Retrospective studies suggest that coffee consumption may exert beneficial effects in patients with nonalcoholic fatty liver; however, prospective data supporting a protective role on liver steatosis ...development are lacking. In this study, we aimed to evaluate the association between coffee consumption and fatty liver onset in the general population. The analysis was performed both in a cross-sectional cohort (n = 347) and, prospectively, in a subcohort of patients without fatty liver at baseline and followed-up for 7 years (n = 147). Fatty liver was diagnosed with abdominal ultrasound and liver steatosis was quantified noninvasively by hepatorenal index (HRI) and SteatoTest, whereas FibroTest was used to assess fibrosis degree. A structured questionnaire on coffee consumption was administrated during a face-to-face interview. Neither the incidence nor the prevalence of fatty liver according to ultrasonography, SteatoTest, and the HRI was associated with coffee consumption. In the cross-sectional study, high coffee consumption was associated with a lower proportion of clinically significant fibrosis ≥F2 (8.8% vs 16.3%; P = 0.038); consistently, in multivariate logistic regression analysis, high coffee consumption was associated with lower odds for significant fibrosis (odds ratio = 0.49, 95% confidence interval, 0.25–0.97; P = 0.041) and was the strongest predictor for significant fibrosis. No association was demonstrated between coffee consumption and the new onset of nonalcoholic fatty liver, but coffee intake may exert beneficial effects on fibrosis progression.
Background & Aims
Non‐alcoholic fatty liver disease (NAFLD) is suspected to confer an increased risk for developing type 2 diabetes (DM). However, only a few prospective studies evaluated NAFLD as a ...predictor for DM, most did not adjust for the full range of potential cofounders and none used an objectively quantified degree of steatosis. Our aim was to evaluate the independent role of NAFLD in predicting the development of pre‐DM in a 7‐year prospective follow‐up of healthy volunteers.
Methods
A prospective cohort of a subsample of the Israeli National Health Survey evaluated at baseline and after 7 years by identical protocols. Metabolic parameters and ultrasonographic evidence of NAFLD were evaluated in 213 subjects, without known liver disease or history of alcohol abuse. Exclusion criteria were pre‐DM at the baseline survey. Steatosis was quantified by ultrasound with the hepato‐renal ultrasound index (HRI).
Results
The study included 141 volunteers (mean age 48.78 ± 9.68, 24.82% with NAFLD) without pre‐DM/DM at baseline. Both NAFLD on regular US (OR=2.93, 1.02–8.41 95%CI) and HRI (OR=7.87, 1.83–33.82) were independent predictors for the development of pre‐DM, adjusting for age, gender, BMI, family history of DM, baseline insulin, adiponectin and glucose. Further adjustment for physical activity and dietary intake did not weaken the association. Furthermore, NAFLD was a stronger predictor for pre‐DM than the metabolic syndrome. Subjects with both NAFLD and glucose ≥89 had 93.3% incidence rate of pre‐DM.
Conclusion
Non‐alcoholic fatty liver disease is a strong and independent risk factor for pre‐DM in the general adult population; thus, NAFLD patients should be classified as a population at risk.
Although colonoscopy is the "gold standard" for colorectal cancer screening, a significant number of adenomas are still missed during standard colonoscopy, often because they are hidden behind ...colonic folds and flexures. The aim of this study was to assess the ability of a novel balloon colonoscope (G-EYE endoscope; Smart Medical Systems, Ra'anana, Israel) to increase adenoma detection and reduce the miss rate compared with standard colonoscopy.
This was a multicenter, randomized, prospective, controlled study in patients (age ≥ 40 years) undergoing colonoscopy for screening or diagnostic work-up (including surveillance). Patients underwent same-day, back-to-back tandem colonoscopy. Patients in Group A underwent standard colonoscopy followed by balloon colonoscopy, and patients in Group B underwent balloon colonoscopy followed by the standard technique. The adenoma detection and miss rates were compared between the two colonoscopy procedures.
A total of 126 patients were enrolled and randomized into Group A (n = 60) or Group B (n = 66). The adenoma miss rate of balloon colonoscopy was significantly lower than that of standard colonoscopy (7.5 % vs. 44.7 %; P = 0.0002). The detection of additional adenomas by balloon colonoscopy was significant (81.0 %; P = 0.0002), in particular, the relative amount of adenomas detected in the ascending colon by balloon colonoscopy was 41 % versus 14 % for standard colonoscopy.
A novel balloon colonoscopy technique detected significantly more adenomas than standard colonoscopy, and missed fewer adenomas. Balloon colonoscopy has the potential to increase the effectiveness of colorectal cancer screening and surveillance colonoscopy.
MicroRNA-132 (miR-132) targets acetylcholinesterase (AChE) and potentiates the cholinergic blockade of inflammatory reactions in cultured cells and experimental mice, but the implications of this ...interaction to human inflammatory disease remained unexplored. This study aimed to test whether miR-132 is causally involved in anti-inflammatory reactions of patients with inflammatory bowel disease (IBD) and modulates vagal tone and consequently inflammation in patients with IBD.
We prospectively measured inflammation readouts and the cholinergic status (total capacity for hydrolyzing acetylcholine in one's circulation), and AChE activity in 2 independent cohorts of patients with IBD and quantified miR-132 levels in intestinal tissue biopsies removed at colonoscopy from inflamed and apparently quiescent tissues of tested volunteers.
MiR-132 levels are higher in inflamed compared with apparently quiescent intestinal biopsies from patients with IBD. Correspondingly, the cholinergic status and AChE activity was significantly lower in patients with IBD suffering from moderate-severe disease as compared with healthy controls or patient with IBD presenting low disease severity. Patients with IBD (n = 16) presented lower AChE activity compared with healthy controls (n = 33; 289 ± 128 AU versus 391 ± 102 AU, P = 0.001), and a negative correlation between AChE activity and C-reactive protein levels (r = -0.47, P = 0.01). Corroborating these observations in an additional cohort of participants, C-reactive protein and AChE activity were negatively correlated in patients with moderate-severe disease (n = 16; r = -0.6, P = 0.04) and positively correlated in healthy controls (n = 74, r = 0.24, P = 0.046).
Taken together, these findings support an inflammation-dependent homeostatic role for the regulation by miR-132 of AChE in IBD, opening new venues for therapeutic interference.
Background & Aims:
New serologic markers of inflammatory bowel disease may be useful for differentiating between Crohn’s disease and ulcerative colitis and for disease stratification. We profiled ...sugar-binding antibodies to identify novel antiglycan antibodies that may be associated with inflammatory bowel disease.
Methods:
Serum samples were obtained from patients with diagnosed Crohn’s disease or ulcerative colitis and from control patients. The presence of antiglycan antibodies was evaluated using either a glycan array (GlycoChip; Glycominds, Ltd, Lod, Israel) in patients with Crohn’s disease (n = 72) or ulcerative colitis (n = 56) and in healthy controls (n = 41) or using an enzyme-linked immunosorbent assay in patients with Crohn’s disease (n = 124), ulcerative colitis (n = 106), and in control patients (n = 101).
Results:
Inaddition to antibodies against mannan, antibodies to laminaribioside (Glcβ1,3Glcβ) and chitobioside (GlcNAcβ1,4GlcNAcβ) had the highest discriminative capability between Crohn’s disease and ulcerative colitis (
P < .001 and
P < .05, respectively). Importantly, 44% (12/27) of anti-
Saccharomyces cerevisiae antibody-negative Crohn’s disease patients were positive for antilaminaribioside or antichitobioside. In patients with inflammatory bowel disease positive for antibodies against either laminaribioside, chitobioside, or mannan, the diagnosis of Crohn’s disease was suggested with a sensitivity of 77.4% and specificity of 90.6%. Having at least 2 of these antibodies increased the specificity to 99.1%. In Crohn’s disease, higher levels of antibodies against laminaribioside or mannan were significantly associated with small intestinal disease (
P = .03 and
P < .0001, respectively).
Conclusions:
Antilaminaribioside and antichitobioside carbohydrate antibodies are novel serologic markers associated with Crohn’s disease. These antibodies may contribute to the diagnosis and improved stratification of Crohn’s disease.
AIM: To examine the association between nonalcoholic fatty liver disease(NAFLD) and general health perception.METHODS: This cross sectional and prospective follow-up study was performed on a cohort ...of a subsample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician’s visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index.RESULTS: Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213(32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association(OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception(OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception(compared to "else") increased among men(OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity(OR = 1.01, 95%CI: 1.00-1.01, P < 0.001, per every minute/week) and decreased with increasing level of BMI(OR = 0.91, 95%CI: 0.84-0.99, P = 0.028, per every kg/m~2) and older age(OR = 0.96, 95%CI: 0.93-0.99, P = 0.033, per one year). Current smoking was not associated with health perception(OR = 1.31, 95%CI: 0.54-3.16, P = 0.552). Newly diagnosed(naive) and previously diagnosed(at the first survey, not naive) NAFLD patients did not differ in their self-health perception. The presence of NAFLD at the first survey as compared to normal liver did not predict health perception deterioration at the 7 years follow-up. In terms of health-services utilization, subjects diagnosed with NAFLD had a similar number of physician’s visits(general physicians and specialty consultants) as in the normal liver group. Parameters in the fatigue impact scale were equivalent between the NAFLD and the normal liver groups.CONCLUSION: Fatty liver without clinically significant liver disease does not have independent impact on selfhealth perception.
Background/Aims There is an increasing body of evidence that serum ferritin is associated with the metabolic syndrome. However, no study has tested for NAFLD. The aim was to test the assumption that ...the association between serum ferritin and the metabolic syndrome is mediated by NAFLD. Methods A cross-sectional study of a sub-sample of the first Israeli national health survey. Exclusion criteria were any known etiology for secondary NAFLD. Participants underwent an abdominal ultrasound (US), biochemical tests, and dietary and anthropometric evaluations. Results Three hundred and forty-nine subjects were included in the analysis. Serum ferritin was higher in the NAFLD group (92.4 ± 63.1 vs. 65.1 ± 58.0, P < 0.001). After adjusting for age and gender, the following variables were significantly associated with increased ferritin levels: abdominal obesity, hyperglycemia, hyperinsulinemia, HOMA, hypertriglyceridemia and the metabolic syndrome itself. After further adjusting for NAFLD, only abdominal obesity 2.1 (1.1–3.9) and hyperinsulinemia 2.3 (1.3–4.2) were still significantly associated with ferritin. In a multivariate analysis the interaction between NAFLD and hyperinsulinemia was the second strongest predictor of serum ferritin ( P = 0.005). Conclusions The association between serum ferritin and the metabolic syndrome is mediated by undiagnosed NAFLD. The interaction between NAFLD and hyperinsulinemia is a major determinant of serum ferritin levels at the population level.
Insulin resistance (IR) is one of the most widespread health problems in modern times. The gold standard for quantification of IR is the hyperinsulinemic-euglycemic glucose clamp technique. During ...the test, a regulated glucose infusion is delivered intravenously to maintain a constant blood glucose concentration. Current control algorithms for regulating this glucose infusion are based on feedback control. These models require frequent sampling of blood, and can only partly capture the complexity associated with regulation of glucose. Here we present an improved clamp control algorithm which is motivated by the stochastic nature of glucose kinetics, while using the minimal need in blood samples required for evaluation of IR. A glucose pump control algorithm, based on artificial neural networks model was developed. The system was trained with a data base collected from 62 rat model experiments, using a back-propagation Levenberg-Marquardt optimization. Genetic algorithm was used to optimize network topology and learning features. The predictive value of the proposed algorithm during the temporal period of interest was significantly improved relative to a feedback control applied at an equivalent low sampling interval. Robustness to noise analysis demonstrates the applicability of the algorithm in realistic situations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The role of screening colonoscopy for colorectal (CR) neoplasia in average-risk population, remains to be determined.
To evaluate the prevalence and anatomic location of CR adenoma and carcinoma and ...the morbidity of colonoscopy in individuals at average risk for CR cancer (CRC).
A retrospective prevalence study of subjects aged 40-80 yr, with no cancer-related symptoms, personal or family history of CR neoplasia, who underwent a colonoscopy.
Enrolled were 1,177 persons; 183 aged 40-49 yr (young), 917 aged 50-75 yr, and 77 aged 76-80 yr (elderly). The prevalence of overall CR neoplasia, advanced neoplasia, and cancer was 20.9%, 6.3%, and 1.1%, respectively. In the 50-75 age group, the prevalence of overall adenoma, advanced neoplasia, and cancer was 21.3%, 6.7%, and 1.2%, respectively. Of the 206 neoplasia cases, 21-43% harbored proximal neoplasia beyond the reach of sigmoidoscopy, without distal lesions. Among the elderly, the prevalence of overall adenoma, advanced neoplasia, and cancer reached 26.0%, 14.3%, and 2.6%, respectively. In the young group, 9.8% had overall neoplasia, 1.1% had advanced adenoma, and none had CRC. Procedure-related morbidity rate was 0.1%, with no perforations, bleedings, or mortality.
Screening colonoscopy in average-risk subjects demonstrated a considerable prevalence of CR neoplasia and proximal lesions beyond the reach of sigmoidoscopy. The morbidity rate was negligible. Primary screening colonoscopy should be considered in health programs for the average-risk population, beginning at the age of 50 yr. The significantly high rate of advanced and proximal neoplasia in the elderly, encourages the inclusion of healthy subjects aged 76-80 yr in future prospective studies.
Background:
Inflammatory bowel disease (IBD) is characterized by increased lymphocytic infiltrate to the lamina propria (LP) and upregulation of inflammatory chemokines and receptors. CXCL12 is a ...constitutive chemokine involved in lung, brain, and joint inflammation. We hypothesized that CXCL12 and its receptor, CXCR4, would have a constitutive and inflammatory role in the gut.
Methods:
Intestinal epithelial cells (IECs) and T lymphocytes were isolated from intestinal mucosa of IBD and control patients undergoing bowel resection. Autologous T cells were isolated from peripheral blood (PB). CXCL12 and CXCR4 expression by IECs was assessed by polymerase chain reaction and immunohistochemistry, lymphocyte phenotype by flow cytometry, and migration by Transwells.
Results:
IECs expressed CXCL12 and expression was increased and more diffuse in IBD compared to normal crypts (ulcerative colitis UC > Crohn's disease CD, inflamed > noninflamed). CXCR4 was expressed by IECs, LP T cells (LPTs), and PB T cells (PBTs), and CXCR4+ cells were increased in IBD LP in situ. PBTs and LPTs from all patients had a high and comparable migration toward CXCL12 (P < 0.0001 and P < 0.05 vs. medium, respectively). Migration toward IBD‐IEC‐derived supernatant was significantly higher compared to normal. Antibodies against CXCR4 and CXCL12 blocked migration.
Conclusions:
CXCL12 is expressed by normal IECs and upregulated and differentially distributed in IBD IECs. CXCR4 is expressed by IECs and LPTs, and CXCR4+ cells are significantly increased in IBD LP. CXCL12 is chemotactic for both PBTs and LPTs. Thus, CXCL12 and CXCR4 have a constitutive and inflammatory role in the intestinal mucosa and their selective therapeutic manipulation may be considered in IBD management. (Inflamm Bowel Dis 2009;)