Comparable quality of bowel preparation with single-day versus three-day low-residue diet: Randomized controlled trial.

BACKGROUND AND AIMS: There is controversy about the length of low-residue diet (LRD) for colonoscopy preparation. The aim of the study was to compare one-day vs. three-day LRD associated to standard laxative treatment for achieving an adequate colonoscopy preparation in average risk subjects with positive fecal immunochemical test undergoing screening colonoscopy. METHODS: A non-inferiority, randomized, controlled, parallel-group clinical trial was performed in the setting of average risk colorectal cancer screening program. Participants were randomized to receive 1-day vs. 3-day LRD in addition to standard polyethilenglicol treatment. Adequacy of preparation was evaluated using the Boston Bowel Preparation Scale (BBPS). Primary outcome was achieving a BBPS ≥ 2 in all colon segments. Analysis was performed for a non-inferiority margin of 5%, a 95% statistical power and one-sided 0.05 significance level. RESULTS: A total of 855 patients were randomized. Adequate bowel preparation was similar between groups: 97.9% of patients in the 1-day LRD group vs 96.9% in the 3-day LRD group achieved the primary outcome (P-value for non-inferiority < 0.001). The percentage of patients with BBPS scores ≥ 8 was superior in the 1-day LRD group (254 vs 221 in the 3-day LRD group, P = 0.032). The 1-day regimen was better tolerated than the 3-day diet. 47.7% (vs 28.7%, P < 0.05) of patients rated the 1-day LRD as very easy to follow. CONCLUSION: The 1-day LRD is non-inferior to 3-day LRD for achieving an adequate colon cleansing before average risk screening colonoscopy and it is better tolerated.

Dominance of highly divergent feline leukemia virus A progeny variants in a cat with recurrent viremia and fatal lymphoma.

BACKGROUND: In a cat that had ostensibly recovered from feline leukemia virus (FeLV) infection, we observed the reappearance of the virus and the development of fatal lymphoma 8.5 years after the initial experimental exposure to FeLV-A/Glasgow-1. The goals of the present study were to investigate this FeLV reoccurrence and molecularly characterize the progeny viruses. RESULTS: The FeLV reoccurrence was detected by the presence of FeLV antigen and RNA in the blood and saliva. The cat was feline immunodeficiency virus positive and showed CD4+ T-cell depletion, severe leukopenia, anemia and a multicentric monoclonal B-cell lymphoma. FeLV-A, but not -B or -C, was detectable. Sequencing of the envelope gene revealed three FeLV variants that were highly divergent from the virus that was originally inoculated (89-91% identity to FeLV-A/Glasgow-1). In the long terminal repeat 31 point mutations, some previously described in cats with lymphomas, were detected. The FeLV variant tissue provirus and viral RNA loads were significantly higher than the FeLV-A/Glasgow-1 loads. Moreover, the variant loads were significantly higher in lymphoma positive compared to lymphoma negative tissues. An increase in the variant provirus blood load was observed at the time of FeLV reoccurrence. CONCLUSIONS: Our results demonstrate that ostensibly recovered FeLV provirus-positive cats may act as a source of infection following FeLV reactivation. The virus variants that had largely replaced the inoculation strain had unusually heavily mutated envelopes. The mutations may have led to increased viral fitness and/or changed the mutagenic characteristics of the virus.

Antiviral therapy increases the risk of bacterial infections in HCV-infected cirrhotic patients awaiting liver transplantation: A retrospective study.

BACKGROUND/AIMS: Recurrence of hepatitis C after liver transplantation (LT) is universal and may cause premature graft loss. We evaluated the efficacy and safety of antiviral therapy in HCV-infected patients with decompensated cirrhosis awaiting LT. METHODS: Fifty-one patients underwent treatment with peginterferon-alfa-2a and ribavirin. A control group of 51 untreated individuals awaiting LT were matched by age, Child-Pugh and MELD scores and time on the waiting list. RESULTS: Case and control patients were comparable for all relevant variables. Fifteen treated patients (29%) had undetectable HCV-RNA at the time of transplantation and 10 (20%) achieved SVR. Early virological response and non-1 genotype were the strongest predictors of viral clearance. There was a higher incidence of bacterial infections in treated patients vs controls, particularly in Child-Pugh B-C individuals (17 vs 3 episodes) (log-rank=0.0016). Importantly, the incidence of spontaneous bacterial peritonitis (SBP) in patients who were not receiving norfloxacin prophylaxis (n=83) was significantly higher in the treated group than in controls (log-rank=0.01). CONCLUSIONS: Our data demonstrate that antiviral treatment prevents hepatitis C recurrence in 20% of HCV-infected patients. However, treatment should be recommended with caution in individuals with poor liver function who do not receive norfloxacin prophylaxis for SBP, since it increases the risk of bacterial infections.

A highly conserved enhancer in mammalian type X collagen genes drives high levels of tissue-specific expression in hypertrophic cartilage in vitro and in vivo.

Previously we have identified a cis-acting regulatory domain in the human type X collagen gene upstream of the transcription start site which acts as a strong enhancer in hypertrophic, but not in resting chondrocytes. Here we show that this enhancer is highly conserved also in the murine and bovine Col10a1 genes, but not found in the known promoter sequences of chicken Col10a1. It contains a functionally active AP-1 site (TPA Responsive Element, TRE) which is essential for the high transcriptional activity of the COL10A1 enhancer in transiently transfected hypertrophic chondrocytes. Gel-shift experiments with nuclear extracts of hypertrophic chondrocytes revealed FosB and Fra-1 as candidates regulating AP-1 factors binding to the TRE site. In fact, coexpression of FosB and Fra-1 in reporter gene assays greatly stimulated transcriptional activity of enhancer bearing reporter genes. Quantitative analysis of AP-1 factor mRNA levels in distinct fractions of fetal bovine epiphyseal chondrocytes by real-time PCR confirmed significant levels of FosB and Fra-1 mRNA besides other AP-1 factors in hypertrophic chondrocytes. A key role of the enhancer element in regulating tissue-specific expression of the Col10a1 gene was shown by establishing transgenic mouse lines with a reporter gene containing a 4.6 kb murine Col10a1 promoter fragment which included the enhancer, exon 1, part of exon 2 and the first intron. Reporter gene expression was seen exclusively in hypertrophic cartilages in the growth plates of long bones, ribs, vertebrae, sternum and mandibles of 17.5-18.5 dpc embryos, confirming that the 4.6 kb promoter is able to drive specific expression of Col10a1 in hypertrophic cartilage. These established transgenic lines should facilitate the genetic analysis of regulatory pathways of chondrocyte maturation and Col10a1 gene expression in the future.

Development and validation of two models for early prediction of response to therapy in genotype 1 chronic hepatitis C.

Early prediction of response to therapy in genotype 1 chronic hepatitis C is difficult. Two predictive models, a pretreatment scoring model (PreT-SM) and a fourth week of therapy scoring model (4w-SM) were constructed in a cohort of 104 patients from a single center (estimation cohort) and validated in a cohort of 141 patients from four independent centers (validation cohort). Individual scores were calculated using variables independently associated with sustained virological response (SVR). Baseline viral load, aspartate aminotransferase/alanine aminotransferase ratio, serum cholesterol, and a numerical score for noninvasive estimation of liver fibrosis were included in the PreT-SM; HCV RNA clearance and PreT-SM scores were included in the 4w-SM. Receiver operating characteristic analysis revealed the area under the curve in the estimation cohort and in the validation cohort to be, respectively, 0.856 and 0.847 for the PreT-SM and 0.908 and 0.907 for the 4w-SM. Low scores were associated with SVR, high scores with non-SVR. The best cutoff scores from the PreT-SM (7 and 9.70) identified, respectively, 36% of patients with SVR and 41% of those with non-SVR from the validation cohort, with high accuracy (> or =90% positive predictive value [PPV] and specificity). Similarly, cutoff scores of 3.20 and 5.60 from the 4w-SM identified, respectively, 71% of patients with SVR and 53% of those with non-SVR from the same cohort with high accuracy (PPV and specificity >92%). In conclusion, these models predicted response to therapy before or after 4 weeks of treatment in approximately 60% of genotype 1 patients and may be valuable for the management of this condition.

Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment.

BACKGROUND & AIMS: Patients with chronic hepatitis C who do not respond rapidly to therapy have a low chance of developing a sustained virologic response (SVR) when treated for 48 weeks. This study investigated whether treatment for 72 weeks increases the rate of SVR in patients with detectable hepatitis C virus (HCV)-RNA levels at week 4 of treatment. METHODS: A total of 510 treatment-naive patients were treated with peginterferon-alfa2a (180 microg/wk) plus ribavirin (800 mg/day). Patients with detectable HCV-RNA levels at week 4 (n = 326) were randomized to complete 48 (group A, n = 165) or 72 weeks (group B, n = 161) of treatment. Patients with undetectable HCV-RNA levels at week 4 (n = 184) were allocated into group C (n = 148) or group D (n = 36), according to HCV genotype and baseline viremia, and treated for 24 or 48 weeks, respectively. All patients were followed-up for 24 weeks after the end of treatment. RESULTS: The end-of-treatment response rate (61%) was similar in groups A and B, but the SVR rate was higher in group B (45% vs 32% in A; P = .01). In genotype 1-infected patients randomized to group A (n = 149) or B (n = 142), SVR rates were 28% and 44%, respectively (P = .003). The incidence of adverse events was similar in all groups. Treatment discontinuation was more frequent in group B (36%) than in group A (18%) (P = .0004). SVR rates in groups C and D were 79% and 64%, respectively. CONCLUSIONS: Extension of treatment with peginterferon-alfa2a plus ribavirin from 48 to 72 weeks significantly increases the rate of SVR in patients with detectable viremia at week 4 of treatment.