoh TRCRapid M.TB and Roche COBAS AMPLICOR was 90% (142 of 157 samples). These results indicate that Tosoh TRCRapid M.TB may be more useful than Roche COBAS AMPLICOR for detecting MTC because of its higher sensitivity and shorter detection time.

[Clinical significance of Cobas Amplicor HCV Monitor test v 2.0 for quantifying a wide range of serum HCV-RNA in patients with chronic hepatitis C].

Recently, we evaluated the clinical significance of a new assay, the semi-automated Cobas Amplicor HCV Monitor test v 2.0 (Roche, Cobas-HIGH-RANGE assay), for quantifying serum hepatitis C virus RNA throughout a wider range than the traditional assay, Amplicor GT HCV Monitor test v 2.0 (GT-ORIGINAL assay). We compared the results of the Cobas-HIGH-RANGE assay with results of the GT-ORIGINAL assay. This study was conducted on serum from 91 patients with chronic hepatitis C at the Gastroenterological Center, Yokohama City University Medical Center. The percent coefficient of variation (CV) for the within-run and between-run reproducibility of the Cobas-HIGH-RANGE assay ranged from 0.7 to 2.3% and from 1.3 to 2.0%, respectively. The Cobas-HIGH-RANGE assay exhibited a linear range extending from 5 to 5000 KIU/ml. The values for all 17 samples determined as less than 0.5 KIU/ml by the GT-ORIGINAL assay were also determined as less than 5 KIU/ml by the Cobas-HIGH-RANGE assay. For the 48 samples with values of 0.5 to 850 KIU/ml determined by the GT-ORIGINAL assay, the values obtained by these two assay methods were significantly correlated (r2 = 0.9117, y = 1.0667x-0.0801, p < 0.001), but the values of HCV-RNA determined by the Cobas-HIGH-RANGE assay were significantly (p < 0.05) higher than those determined by the GT-ORIGINAL assay. Consequently, these data indicate that the HIGH-RANGE assay is a useful alternative assay method for measurement of HCV-RNA instead of the ORIGINAL assay, and that the HIGH-RANGE assay could be a useful tool for monitoring the efficacy of antiviral treatment.