Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ...ciRrhosis (ANSWER) study was designed to clarify this issue.
We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794.
From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 95% CI 0·40–0·95). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events.
In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis.
Italian Medicine Agency.
Blue-light imaging (BLI) is a new chromoendoscopy technique, potentially useful for differentiating neoplastic from nonneoplastic lesions. The present study was aimed at comparing BLI with ...high-definition white light (HDWL) in the real-time histology prediction of colon polyps <10 mm.
Consecutive outpatients undergoing colonoscopy with the ELUXEO 7000 endoscopy platform and 760 series video colonoscopes (Fujifilm Co, Tokyo, Japan) who had at least 1 polyp <10 mm were randomized to BLI or HDWL for polyp characterization. The accuracy of high-confidence real-time histology prediction (adenoma vs not adenoma) by either BLI or HDWL for polyps <10 mm (primary end-point) and diminutive (≤5 mm) polyps was calculated, along with sensitivity, specificity, and positive and negative predictive values, with histopathology as the reference standard.
A total of 483 polyps were detected in 245 randomized patients (125 and 120 in the BLI and HDWL arms, respectively). A total of 358 were diminutive, and 283 were adenomas. Overall, 222 (85.7%) and 193 (86.1%) polyps were characterized with high confidence by BLI and HDWL, respectively (P = .887), with an overall accuracy of 92% and 84%, respectively (P = .011). The accuracy was significantly higher by BLI than HDWL, also for diminutive polyps (92% vs 83%; P = .008). When BLI was used, the negative predictive value for diminutive rectosigmoid polyps was 88%, and the post-polypectomy surveillance interval was correctly attributed in 85.7% and 93.7% of patients, respectively, according to U.S. and European guidelines.
BLI was superior to HDWL for the real-time prediction of histology in polyps <10 mm. A BLI-dedicated classification might further improve the endoscopist performance. (Clinical trial registration number: NCT03274115.)
Many endoscopic technological innovations have claimed to increase the adenoma detection rate (ADR), but their role in population-based organized screening programs is debated.
We searched PubMed, ...EMBASE, and Cochrane Library databases through January 2020 for randomized controlled trials (RCTs) evaluating the role of technological innovations in fecal immunochemical test (FIT)/fecal occult blood test+ subjects. The primary outcome was ADR, and secondary outcomes were advanced ADR, proximal colon ADR, mean adenoma per procedure (MAP), and cancer detection rate. We calculated pooled proportion rates (%) or risk ratio with 95% confidence interval (CI) and degree of heterogeneity (I2).
Overall, 8 high quality RCTs met inclusion criteria with 3645 patients, 1813 (49.7%) in the intervention arm (advanced imaging, 3 studies; mechanical, 5 studies) and 1832 (50.3%) in the standard colonoscopy arm (mean age, 63.6 years). Pooled ADR was 56.5% (95% CI, 49.9%-62.9%) in the intervention arm and 55.9% (95% CI, 48.6%-63%) in the standard colonoscopy arm (relative risk RR, 1.01; 95% CI, .93-1.10; I2 = 50.4%). Similarly, no difference was observed for advanced imaging studies (RR, .95; 95% CI, .85-1.07; I2 = 50.4%) or those with mechanical innovations (RR, 1.04; 95% CI, .92-1.17; I2 = 69.49%). The pooled MAP was 1.5 in the intervention arm (95% CI, 1.2-1.8) and 1.5 in the standard colonoscopy (95% CI, 1.1-1.8), with no significant difference (unstandardized mean difference, .04; 95% CI, –.13 to .20; I2 = 53.6%). No difference in advanced ADR, proximal colon ADR, or cancer detection was found. No significant publication bias was found.
In our systematic review and meta-analysis, no technological improvement significantly increased detection rate of colorectal neoplasia in FIT+ subjects undergoing high-quality colonoscopy by high detectors, arguing against their implementation in organized programs.
A dietary interview performed by expert personnel is considered to be the most appropriate tool to check whether patients with coeliac disease follow a strict gluten-free diet. However, we currently ...have no straightforward and non-subjective method for performing such a dietary interview. We therefore developed a fast questionnaire based on four simple questions with a five-level score (0–IV). To verify whether our questionnaire is an efficient tool, we applied it to 168 coeliac patients (126 females and 42 males; mean age 42·4 (sd 12·9) years) on a gluten-free diet (median 82, 25th–75th percentile 50–108, range 15–389 months). The score we obtained was compared with the persistence of both villous atrophy and endomysial antibodies while on a gluten-free diet. A comparison with survival of the patients was also performed. Patients were interviewed over the phone by non-expert personnel. The questionnaire was completed in less than 1 min. The lowest results were significantly more frequent among the patients with a persistence of both villous atrophy and positive endomysial antibodies. Death risk was also significantly correlated with the lowest score results. We conclude that our questionnaire is a reliable and simple method of verifying compliance with a gluten-free diet.
Background & Aims Terlipressin and albumin is the standard of care for classical type-1 hepatorenal syndrome (HRS) not associated with active infections. However, there is no information on efficacy ...and safety of this treatment in patients with type-1 HRS associated with sepsis. Study aim was to investigate the effects of early treatment with terlipressin and albumin on circulatory and kidney function in patients with type-1 HRS and sepsis and assess factors predictive of response to therapy. Methods Prospective study in 18 consecutive patients with type-1 HRS associated with sepsis. Results Treatment was associated with marked improvement in arterial pressure and suppression of the high levels of plasma renin activity and norepinephrine. Response to therapy (serum creatinine <1.5 mg/dl) was achieved in 12/18 patients (67%) and was associated with improved 3-month survival compared to patients without response. Non-responders had significantly lower baseline heart rate, poor liver function tests, slightly higher serum creatinine, and higher Child-Pugh and MELD scores compared to responders. Interestingly, non-responders had higher values of CLIF-SOFA score compared to responders (14 ± 3 vs. 8 ± 1, respectively p <0.001), indicating greater severity of acute-on-chronic liver failure (ACLF). A CLIF-SOFA score ⩾11 had 92% sensitivity and 100% specificity in predicting no response to therapy. No significant differences were observed between responders and non-responders in baseline urinary kidney biomarkers. Treatment was safe and no patient required withdrawal of terlipressin. Conclusions Early treatment with terlipressin and albumin in patients with type-1 HRS associated with sepsis is effective and safe. Patients with associated severe ACLF are unlikely to respond to treatment.
A dietary interview performed by expert personnel is the best method to check whether patients with coeliac disease follow a strict gluten-free diet (GFD). We previously developed a score based on ...four fast and simple questions that can be administered even by non-expert personnel. The aim of the present study is to verify the reliability of our questionnaire in a new cohort of patients. The questionnaire has a five-level score. From March 2008 to January 2011, the questionnaire was administered to 141 coeliac patients on a GFD, who were undergoing re-evaluation. The score obtained was compared with persistence of both villous atrophy and endomysial antibodies (EMA). The rate of lower scores was higher among the patients with persistence of either villous atrophy (Fisher's exact, P < 0·001; test for trend, P < 0·001) or positive EMA (Fisher's exact, P = 0·001; test for trend, P = 0·018). Given that the coeliac patients have been well instructed on what a GFD means and on how to follow it, our questionnaire is a reliable and simple method to verify compliance to a GFD.
The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and ...remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy.
Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score.
Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5–4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal.
Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin – 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration.
The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.
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•Baseline serum albumin per se should not guide the decision to start albumin therapy.•1-month on-treatment serum albumin levels predict survival and can be used to guide therapy.•The serum albumin target threshold to be pursued is 4.0 g/dl.•Baseline serum albumin and MELD score predict the achievement of this target.•A survival benefit is seen even when on-treatment serum albumin does not normalize.
Both computer-aided detection (CADe)-assisted and Endocuff-assisted colonoscopy have been found to increase adenoma detection. We investigated the performance of the combination of the 2 tools ...compared with CADe-assisted colonoscopy alone to detect colorectal neoplasias during colonoscopy in a multicenter randomized trial.
Men and women undergoing colonoscopy for colorectal cancer screening, polyp surveillance, or clincial indications at 6 centers in Italy and Switzerland were enrolled. Patients were assigned (1:1) to colonoscopy with the combinations of CADe (GI-Genius; Medtronic) and a mucosal exposure device (Endocuff Vision ECV; Olympus) or to CADe-assisted colonoscopy alone (control group). All detected lesions were removed and sent to histopathology for diagnosis. The primary outcome was adenoma detection rate (percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy, advanced adenomas and serrated lesions detection rate, the rate of unnecessary polypectomies (polyp resection without histologically proven adenomas), and withdrawal time.
From July 1, 2021 to May 31, 2022, there were 1316 subjects randomized and eligible for analysis; 660 to the ECV group, 656 to the control group). The adenoma detection rate was significantly higher in the ECV group (49.6%) than in the control group (44.0%) (relative risk, 1.12; 95% CI, 1.00–1.26; P = .04). Adenomas detected per colonoscopy were significantly higher in the ECV group (mean ± SD, 0.94 ± 0.54) than in the control group (0.74 ± 0.21) (incidence rate ratio, 1.26; 95% CI, 1.04–1.54; P = .02). The 2 groups did not differ in term of detection of advanced adenomas and serrated lesions. There was no significant difference between groups in mean ± SD withdrawal time (9.01 ± 2.48 seconds for the ECV group vs 8.96 ± 2.24 seconds for controls; P = .69) or proportion of subjects undergoing unnecessary polypectomies (relative risk, 0.89; 95% CI, 0.69–1.14; P = .38).
The combination of CADe and ECV during colonoscopy increases adenoma detection rate and adenomas detected per colonoscopy without increasing withdrawal time compared with CADe alone. ClinicalTrials.gov, Number: NCT04676308.
Including a mucosal exposure device in artificial intelligence–assisted colonoscopy examinations increased detection of adenomas without affecting safety in a randomized controlled study.
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